Erratum zu:
HNO 2018 66:472–479
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Die Autoren möchten auf einen Tippfehler im Manuskript hinweisen. Dabei wurde die Arbeit von Maxwell et al. [40] zitiert, welche die Bedeutung der Kopf-Anteflexion für die Durchführung des vKIT untersucht hat. Diese Arbeit kam zu dem …
Multinucleate cell angiohistiocytoma (MCAH) is a rare cutaneous disease entity characterized by multiple red‐to‐brown or violaceous papules usually located on the acral regions such as the face and the distal arms and legs. It affects elderly women more than men and hardly occurs at a young age. The exact pathogenic mechanism of MCAH is not yet clearly understood.
We report an exceptionally rare case of a 14‐year old boy who presented with multiple asymptomatic erythematous papules and a single flat brownish plaque on the left chest. The brownish plaque lesion histologically showed proliferation of dilated small vessels in the upper‐mid dermis and numerous oddly shaped multinucleate cells intermingled with lymphocytes and macrophages. The erythematous papules also showed dilated small vessels in the upper‐mid dermis and multiple interstitial histiocytic infiltrations, but no multinucleate cells were detected. In immunohistochemistry studies, CD68 and vimentin staining were positive for both specimens. Based on the clinicopathological findings and immunohistochemistry studies, MCAH was diagnosed.
To the best of our knowledge, this is the first case report of MCAH occurring in young age and showing two different clinical and histological phases at the same time.
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AbstractBackground.Interventions aimed at improving access to timely cancer care for patients in low‐ and middle‐income countries (LMIC) are urgently needed. We aimed to evaluate a patient navigation (PN) program to reduce referral time to cancer centers for underserved patients with a suspicion or diagnosis of cancer at a public general hospital in Mexico City.Materials and Methods.From January 2016 to March 2017, consecutive patients aged >18 years with a suspicion or diagnosis of cancer seen at Ajusco Medio General Hospital in Mexico City who required referral to a specialized center for diagnosis or treatment were enrolled. A patient navigator assisted patients with scheduling, completing paperwork, obtaining results in a timely manner, transportation, and addressing other barriers to care. The primary outcome was the proportion of patients who obtained a specialized consultation at a cancer center within the first 3 months after enrollment.Results.Seventy patients (median age 54, range 19–85) participated in this study. Ninety‐six percent (n = 67) identified >1 barrier to cancer care access. The most commonly reported barriers to health care access were financial burden (n = 50) and fear (n = 37). Median time to referral was 7 days (range 0–49), and time to specialist appointment was 27 days (range 1–97). Ninety‐one percent of patients successfully obtained appointments at cancer centers in <3 months.Conclusion.Implementing PN in LMIC is feasible, and may lead to shortened referral times for specialized cancer care by helping overcome barriers to health care access among underserved patients.Implications for Practice.A patient navigation program for patients with suspicion or diagnosis of cancer in a second‐level hospital was feasible and acceptable. It reduced patient‐reported barriers, and referral time to specialized appointments and treatment initiation were within international recommended limits. Patient navigation may improve access to care for underserved patients in developing countries.
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Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0787-1382
Background Enhanced platelet reactivity represents one of the major determinants of cardiovascular risk among diabetic patients. The aim of the present study was to evaluate the impact of metformin use on platelet reactivity in diabetic patients receiving dual antiplatelet therapy (DAPT). Methods We included diabetic patients treated with DAPT after an acute coronary syndrome or percutaneous coronary intervention. Platelet reactivity was assessed at 30–90 days by Multiple-electrode aggregometry. In an additional cohort of diabetic patients naïve to antiplatelet therapy, we assessed platelet reactivity by light transmission aggregometry, surface expression of P-selectin and plasma concentration of Thromboxane B2 (TxB2). Results We included 219 diabetic patients, 117 (53.4%) treated with metformin. Metformin was associated with younger age (p=0.03), male gender (p=0.02), lower rate of hypertension (p=0.04), active smoker (p=0.002), previous MI (p<0.001) renal failure (p<0.001), fibrinogen (p<0.001) and C-reactive protein (p=0.04), larger use of diuretics (p=0.04) calcium antagonists (p=0.05), better glycemic control (p<0.001) and higher haemoglobin (p=0.003). The prevalence of HAPR did not significantly differ according to hypoglycemic treatment (p=0.73; adjusted OR[95%CI]=5.63[0.42-76], p=0.19). Moreover, no impact of metformin was observed for HRPR (p=0.77; adjusted OR[95%CI]=1.15[0.55-2.4], p=0.71). Among an additional cohort of 42 diabetic patients naïve to antiplatelet therapy, we confirmed no impact of metformin or insulin on aggregation. Conclusions Our study found no apparent association in diabetic patients treated with DAPT, between the use of metformin and platelet reactivity or the rate of HPR.
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Presentation of Case. Dr. Seth N. Levin (Neurology): A 23-year-old right-handed woman with a history of migraines was evaluated at this hospital for vertigo and vision loss affecting the right eye. Six days before admission, a right frontal headache and right retro-orbital pain developed; these…
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Presentation of Case. Ms. Diane P. Doyle, M.S.N. (Medicine): A 68-year-old woman with a history of bilateral breast cancer was evaluated at the oncology clinic of this hospital for back and pelvic pain. Twenty-five years before the current evaluation, the patient was noted to have a small lump in…
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Phosphorylcholine (PC) is a structural component of Streptococcus pneumoniae (Spn) and nontypeable Haemophilus influenzae (NTHi), and is known to be associated with adherence through the platelet activating factor receptor (PAF-R). Furthermore, high PC expression is considered to be involved in Spn and NTHi virulence. In this study, we examined the influence of PC expression on the adherence of Spn and NTHi to epithelial cells in order to clarify the potential effectiveness of a vaccine targeting PC.
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To employ magnetic resonance imaging (MRI) to measure the volume of the inner ear endolymphatic space (ELS) in patients with acute low-tone sensorineural hearing loss (ALHL), sudden deafness (SD), cochlear Meniere's disease (cMD), and unilateral MD (uMD) compared with control subjects (CS) with chronic rhinosinusitis.
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In the ethical considerations section of the article, the ethical committee should read as follows: "The University of Tokyo, Graduate School of Medicine".
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While systematic reviews are regarded as the strongest level of medical evidence, inconsistency in the quality and rigor of systematic reviews raises concerns about their use as a tool in guiding quality delivery in evidence-based clinical practice. The objective of this present study was to assess methodological soundness of systematic reviews with a particular focus on peripheral nerve repair and reconstruction.We performed a comprehensive search using PubMed and Scopus to identify all systematic reviews published on peripheral nerve reconstruction in 9 high-impact surgical journals.
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Atopic dermatitis (AD) results from a complex interplay of host genetic and environmental factors. There is a long established association between AD and Staphylococcus aureus. In healthy individuals this organism has a dichotomous relationship with the host, being a frequent component of the human microbiome, carried asymptomatically, and on occasion, an opportunistic pathogen capable of causing or influencing a broad ranging disease. In AD, high carriage rates of S. aureus on affected skin is commonly observed, with recent meta-analysis evidence demonstrating colonisation in approximately 70% of affected individuals 1.
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Interleukin(IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) underlie the crosstalk between epithelial cells and dendritic cells (DCs) during the development of Th2 responses. This study aimed to measure...
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The aim of this study was to study the incidence of Y chromosome microdeletions in a Caucasian population of Klinefelter syndrome (KS) patients and to investigate the possible association between Y chromosome microdeletions and KS.
We conducted a retrospective study on 118 KS patients, 429 patients with non-obstructive azoospermia (NOA), and 155 normozoospermic men. Eight of the 118 KS patients had undergone testicular sperm extraction (TESE). All patients underwent semen examination and Y chromosome microdeletions evaluated by PCR, using specific sequence tagged site (STS) primer sets, which spanned the azoospermia factor AZFa, AZFb, and AZFc regions of the Y chromosome.
Semen analysis of the KS group revealed: 1 patient with oligozoospermia, 1 with severe oligoasthenoteratozoospermia, 2 with cryptozoospermia, and 114 with azoospermia. Eight of the 114 azoospermic KS patients underwent TESE, and spermatozoa were recovered from three of these, all of whom had non-mosaic karyotype 47, XXY. 10.7% of the NOA patients presented AZF microdeletions. In 429 cases with NOA, 8 cases had AZFa + b + c deletion, 6 cases had AZF b + c deletion, 4 cases had AZFa microdeletion, 8 cases had AZFb microdeletion, and 20 cases had AZFc microdeletion. Just one KS patient (0.8%) presented microdeletion in the AZFc region.
The percentage of microdeletions in KS patients was lower than in NOA patients, suggesting that AZF microdeletions and KS do not have a causal relationship and that Y chromosome microdeletions are not a genetic factor linked to KS.
The main aim of this study was to describe switching practices in daily practice. Patients included were those seen in daily routine practice. Efficacy was defined as the achievement of at least 75% improvement in the PASI score (PASI75). A total of 1,157 patients were included. The frequency of switching was 29.9% and switching was efficient in 71.9% of the cases. The study's results allows a better understanding of the profile of patients who require switch and he appears a change of therapeutic class appears to be more effective in psoriasis patients who require a switch in their therapy.
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The main aim of this study was to describe switching practices in daily practice. Patients included were those seen in daily routine practice. Efficacy was defined as the achievement of at least 75% improvement in the PASI score (PASI75). A total of 1,157 patients were included. The frequency of switching was 29.9% and switching was efficient in 71.9% of the cases. The study's results allows a better understanding of the profile of patients who require switch and he appears a change of therapeutic class appears to be more effective in psoriasis patients who require a switch in their therapy.
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The incidence of viral hepatitis B or C (HBV/HCV) infection and hepatocellular carcinoma is higher in male compared to female populations, showing a faster disease progression and results in a worse overall survival. Indeed, women are in general better protected from viral infections and show a lower risk of death from malignant cancer in comparison to men. Females mount stronger innate and adaptive immune responses than males, and therefore, most of the autoimmune diseases occur predominantly in females. Next to occupational and/or behavioral factors, cellular and molecular differences between the two sexes contribute to this observation. In this review, we will discuss underlying mechanisms that are important for the observed sex-related differences in liver diseases. A better appreciation of these differences between the two sexes might be of value for better and gender-specific treatment options.
Publication date: January 2019
Source: Molecular Immunology, Volume 105
Author(s): Ali N. Kamali, Seyedeh Masoomeh Noorbakhsh, Haleh Hamedifar, Farhad Jadidi-Niaragh, Reza Yazdani, José M. Bautista, Gholamreza Azizi
The T helper 17 (Th17) cells contain a dynamic subset of CD4+ T-cells that are able to develop into other different lineage subsets, including the Th1-like Th17 cells. These cells co-express retinoic acid-related orphan receptor gamma t (RORγt) and transcription factor T-box-expressed-in-T-cells (T-bet) and produce both interleukin (IL)-17 and interferon (IFN)-γ. Recent reports have shown that Th1-like Th17 cells play crucial roles in the pathogenesis of autoimmune diseases such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, as well as, some primary immunodeficiency with autoimmune features. Here, the actual mechanisms for Th17 cells plasticity to Th1-like Th17 cells are discussed and reviewed in association to the role that Th1-like Th17 cells have on inflammatory and autoimmune disorders.
Publication date: January 2019
Source: Molecular Immunology, Volume 105
Author(s): Susannah C. Shissler, Tonya J. Webb
Natural killer T (NKT) cells are innate-like lymphocytes that bridge the gap between the innate and adaptive immune responses. Like innate immune cells, they have a mature, effector phenotype that allows them to rapidly respond to threats, compared to adaptive cells. NKT cells express T cell receptors (TCRs) like conventional T cells, but instead of responding to peptide antigen presented by MHC class I or II, NKT cell TCRs recognize glycolipid antigen in the context of CD1d. NKT cells are subdivided into classes based on their TCR and antigen reactivity. This review will focus on type I iNKT cells that express a semi invariant Vα14Jα18 TCR and respond to the canonical glycolipid antigen, α-galactosylceramide. The innate-like effector functions of these cells combined with their T cell identity make their developmental path quite unique. In addition to the extrinsic factors that affect iNKT cell development such as lipid:CD1d complexes, co-stimulation, and cytokines, this review will provide a comprehensive delineation of the cell intrinsic factors that impact iNKT cell development, differentiation, and effector functions – including TCR rearrangement, survival and metabolism signaling, transcription factor expression, and gene regulation.
Publication date: Available online 28 November 2018
Source: Molecular Immunology
Author(s): Anju Manuja, Balvinder K. Manuja, Harisankar Singha
Significant structural differences in the extracellular domain of toll-like receptor 9 (TLR9) account for species-specific recognition of its ligand CpG-ODN sequences. TLR9 is extensively studied in human, mice and some domestic animals. The recognition ability appears to be utilized differently by various species and breeds, but so far no comprehensive study exists about the equine TLR9 gene. We characterized TLR9 sequences of Marwari and Zanskari breeds of horses and Poitu donkey. We sequenced and identified the protein coding regions of equine TLR9 and compared with other animals and human beings. Furthermore, we also analyzed the amino acid substitutions and their likely implications on functions. The analysis revealed 14% evolutionary divergence between equine and human TLR9, while it was 1% between the Equus caballus and Equus asinus and less than 1% within Equus caballus. In phylogenetic analysis of predicted amino acids, the indigenous equines grouped with thoroughbred Equus caballus, while human, cattle, dog, sheep, mice, and buffalo formed separate clades. Furthermore, we also analyzed the amino acid substitutions and their likely implications on functions by sorting intolerant from tolerant (SIFT) analysis and predicted two substitutions of amino acids (D80N and S822P) in Marwari horses in leucine rich repeat 1 (LRR1) without any functional effects. The substitutions (V214A and Y579C) in LRR 3 and LRR11 in Zanskari horses were predicted to have functional consequences. Out of overall 8 substitutions, three substitutions (I420V, S970R and R1001C) were found in Equus asinus in LRR7, LRR 13, and toll interleukin receptor (TIR) domains, while the substitution G649S is observed in Poitu donkey only. We report for the first time that despite the conserved residues, the striking effect of substitutions, found within the TLR9 genes of different equine breeds/species may have possible implications.
Publication date: Available online 29 November 2018
Source: Cortex
Author(s): Elena Daprati, Angela Sirigu, Daniele Nico
It has been suggested that agency signals generated by enactment provide memories with an enduring, episodic, marker that can successively be exploited to facilitate recall. Current theories of motor awareness highlight the role of prospective and retrospective sensorimotor cues in the construction of sense of agency (SA). To explore how these signals impact on memory for actions, we studied the effect of enactment in a patient with complete loss of somatic sensation below nose level, and compared her performance to that of a group of neurologically intact individuals. A memory advantage for enacted material was clearly detectable in the control group and, interestingly, also in sensory deafferented patient GL. This novel finding shows that robust memory for actions can be obtained even in the absence of somatosensory reafferences. We hypothesize that the neural processes evoked by intention to move, together with visual experience about one's actions, provide the long-lasting agency signals that are responsible for the special quality of self-performed actions and may support autobiographical experience. Proprioceptive cues, being more time-constrained, are critical to online SA but do not necessarily partake in offline action representations.
Publication date: Available online 28 November 2018
Source: Cortex
Author(s): Elisa Battistoni, Daniel Kaiser, Clayton Hickey, Marius V. Peelen
In daily life, attention is often directed to high-level object attributes, such as when we look out for cars before crossing a road. Previous work used MEG decoding to investigate the influence of such category-based attention on the time course of object category representations. Attended object categories were more strongly represented than unattended categories from 180 ms after scene onset. In the present study, we used a similar approach to determine when attention is spatially focused on the target. Participants completed two tasks. In the first, they detected cars and people at varying locations in photographs of real-world scenes. In the second, they detected a cross that appeared at salient locations in an array of lines. Multivariate classifiers were trained on data of the artificial salience experiment and tested on data of the naturalistic visual search experiment. Results showed that the location of both target and distracter objects could be accurately decoded shortly after scene onset (50 ms). However, the emergence of spatial attentional selection – reflected in better decoding of target location than distracter location – emerged only later in time (240 ms). Target presence itself (irrespective of location and category) could be decoded from 180 ms after stimulus onset. Combined with earlier work, these results suggest that naturalistic category search operates through an initial spatially-global modulation of category processing that then guides attention to the location of the target.
The clinical sequelae of oestrogen deficiency during menopause are undoubted. However, the pathophysiological role of testosterone during the menopause is less clear. Several randomised, placebo–controlled clinical trials suggest that testosterone therapy improves sexual function in post‐menopausal women. Some studies suggest that testosterone therapy has additional effects which include increased bone mineral density and decreased serum high density lipoprotein (HDL) cholesterol. Furthermore, the long‐term safety profile of testosterone therapy in post‐menopausal women is not clear. This article will provide a concise and critical summary of the literature, to guide clinicians treating post‐menopausal women.
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TSH receptor antibodies (TRAb) are responsible for autoimmune hyperthyroid disease (Graves' disease; GD) with TRAb levels tending to decrease following treatment. Measurement of TRAb activity during follow up could prove valuable to better understand treatment effectiveness.
TRAb concentration and stimulating (TSAb) and blocking (TSBAb) activity of patient serum were assessed following different treatment modalities and follow up length.
Sixty‐six subjects were recruited following treatment with carbimazole (n=26), radioiodine (n=27) or surgery (n=13). TRAb, TPO‐Ab, Tg‐Ab and GAD‐Ab were measured at a follow up visit as well as bioassays of TSAb and TSBAb activity.
Forty five percent of all patients remained TRAb positive for more than one year and 23% for more than 5 years after diagnosis, irrespective of treatment method. Overall, TRAb concentration fell from a median (IQR) of 6.25 (3.9‐12.7) to 0.65 (0.38‐3.2) U/L. Surgery conferred the largest fall in TRAb concentration from 11.4 (6.7‐29) to 0.58 (0.4‐1.4) U/L. Seventy percent of TRAb positive patients were positive for TSAb and 1 patient (3%) was positive for TSBAb. TRAb and TSAb correlated well (r = 0.83). In addition, 38/66 patients were Tg‐Ab positive, 47/66 TPO‐Ab positive and 6/66 were GADAb positive at follow up.
TRAb levels generally decreased after treatment but persisted for over 5 years in some patients. TRAb activity was predominantly stimulatory, with only one patient demonstrating TSBAb. A large proportion of patients were Tg‐Ab/TPO‐Ab positive at follow up. All treatment modalities reduced TRAb concentrations, however surgery was most effective.
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Glucocorticoids have been shown to improve outcome in community‐acquired pneumonia (CAP). However, glucocorticoids have potential side‐effects, and treatment response may vary. It is thus crucial to select patients with high likelihood to respond favorably. In critical illness, cosyntropin testing is recommended to identify patients in need for glucocorticoids. We investigated whether consyntropin testing predicts treatment response to glucocorticoids in CAP.
We performed 1μg cosyntropin tests in a randomized trial comparing prednisone 50mg for seven days to placebo. We investigated whether subgroups based on baseline and stimulated cortisol levels responded differently to glucocorticoids with regards to time to clinical stability (TTCS) and other outcomes by inclusion of interaction terms into statistical models.
326 patients in the prednisone and 309 patients in the placebo group were evaluated. Neither basal cortisol nor a Δcortisol<250nmol/L after stimulation nor the combination of basal cortisol and Δcortisol predicted treatment response as measured by TTCS (all p for interaction>0.05). Similarly, we found no effect modification with respect to mortality, rehospitalization, antibiotic treatment duration or CAP‐related complications (all p for interaction>0.05). However, glucocorticoids had a stronger effect on shortening length of hospital stay in patients with a baseline cortisol of ≥938 nmol/L (p for interaction=0.015).
Neither baseline nor stimulated cortisol after low‐dose cosyntropin testing at a dose of 1 μg predicted glucocorticoid responsiveness in mild to moderate CAP. A treatment decision for or against adjunct glucocorticoids in CAP should not be made depending on cortisol values or cosyntropin testing results.
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Little is known about the attitudes of radiation oncologists towards palliative care, about their competences in this field, and about the collaboration with palliative care specialists. Our aim was to close this gap and understand more about the importance of an additional qualification in palliative care.
Medical members of the German Society for Radiation Oncology (DEGRO) were electronically surveyed during November–December 2016.
The survey was emailed successfully to 1110 addressees, whereas a total of 205 questionnaires were eligible for analysis (response rate 18.4%). 55 (26.8%) of the respondents had an additional qualification in palliative care. Physicians who had an additional qualification in palliative care (PC qualification) reported palliative care needs for their patients more frequently than the other respondents (89.0 vs. 82.7%, p = 0.008). Furthermore, they were most likely to report a high confidence in palliative care competences, such as "communication skills & support for relatives" (83.6 vs. 59.3%, p = 0.013), "symptom control," and "pain management" (94.5 vs. 67.7%, p < 0.001 and 90.9 vs. 73.3%, p = 0.008, respectively). Respondents with a PC qualification more often involved palliative care specialists than the other respondents (63.3 vs. 39.3%, p = 0.007). Perceived main barriers regarding palliative care in radiation oncology included time aspects (9.2%), stigmata (8.5%), and the lack of interdisciplinary collaboration (8.5%).
This analysis demonstrated that aspects of palliative care strongly impact on daily practice in radiation oncology. Additional qualifications and comprehensive training in palliative medicine may contribute to improved patient care in radiation oncology.
To date, 16 states in the US restrict minors from using tanning beds.1 The principal argument against policy restricting indoor tanning is the concern it would harm small businesses.2‐4 One counterargument is that tanning businesses could stay financially viable by offering UV‐free sunless tanning services (e.g., spray or airbrush tanning) which would serve customers' desire for a tan while not exposing them to the risks associated with ultraviolet (UV) radiation exposure. Sunless only tanning businesses are already in existence and owners may provide insights on this alternative business model.
This article is protected by copyright. All rights reserved.
Vemurafenib is approved in more than 90 countries for the treatment of patients with BRAF V600‐mutated metastatic melanoma.1,2 In the pivotal BRIM‐3 trial, treatment‐emergent cutaneous side effects were associated with vemurafenib, including the development of epithelial tumours and, in rare cases, new primary melanomas.3,4 QTc interval prolongation and hepatic laboratory abnormalities were also noted.3,4
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Autologous cell suspension is a well‐demonstrated effective approach for treating segmental or stable and localized forms of vitiligo1. Full surface dermabrasion is considered as the gold standard technique for preparing the skin before grafting. Fractional ablative laser or microneedling have been shown to enhance the penetration into the skin of topical agents2.
This article is protected by copyright. All rights reserved.
Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterised by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS.
To investigate the association of variants of the MEFV gene with a complex HS phenotype.
First, we identified the clinical characteristics of 119 HS patients with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (OR) for pathogenic MEFV mutations were calculated using data from these HS patients and 191 healthy controls.
The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with HS patients in general. Five of the HS patients (4.2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 (CI: 16.50‐99.84, p<0.001) when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The odds ratio for carrying a pathogenic MEFV allele was 2.80 (CI: 1.31‐5.97, p<0.001).
The frequency of MEFV mutations in a group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies.
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Long‐term evaluation is required to confirm the safety profile of newer biologic agents. Objectives
To report on pooled safety data from the on‐going VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244) trials through 100 weeks of follow‐up.
Patients were randomized to guselkumab 100 mg at weeks 0 and 4 and every‐8‐weeks thereafter; placebo at weeks 0, 4, 12 followed by guselkumab 100 mg at weeks 16 and 20 and every‐8 weeks thereafter; or adalimumab 80 mg at week 0, 40 mg at week 1, and 40 mg every 2 weeks thereafter. Adalimumab patients crossed over to guselkumab at week 52 (VOYAGE1) and at/after week 28 based on clinical response (VOYAGE2). Open‐label extensions, when all patients received guselkumab, started at week 52 (VOYAGE1) and week 76 (VOYAGE2). Rates of adverse events (AEs) per 100 patient‐years [PY] are presented through 100 weeks of follow up.
Through week 52, observed rates for guselkumab‐ and adalimumab‐treated patients, respectively, were 262.45/100PY and 328.28/100PY for AEs, 6.20/100PY and 7.77/100PY for serious AEs (SAEs), 1.22/100PY and 1.79/100PY for serious infections (SIs), 0.28/100PY and 0.40/100PY for malignancies other than nonmelanoma skin cancers (NMSCs), 0.56/100PY and 0.40/100PY for NMSCs, and 0.47/100PY and 0.40/100PY for MACE. Rates among guselkumab‐treated patients through week 52 and week 100, respectively, were (262.45/100PY and 210.41/100PY) for AEs, 6.20 and 6.29/100PY), for SAEs, 1.22/100PY and 1.06/100PY for SIs, 0.28/100PY and 0.38/100PY for malignancies, 0.56/100PY and 0.39/100PY for NMSCs, and 0.47/100PY and 0.38/100PY for MACE. Among adalimumab‐treated patients, rates of AEs (328.28/100PY vs 160.15/100PY), SAEs (7.77/100PY vs 4.44/100PY), SIs (1.79/100PY vs 0/100PY), malignancies (0.40/100PY vs 0.40/100PY), NMSCs (0.40/100PY vs 0.81/100PY), and MACE (0.40/100PY vs 0.20/100PY) showed some variability before and after crossover to guselkumab, though no new safety signals were noted after crossover.
The safety profile for guselkumab remains favorable through 100 weeks of treatment in patients with moderate‐to‐severe psoriasis.
This article is protected by copyright. All rights reserved.
To date, 16 states in the US restrict minors from using tanning beds.1 The principal argument against policy restricting indoor tanning is the concern it would harm small businesses.2‐4 One counterargument is that tanning businesses could stay financially viable by offering UV‐free sunless tanning services (e.g., spray or airbrush tanning) which would serve customers' desire for a tan while not exposing them to the risks associated with ultraviolet (UV) radiation exposure. Sunless only tanning businesses are already in existence and owners may provide insights on this alternative business model.
This article is protected by copyright. All rights reserved.
Vemurafenib is approved in more than 90 countries for the treatment of patients with BRAF V600‐mutated metastatic melanoma.1,2 In the pivotal BRIM‐3 trial, treatment‐emergent cutaneous side effects were associated with vemurafenib, including the development of epithelial tumours and, in rare cases, new primary melanomas.3,4 QTc interval prolongation and hepatic laboratory abnormalities were also noted.3,4
This article is protected by copyright. All rights reserved.
Autologous cell suspension is a well‐demonstrated effective approach for treating segmental or stable and localized forms of vitiligo1. Full surface dermabrasion is considered as the gold standard technique for preparing the skin before grafting. Fractional ablative laser or microneedling have been shown to enhance the penetration into the skin of topical agents2.
This article is protected by copyright. All rights reserved.
Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterised by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS.
To investigate the association of variants of the MEFV gene with a complex HS phenotype.
First, we identified the clinical characteristics of 119 HS patients with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (OR) for pathogenic MEFV mutations were calculated using data from these HS patients and 191 healthy controls.
The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with HS patients in general. Five of the HS patients (4.2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 (CI: 16.50‐99.84, p<0.001) when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The odds ratio for carrying a pathogenic MEFV allele was 2.80 (CI: 1.31‐5.97, p<0.001).
The frequency of MEFV mutations in a group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies.
This article is protected by copyright. All rights reserved.
Long‐term evaluation is required to confirm the safety profile of newer biologic agents. Objectives
To report on pooled safety data from the on‐going VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244) trials through 100 weeks of follow‐up.
Patients were randomized to guselkumab 100 mg at weeks 0 and 4 and every‐8‐weeks thereafter; placebo at weeks 0, 4, 12 followed by guselkumab 100 mg at weeks 16 and 20 and every‐8 weeks thereafter; or adalimumab 80 mg at week 0, 40 mg at week 1, and 40 mg every 2 weeks thereafter. Adalimumab patients crossed over to guselkumab at week 52 (VOYAGE1) and at/after week 28 based on clinical response (VOYAGE2). Open‐label extensions, when all patients received guselkumab, started at week 52 (VOYAGE1) and week 76 (VOYAGE2). Rates of adverse events (AEs) per 100 patient‐years [PY] are presented through 100 weeks of follow up.
Through week 52, observed rates for guselkumab‐ and adalimumab‐treated patients, respectively, were 262.45/100PY and 328.28/100PY for AEs, 6.20/100PY and 7.77/100PY for serious AEs (SAEs), 1.22/100PY and 1.79/100PY for serious infections (SIs), 0.28/100PY and 0.40/100PY for malignancies other than nonmelanoma skin cancers (NMSCs), 0.56/100PY and 0.40/100PY for NMSCs, and 0.47/100PY and 0.40/100PY for MACE. Rates among guselkumab‐treated patients through week 52 and week 100, respectively, were (262.45/100PY and 210.41/100PY) for AEs, 6.20 and 6.29/100PY), for SAEs, 1.22/100PY and 1.06/100PY for SIs, 0.28/100PY and 0.38/100PY for malignancies, 0.56/100PY and 0.39/100PY for NMSCs, and 0.47/100PY and 0.38/100PY for MACE. Among adalimumab‐treated patients, rates of AEs (328.28/100PY vs 160.15/100PY), SAEs (7.77/100PY vs 4.44/100PY), SIs (1.79/100PY vs 0/100PY), malignancies (0.40/100PY vs 0.40/100PY), NMSCs (0.40/100PY vs 0.81/100PY), and MACE (0.40/100PY vs 0.20/100PY) showed some variability before and after crossover to guselkumab, though no new safety signals were noted after crossover.
The safety profile for guselkumab remains favorable through 100 weeks of treatment in patients with moderate‐to‐severe psoriasis.
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Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2‐mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic need. Dupilumab, a fully human monoclonal antibody targeting the interleukin‐4 receptor α (IL‐4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (e.g. atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo‐controlled, phase 2 trial (NCT01920893).
Cytokines, chemokines, and total immunoglobulin E (IgE) levels were measured using immunoassay techniques in nasal secretions and nasal polyp tissue homogenates of CRSwNP patients receiving dupilumab 300 mg or placebo weekly for 16 weeks.
With dupilumab, type 2 biomarker concentrations decreased in nasal secretions (LS mean area under the curve from 0–16 weeks for the change from baseline) vs placebo for eotaxin‐3 (−30.06 vs −0.86 pg/mL; P=0.0008) and total IgE (−7.90 vs −1.86 IU/mL; P=0.022)). Dupilumab treatment also decreased type 2 biomarker levels in nasal polyp tissues at Week 16 versus baseline for ECP (P=0.008), eotaxin‐2 (P=0.008), eotaxin‐3 (P=0.031), pulmonary and activation‐regulated chemokine (P=0.016), IgE (P=0.023), and IL‐13 (P=0.031).
Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL‐4Rα signaling suppresses IL‐4‐/IL‐13‐dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa.
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Wounds close by keratinocytes migrating from the edge of the wound and re‐epithelializing the epidermis. It has been proposed that the major stimuli for wound closure are blood‐derived growth factors, chemokines, and cytokines. The small GTPase R‐Ras, a known integrin activator, also regulates vascular permeability during angiogenesis, and blood vessels lacking R‐Ras leak plasma proteins constantly. We explored whether the access to blood‐derived proteins influences skin wound healing in R‐Ras knockout (KO) mice. In skin wounds, R‐Ras expression was mostly restricted to the vasculature in the granulation tissue. Angiogenic blood vessels in the R‐Ras KO mice were significantly more permeable than in wild‐type (WT) controls. Although the distances between epidermal tongues, and the panniculus carnosus muscles, were significantly longer in R‐Ras KO than WT controls before the granulation tissue formation took place, there were no differences in the wound closure or re‐epithelialization rates or granulation tissue formation. These findings were also corroborated in a special splint excision wound model. Our study shows that although R‐Ras does not influence the skin wound healing itself, but the blood vessels lacking R‐Ras are leaky and thus could facilitate the access of blood‐derived proteins to the wound.
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Empty nose syndrome (ENS) is a rare and debilitating disease with a controversial definition, etiology, and treatment. One puzzling fact is that patients who undergo an endoscopic endonasal approach (EEA) often have resection of multiple anatomic structures, yet seldom develop ENS. In this pilot study, we analyzed and compared the computational fluid dynamics (CFD) and symptoms among post‐EEA patients, ENS patients, and healthy subjects.
Computed tomography scans of 4 post‐EEA patients were collected and analyzed using CFD techniques. Two patients had significant ENS symptoms based on results of the Empty Nose Syndrome 6‐item Questionnaire (score >11), whereas the other 2 were asymptomatic. As a reference, their results were compared with previously published CFD results of 27 non‐EEA ENS patients and 42 healthy controls.
Post‐EEA patients with ENS symptoms had a similar nasal airflow pattern as non‐EEA ENS patients. This pattern differed significantly from that of EEA patients without ENS symptoms and healthy controls. Overall, groups with ENS symptoms exhibited airflow dominant in the middle meatus region and a significantly lower percentage of airflow in the inferior turbinate region (EEA with ENS, 17.74 ± 4.00% vs EEA without ENS, 51.25 ± 3.33% [t test, p < 0.02]; non‐EEA ENS, 25.8 ± 17.6%; healthy subjects, 36.5 ± 15.9%) as well as lower peak wall shear stress (EEA with ENS, 0.30 ± 0.13 Pa vs EEA without ENS, 0.61 ± 0.03 Pa [p = 0.003]; non‐EEA ENS, 0.58 ± 0.24 Pa; healthy subjects, 1.18 ± 0.81 Pa).
These results suggest that turbinectomy and/or posterior septectomy may have a varying functional impact and that ENS symptoms go beyond anatomy and correlate with aerodynamic changes. The findings open the door for CFD as a potential objective diagnosis tool for ENS.
Exosomes are secreted epithelial‐derived vesicles that contain a conserved protein array representative of their parent cell. Exosomes may be reproducibly and noninvasively purified from nasal mucus. The exosomal proteome can be quantified using SOMAscanTM, a highly multiplexed, aptamer‐based proteomic platform. The purpose of this study was to determine whether chronic rhinosinusitis with nasal polyps (CRSwNP) has a unique predictive exosomal proteomic biosignature.
Exosomes were isolated from whole mucus sampled from control and CRSwNP patients (n = 20 per group) by differential ultracentrifugation. The SOMAscanTM platform was used to simultaneously quantify 1310 biologically relevant human proteins. Matched tissue and whole mucus proteomes were also analyzed. Differential protein expression and discriminatory power were calculated using the unweighted pair group method with arithmetic‐mean and principal component analysis, respectively. Bioinformatic analysis was performed using Ingenuity Pathway, MetaCore, and GeneMANIA analyses.
The exosomal proteome demonstrated 123 significantly (p < 0.05) differentially regulated proteins in CRSwNP relative to control. Eighty of these proteins overlapped with the matched CRSwNP tissue proteome as compared with only 4 among matched whole mucus samples. Forty‐three significantly dysregulated pathway networks overlapped between the exosomal and tissue proteome in CRSwNP as compared with only 3 among matched whole mucus samples. The best‐performing protein set (cystatin‐SN, peroxiredoxin‐5, and glycoprotein VI) achieved an area under the curve (AUC) value of up to 99%.
Our data contribute a significant advance in the development of a reproducible, noninvasive, serial, and quantitative "liquid biopsy" for rhinosinusitis. The exosomal proteomic approach has revealed a unique biosignature associated with CRSwNP, which outperforms whole mucus sampling, and thus provides a method of noninvasive disease detection and proposes new potential therapeutic targets.
Signs of inflammation are commonly encountered during endoscopic examination of the Eustachian tube (ET) region. The clinical applicability of these findings may be enhanced by use of a standardized assessment score.
Digital video recordings were obtained of 50 nasal endoscopy examinations of the nasopharyngeal portion of the ET. Four fellowship‐trained rhinologists independently reviewed the videos with regard to specific physical findings: edema of the ET torus, erythema of the ET torus, exudate at the ET orifice, and presence of tubal tonsil. Scoring of this Endoscopic Evaluation of the Eustachian Tube (3ET) was reported using both 2‐point and 3‐point scales. Each reviewer repeated the scoring at a 10‐day interval. Interrater and intrarater agreement were calculated for each item and the total scores.
Interrater and intrarater agreement were greater for the 3‐point scale than the 2‐point scale. Interrater agreement for overall instrument using the 3‐point scale was in the "acceptable" range for Krippendorff's alpha on both the first trial (0.6922) and second trial (0.7238). Intrarater agreement was generally "excellent" for individual items as well as the overall instrument.
The 3ET comprising these 4 physical findings has acceptable interrater and intrarater reliability, and may be applied to future clinical studies of ET function and disease.
Olfactory dysfunction is a common symptom of chronic rhinosinusitis (CRS). We previously identified several cytokines potentially linked to smell loss, potentially supporting an inflammatory etiology for CRS‐associated olfactory dysfunction. In the current study we sought to validate patterns of olfactory dysfunction in CRS using hierarchical cluster analysis, machine learning algorithms, and multivariate regression.
CRS patients undergoing functional endoscopic sinus surgery were administered the Smell Identification Test (SIT) preoperatively. Mucus was collected from the middle meatus using an absorbent polyurethane sponge and 17 inflammatory mediators were assessed using a multiplexed flow‐cytometric bead assay. Hierarchical cluster analysis was performed to characterize inflammatory patterns and their association with SIT scores. The random forest approach was used to identify cytokines predictive of olfactory function.
One hundred ten patients were enrolled in the study. Hierarchical cluster analysis identified 5 distinct CRS clusters with statistically significant differences in SIT scores observed between individual clusters (p < 0.001). A majority of anosmic patients were found in a single cluster, which was additionally characterized by nasal polyposis (100%) and a high incidence of allergic fungal rhinosinusitis (50%) and aspirin‐exacerbated respiratory disease (AERD) (33%). A random forest approach identified a strong association between olfaction and the cytokines interleukin (IL)‐5 and IL‐13. Multivariate modeling identified AERD, computed tomography (CT) score, and IL‐2 as the variables most predictive of olfactory function.
Olfactory dysfunction is associated with specific CRS endotypes characterized by severe nasal polyposis, tissue eosinophilia, and AERD. Mucus IL‐2 levels, CT score, and AERD were independently associated with smell loss.
Publication date: Available online 28 November 2018
Source: American Journal of Otolaryngology
Author(s): Feng-Ming Gu, Fang-Lu Chi
To evaluate surgical outcomes for chronic otitis media with mucosa defect underwent titanium ossicular chain reconstruction (OCR) in single stage canal wall down tympanoplasty (CWD).
A clinical retrospective study was performed on 83 cases of the chronic otitis media with mucosa defect and 123 ears with mucosa integrity according to intraoperative findings that underwent synchronous titanium OCR in single stage CWD form January 2012 to January 2018. Pre- and postoperative air conduction threshold (AC), air-bone gap (ABG) and ABG closure at 0.5, 1, 2, and 4 kHz were investigated.
The overall mean AC threshold of 53.4 ± 16.5 dB was lowered to 41.2 ± 15.9 dB postoperatively (p < 0.01). The mean pre- and postoperative ABG of all patients were 27.9 ± 9.9 dB and 17.2 ± 9.3 dB (p < 0.01), respectively, with a mean ABG closure of 10.7 ± 8.4 dB. The total rate of success, postoperative ABG ≤ 20 dB was achieved in 71.4%. In the mucosa defect group underwent TORP, the mean pre- and postoperative ABG were 28.1 ± 9.8 dB and 20.1 ± 9.0 dB (p < 0.01), respectively, with the ABG closure was 8.0 ± 7.9 dB. In the mucosa defect group underwent PORP, the mean pre- and postoperative ABG were 27.9 ± 10.1 dB and 16.5 ± 9.1 dB (p < 0.01), respectively, with the ABG closure was 11.4 ± 8.6 dB. Furthermore, in the mucosa defect group, there was significant difference in success rate of achieved postoperative ABG ≤ 20 dB between the TORP (48.9%) and PORP (77.5%) (p < 0.05).
It is revealed PORP in single stage CWD tympanoplasty for the patients suffered from chronic otitis media with mucosa defect is favored.
Reports detailing the acute formation of aluminum granulomas, which can cause persistent, intensely pruritic nodules secondary to the administration of aluminum‐containing vaccines, are infrequently described in medical literature. To our knowledge, this is the first report describing the development of an aluminum granuloma causing a persistent, pruritic nodule at the injection site following the administration of the DTaP‐IPV vaccine. We present the case of a 6‐year‐old girl who developed a severely pruritic subcutaneous nodule on her anterior right thigh at the injection site three weeks after the administration of the aluminum‐containing DTaP‐IPV (Kinrix) vaccine. The nodule was eventually excised 14 months after its initial appearance, after which her symptoms resolved. Histologic inspection demonstrated a dense, deep dermal and subcutaneous nodular mixed infiltrate of lymphocytes, histiocytes, and eosinophils, with germinal center formation. The bluish, amphophilic granular cytoplasm found in most of the histiocytes is a characteristic feature of "aluminum granulomas." This adverse reaction should be considered in any patient presenting with similar findings in the weeks following a DTaP‐IPV vaccination or other aluminum‐containing vaccines. Furthermore, the self‐limiting tendency of these nodules should not preclude affected patients from any future vaccinations, though vaccines without aluminum should be preferentially selected when possible.
Diaper dermatitis is often caused by irritant contact occurring beneath the diaper of an infant, and it is aggravated by factors such as dampness, friction, urea, and feces. Food‐allergic patients are known to exhibit various skin lesions ranging from urticaria to eczema. This study aims to determine the relationship between persistent diaper dermatitis and food allergy.
A retrospective chart review was conducted of pediatric patients with a diagnosis of persistent diaper dermatitis between August 2015 and November 2017.
The study included 157 patients diagnosed with persistent diaper dermatitis (67 male, 72 female; median age: 13 months). Diaper dermatitis was more common and included the whole perineum in children who had multiple food allergies (P = 0.001). In children with multiple food allergies, the course of diaper dermatitis was more severe, and the condition did not respond to topical treatment (P = 0.025). A longer elimination diet was required for patients with Type I reactions and persistent diaper dermatitis (P = 0.018). In patients with Type II and mixed reactions, diaper dermatitis was more diffuse and covered the whole perineum (P = 0.025). In patients with Type II and mixed reactions, diaper dermatitis was more severe and did not respond to topical treatment (P = 0.025).
Persistent diaper dermatitis lasting longer than a month may be associated with food allergy. The diaper rash may also be the only indicator of the food allergy. Elimination of the responsible food may allow these patients to recover from persistent diaper dermatitis.
The impacts of physical fatigue upon some facial signs, induced by a whole day work, have been previously described on Caucasian women. The present study aimed at assessing those possibly experienced by Chinese working women under comparable conditions.
Standard photographs of 60 Chinese women working in the same company (aged 20–40 y) were taken at three occasions during their working day (just before, at 4 and 8 hours). Focusing on facial signs allowed a panel of experts to grade their respective severities, helped by a referential atlas dedicated to Asian skin. A naïve panel, comprising 64 Chinese women (aged 20–60 y) graded, through an analogic 0–10 scale, the global facial aspect of each subject, particularly its tired‐look and dullness and estimated the age of each subject (perceived age). Paired‐comparisons in blind and random modes (T0/T4, T4/T8, T0/T8) allowed this naive panel to assess the subjects with a younger/older look, a dullest aspect.
A daily work induces, in Chinese women, changes in some facial signs (Nasolabial, Periorbital and Inter‐ocular wrinkles, Cheek skin pores). The latter appear more marked between T0 and T4 than between T4 and T8. As compared to those observed among Caucasian women, these changes, although subtle, are of a higher amplitude and concern different facial signs. The naïve panel allowed to describe an increase in the tired look and dullness along the day, more so among the older group (31–40 y), together with an increased perceived age. Tired look, dullness and perceived age appear strongly linked.
Despite some possible differences in working conditions, some facial signs of Chinese women seem more affected by a fatigue induced by a working day in urban environment, than those of Caucasian women in similar conditions.
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Publication date: Available online 28 November 2018
Source: European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): D. Chaillou, G. Mortuaire, V. Deken-Delannoy, B. Rysman, D. Chevalier, F. Mouawad
In oncology, multi-disciplinary team meetings improve overall survival and reduce time to treatment in head and neck cancer. Interestingly, no study has examined the experience of patients attending an MTM. The present study addressed two questions: Does the MTM cause anxiety/depression for patients who are present? Are patients satisfied at the end of the meeting?
The study included all patients attending an MTM, who agreed to participate in the study and who fully completed two questionnaires. The Hospital Anxiety and Depression Scale (HADS) and a satisfaction questionnaire were filled out at three time-points: T0 before MTM, T1 at end of MTM, and T2 1 month after MTM for the HADS; and T1 and T2 for the satisfaction questionnaire.
There were no significant differences in the number of patients experiencing anxiety between T0 and T1 (P = 0.6085), T0 and T2 (P = 1) or T1 and T2 (P = 1). Likewise, there were no significant differences in the number of patients in depression between T0 and T1 (P = 0.9397), T0 and T2 (P = 1) or T1 and T2 (P = 1). Mean satisfaction was good (question 14 on the satisfaction questionnaire: 8.7/10 at T1 and 7.7/10 at T2), but with a significant decrease between T1 and T2 (P = 0.0009: i.e., < 0.05). Percentage information remembered (question 12) significantly decreased between T1 (mean 86%, standard deviation 0.2, median 94%) and T2 (78% ± 0.2, median 81%) (P = 0.03). Presence in the MTM did not appear to induce or increase anxiety or pre-existing depressive syndrome.
Publication date: Available online 29 November 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Zhenfeng Gao, Mengmeng Huang, Zhe Qu, Junchao Wang, Xiaolan Cai
In this study, we aimed to characterize the significant DNA methylation module of seasonal allergic rhinitis.
Methylation profiling E-GEOD-50222 was obtained from ArrayExpress database. Differential co-methylation network (DCN) was constructed based on the methylation data. From the DCN, we characterized multiple differential modules (M-DMs). Significant module was mapped to pathways to identify significant enriched pathways.
At the criteria of absolute Pearson coefficient value > 0.8, the edges were chose to construct DCN. In the DCN, 16 seed genes were identified. Seed genes were used to construct M-DMs. After statistical analysis, one significant module with p<0.05 were obtained. After pathways enrichment analysis, 17 significant pathways with p<0.05 were obtained, and most of these pathways were associated with DNA replication.
One multiple differential module was identified in SAR, and seventeen significant pathways mapped by the module were identified as important factors in SAR. These results may provide new insights into the molecular mechanism of DNA methylation in SAR.
Publication date: Available online 29 November 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Elizabeth Burckardt, Whitney Rebholz, Samantha Allen, Elizabeth Cash, Julie Goldman
To determine risk factors and trends for posttonsillectomy hemorrhage (PTH) following adenotonsillectomy (T&A) at a single children's tertiary referral hospital.
Charts from all patients 2-12 years old undergoing T&A alone at a single children's hospital from January 1, 2010 through December 31, 2015 were reviewed. Data was collected on patient demographics, indication for procedure, time of year, academic affiliation of surgeon, surgical technique and method, post-operative pain medication prescribed, and readmission for PTH. Univariate chi-square analyses and logistic regression along with multivariable stepwise logistic regression were used to identify predictors of PTH. SPSS version 24 was used for statistical analyses with p<0.05 indicating statistical significance.
There were 2,565 children undergoing T&A during the study period. One hundred seventy-three (6.7%) patients were readmitted, of which 53 (30.6%) were due to PTH. Univariate analyses identified children at the highest age quartile of the study, 7.72-12.97 years old (odds ratio [OR]=5.775, 95% confidence interval [CI] = 2.248-14.837, p<.001) and children with a BMI z-score of 2 or greater (OR=3.391, 95% CI=1.497-7.680, p=.003) were at increased risk for PTH. Multivariable analyses also identified both the highest age quartile and BMI z-score of 2 or greater to be a risk factor for PTH.
In children undergoing T&A, age greater than 7.72 years old and BMI z-score of 2 or greater are significant risk factors for PTH. Replication of these findings in a more highly powered trial is needed.
Publication date: Available online 28 November 2018
Source: Archives of Oral Biology
Author(s): Jitsuro Yano, Sayako Yamamoto-Shimizu, Tomonori Yokoyama, Isami Kumakura, Kozo Hanayama, Akio Tsubahara
The aim of the present study was to investigate whether anterior tongue muscle strengthening exercises can affect the strength of posterior tongue muscles.
Eleven healthy subjects (20.6 ± 1.2 years) were included. The subjects exercised by pushing the anterior tongue to the palate 30 times, three times a day, 3 days a weekfor 8 weeks. The exercise intensity was set at 60% of maximum tongue pressure (MTP) in the first week and 80% of MTP for the remainder of training. After the completion of training, MTP measurements were continued every month for another 3 months to evaluate whether training effects were sustained.
MTP was significantly increased after 8 weeks of training compared with before training. No significant differences were seen between MTP immediately after completion of training and MTP 1-3 months after completion of training. However, MTP was significantly higher 1-3 months after completion of training than before training.
The present study showed significant increases in both anterior and posterior MTPs by anterior tongue muscle strengthening exercises. In the future, a database on tongue muscle strengthening exercises in elderly persons,patients with dysphagia, etc. will need to be generated, with the aim of preventing frailty.
Publication date: December 2018
Source: Journal of Autoimmunity, Volume 95
Author(s):
Publication date: Available online 29 November 2018
Source: Journal of the American Academy of Dermatology
Author(s): Uyen Ngoc Mui, Christopher T. Haley, Ramya Vangipuram, Stephen K. Tyring
In 1964, the first human oncovirus, Epstein-Barr virus (EBV), was identified in Burkitt lymphoma cells. Since then, six other human oncoviruses have been identified: human papillomavirus (HPV), Merkel cell polyomavirus (MCPyV), hepatitis B and C viruses (HBV and HCV), human T-cell lymphotropic virus-1 (HTLV-1), and human herpesvirus-8 (HHV-8). These viruses are causally linked to 12% of all cancers, many of which have mucocutaneous manifestations. Additionally, oncoviruses are associated with many benign mucocutaneous diseases. Research regarding the pathogenic mechanisms of oncoviruses as well as virus-specific treatment and prevention is rapidly evolving. Preventive vaccines for HPV and HBV are already available. This review discusses the mucocutaneous manifestations, pathogenesis, diagnosis, treatment, and prevention of oncovirus-related diseases. Part I of the review focuses on diseases associated with HPV and MCPyV, while part II focuses on diseases associated with HBV, HCV, HTLV-1, HHV-8, and EBV.
As our knowledge base continues to increase, many of the diseases we see and treat seem to have become more complex. This may come from a variety of factors, including better technology, better research, and better diagnostic techniques, among other factors. Not that long ago, asthma was classified more simply as either "intrinsic" or "extrinsic," and rhinitis was either "allergic" or "nonallergic." Now, with the vast improvements we enjoy in the practice of medicine, we have phenotypes and endotypes; we have biomarkers, treatment guidelines, practice parame-->ters, and more.
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Eosinophilic esophagitis (EoE) is a complex allergic disease commonly associated with food-induced symptomatic esophageal dysfunction.1 This includes reflux, dysphagia, and dysmotility.2 Consensus guidelines have provided clinical information to guide EoE evaluation, including the use of proton pump inhibitors (PPIs), to distinguish gastroesophageal reflux disease from EoE, and observations that a unique subset of eosinophilic esophageal infiltration might be largely resolved using a PPI, also termed PPI-REE (PPI-responsive esophageal eosinophilia).
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In the Original Article, "Omalizumab chronic spontaneous urticaria: Efficacy, safety, predictors of treatment outcome, and time to response" (Ann Allergy Asthma Immunol. 2018;121:474-478), the title should have been set as "Omalizumab in chronic spontaneous urticaria: Efficacy, safety, predictors of treatment outcome, and time to response."
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Die Behandlung des metastasierten nichtkleinzelligen Lungenkarzinoms (NSCLC) ohne behandelbare Treibermutation hat sich in den vergangenen Jahren insbesondere durch die Einführung der Immuncheckpointinhibitoren (ICI) rasch verändert.
Ein kurzer historischer Abriss sowie der aktuelle Stand der Behandlung des NSCLC Stadium IV sollen knapp zusammengefasst werden.
Eine selektive Literaturrecherche der Datenbank Pubmed wurde durchgeführt. Suchbegriffe: NSCLC stage IV, checkpointinhibitors, chemotherapy.
Immuncheckpointinhibitoren wurden zunächst in der Zweitlinientherapie eingeführt, weil sie sich in mehreren großen Phase-III-Studien einer Standard-Docetaxel-Therapie als deutlich überlegen erwiesen hatten. Mittlerweile wird Pembrolizumab als Standard-Erstlinientherapie bei hoher Programmed-death-ligand-1(PD-L1)-Expression (Tumor Proportion Score [TPS] > 50 %) eingesetzt. In mehreren Phase-III-Studien hat sich eine Kombination mit ICI und Chemotherapie in der Erstlinientherapie einer Standardchemotherapie als überlegen erwiesen. Zulassungen für die Kombinationserstlinientherapie liegen für das nichtsquamöse NSCLC (nsNSCLC) bereits vor und weitere Zulassungen sind zu erwarten. Erst seit Einführung der ICI lässt sich bei einem Teil der Patienten mit metastasiertem NSCLC ein Langzeitüberleben von 3 Jahren und mehr erzielen.
"Hot potato voice" (HPV) is a thick, muffled voice caused by pharyngeal or laryngeal diseases characterized by severe upper airway obstruction, including acute epiglottitis and peritonsillitis. To develop a method for determining upper‐airway emergency based on this important vocal feature, we investigated the acoustic characteristics of HPV using a physical, articulatory speech synthesis model. The results of the simulation were then applied to design a computerized recognition framework using a mel‐frequency cepstral coefficient domain support vector machine (SVM).
Quasi‐experimental research design.
Changes in the voice spectral envelope caused by upper airway obstructions were analyzed using a hybrid time‐frequency model of articulatory speech synthesis. We evaluated variations in the formant structure and thresholds of critical vocal tract area functions that triggered HPV. The SVMs were trained using a dataset of 2,200 synthetic voice samples generated by an articulatory synthesizer. Voice classification experiments on test datasets of real patient voices were then performed.
On phonation of the Japanese vowel /e/, the frequency of the second formant fell and coalesced with that of the first formant as the area function of the oropharynx decreased. Changes in higher‐order formants varied according to constriction location. The highest accuracy afforded by the SVM classifier trained with synthetic data was 88.3%.
HPV caused by upper airway obstruction has a highly characteristic spectral envelope. Based on this distinctive voice feature, our SVM classifier, who was trained using synthetic data, was able to diagnose upper‐airway obstructions with a high degree of accuracy.
2c Laryngoscope, 2018
Based on current guidelines, surgical and nonsurgical therapies are viable frontline treatment for patients with locoregional oropharyngeal carcinoma (OPC). We sought to compare financial parameters between chemoradiation and transoral robotic surgery (TORS) in this patient population.
Case‐control study.
In this study we identified patients with selected American Joint Committee on Cancer 7th Edition stage II to IVa OPC treated with TORS between January 2013 and December 2014. Fifteen patients who underwent TORS were stage matched with 15 patients treated with chemoradiation. Total charges and cost data for each patient were analyzed at 4‐month and 1‐year time points; functional and oncologic outcomes were assessed.
There were no significant differences in functional and oncologic outcomes. Patients undergoing TORS had a longer inpatient hospital stay, and most required a nasogastric tube for an average of 3.5 days. There were no local or regional recurrences. Across all time points, the TORS group had lower charges and costs compared to the chemoradiation group, with 14% lower costs at 1 year. In the chemoradiation group, nearly two‐thirds of costs came from radiation therapy and pharmacy expenses. Chemotherapy accounted for most pharmacy costs. The costs of operating the surgical robot accounted for a about half of surgical costs.
Selected patients with stage II to IVa oropharyngeal carcinoma treated with TORS may incur lower costs than those treated nonsurgically. With rising healthcare spending, the financial impact of treatment might be considered for those patients eligible for treatment regimens with comparable functional and oncologic outcomes.
3b Laryngoscope, 2018
To investigate the simultaneous application of cartilage tympanoplasty combined with eustachian tube (ET) balloon dilatation in the treatment of adhesive otitis media (AdOM).
Multicenter, prospective, double‐blind, randomized, controlled clinical trial.
Patients with AdOM were randomly divided into four groups: control group (conservative treatment), ET balloon dilatation (ETBD) group, cartilage tympanoplasty (CT) group, and cartilage tympanoplasty combined with ET balloon dilatation (ETBD+CT) group. Patients were followed up at 3 months, 6 months, 1 year, and 2 years after treatment, receiving otoendoscopy and pure‐tone audiometry, and were evaluated using the Tinnitus Handicap Inventory (THI), visual analogue scale (VAS) for the symptom of ear stuffiness, Chronic Otitis Media Outcome Test (COMOT‐15), and eustachian tube scores (ETS).
There was no improvement in tympanic membrane (TM) morphology and mean pure‐tone air‐bone gap (ABG) after treatment in the control and ETBD groups. The postoperative TM morphology was improved in the CT group and ETBD+CT group, although retraction pockets reoccurred in two cases of CT group. Reduced ABG and improvements in ETS, THI, VAS, and COMOT‐15 were all achieved in these two groups, but the difference was not statistically significant.
Cartilage tympanoplasty combined with ET balloon dilatation could be used as an appropriate surgical technique for AdOM, which could relieve the symptoms of tinnitus and ear stuffiness, and improve postoperative TM morphology, hearing level, ET functions, and quality of life, with low incidence of complications.
2 Laryngoscope, 2018
