Trends in Atopic Dermatitis Management: Comparison of 1990-1997 to 2003-2012.
J Drugs Dermatol. 2018 Feb 01;17(2):135-140
Authors: He A, Feldman SR, Fleischer AB
BACKGROUND: Atopic dermatitis (AD) is primarily treated with topical therapies, systemic immunosuppressants, or adjunctive therapies.
OBJECTIVE: As novel treatment approaches for AD emerge, we characterize AD treatment and examine trends in treatment over time.
METHODS: Visits for AD were identified in the 2003-2012 National Ambulatory Medical Care Survey (NAMCS). We identified topical corticosteroids (TCS), antibiotics (Abx), antihistamines (AH), topical calcineurin inhibitors (TCI), and systemic immunosuppressants (SI) prescribed at AD visits.
RESULTS: There were 990,000 annual visits for AD from 2003-2012 (3.2 visits/1000 people/year). TCS were the most frequently used medication (59% of visits). Topical calcineurin inhibitors (TCI) were the second most prescribed medication for AD among dermatologists (23% of visits), while antihistamines were second among all other physicians (16-44% of visits). Unlike other medications, use of TCIs decreased over time.
LIMITATIONS: The NAMCS does not follow individual patients over time.
CONCLUSIONS: TCI use has been decreasing. New topical AD treatments may provide an alternative to TCS, better treatment outcomes for moderate-to-severe atopic dermatitis, and an alternative to systemic antihistamines whose efficacy in AD is unproven and whose general use in AD management is discouraged by the American Academy of Dermatology. J Drugs Dermatol. 2018;17(2):135-140.
PMID: 29462220 [PubMed - in process]
Circulating tumour DNA, a promising biomarker for the management of colorectal cancer.
Crit Rev Oncol Hematol. 2018 Feb;122:72-82
Authors: Khakoo S, Georgiou A, Gerlinger M, Cunningham D, Starling N
Circulating cell free tumour DNA (ctDNA) maintains the same genomic alterations that are present in the corresponding tumour, thereby allowing for quantitative and qualitative real-time evaluation in body fluids as an alternative to onerous repeat biopsies. Improvements in the sensitivity of techniques used to identify ctDNA has led to a surge of research investigating its role in the detection of: early disease, relapse, response to therapy and emerging drug resistance mechanisms. Following curative surgery, ctDNA detection is a promising marker of minimal residual disease and could better select patients for adjuvant chemotherapy. Longitudinal monitoring could help identify early relapse. In metastatic disease, ctDNA can predict response to chemotherapy prior to evidence of disease progression on imaging and investigate novel primary and acquired resistance mechanisms to targeted therapies. More experience in detecting, analysing and interpreting ctDNA within prospective trials, will better define its role for implementation into routine clinical practice.
PMID: 29458792 [PubMed - in process]
Novel targeted therapies and immunotherapy for advanced thyroid cancers.
Mol Cancer. 2018 Feb 19;17(1):51
Authors: Naoum GE, Morkos M, Kim B, Arafat W
Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC. These advanced therapies exert their effects by blocking the MAPK pathway, which has been widely correlated to different types of thyroid cancers. While these drugs remain reserved for thyroid cancer patients who failed all treatment options, their ability to improve patients' overall survival remain hindered by their low efficacy and other molecular factors. Among these factors is the tumor's ability to activate parallel proliferative signaling pathways other than the cascades blocked by these drugs, along with overexpression of some tyrosine kinase receptors (TKR). These facts urge the search for novel different treatment strategies for advanced thyroid cases beyond these drugs. Furthermore, the growing knowledge of the dynamic immune system interaction with tumor microenvironment has revolutionized the cancer immune therapy field. In this review, we aim to discuss the molecular escape mechanisms of thyroid tumors from these drugs. We also highlight novel therapeutic options targeting other pathways than MAPK, including PI3K pathway, ALK translocations and HER2/3 receptors and their clinical impact. We also aim to discuss the usage of targeted therapy in restoring thyroid tumor sensitivity to RAI, and finally turn to extensively discuss the role of immunotherapy as a potential alternative treatment option for advanced thyroid diseases.
PMID: 29455653 [PubMed - in process]
Auditory Stimulus Processing and Task Learning Are Adequate in Dyslexia, but Benefits From Regularities Are Reduced.
J Speech Lang Hear Res. 2017 Feb 01;60(2):471-479
Authors: Daikhin L, Raviv O, Ahissar M
Purpose: The reading deficit for people with dyslexia is typically associated with linguistic, memory, and perceptual-discrimination difficulties, whose relation to reading impairment is disputed. We proposed that automatic detection and usage of serial sound regularities for individuals with dyslexia is impaired (anchoring deficit hypothesis), leading to the formation of less reliable sound predictions. Agus, Carrión-Castillo, Pressnitzer, and Ramus, (2014) reported seemingly contradictory evidence by showing similar performance by participants with and without dyslexia in a demanding auditory task that contained task-relevant regularities. To carefully assess the sensitivity of participants with dyslexia to regularities of this task, we replicated their study.
Method: Thirty participants with and 24 without dyslexia performed the replicated task. On each trial, a 1-s noise stimulus was presented. Participants had to decide whether the stimulus contained repetitions (was constructed from a 0.5-s noise segment repeated twice) or not. It is implicit in this structure that some of the stimuli with repetitions were themselves repeated across trials. We measured the ability to detect within-noise repetitions and the sensitivity to cross-trial repetitions of the same noise stimuli.
Results: We replicated the finding of similar mean performance. However, individuals with dyslexia were less sensitive to the cross-trial repetition of noise stimuli and tended to be more sensitive to repetitions in novel noise stimuli.
Conclusion: These findings indicate that online auditory processing for individuals with dyslexia is adequate but their implicit retention and usage of sound regularities is indeed impaired.
PMID: 28114605 [PubMed - indexed for MEDLINE]
Audiogenic seizure activity following HSV-1 GAD65 sense or antisense injection into inferior colliculus of Long-Evans rat.
Epilepsy Behav. 2017 Jun;71(Pt B):238-242
Authors: Coleman JR, Thompson KC, Wilson MA, Wilson SP
Herpes virus technology involving manipulation of GAD65 was used to study effects on audiogenic seizures (AGS). Audiogenic seizure behaviors were examined following injections of replication-defective herpes simplex virus (HSV-1) vectors incorporating sense or antisense toward GAD65 along with 10% lac-Z into the central nucleus of inferior colliculus (CNIC) of Long-Evans rats. In seizure-sensitive animals developmentally primed by intense sound exposure, injection of GAD65 in the sense orientation increased wild running latencies and reduced incidence of clonus compared with lac-Z only, unoperated, and vehicle seizure groups. In contrast, infection of CNIC with GAD65 antisense virus resulted in 100% incidence of wild running and clonus behaviors in AGS animals. Unprimed animals not operated continued to show uniform absence of seizure activity. Administration of GAD65 antisense virus into CNIC produced novel wild running and clonus behaviors in some unprimed animals. Staining for β-galactosidase in all vector animals revealed no differences in pattern or numbers of immunoreactive cells at injection sites. Qualitatively, typical small and medium multipolar/stellate and medium fusiform neurons appeared in the CNIC of vector animals. These results demonstrate that HSV-1 vector constructs implanted into the CNIC can predictably influence incidence and severity of AGS and suggest that viral vectors can be useful in studying GABA mechanisms with potential for therapeutic application in epilepsy. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
PMID: 27993512 [PubMed - indexed for MEDLINE]
Music Perception in Dementia.
J Alzheimers Dis. 2017;55(3):933-949
Authors: Golden HL, Clark CN, Nicholas JM, Cohen MH, Slattery CF, Paterson RW, Foulkes AJM, Schott JM, Mummery CJ, Crutch SJ, Warren JD
Despite much recent interest in music and dementia, music perception has not been widely studied across dementia syndromes using an information processing approach. Here we addressed this issue in a cohort of 30 patients representing major dementia syndromes of typical Alzheimer's disease (AD, n = 16), logopenic aphasia (LPA, an Alzheimer variant syndrome; n = 5), and progressive nonfluent aphasia (PNFA; n = 9) in relation to 19 healthy age-matched individuals. We designed a novel neuropsychological battery to assess perception of musical patterns in the dimensions of pitch and temporal information (requiring detection of notes that deviated from the established pattern based on local or global sequence features) and musical scene analysis (requiring detection of a familiar tune within polyphonic harmony). Performance on these tests was referenced to generic auditory (timbral) deviance detection and recognition of familiar tunes and adjusted for general auditory working memory performance. Relative to healthy controls, patients with AD and LPA had group-level deficits of global pitch (melody contour) processing while patients with PNFA as a group had deficits of local (interval) as well as global pitch processing. There was substantial individual variation within syndromic groups. Taking working memory performance into account, no specific deficits of musical temporal processing, timbre processing, musical scene analysis, or tune recognition were identified. The findings suggest that particular aspects of music perception such as pitch pattern analysis may open a window on the processing of information streams in major dementia syndromes. The potential selectivity of musical deficits for particular dementia syndromes and particular dimensions of processing warrants further systematic investigation.
PMID: 27802226 [PubMed - indexed for MEDLINE]
The genetic audiogenic seizure hamster from Salamanca: The GASH:Sal.
Epilepsy Behav. 2017 Jun;71(Pt B):181-192
Authors: Muñoz LJ, Carballosa-Gautam MM, Yanowsky K, García-Atarés N, López DE
The hamster has been previously described as a paroxysmal dystonia model, but our strain is currently recognized as a model of audiogenic seizures (AGS). The original first epileptic hamster appeared spontaneously at the University of Valladolid, where it was known as the GPG:Vall line, and was transferred to the University of Salamanca where a new strain was developed, named GASH:Sal. By testing auditory brainstem responses, the GASH:Sal exhibits elevated auditory thresholds that indicate a hearing impairment. Moreover, amplified fragment length polymorphism analysis distinguished genetic differences between the susceptible GASH:Sal hamster strain and the control Syrian hamsters. The GASH:Sal constitutes an experimental model of reflex epilepsy of audiogenic origin derived from an autosomal recessive disorder. Thus, the GASH:Sal exhibits generalized tonic-clonic seizures, characterized by a short latency period after auditory stimulation, followed by wild running, a convulsive phase, and finally stupor, with origin in the brainstem. The seizure profile of the GASH:Sal is similar to those exhibited by other models of inherited AGS susceptibility, which decreases after six months of age, but the proneness across generations is maintained. The GASH:Sal can be considered a reliable model of audiogenic seizures, suitable to investigate current antiepileptic pharmaceutical treatments as well as novel therapeutic drugs. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
PMID: 27072920 [PubMed - indexed for MEDLINE]
Overexpression of the immediate-early genes Egr1, Egr2, and Egr3 in two strains of rodents susceptible to audiogenic seizures.
Epilepsy Behav. 2017 Jun;71(Pt B):226-237
Authors: López-López D, Gómez-Nieto R, Herrero-Turrión MJ, García-Cairasco N, Sánchez-Benito D, Ludeña MD, López DE
Genetic animal models of epilepsy are an important tool for further understanding the basic cellular mechanisms underlying epileptogenesis and for developing novel antiepileptic drugs. We conducted a comparative study of gene expression in the inferior colliculus, a nucleus that triggers audiogenic seizures, using two animal models, the Wistar audiogenic rat (WAR) and the genetic audiogenic seizure hamster (GASH:Sal). For this purpose, both models were exposed to high intensity auditory stimulation, and 60min later, the inferior colliculi were collected. As controls, intact Wistar rats and Syrian hamsters were subjected to stimulation and tissue preparation protocols identical to those performed on the experimental animals. Ribonucleic acid was isolated, and microarray analysis comparing the stimulated Wistar and WAR rats showed that the genomic profile of these animals displayed significant (fold change, |FC|≥2.0 and p<0.05) upregulation of 38 genes and downregulation of 47 genes. Comparison of gene expression profiles between stimulated control hamsters and stimulated GASH:Sal revealed the upregulation of 10 genes and the downregulation of 5 genes. Among the common genes that were altered in both models, we identified the zinc finger immediate-early growth response gene Egr3. The Egr3 protein is a transcription factor that is induced by distinct stress-elicited factors. Based on immunohistochemistry, this protein was expressed in the cochlear nucleus complex, the inferior colliculus, and the hippocampus of both animal models as well as in lymphoma tumors of the GASH:Sal. Our results support that the overexpression of the Egr3 gene in both models might contribute to neuronal viability and development of lymphoma in response to stress associated with audiogenic seizures. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
PMID: 26775236 [PubMed - indexed for MEDLINE]