Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
The cover image is based on the Original Article Detection of high‐grade dysplasia, carcinoma in situ and squamous cell carcinoma in the upper aerodigestive tract: Recommendations for optimal use and interpretation of narrow‐band imaging, by Manon A. Zwakenberg et al., https://doi.org/10.1111/coa.13229.
Continuous positive airway pressure (CPAP) is the mainstay therapy for patients with obstructive sleep apnea (OSA) however compliance with CPAP is variable. Nasal ailments, such as nasal congestion are frequently mentioned as a cause for CPAP non-compliance, and potentially could be addressed prior to CPAP initiation, however, no specific criteria or recommendations for the evaluation and management of these patients exist. The aim of this retrospective study is to evaluate the effects of nasal anatomic features and disease on adherence to CPAP therapy for patients with OSA and determine the indications for pre-CPAP nasal treatment by using data obtained at clinical examination.
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To explore the inhibition of the proliferation of vulvar squamous cell carcinoma (VSCC) by astragaloside IV.
MTT examined the cell proliferation of VSCC. Flow cytometry analyzed cell cycle and apoptosis. Western blot assay detected the expression of some relevant proteins.
AS‐IV reduced the proliferation of SW962 cells in a concentration‐ and time‐dependent manner, induced cell‐cycle arresting in G0/G1 phase, as demonstrated by the up‐regulation of P53 and P21 expression, and the down‐regulation of cyclin D1 expression. AS‐IV enhanced the expression of Bax and cleaved‐caspase 3, and suppressed Bcl‐2 and Bcl‐xl expression, which resulted in apoptosis increased. Furthermore, the expression of Beclin‐1 and LC3‐B was upregulated and that of P62 was downregulated, which suggested that AS‐IV could increase the incidence of autophagy in SW962 cells. After inhibiting autophagy by 3‐methyladenine, cell apoptosis decreased upon AS‐IV treatment. Similarly, TGF‐β1 stimulated SW962 cells, cell proliferation enhanced, and the expression of TGF‐βRII and Smad4 was decreased. Furthermore, the expression of proteins that promote apoptosis and autophagy decreased. After AS‐IV treatment, the expression levels of the above proteins exhibited the opposite effect.
AS‐IV inhibits cell proliferation and induces apoptosis and autophagy through the TGF‐β/Smad signaling pathway in VSCC.
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To describe the histopathologic findings and clinical presentation of arachnoid cysts (ACs) within the human temporal bone.
Retrospective cohort analysis.
An analysis of all medical records of patients diagnosed with an AC was performed. Temporal bones underwent standard processing for histologic examination. The slides were examined by light microscopy. The histologic findings were compared to premortem clinical data.
Twenty‐seven ACs were identified in 22 patients. Twenty ears (74%) had no identified risk factor for AC development. The median volume was 12.8 mm3. The most prevalent location of the ACs was at the fundus (16 ACs) followed by the middle portion of the internal auditory canal (IAC) (six ACs). Nine ACs were asymptomatic. Among the 18 symptomatic ACs, the most common presentation was sensorineural hearing loss (SNHL) (94%), followed by tinnitus (22%). The most affected structure was the cochlear nerve (59%), followed by the vestibular nerve (41%). The average hearing threshold was of moderately severe SNHL and speech discrimination was in the range of 50% on monosyllabic word tests. The median time interval from initial presentation to death was 12 years. No correlation was found between duration of symptoms and AC volume.
AC of the IAC is not uncommon. Its presentation is variable, ranging from asymptomatic to SNHL, with poor speech discrimination, tinnitus, and vertigo. This diagnosis should be kept in the differential diagnosis of retrocochlear pathologies.
4
Despite the importance, impact, and prevalence of pediatric hearing loss (HL), there are very few published clinical practice guidelines (CPG) supporting the evaluation and management of pediatric patients with HL. Our objective was to appraise existing CPGs to ensure safe and effective practices.
A literature search was conducted in PubMed, Google Scholar, EBSCO, as well as a manual Google search. Three independent assessors using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument evaluated CPGs related to HL in children. Standardized domain scores were calculated for each guideline.
A total of four guidelines met the inclusion criteria and were appraised. Scope and purpose achieved a high median score of 83%. Stakeholder involvement, clarity of presentation, and editorial independence achieved intermediate scores of 67%, 54%, and 50%, respectively. The areas that required most improvement and achieved low scores were rigor of development and applicability, with scores of 22% and 38%, respectively. Based on the AGREE II measures, the four guidelines had domain scores less than 60% for each domain, and without modification no guideline could be recommended.
Based on the AGREE II, the qualities of CPGs for pediatric HL have several shortcomings, and the need for a comprehensive CPG remains. Rigor of development and applicability present the greatest opportunities for improvement of these CPGs. Laryngoscope, 2018
Although much is known about the incidence and risk factors for hemorrhage after tonsil surgery, the incidence and factors related to multiple episodes of hemorrhage are not well examined. Our objective was to identify risk factors that may contribute to multiple hemorrhages following tonsil surgery in children.
Retrospective chart review.
A retrospective review was conducted of pediatric patients who experienced one or more hemorrhages following tonsillectomy/tonsillotomy, with or without adenoidectomy, between 2010 and 2016 at a single, tertiary‐care hospital. Risk factors for multiple hemorrhages were examined using a multivariable logistic regression model.
Among the 11,140 patients who underwent tonsil surgery, 452 patients experienced one or more hemorrhages; 32 of these had multiple episodes of hemorrhage (7.1% of all patients with bleeds/0.3% of all patients). Older age (≥12 years: adjusted odds ratio [OR]: 3.13; 95% confidence interval [CI]: 1.47‐6.68) and high body mass index for age (≥85th percentile: adjusted OR: 2.26; 95% CI: 1.06‐4.85) were significantly associated with an increased risk of multiple hemorrhages in the multivariable model. Medical comorbidities, indications for surgery, surgical technique, intraoperative blood loss, and perioperative medications were not associated with multiple episodes of bleeding.
Multiple hemorrhages after tonsillectomy/tonsillotomy are uncommon. The risk of a second PTH after an initial episode is 7.1%, almost double the risk of a bleed after the initial tonsil surgery. Age > 12 years and high BMI for age may be associated with increased risk of rebleeding. After an initial bleed, increased surveillance may be warranted, particularly for patients with risk factors.
4 Laryngoscope, 2018
The field of pediatric dermatology treatment has been rich in new developments. Several recent therapeutic advances in pediatric dermatology have been made. This review will focus on critical approach to the new treatments for several entities encountered in pediatric dermatology. The use of biologics and small molecules in children with atopic dermatitis and psoriasis, exciting advances in the use of propranolol and other beta‐blockers for the treatment of infantile hemangiomas, the use of sirolimus for vascular anomalies will be discussed.
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Cyclooxygenase‐2 (COX‐2) and its metabolic product prostaglandin E2 (PGE2) are induced in response to growth factors, inflammatory cytokines, tumour promoters, activated oncogenes and, in the skin, ultraviolet (UV) radiation. Accumulating evidence suggests a role for the COX‐2/PGE2 pathway in tumourigenesis in various tissue types including cutaneous squamous cell carcinoma. There is also strong evidence for a role in the development of actinic keratoses (AKs) – common dysplastic lesions of the skin associated with UV radiation overexposure – considered as part of a continuum with skin cancer. Non‐steroidal anti‐inflammatory drugs (NSAIDs) exert their anti‐inflammatory, analgesic and antipyretic effects by reversibly or irreversibly acetylating COX isoforms, inhibiting downstream prostaglandins, and may have a chemo‐preventive role in malignancies, including skin cancer. Topical treatment of AK lesions with the NSAID diclofenac sodium 3% in combination with hyaluronic acid 2.5% has been shown to be effective and well tolerated, although the mechanism of action remains to be elucidated.
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Recently, advances in understanding the etiology of urticaria and updates of diagnostic and therapeutic management guidelines have drawn attention to chronic urticaria (CU) morbidity. This study aimed to evaluate Iranian dermatologists' practice and real life management of CU patients. A total of 35 dermatologists and 443 patients were included in the study. Number of female patients was 321 (72.5%). Mean (Standard Deviation) age of the study patients was 38 (13) years and the median (Inter Quartile Range) of disease duration was 12 (6‐ 48) months. Severity of patients' symptoms was mild for 32.1%, moderate for 38.7%, severe for18.8% and 10.4% of them had no evident signs or symptoms. The most common diagnostic methods were physical examination (96.6%), differential blood count (83.5%), erythrocyte sedimentation rate (77.4%), and C‐reactive protein (62.8%). The number of dermatologists prescribed non‐sedating antihistamines (nsAH) in regular dose and high dose mono therapy were 26 (74%) and 6 (17%), respectively. About 66% of dermatologists were familiar with British Association of Dermatologists (BAD) guideline. The most common first‐line treatment for CU by Iranian dermatologists was non‐sedating antihistamines in regular or high doses. The real‐life management of patients with CU in Iran was in accordance with the available practice guidelines.
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As skin cancer rates continue to rise, targeted efforts to reduce excessive exposure to ultraviolet radiation are crucial. Adolescents are a high‐risk population for intentional tanning; thus, we sought to determine whether the novel use of skin age analysis with ultraviolet (UV) photography would be an effective tool for reducing intentions to tan in adolescents with a calculated skin age (measured by complexion analysis software) that exceeds their actual age. Surveying 85 students in this study, skin age difference above zero was associated with reduced intentions to tan (P = 0.006) and high‐risk sun exposure behaviors were identified. This provides rationale for skin age analysis as a potentially effective intervention in decreasing intentions to tan in this high‐risk young population.
Collagen type XVIII regulates cellular activities of adjacent cells at the dermal‐epidermal junction (DEJ). To investigate its possible changes during aging, we compared its mRNA levels and protein localization in skin samples from female participants aged 20‐70 years old. In addition, we evaluated the beneficial effects of unripe peach extracts in a 3D skin model.
Sun‐exposed or sun‐protected female skin samples were compared by DNA array or by immunohistochemistry for basement membrane components. To evaluate protective effects of fresh unripe peach extract, UV‐B irradiated human 3D skin models were incubated in the presence or absence of the extract, followed by measurements of mRNA levels by real‐time PCR, or by immunohistochemistry.
In aged skin samples, COL18A1 mRNA levels were lower and the protein localization exhibited less intensive signal by anti‐collagen type XVIII immunostaining. As observed in the skin tissues, collagen type XVIII exists at the DEJ in the 3D skin model. Fresh unripe peach extract significantly improved mRNA levels and partially localizations of collagen type XVIII, suggesting that fresh unripe peach extract ameliorates DEJ damages caused by UV‐B irradiation.
Collagen type XVIII and fresh unripe peach extract can be promising protective cosmetic strategies against skin aging.
High dose of radiation to bone may cause necrosis. Osteoradionecrosis of the cervical vertebrae is a rare adverse event of radiotherapy in patients treated for head and neck cancer. The risk on osteoradionecrosis will increase with doses exceeding 60 Gy. Minimal trauma of the overlying mucosa of the heavily irradiated cervical spine causes subsequent infections or instability may cause neck pain and severe neurological disability. In four patients the cervical spine received up to 100 Gy due to reirradiation. Clinically the patients presented with neck pain. All patients had defects in the pharyngeal posterior wall and cervical instability due to osteoradionecrosis of several cervical vertebrae. Despite optimal conservative treatment the patients developed sensory and motor function loss of the upper extremities. Laminectomies were performed and the cervical spine was stabilized. The pharyngeal posterior wall defects could not be reconstructed. All patients received lifelong antibiotic treatment. Pain and neurological deficits declined after surgery and initiating antibiotics. Eventually all patients could take up their daily activities. Three patients died between 6 months and 2 years after surgery. The cause of death was not related to the osteoradionecrosis. In case of cervical osteoradionecrosis, with secondary infections, stability of the spine should be restored even when the integrity of the pharyngeal posterior wall cannot be restored. Our cases demonstrate that even when an anterior approach is impossible, due to irradiation changed tissue structures of the pharyngeal posterior wall, a combination of lifelong antibiotic treatment and posterior stabilization is a good alternative. The vertebrae affected by osteoradionecrosis and secondary infection can be left in situ. This intervention leads to improvement in quality of life.
High dose of radiation to bone may cause necrosis. Osteoradionecrosis of the cervical vertebrae is a rare adverse event of radiotherapy in patients treated for head and neck cancer. The risk on osteoradionecrosis will increase with doses exceeding 60 Gy. Minimal trauma of the overlying mucosa of the heavily irradiated cervical spine causes subsequent infections or instability may cause neck pain and severe neurological disability. In four patients the cervical spine received up to 100 Gy due to reirradiation. Clinically the patients presented with neck pain. All patients had defects in the pharyngeal posterior wall and cervical instability due to osteoradionecrosis of several cervical vertebrae. Despite optimal conservative treatment the patients developed sensory and motor function loss of the upper extremities. Laminectomies were performed and the cervical spine was stabilized. The pharyngeal posterior wall defects could not be reconstructed. All patients received lifelong antibiotic treatment. Pain and neurological deficits declined after surgery and initiating antibiotics. Eventually all patients could take up their daily activities. Three patients died between 6 months and 2 years after surgery. The cause of death was not related to the osteoradionecrosis. In case of cervical osteoradionecrosis, with secondary infections, stability of the spine should be restored even when the integrity of the pharyngeal posterior wall cannot be restored. Our cases demonstrate that even when an anterior approach is impossible, due to irradiation changed tissue structures of the pharyngeal posterior wall, a combination of lifelong antibiotic treatment and posterior stabilization is a good alternative. The vertebrae affected by osteoradionecrosis and secondary infection can be left in situ. This intervention leads to improvement in quality of life.
Myxomas account for approximately half of all primary cardiac neoplasms. Most occur in the left atrium and only rarely are attached to the mitral valve, with just over 30 such cases reported in the literature....
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Angioedema is a rare adverse effect of the commonly used angiotensin converting enzyme inhibitors (ACEi) and is reported to occur with a prevalence of 0.1 – 0.7%. Although most ACEi‐induced angioedema (ACEi‐A) cases are mild, severe cases requiring intensive care and even resulting in death have been reported in the literature. The mechanisms underlying ACEi–A are not yet fully understood, but bradykinin and/or substance P accumulation resulting from inhibition of ACE, is believed to play a crucial role. ACEi‐A occurs at variable frequencies across different racial groups, suggesting a genetic association to the development of ACEi‐A. To date, one genome wide association study and several candidate gene studies have been published on the association of genetic variation with ACEi‐A. Genetic associations reported have been attributed to several distinct mechanisms: (1) genes coding for alternative enzymes responsible for the degradation of bradykinin and/or substance P in the diminution of ACE activity (2) ACE gene function, (3) bradykinin receptor genes, (4) genes implicated in immune and inflammation regulation, and (5) genes in the fibrinolytic and coagulation pathway. Despite several plausible genetic associations, there are currently no genetic variants with sufficient effect to be clinically useful. The low incidence of ACEi‐A suggests that a combination of genomic approaches with the capability to detect potentially important variants might be required to shed light on the mechanism of this adverse reaction. Additionally, many non‐genetic risk factors associated with ACEi‐A suggest the potential contribution of epigenetic dysregulation.
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Conventional laboratory diagnosis of dermatophyte infection is cumbersome and time‐consuming.
We aimed to establish a simple, robust, and rapid molecular diagnostic assay for detection of dermatophytes and optionally non‐dermatophytes in clinical specimens.
We developed a two‐tube pan‐dermatophyte PCR assay using six sloppy molecular beacon (SMB) probes. The first PCR uses dermatophyte specific primers and enables detection and identification of most dermatophyte species. The second PCR with pan‐fungal primers allows further differentiation of T. interdigitale and T. mentagrophytes/T. quinckeanum, T. violaceum and T. soudanense, and T. tonsurans and T. equinum, and detection of non‐dermatophytes. The test was evaluated with 306 clinical specimens by comparing it to the results of microscopy and culture.
In melting curve analyses, species‐specific Tm signatures of the SMBs were defined. Thus, our new PCR enabled detection and species‐level identification of at least 19 dermatophyte species. Sensitivity and specificity of PCR for detection of dermatophytes in clinical samples were estimated to be 96.9% and 90.4%, for culture 46.7% and 98.7%, and for microscopy 91.4% and 84.0%, respectively. The detection of non‐dermatophytes by PCR and culture did not correlate.
The new assay showed excellent performance characteristics for the detection of dermatophytes and is significantly faster than culturing techniques what makes it very promising for routine diagnostics of dermatophytosis. We noticed that the detection of non‐dermatophytes in our assay currently has no benefit.
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Reprogramming of energy metabolism to enhanced aerobic glycolysis has been defined as a hallmark of cancer.
To investigate the role of the mitochondrial proteins, β‐subunit of the H+‐ATP synthase (β‐F1‐ATPase), and heat‐shock protein 60 (HSP60), and the glycolytic markers, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and pyruvate kinase M2 (PKM2), as well as the bioenergetic cellular (BEC) index, in melanoma progression.
The expression of energy metabolism proteins were assessed on a set of different melanoma cells representing the natural biological history of the disease: primary cultures of melanocytes, radial (WM35) and vertical (WM278) growth phases, and poorly (C81‐61‐PA) and highly (C8161‐HA) aggressive melanoma cells. Cohorts of 63 melanocytic nevi, 55 primary melanomas and 35 metastases were used; and 108 primary melanoma and 30 metastases were used for validation.
The BEC index was significantly reduced in melanoma cells and correlated with their aggressive characteristics. Overexpression of HSP60, GAPDH and PKM2 was detected in melanoma human samples compared with nevi, showing a gradient of increased expression from radial growth phase to metastatic melanoma. The BEC index was also significantly reduced in melanoma samples and correlated with worse overall and disease‐free survival; the multivariate Cox analysis showed that BEC index (HR, 0.64; CI95%, 0.4‐1.2) is an independent predictor for overall survival.
A profound alteration in the mitochondrial and glycolytic proteins and in the BEC index occurs in the progression of melanoma, which correlates with worse outcome supporting that the alteration of the metabolic phenotype is crucial in melanoma transformation.
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Publication date: January 2019
Source: Molecular Immunology, Volume 105
Author(s): Nannan Lai, Qing Min, Ermeng Xiong, Jun Liu, Lumin Zhang, Shoya Yasuda, Ji-Yang Wang
CD40 ligand (CD40 L) expressed by activated T cells interacts with CD40 on B cells and triggers B cell survival, proliferation and differentiation. Deficiency in CD40 L or CD40 in humans causes hyper IgM syndrome due to a defect in T-B interaction that is essential for Ig gene class switch recombination (CSR). CD40 L belongs to the tumor necrosis factor family and normally forms a homotrimer on the cell surface, which is important for its biological activity. To generate a multimeric CD40 L that can be used to stimulate both mouse and human B cells, we fused the extracellular domain of mouse CD40 L, which is known to also bind human CD40, with streptavidin (SA) that forms a stable tetramer under physiological conditions. As expected, 293 T cells transiently transfected with an SA-CD40 L expression vector secreted tetrameric SA-CD40 L in the culture supernatant. The secreted SA-CD40 L exhibited > 25-fold stronger activities in inducing the survival, activation and proliferation of both mouse and human primary B cells than did an agonistic anti-mouse or anti-human CD40 antibody. In the presence of IL-4, SA-CD40 L also induced efficient CSR and plasma cell differentiation in both mouse and human B cells. Moreover, administration of SA-CD40 L in mice induced activation and proliferation of spleen B cells in vivo. These results demonstrate that the SA-CD40 L fusion protein generated in the present study recapitulates the function of membrane-bound trimeric CD40 L and has potent biological activities in both mouse and human primary B cells.
Publication date: Available online 7 December 2018
Source: American Journal of Otolaryngology
Author(s): Andrea Castellucci, Pasquale Malara, Cristina Brandolini, Valeria Del Vecchio, Davide Giordano, Angelo Ghidini, Gian Gaetano Ferri, Antonio Pirodda
To describe a unique case of acute vertigo presenting with spontaneous horizontal nystagmus (SHN) and a clinical picture consistent with right acute peripheral vestibular loss (APVL) in which an isolated hypofunction of a horizontal semicircular canal (HSC) permitted to detect a spontaneous canalith jam and treat the patient accordingly.
Case report and literature review.
A 74-year old woman presented with acute vertigo, left-beating SHN and a clinical picture consistent with right APVL. Nevertheless, vestibular evoked myogenic potentials were normal with symmetrical amplitudes and the video head impulse test (vHIT) revealed an isolated hypofunction of the right HSC. After repeated head shakings, the supine roll test evoked bilaterally a positioning paroxysmal geotropic horizontal nystagmus suggesting benign paroxysmal positional vertigo involving the non-ampullated arm of the right HSC. vHIT and caloric testing confirmed restitution of HSC function after repositioning maneuvers.
In case of acute vertigo with SHN, a complete functional assessment of vestibular receptors and afferents should always be given in order to avoid misdiagnosis. Canalith jam should be considered in case of spontaneous nystagmus and isolated canal hypofunction.
Publication date: Available online 8 December 2018
Source: American Journal of Otolaryngology
Author(s): Tao Yan, Fangru Zong, Xiaojie Ma, Xinbo Xu, Weiliang Chen, Zhongyi Song, Xiao Han, Xiaojing Wang, Hanbing Zhang
The timing of CI for postmeningitic deafness is controversial and differential outcomes have been reported. To review and share our surgical and auditory outcomes.
17 patients with ossified cochleas who received CI were enrolled. Clinical data including the cause of cochlear ossification, preoperative examination, onset of deafness, age at implantation, surgical findings, and relevant auditory outcomes was analysed.
Cochlear ossification was observed in 53% of patients with HRCT, whereas the corresponding value for MRI was 59%. Patients in both stage I and II received complete insertion of the electrode array, however, stage III patients only received partial insertion. 1 patient in stage II received bilateral CI. Hearing tests showed increased average hearing threshold for stage III patients than those in stage I and II (P < 0.05). CAP scores were much lower for stage III patients than those in stage I and II (P < 0.05). Postlingual deafness patients showed higher SIR scores than prelingual deafness children (P < 0.05).
HRCT and MRI have comparable value in predicting the occurrence of ossification in cochleas. We recommend fast surgical intervention in the patients with bilateral profound postmeningitic deafness. If possible, bilateral cochlear implantation is recommended.
Publication date: Available online 7 December 2018
Source: American Journal of Otolaryngology
Author(s): Kayvon F. Sharif, Fred M. Baik, Lauren E. Yue, Muhammad Qazi, Margaret Brandwein-Weber, Azita S. Khorsandi, Mark L. Urken
Osteoradionecrosis (ORN) is a well-known complication following irradiation of head and neck malignancies. ORN commonly occurs in the mandible but is rarely reported in the hyoid bone.
A 76-year-old female with a history of oropharyngeal squamous cell carcinoma presented with pharyngocutaneous fistula 14 years after primary chemoradiation. Imaging showed necrosis of the hyoid bone. She underwent excision of the hyoid to rule out malignancy. Pathology was negative for carcinoma, but did show extensive fragmentation and bony necrosis consistent with ORN. The patient's clinical course, surgical treatment, and management considerations are discussed here.
Hyoid ORN should remain in the differential during diagnostic workup of previously irradiated head and neck cancer patients. The presentation of a pharyngocutaneous fistula should prompt workup to rule out malignancy before assigning a diagnosis of ORN.
Publication date: Available online 7 December 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Caroline Galeotti, Emmanuel Stephen-Victor, Anupama Karnam, Mrinmoy Das, Laurent Gilardin, Mohan S. Maddur, Sandra Wymann, Cédric Vonarburg, Alain Chevailler, Jordan D. Dimitrov, Olivier Benveniste, Pierre Bruhns, Srini V. Kaveri, Jagadeesh Bayry
Therapeutic normal immunoglobulin G or intravenous immunoglobulin (IVIG) exerts anti-inflammatory effects via several mutually nonexclusive mechanisms. Recent data in mouse models of autoimmune diseases suggest that IVIG induces IL-4 in basophils by enhancing IL-33 in SIGN-R1+ innate cells. However, translational insight on these data is lacking.
We sought to investigate the effect of IVIG on human basophil functions.
Isolated circulating basophils from the healthy donors were cultured in the presence of IL-3, IL-33, GM-CSF, TSLP or IL-25. The effect of IVIG, F(ab')2 and Fc fragments of IVIG was examined on the expression of various surface molecules, phosphorylation of Syk, induction of cytokines, and histamine release. Phenotype of basophils was also analyzed from IVIG-treated myopathy patients. Approaches such as depletion of anti-IgE-reactivity from IVIG, blocking antibodies or inhibitors were used to investigate the mechanisms.
We report that IVIG directly induces activation of IL-3-primed human basophils, but IL-33 and other cytokines were dispensable for this effect. The activation of basophils by IVIG led to enhanced expression of CD69 and secretion of IL-4, IL-6 and IL-8. IVIG-treated myopathy patients displayed enhanced expression of CD69 on the basophils. Syk pathway is implicated in these functions of IVIG and were mediated via F(ab')2 fragments. Mechanistically, IVIG induced IL-4 in human basophils by interacting with basophil surface-bound IgE but independent of FcγRII, type II Fc receptors, C-type lectin receptors and Siglecs.
These results uncovered a pathway of promoting Th2 response by IVIG through direct interaction of IgG with human basophils.
Publication date: Available online 7 December 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Markus J. Ege, Catharina Schuetz, Eva-Maria Jacobsen, Susanna M. Müller-Langer, Ingrid Furlan, Mehtap Sirin, Ulrich Pannicke, Klaus Schwarz, Klaus-Michael Debatin, Manfred Hönig, Ansgar Schulz, Wilhelm Friedrich
Publication date: Available online 7 December 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Mayte Suárez-Fariñas, Maria Suprun, Helena L. Chang, Gustavo Gimenez, Galina Grishina, Robert Getts, Kari Nadeau, Robert A. Wood, Hugh A. Sampson
In a recent trial of milk oral immunotherapy (MOIT) with or without omalizumab in 55 patients with milk allergy treated for 28 months, 44 of 55 subjects passed a 10-g desensitization milk protein challenge; 23 of 55 subjects passed the 10-g sustained unresponsiveness (SU) challenge 8 weeks after discontinuing MOIT.
We sought to determine whether IgE and IgG4 antibody binding to allergenic milk protein epitopes changes with MOIT and whether this could predict the development of SU.
By using a novel high-throughput Luminex-based assay to quantitate IgE and IgG4 antibody binding to 66 sequential epitopes on 5 milk proteins, serum samples from 47 subjects were evaluated before and after MOIT. Machine learning strategies were used to predict whether a subject would have SU after 8 weeks of MOIT discontinuation.
MOIT profoundly altered IgE and IgG4 binding to epitopes, regardless of treatment outcome. At the initiation of MOIT, subjects achieving SU exhibited significantly less antibody binding to 40 allergenic epitopes than subjects who were desensitized only (false discovery rate ≤ 0.05 and fold change > 1.5). Based on baseline epitope-specific antibody binding, we developed predictive models of SU. Using simulations, we show that, on average, IgE-binding epitopes alone perform significantly better than models using standard serum component proteins (average area under the curve, >97% vs 80%). The optimum model using 6 IgE-binding epitopes achieved a 95% area under the curve and 87% accuracy.
Despite the relatively small sample size, we have shown that by measuring the epitope repertoire, we can build reliable models to predict the probability of SU after MOIT. Baseline epitope profiles appear more predictive of MOIT response than those based on serum component proteins.
Publication date: Available online 7 December 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Jeffrey Cheng, Beiyu Liu, Hui-Jie Lee
Identify adverse events associated with surgical management of head and neck lymphatic malformations in children by investigating a US national database.
Pediatric American College of Surgeons (ACS) National Surgical Quality Improvement Program® (ACS NSQIP® - pediatric), years 2012 – 2016.
Subjects included children under 18 years with a postoperative diagnosis of International Classification of Diseases (ICD), 9th revision code: 228.1 – lymphangioma, any site or ICD-10 code D18.1.
163 patients were identified. 67 (41.1%) were female and 96 (58.9%) were male. The median age was 4.2 years (interquartile range [IQR] 1.6 to 11.3 years). Sixty-five (39.9%) underwent head and neck procedures. 19 (11.7%) patients with 30-day adverse events were identified, with unplanned reoperation being the most common; in the head and neck surgery group, there were 5 (7.7%). There was no significant difference in the occurrence of adverse events between head and neck surgery and the non-head and neck surgery group (p = 0.2238).
No individual patient clinical factors were identified to be associated with increased rates of 30-day adverse event rates for surgical management of lymphatic malformations in children. Our investigation highlights the need for quality improvement to help decrease 30-day adverse events for surgery for this group, as the rate was quite high overall (11.7%). The wound complication rate was very low, but we observed a non-negligible number of reoperations and readmissions. Improving quality of care for surgical management of lymphatic malformations in children should focus future investigations on limiting reoperations and readmissions within the first 30 days postoperatively.
Publication date: Available online 7 December 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Bee See Goh, Chian Ling Tang, Noor Dina Hashim, Tiagarajan Annamalay, Fairuz Nazri Abd Rahman
There is a dearth of studies on long term hearing status and behavioural patterns among cleft lip and/or palate children after their primary lip and palate closure in Malaysia. This study describes the audiology status and behavioural patterns in a group of school aged children with cleft lip and/or palate.
A cross sectional study was carried out where caretakers of cleft lip and/or palate were asked to complete the translated Malay language version of Strength Difficulties Questionnaire. The hearing status of the children was analyzed based on recent pure tone audiometric and tympanogram results. The patients' age, gender, type of cleft pathology, age of palatal surgery and behavioural patterns were examined for their potential relationship with hearing status.
A total of 74 children (148 ears) aged between 7 and 17 years with cleft lip and/or palate were recruited. The result showed 37 ears (25.0%) had hearing loss with majority suffered from mild conductive hearing loss. There were 16 ears (10.8%) that had persistent middle ear effusion. Hearing improvement occurred when palatal repair was performed at the age of less than 1 year old. (p =0.015) There was no significant relationship between patients' gender, age, type of cleft and history of myringotomy with their hearing status. In terms of behavioural patterns, 16.3% were abnormal for total behavioural score, 39.2% for peer problem and 17.6% for conduct problem. For prosocial behaviour, 16.3% were rated low and very low. There was fair correlation between age and hyperactivity problems (r =0.44). Patients' gender, type of cleft pathology, had been teased apart and hearing status was found not related to behavioural problems.
Cleft lip and/or palate patients have a good longterm hearing outcome. Majority had normal hearing and if there is hearing impairment, it is only a mild loss. Early palatal repair surgery before the age of 1 year can significantly reduce the risk of hearing loss. Cleft lip and/or palate patients experienced peer problems. There was no significant correlation between behavioural difficulty and hearing status among school-aged children with cleft lip and palate.
Publication date: Available online 7 December 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Kamran Asif Syed, P. Naina, Apar Pokharel, Mary John, Ajoy Mathew Varghese
To review the key parameters related to the proposed modified pediatric tracheostomy technique with to determine the efficacy, safety and outcomes in a tertiary hospital in south India. Patients and Methods A retrospective chart review of all children aged below 16 years who underwent tracheostomy at a tertiary hospital in south India during the period of August 2014 to August 2016. Data on age, gender, indication for tracheostomy, primary disease condition, duration of intubation, complications and decannulation rate were recorded.
Fifty children aged below 16 years underwent tracheostomy between August 2014 and August 2016. The average of the children was 5.35 years. (Range14 days to 14 years). The male female ratio was 1.6:1. In our study prolonged intubation was the most common indication (62%). None of the children had early post-operative complications such as bleeding, pneumothorax, surgical emphysema or accidental decannulation. Peristomal granulations (24%) was the most common complication although none was severe to warrant operative intervention. One child had a lifethreatening tube block requiring cardiopulmonary resuscitation. None of the children had accidental decannulation during the period of the study. Tracheocutaneous fistula was seen in 2 children (4%) and was the only long-term complication. These children required surgical decannulation. There was no clinical evidence of tracheal stenosis or tracheomalacia in any child.
Pediatric tracheostomy is challenging for both the surgeon and the care-giver specially in the early post-operative period. Our proposed modified technique addresses these concerns and without any significant complications.
Publication date: Available online 7 December 2018
Source: Annals of Allergy, Asthma & Immunology
Author(s): Eustachio Nettis, Elisabetta Di Leo, Gianfranco Calogiuri, Caterina Foti, Luigi Macchia
Publication date: Available online 7 December 2018
Source: Annals of Allergy, Asthma & Immunology
Author(s): Vivian Wang, Matthew Keefer, Peck Y. Ong
The invasion of Russia by the Napoleonic Grande Armée was a complete disaster. The French army was decimated during the retreat from Russia. Thousands of victims were buried in mass graves located near several cities during the retreat. One of these mass graves was discovered in in the center of Kaliningrad (formerly Königsberg), presently the most occidental oblast of the Russian Federation. Some skeletons revealed evidence of violence related traumatic injuries. Among them, the skeleton C2 belonged to a young male, who had suffered a serious injury to the lower face. The state of post‐traumatic remodeling indicated survival of about 2 months (between more than 6 weeks and less than 3 months).
The 3D reconstruction of the mandible and the maxilla contributed additional information about the injury, its cause and treatment. This permitted pre‐traumatic reconstruction of the viscerocranium and mandible through the application of two new techniques: virtual osteotomy and virtual bone transplant from another individual and perform an approximation of the face (to recreate the soft tissues) of this unidentified soldier using AFA3D software. These results highlight the use of 3D methods in paleopathology and forensic anthropology to reconstruct traumatic facial injuries and the pre‐traumatic facial appearance.
Finasteride 1 mg is considered to be the standard treatment method for male androgenetic alopecia (AGA). However, there have only been a few studies investigating its long‐term efficacy. Moreover, its effect on various types of AGA remains unknown. In this study, the authors investigated the 5‐year efficacy of finasteride 1 mg in Korean men with AGA and analyzed the changes in hair growth according to the distribution of hair loss. The medical records of male AGA patients who were treated with oral finasteride for a period of at least 5 years at two university hospitals were retrospectively reviewed. Patients' photographs were evaluated using the basic and specific (BASP) classification and investigator's global assessment. Of the total 126 patients, 108 (85.7%) showed improvement after 5 years of treatment. According to the BASP classification, hair loss of the anterior hair line (basic type), vertex (V type), and frontal area (F type) was improved in 44.4%, 89.7% and 61.2% of patients, respectively. The V type showed a more rapid and steady improvement compared with the other types. Progression of alopecia after peak improvement was seen in 10.3% of cases of the V type, 16.2% of the F type and 0% of the basic type. In conclusion, finasteride 1 mg showed a sustainable effect for at least 5 years in Korean male AGA patients. The exact time points showing signs of first clinical improvement and sustainability were different depending on the type of alopecia.
Histiocytoses, including Langerhans cell histiocytosis (LCH), juvenile or adult xanthogranuloma (AXG) and Rosai–Dorfman disease (RDD), are rare disorders characterized by the proliferation of cells derived from monocyte/macrophage lineages. A few cases of LCH coexisting with xanthogranuloma or RDD have been reported. The etiology of these diseases remains unclear. However, oncogenic BRAFV600E mutations have been identified in LCH. Here, we report the case of a 26‐year‐old Japanese man with a 3‐month history of a solitary occipital nodule. No abnormality was detected in his other organs, and a total resection of the nodule was performed. Histopathological examination revealed the coexistence of LCH and AXG with prominent emperipolesis characteristic of RDD. Immunohistochemistry showed that most of the large histiocytes were positive for CD68, weakly positive or negative for S100, and negative for CD207 and CD1a, supporting the diagnosis of AXG. The tumor cells with emperipolesis did not show S100‐positive findings characteristic of RDD. The focally aggregated oval histiocytic cells were positive for CD1a, CD207, CD68 and S100, and were compatible with the immunophenotype of LCH cells. In addition, these cells were positive for BRAFV600E mutation. The tumor cells in our patient exhibited a cellular morphology characteristic of multiple histiocytoses in a solitary cutaneous nodule, which may imply an etiological association among LCH, AXG and RDD. To our knowledge, this is the first report of a BRAFV600E mutation‐positive case of LCH coexisting with AXG. Because patients with BRAFV600E mutation have higher risks of multisystemic LCH and recurrence, we should carefully follow up the patient.
Publication date: December 2018
Source: Oral Oncology, Volume 87
Author(s): Bharat Dua, Kundan S. Chufal, Anshul Bhatnagar, Anil Thakwani
Nodal volume as a prognostic factor has been extensively evaluated in head and neck cancer, however there is still no consensus. We attempted to analyze nodal volume as a prognostic factor in head and neck cancer treated with chemoradiation (CCRT) without an elective neck dissection with image guided intensity modulated radiotherapy (IG-IMRT).
We prospectively analysed 87 patients of Stage III-IV cancer of the oropharynx (57), and hypopharynx (30), who subsequently received definitive concurrent chemoradiation. Total Nodal volume (TNV) was the sum of all lymph node volumes calculated by volume algorithm from the planning CT. The impact of TNV on overall survival (OS) & regional control (RC) was assessed. Survival analysis was done using SPSS version 20.0 (SPSS, Chicago, Illinois). A receiver operating characteristics (ROC) curve analysis was done for estimation of cut offs.
The 2 year OS & RC were 64% and 83% respectively. On multivariate analysis, the TNV was a significant prognostic factor for OS &RC. ROC curve analysis found an optimal volumetric cut off of 15cc for OS & RC. The 2 year OS & RC for <15cc/>15cc group were 78% /30% (p = 0.001) & 100%/52% (p = 0.001). Similar results were obtained on subset analysis of our oropharyngeal patients with 2 year OS 75%/24% for the <15cc and >15cc group (p = 0.001).
TNV is an independent prognostic factor for OS & RC in head and neck cancer. TNV can identify patients for consideration of elective neck dissection post CCRT ie for patients with TNV > 15CC.
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Konstantinos Mantsopoulos, Miguel Goncalves, Michael Koch, Maximilian Traxdorf, Mirco Schapher, Heinrich Iro
The aim of this study was to evaluate the potential for reducing surgical invasiveness in parotid cystadenolymphomas by means of capsular dissection based on the experience made in our department and on various aspects of these lesions gained from the relevant literature.
All patients treated for cystadenolymphomas with extracapsular or capsular dissection at a tertiary referral center between 2000 and 2017 were examined retrospectively. A literature review of various aspects and of different treatment strategies for this lesion was also performed.
629 patients were included in the study. 499 had solitary tumors (79.3%) and 130 had unilateral multicentric lesions (20.7%). 595 patients were managed by means of ED, while 34 patients underwent a CD. Our analysis detected an overall occurrence rate of ipsilateral metachronous tumors of 2.06% (13/629), all after extracapsular dissection, with a mean follow-up of 104.1 months. No statistical difference could be found between ED and CD in the overall occurrence rate of ipsilateral metachronous tumors or in the complication rate. No cases of a malignancy arising from a preexisting Warthin tumor could be detected in our study sample.
A clear potential for reducing surgical invasiveness could be shown. A reliable imaging diagnosis, appropriate patient counseling and high compliance with close follow-up are the basic prerequisites for an acceptable outcome.
Publication date: December 2018
Source: Oral Oncology, Volume 87
Author(s): Muriel Abbaci, Frederic De Leeuw, Ingrid Breuskin, Odile Casiraghi, Aïcha Ben Lakhdar, Wahib Ghanem, Corinne Laplace-Builhé, Dana Hartl
New optical technologies enhancing localization or assessing viability of parathyroid glands (PG) during endocrine surgery have been reported in clinical studies. These technologies could become complementary to the surgeon's eyes and may improve surgical outcomes in thyroidectomy and parathyroidectomy. Here, we conducted a systematic review focusing on PG identification and functional assessment using optical methods to enhance surgery.
A systematic literature review was performed using MEDLINE and Embase database. Two authors selected studies and extracted data; qualitative analysis was performed to summarize the characteristics of reported optical tools for thyroidectomy or parathyroidectomy. Identification and vascularisation of PG during surgery were evaluated. Clinical and biochemical outcomes were appraised when reported.
Studies relating to parathyroidectomy or thyroidectomy combined with autofluorescence, fluorescent methylene blue, 5-aminolevulinic acid, indocyanine green (ICG), optical coherence tomography, laser speckle contrast imaging, dynamic optical contrast imaging and Raman spectroscopy were identified with MEDLINE and Embase. We included a total of 47 relevant articles with a total of 1615 patients enrolled. Each optical technique is described and appreciated related to its surgical purpose.
Autofluorescence and ICG imaging of PG are the most widely reported optical technologies for identification and assessment of vascularisation of PG. Results are mainly based on observational studies and argue for the feasibility of both techniques in endocrine surgery but prospective randomized studies have not been performed. In vivo applications are still limited for the other methods and further investigations correlating these techniques with post-operative parathormone measurements are still needed before considering these technologies in clinical practice.
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): R.T. Karsten, M.M. Stuiver, L. van der Molen, A. Navran, J.P. de Boer, F.J.M. Hilgers, W.M.C. Klop, L.E. Smeele
Feeding tubes are placed unnecessarily in a proportion of head and neck cancer (HNC) patients treated with chemoradiotherapy (CRT) when prophylactic tube placement protocols are used. This may have a negative impact on the risk of long-term dysphagia. Reactive tube placement protocols, on the other hand, might result in weight loss and treatment interruption. The objective of this study is to identify patients at risk for prolonged tube dependency in order to implement a personalized strategy regarding proactive tube placement.
A retrospective study was performed in a consecutive cohort of HNC patients treated with primary CRT for whom a reactive tube placement protocol was used. A prediction model was developed to predict prolonged (> 90 days) feeding tube dependency. Model performance and clinical net benefit of the model were assessed.
Of the 336 included patients, 229 (68%) needed a feeding tube during CRT and 151 (45%) were prolonged feeding tube dependent. The prediction model includes the predictors pretreatment BMI, weight loss, Functional Oral Intake Scale and T-stage. Discriminatory ability is fair (area under the ROC-curve of 0.69) and calibration is adequate (Hosmer and Lemeshow test p = .254). The model shows net benefit over current practice for probability thresholds from 35 to 80%.
The developed model can be used to select patients for proactive feeding tube placement during primary CRT for HNC. The nomogram with easily obtainable parameters is a useful tool for clinicians to support shared decision making regarding proactive tube placement.
Publication date: December 2018
Source: Oral Oncology, Volume 87
Author(s):
Combined cosmetic treatments are becoming increasingly popular. The objective of this clinical evaluation was to assess the long-term safety and efficacy of combining microfocused ultrasound with visualization (MFU-V) treatment with a calcium hydroxylapatite (CaHA) dermal filler to tighten skin at the submental region and contour the jawline.
Women with loss of contour and skin laxity in the lower face received MFU-V treatment. If subjects did not respond satisfactorily after 12 weeks, they received CaHA to the jawline. Evaluations—which were performed by blinded raters at baseline and after 12, 24, and 48 weeks—included live Global Aesthetic Improvement Scale (GAIS) ratings, Merz Aesthetic Scale (MAS) ratings, skin parameters, and tolerability.
Of the 22 subjects, 9 received combined treatments. GAIS scores showed that subjects were much and very much improved (50% each) at 48 weeks. The MAS score was decreased by at least one point in 89% of subjects. Skin thickness was significantly improved after 24 weeks (p < 0.05) and remained above baseline after 48 weeks. Skin firmness was significantly improved after 48 weeks (p < 0.05). No unexpected adverse events were reported.
Combined MFU-V and CaHA treatments for laxity in the lower face did not alter skin barrier function, improved appearance, and slowed visible skin aging processes for at least 48 weeks.
Merz Pharmaceuticals GmbH.
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