Neural Regeneration Research (Neural Regen Res)

Bridging larger gaps in peripheral nerves using neural prosthetics and physical therapeutic agents Muhammad Sana Ullah Sahar, Matthew Barton, Geoffrey Douglas Tansley Neural Regeneration Research 2019 14(7):1109-1115 Peripheral nerve injuries are relatively common and can be caused by a variety of traumatic events such as motor vehicle accidents. They can lead to long-term disability, pain, and financial burden, and contribute to poor quality of life. In this review, we systematically analyze the contemporary literature on peripheral nerve gap management using nerve prostheses in conjunction with physical therapeutic agents. The use of nerve prostheses to assist nerve regeneration across large gaps (> 30 mm) has revolutionized neural surgery. The materials used for nerve prostheses have been greatly refined, making them suitable for repairing large nerve gaps. However, research on peripheral nerve gap management using nerve prostheses reports inconsistent functional outcomes, especially when prostheses are integrated with physical therapeutic agents, and thus warrants careful investigation. This review explores the effectiveness of nerve prostheses for bridging large nerve gaps and then addresses their use in combination with physical therapeutic agents.

Magnesium: Pathophysiological mechanisms and potential therapeutic roles in intracerebral hemorrhage Jason J Chang, Rocco Armonda, Nitin Goyal, Adam S Arthur Neural Regeneration Research 2019 14(7):1116-1121 Intracerebral hemorrhage (ICH) remains the second-most common form of stroke with high morbidity and mortality. ICH can be divided into two pathophysiological stages: an acute primary phase, including hematoma volume expansion, and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion. To date, all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control, surgical evacuation, and hemostasis. However, none of these trials has resulted in improved clinical outcomes. Magnesium is a ubiquitous element that also plays roles in vasodilation, hemostasis, and blood-brain barrier preservation. Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms. Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume, hematoma expansion, and clinical outcome in patients with ICH. These associations, coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH, suggest that magnesium may be a viable target of study in future ICH studies.

Network-centric medicine for peripheral nerve injury: Treating the whole to boost endogenous mechanisms of neuroprotection and regeneration David Romeo-Guitart, Caty Casas Neural Regeneration Research 2019 14(7):1122-1128 Peripheral nerve injuries caused by accidents may lead to paralysis, sensory disturbances, anaesthesia, and lack of autonomic functions. Functional recovery after disconnection of the motoneuronal soma from target tissue with proximal rupture of axons is determined by several factors: motoneuronal soma viability, proper axonal sprouting across inhibitory zones and elongation toward specific muscle, effective synapse contact rebuilding, and prevention of muscle atrophy. Therapies, such as adjuvant drugs with pleiotropic effects, that promote functional recovery after peripheral nerve injury are needed. Toward this aim, we designed a drug discovery workflow based on a network-centric molecular vision using unbiased proteomic data and neural artificial computational tools. Our focus is on boosting intrinsic capabilities of neurons for neuroprotection; this is in contrast to the common approach based on suppression of a pathobiological pathway known to be associated with disease condition. Using our workflow, we discovered neuroheal, a combination of two repurposed drugs that promotes motoneuronal soma neuroprotection, is anti-inflammatory, enhances axonal regeneration after axotomy, and reduces muscle atrophy. This drug discovery workflow has thus yielded a therapy that is close to its clinical application.

Exogenous neural stem cell transplantation for cerebral ischemia Ling-Yi Liao, Benson Wui-Man Lau, Dalinda Isabel Sánchez-Vidaña, Qiang Gao Neural Regeneration Research 2019 14(7):1129-1137 Cerebral ischemic injury is the main manifestation of stroke, and its incidence in stroke patients is 70–80%. Although ischemic stroke can be treated with tissue-type plasminogen activator, its time window of effectiveness is narrow. Therefore, the incidence of paralysis, hypoesthesia, aphasia, dysphagia, and cognitive impairment caused by cerebral ischemia is high. Nerve tissue regeneration can promote the recovery of the aforementioned dysfunction. Neural stem cells can participate in the reconstruction of the damaged nervous system and promote the recovery of nervous function during self-repair of damaged brain tissue. Neural stem cell transplantation for ischemic stroke has been a hot topic for more than 10 years. This review discusses the treatment of ischemic stroke with neural stem cells, as well as the mechanisms of their involvement in stroke treatment.

Potential therapeutic molecular targets for blood-brain barrier disruption after subarachnoid hemorrhage Hideki Kanamaru, Hidenori Suzuki Neural Regeneration Research 2019 14(7):1138-1143 Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities. Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure, followed by global cerebral ischemia. Post-subarachnoid hemorrhage ischemia, tissue injuries as well as extravasated blood components and the breakdown products activate microglia, astrocytes and Toll-like receptor 4, and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades. Once blood-brain barrier is disrupted, brain tissues are directly exposed to harmful blood contents and immune cells, which aggravate brain injuries furthermore. Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins. Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage, but the exact mechanisms remain unclear. Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage. This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage.

Choroid plexus tumor necrosis factor receptor 1: A new neuroinflammatory piece of the complex Alzheimer's disease puzzle Sophie Steeland, Roosmarijn E Vandenbroucke Neural Regeneration Research 2019 14(7):1144-1147 Due to the aging of the population and despite the enormous scientific effort, Alzheimer’s disease remains one of the biggest medical and pharmaceutical challenges in current medicine. Novel insights highlight the importance of neuroinflammation as an undeniable player in the onset and progression of Alzheimer’s disease. Tumor necrosis factor is a master inflammatory cytokine that signals via tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2, but that also regulates several brain functions in health and disease. However, clinical trials investigating drugs that interfere with the tumor necrosis factor pathway in Alzheimer’s disease led to inconclusive results, partially because not only the pro-inflammatory tumor necrosis factor/tumor necrosis factor receptor 1, but also the beneficial tumor necrosis factor/tumor necrosis factor receptor 2 signaling was antagonized in these trials. We recently found that tumor necrosis factor is the main upregulated cytokine in the choroid plexus of Alzheimer’s disease patients, signaling via tumor necrosis factor receptor 1. In agreement with this, choroidal tumor necrosis factor/tumor necrosis factor receptor 1 signaling was also upregulated in different Alzheimer’s disease mouse models. Interestingly, both genetic and nanobody-based pharmacological blockage of tumor necrosis factor receptor 1 signaling was accompanied by favorable effects on Alzheimer’s disease-associated inflammation, choroidal morphology and cognitive functioning. Here, we briefly summarize the detrimental effects that can be mediated by tumor necrosis factor/tumor necrosis factor receptor 1 signaling in (early) Alzheimer’s disease, and the consequences this might have on the disease progression. As the main hypothesis in Alzheimer’s disease clinical trials is still based on the amyloid beta-cascade, the importance of Alzheimer’s disease-associated neuroinflammation urge the development of novel therapeutic strategies that might be effective in the early stages of Alzheimer’s disease and prevent the irreversible neurodegeneration and resulting memory decline.

Transcriptional dysregulation in neurodegenerative diseases: Who tipped the balance of Yin Yang 1 in the brain? Zhefan Stephen Chen, Ho Yin Edwin Chan Neural Regeneration Research 2019 14(7):1148-1151 Yin Yang 1 (YY1) is a multi-functional transcription factor that regulates gene expression in a range of cell types, including neurons. It controls neuronal differentiation, as well as neuronal specification and migration during the development of the mammalian nervous system. Besides, YY1 also mediates the transcription of genes that are required for neuronal survival. An impairment of the transcriptional function of YY1 causes neuronal death. This review summarizes recent research findings that unveil the dysfunction of YY1 in multiple neurodegenerative disorders. The expression of disease proteins perturbs the function of YY1 via distinct molecular mechanisms, including recruitment to protein aggregates, protein degradation and aberrant nuclear/cytoplasmic shuttling. Understanding the pathogenic roles of YY1 will further broaden our knowledge of the disease mechanisms in distinct neurodegenerative disorders.

Effects of Ginkgo biloba extract EGb761 on neural differentiation of stem cells offer new hope for neurological disease treatment Chao Ren, Yong-Qiang Ji, Hong Liu, Zhe Wang, Jia-Hui Wang, Cai-Yi Zhang, Li-Na Guan, Pei-Yuan Yin Neural Regeneration Research 2019 14(7):1152-1157 Stem cell transplantation has brought new hope for the treatment of neurological diseases. The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells. Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors, the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located. Accordingly, the optimal microenvironment for inducing stem cell differentiation is a hot topic. EGb761 is extracted from the leaves of the Ginkgo biloba tree. It is used worldwide and is becoming one of the focuses of stem cell research. Studies have shown that EGb761 can antagonize oxygen free radicals, stabilize cell membranes, promote neurogenesis and synaptogenesis, increase the level of brain-derived neurotrophic factors, and replicate the environment required during the differentiation of stem cells into nerve cells. This offers the possibility of using EGb761 to induce the differentiation of stem cells, facilitating stem cell transplantation. To provide a comprehensive reference for the future application of EGb761 in stem cell therapy, we reviewed studies investigating the influence of EGb761 on stem cells. These started with the composition and neuropharmacology of EGb761, and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.

Amelioration of Alzheimer's disease pathology and cognitive deficits by immunomodulatory agents in animal models of Alzheimer's disease Bridget Martinez, Philip V Peplow Neural Regeneration Research 2019 14(7):1158-1176 The most common age-related neurodegenerative disease is Alzheimer’s disease (AD) characterized by aggregated amyloid-β (Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles, together with loss of cholinergic neurons, synaptic alterations, and chronic inflammation within the brain. These lead to progressive impairment of cognitive function. There is evidence of innate immune activation in AD with microgliosis. Classically-activated microglia (M1 state) secrete inflammatory and neurotoxic mediators, and peripheral immune cells are recruited to inflammation sites in the brain. The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects. Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials. Treatment with immunomodulatory/anti-inflammatory agents early in the disease process, while not preventive, is able to inhibit the inflammatory consequences of both Aβ and tau aggregation. The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD. The majority of the animal studies reviewed had used transgenic models of early-onset AD. More effort needs to be given to creat models of late-onset AD. The effects of a combinational therapy involving two or more of the tested pharmaceutical agents, or one of these agents given in conjunction with one of the cell-based therapies, in an aged animal model of AD would warrant investigation.

Precision medicine in pantothenate kinase-associated neurodegeneration Mónica Alvarez-Cordoba, Marina Villanueva-Paz, Irene Villalón-García, Suleva Povea-Cabello, Juan M Suárez-Rivero, Marta Talaverón-Rey, Javier Abril-Jaramillo, Ana Belén Vintimilla-Tosi, José A Sánchez-Alcázar Neural Regeneration Research 2019 14(7):1177-1185 Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas, mainly the basal ganglia. The predominant clinical symptoms include spasticity, progressive dystonia, Parkinson’s disease-like symptoms, neuropsychiatric alterations, and retinal degeneration. Among the neurodegeneration with brain iron accumulation disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2 (PANK2) which catalyzed the first reaction of the coenzyme A biosynthesis pathway. Currently there is no effective treatment to prevent the inexorable course of these disorders. The aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in PKAN. Recently, we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules, mitochondrial dysfunction and a pronounced increase of markers of oxidative stress. In addition, PKAN fibroblasts showed a morphological senescence-like phenotype. Interestingly, pantothenate supplementation, the substrate of the PANK2 enzyme, corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme expression. However, pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete protein. The correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN fibroblasts. Our observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in specific mutations. Fibroblasts and induced neurons derived from patients can provide a useful tool for recognizing PKAN patients who can respond to pantothenate treatment. The presence of low but significant PANK2 expression which can be increased in particular mutations gives valuable information which can support the treatment with high dose of pantothenate. The evaluation of personalized treatments in vitro of fibroblasts and neuronal cells derived from PKAN patients with a wide range of pharmacological options currently available, and monitoring its effect on the pathophysiological changes, can help for a better therapeutic strategy. In addition, these cell models will be also useful for testing the efficacy of new therapeutic options developed in the future.

Mediterranean diet, alkaline water may be as effective as PPIs for laryngopharyngeal reflux

Alkaline water is water that's less acidic than regular tap water. This means it is rich in alkalizing compounds, including calcium, silica, potassium, magnesium, and bicarbonate.https://www.precisionnutrition.com/alkaline-water-legit-or-hoax

Seeing little relief with PPIs for patients, study author looked to dietary treatment for LPR

Treatment of laryngopharyngeal reflux (LPR) with alkaline water and the Mediterranean diet may be as effective as treatment with proton-pump inhibitors (PPIs), according to research published online in JAMA Otolaryngology–Head & Neck Surgery in September. Like gastroesophageal reflux disease, a similar condition, LPR occurs when acidic gastric juices in the stomach back up into the esophagus, but in LPR, the gastric juices reach the throat, resulting in symptoms such as hoarseness, sore throat, cough, and excessive mucous. 

In the study, researchers conducted a retrospective medical c­hart review comparing the change in Reflux Symptom Index (RSI) in two groups of patients, those treated between 2010 and 2012 with PPIs and standard reflux precautions and those treated between 2013 and 2015 with a plant-based Mediterranean diet and alkaline water that had a pH of at least 8. The team found that 54.1% of patients in the PPI group achieved a clinically meaningful reduction of at least 6 points, but 62.5% in the dietary group achieved similar results. Furthermore, those in the dietary group achieved a greater reduction in RSI: 39.8% compared with 27.2% in the PPI group.

"It's pretty clear that this data suggests that we, as health care professionals, need to start getting patients educated so they understand how important a role diet plays," said study lead author Craig H. Zalvan, MD, FACS, chief of otolaryngology and medical director at The Institute for Voice and Swallowing Disorders at Phelps Hospital in Sleepy Hollow, NY.

Zalvan said he thought to study dietary treatment for LPR after seeing that a sizable number of patients don't get much relief with PPIs.

"The standard of care for LPR has always been PPIs, and many of my patients got better with them, but a bunch didn't. At most it helps about 50% of patients," Zalvan said. "I looked at chronic diseases like heart disease, diabetes, and stroke, and their successful treatment with a plant-based diet, so I thought there's got to be a better way to treat LPR with diet [as well] and not have people constantly taking pills."

Zalvan added that the idea to incorporate alkaline water into treatment stemmed from prior research conducted by Jaime Koufman, MD, at the Voice Institute of New York in New York City, which suggests that alkaline water may benefit patients with reflux because it deactivates pepsin and acts as an acid buffer.

Zalvan said that as medication experts and readily accessible members of the health care team, pharmacists can help boost the signal about treatment options for LPR.

"Pharmacists can reinforce that PPIs are meant to be short-term medications for an acute problem, and that in order to get off them, diet will play a major part," Zalvan said. "If patients come to me and I say they should try diet, and then they go to the pharmacy and the pharmacist says they should try diet, patients are more likely to try diet."

For the full article, please visit www.pharmacytoday.org for the November 2017 issue of Pharmacy Today.

Clinical Thyroidology® for the Public – Highlighted Article

From Clinical Thyroidology^® for the Public: It is unclear if there is a link between hypothyroidism during pregnancy and the risk of asthma in children. The goal of this study is to examine whether hypothyroidism during pregnancy affected the risk of developing childhood asthma. Read More…

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Vorgehen bei Schilddrüsenkarzinomen in einer medianen Halszyste

Laryngo-Rhino-Otol
DOI: 10.1055/a-0850-0154

Schilddrüsenkarzinome aus Residuen des Ductus thyreoglossus sind eine Seltenheit und werden meist als Zufallsbefund postoperativ festgestellt. Es gibt keine klaren Richtlinien für das korrekte therapeutische Vorgehen nach erfolgter Resektion, insbesondere bezüglich der Notwendigkeit einer totalen Thyroidektomie und Radioiodtherapie. Vor dem Hintergrund der aktuellen Literatur wird eine Fallserie von fünf Patienten mit Schilddrüsenkarzinomen in einer medianen Halszyste präsentiert. Es erfolgte eine retrospektive Analyse aller Patienten mit einem Schilddrüsenkarzinom in einer medianen Halszyste im Zeitraum zwischen 2002 und 2017.Von 578 Patienten, die aufgrund einer medianen Halszyste operiert wurden, konnte bei fünf dieser Patienten (3 Frauen, 2 Männer), im Alter von 16–73 Jahren (Altersmittelwert 51; Median 56 Jahre) ein Schilddrüsenkarzinom gesichert werden. Klinisch stellten sich alle Patienten mit einer schmerzlosen Schwellung im Bereich des Zungenbeins vor. Die Diagnose wurde in allen Fällen postoperativ gestellt, in einem Fall wurde in der präoperativen Bildgebung bereits ein Malignom vermutet. Histologisch zeigte sich in allen Fällen ein papilläres Schilddrüsenkarzinom. Vier Patienten erhielten im Intervall eine totale Thyroidektomie und Radioiodtherapie, zwei davon zusätzlich eine Neck dissection des medialen und lateralen Kompartiments, der fünfte Patient hat sich einer weiteren Diagnostik und Therapie entzogen. Es wurden in allen vier Fällen keine Karzinome der Schilddrüse oder Lymphknotenmetastasen nachgewiesen.Aufgrund der Seltenheit von Schilddrüsenkarzinomen in medianen Halszysten existiert derzeit kein standardisiertes therapeutisches Vorgehen. Es sollte eine Risikostratifizierung vorgenommen werden, um Patienten, die von einer zusätzlichen Thyroidektomie profitieren könnten, zu identifizieren. Die Prognose ist sehr gut.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Der neuartige Propel mini Stent – Indikationen, Operationstechnik und erste klinische Erfahrungen

Laryngo-Rhino-Otol
DOI: 10.1055/a-0839-5206

Hintergrund Die Therapie der chronischen Sinusitis frontalis stellt sich aufgrund des anatomisch engen Abflusses in die Nasenhaupthöhle häufig als problematisch dar. Neben konservativen Methoden wurden bisher auch viele chirurgische Therapieverfahren, sowohl mit als auch ohne Einsatz von Platzhaltern, jedoch ohne längerfristigen Therapieerfolg erprobt. Ziel dieser Arbeit war die klinische Testung der allgemeinen Praktikabilität und der kurz- sowie langfristige Therapieerfolg des neuartigen bioresorbierbaren Propel mini Stents. Material und Methoden In einer prospektiven Studie an 21 Patienten mit chronischer Rhinosinusitis mit Polyposis nasi wurde die chirurgische Therapie und das Einbringen des Stents dargestellt und die Degradation von insgesamt 31 Stents sowie der Erfolg dieser Therapieform über einen Zeitraum von 6 Monaten endoskopisch kontrolliert und analysiert. Ergebnisse Hinsichtlich chirurgischer Praktikabilität erwies sich der Stent mit Einführungstool als unkompliziertes und leicht bedienbares System. Alle Patienten haben die Stents gut toleriert. Die durchschnittliche, nachweisbare Materialabsorption überdauerte 28 Tage. Das Patientenkollektiv zeigte in 94 % der Fälle nach 3 Monaten und in 87 % der Fälle nach 6 Monaten einen vollständig sondierbares Neo-Ostium des Sinus frontalis. Schlussfolgerung Die Ergebnisse der prospektiven Studie zeigen insgesamt eine gute Akzeptanz bei den Patienten ohne Komplikationen sowie eine vollständige Stentdegradation. Auch die Follow-Up-Untersuchungen ergaben zufriedenstellende Ergebnisse über 6 Monate. Insbesondere unter dem Aspekt der endoskopischen Operation erwies sich das Stent-System als sehr praktikabel.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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High expression of MLANA in the plasma of patients with head and neck squamous cell carcinoma as a predictor of tumor progression

Background

There is a paucity of plasma‐based biomarkers that predict outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation therapy (CRT). Here, we evaluate the prognostic potential of plasma Melanoma‐Antigen Recognized by T‐cells 1 (MLANA) in this setting.

Methods

MLANA expression in HNSCC lines were evaluated by reverse transcription polymerase chain reaction, whereas plasma levels were quantified using ELISA in 48 patients with locally advanced HNSCC undergoing a phase 2 trial with CRT.

Results

MLANA is expressed at variable levels in a panel of HNSCC lines. In plasma, levels were elevated in patients with tumor relapse compared to those without (P < .004); 73.9% of the patients expressing high plasma MLANA levels progressed with recurrent disease (P = .020). Multivariate analysis showed that plasma MLANA levels and tumor resectability were independent prognostic factors for progression free survival.

Conclusion

Plasma MLANA expression appears to be an effective noninvasive biomarker for outcomes in patients treated with CRT, and could potentially guide therapeutic decisions in this context.

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Which imaging modality in cochlear implant candidates?

Abstract

Purpose

There is no guideline or consensus on preoperative radiologic imaging modality despite the fact that it has a vital importance in appropriate candidacy selection of cochlear implantation. We aimed to find out the role of high-resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) on surgical planning, intraoperative technique in cochlear implant candidates.

Methods

The clinical charts, imagings, and operative reports of patients who underwent cochlear implant surgery at a tertiary institution were retrospectively examined.

Results

611 patients (503 children and 108 adult) were enrolled into the study. We found 11 different pathologies in MRI which could not be seen in HRCT. However, we decided the side of surgery according to MRI in only three of them in which the pathology was cochlear nerve hypoplasia. Two patients with cochlear nerve hypoplasia were children with prelingual deafness and one was adult with perilingual deafness. Moreover, we changed the surgical planning of side according to both imaging modalities in nine patients. Seven of them were children and two were adult. One of these adults had cochlear anomaly, and another had bilateral temporal bone fracture.

Conclusions

We suggest both imaging modalities in pediatric candidates. However, in adults, we think that superiority of either imaging modalities is still contradictive. We had only three adult patients and the decision of the side of surgery was made according to MRI in one of them and to both imaging modalities in the other two adults.

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Adjuvant Radiotherapy in Early Stage Oral Cancers

Conditions:   Cancer of Mouth;   Cancer of the Tongue;   Cancer of the Head and Neck;   Buccal Mucosa Cancer;   Floor of Mouth Carcinoma
Intervention:   Radiation: Post-operative adjuvant radiotherapy
Sponsor:   Tata Memorial Hospital
Recruiting

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A Phase Ib/II Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, for Advanced Solid Tumors or With mXELOX as First-line Therapy for Advanced Gastric or GEJ Adenocarcinoma

Conditions:   Gastric Adenocarcinoma;   Advanced Solid Tumors;   Gastroesophageal Junction Adenocarcinoma
Interventions:   Biological: AK104;   Drug: Oxaliplatin;   Drug: Capecitabine
Sponsors:   Akeso;   Akeso Pharmaceuticals, Inc.
Recruiting

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Quality of Life in Head and Neck Cancer Patients

Abstract

To assess the quality of life in head and neck cancer patients and the various factors which affect the quality of life in head and neck cancer patients was the main aim of the study. A prospective longitudinal study with a sample size of 130 patients was done within the time period of one and a half years. Patients with biopsy proven squamous cell carcinoma of the head and neck were treated as per their treatment protocol either by combined modality or single modality. Follow up at the completion of treatment was done and the quality of life questionnaire was filled out. QoL was assessed pre-treatment and at 4 times at different stages of follow up period. Demographic data was also taken into consideration for comparison which showed that head and neck cancer is more common in the males (80%) between the age group of 35–50 years, chronic tobacco chewers (45%) with most common site of cancer being the oral cavity (61%). Majority of the patients presented at Stage IV of their disease (35%) with largest HRQoL changes seen within the first three months after commencement of treatment. The most debilitating modality of treatment was Surgery + CTRT. Detailed assessment of the various factors which hamper the QoL in head and neck cancer patients should be done by which we can provide quality care and a completely new view into the health care experience and improving patient satisfaction.

https://ift.tt/2VkKno0

Quality of Life in Head and Neck Cancer Patients

Abstract

To assess the quality of life in head and neck cancer patients and the various factors which affect the quality of life in head and neck cancer patients was the main aim of the study. A prospective longitudinal study with a sample size of 130 patients was done within the time period of one and a half years. Patients with biopsy proven squamous cell carcinoma of the head and neck were treated as per their treatment protocol either by combined modality or single modality. Follow up at the completion of treatment was done and the quality of life questionnaire was filled out. QoL was assessed pre-treatment and at 4 times at different stages of follow up period. Demographic data was also taken into consideration for comparison which showed that head and neck cancer is more common in the males (80%) between the age group of 35–50 years, chronic tobacco chewers (45%) with most common site of cancer being the oral cavity (61%). Majority of the patients presented at Stage IV of their disease (35%) with largest HRQoL changes seen within the first three months after commencement of treatment. The most debilitating modality of treatment was Surgery + CTRT. Detailed assessment of the various factors which hamper the QoL in head and neck cancer patients should be done by which we can provide quality care and a completely new view into the health care experience and improving patient satisfaction.

https://ift.tt/2VkKno0

Regulatory aspects of prospective and retrospective clinical research in France in 2018

Publication date: Available online 23 February 2019

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): P. Gorphe, C. Jannin

Abstract

In France, the so-called "Jardé law" (named for its proposer) on human research, implemented since 2016, defines the regulatory and legal framework for "prospective" studies, formerly known as "biomedical research" or "common care". Three categories are distinguished: type 1 is at-risk drug or non-drug interventional research, type 2 is low-risk, low-burden interventional research, and type 3 is non-interventional research. The decrees of April 12, 2018 precisely define a list of research categories for types 2 and 3, thereby clarifying the regulatory procedures. The Sponsor registers the trial on the database of the National Drug Safety Agency (ANSM), or the European EudraCT database for drug studies, to obtain an identification number. Regulatory procedures are undertaken with the IRB and ANSM and then the Data Protection Commission (CNIL). Retrospective research on previously collected data (other than genetic) does not come under the Jardé law, and is governed by the 1978 data protection law, updated by the application decree of December 2016 and the law No. 2018-493 of June 20, 2018 on protection of personal data. This article presents a clarification of the key methodologic and regulatory steps.

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Vestibular Infant Screening – Flanders: the implementation of a standard vestibular screening protocol for hearing-impaired children in Flanders

Publication date: Available online 25 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Sarie Martens, Ingeborg Dhooge, Cleo Dhondt, Laura Leyssens, Marieke Sucaet, Saartje Vanaudenaerde, Lotte Rombaut, Leen Maes

Abstract

Objectives

The Vestibular Infant Screening – Flanders (VIS-Flanders) project aims to implement and refine a vestibular screening protocol for all children with neonatal hearing loss in Flanders (Belgium) to limit the impact of a vestibular dysfunction on the motor, cognitive and psychosocial development of hearing-impaired children.

Methods

Each child with a confirmed neonatal hearing loss in Flanders will undergo a vestibular screening at the age of 6 months in the reference centers involved in the neonatal hearing screening program. The cervical Vestibular Evoked Myogenic Potential (cVEMP) test will be used as a screening tool. The test is short, child-friendly, feasible at a young age and highly correlated with motor and balance performance. The results of an extensive follow-up protocol at the Ghent University Hospital will enable further refinement of the screening protocol.

Results

Data collection in all reference centers has started since June 2018. This paper outlines the rationale for the screening and the set-up of this four-year project.

Conclusions

Current available literature strongly favors vestibular assessment in congenitally hearing-impaired children. A standard vestibular screening for these children should lead to early identification of vestibular deficits and subsequent prompt referral for further motor assessment and rehabilitation, in order to limit the impact of a vestibular dysfunction in developing children and improve their quality of life.

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Recurrent Periorbital Cellulitis Associated with Rhinosinusitis in Children: Characteristics, Course of Disease, and Management Paradigm

Publication date: Available online 25 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Sharon Tzelnick, Ethan Soudry, Eyal Raveh, Dror Gilony

Abstract

Background

Recurrent periorbital cellulitis (RPOC) associated with rhinosinusitis is rarely noted and scarcely discussed in the literature. The aim of our study was to analyze the characteristics and disease course of a group of pediatric patients with RPOC.

Methods

The medical records of all pediatric patients with a diagnosis of RPOC treated in a tertiary children's hospital were retrieved. Included were patients with a history of two or more episode of RPOC.

Results

A total of 14 children were included. Mean follow up was 3 years (SD ±2.5). Median age of first POC episode was 12 months (range 5 months – 12 years). Overall, 75 events of RPOCs were documented. A median of 3 events per patient was noted (range 2-16). Preseptal cellulitis was diagnosed in all but five patients, in whom orbital cellulitis or subperiosteal abscess were identified, one following failure of conservative treatment, and the remaining at first presentation or recurrence. Rhinorrhea was present in only five patients (35%). The majority of patients were treated with intra-venous antibiotics. Imaging studies were performed in all patients revealing ethmoidal sinusitis in all patients, with lamina papyracea dehiscence in two patients. Immune deficiency was diagnosed in one patient. Endoscopic sinus surgery was performed in seven patients, in four as preventive procedure and in three during an acute phase. Post-operative recurrent disease was noted in two patients that were operated during the acute phase.

Conclusions

RPOC is a rare entity. Rhinosinusitis should be suspected in events of recurrent preseptal cellulitis even in the absence of nasal symptoms. CT scan is diagnostic for sinus origin of disease and possible anatomical abnormalities. In the majority of patients no evident etiology was identified. Elective Surgery or prophylactic antibiotic treatment should be strongly considered in this subgroup of patients as it seems beneficial.

https://ift.tt/2NstF3f

Serious complications due to acute rhinosinusitis in children up to five years old in Stockholm, Sweden – still a challenge in the pneumococcal conjugate vaccine era

Publication date: Available online 25 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): S.Hultman Dennison, L.Schollin Ask, M. Eriksson, A. Granath, O. Hertting, R. Bennet, A. Lindstrand, P. Masaba, P. Dimitriou, P. Stjärne

Abstract

Objectives

The aim of this study was to analyze the rate of admissions, the rate of serious complications (postseptal orbital complications and surgery) and the bacterial etiology of acute rhinosinusitis in hospitalized children under five years old in Stockholm County, eight years after the introduction of the pneumococcal conjugate vaccine (PCV). The secondary aim was to compare this period with the period four years prior to the vaccine's introduction.

Methods

This was a population-based, descriptive observational study with retrospectively collected data from 1 July 2008 to 30 June 2016 in Stockholm County. Hospital admissions of children with a discharge diagnosis of rhinosinusitis and related complications were reviewed and compared to the pre-PCV period of 2003 to 2007.

Results

A total of 215 children were admitted, for a yearly incidence of 18.8 per 100 000 children (22.8 for boys, 14.6 for girls). Computer tomography-verified postseptal orbital complications occurred in 29 cases (13.5%) and surgery was necessary in nine (4.2%). Pathogens other than Streptococcus pneumoniae were found in the cases with postseptal complication or surgery (Streptococcus pyogenes in four, Haemophilus influenzae in three and Staphylococcus aureus in one case). In comparison to the four years pre-PCV, the incidence of admission decreased from 43.81 to 20.31 and 17.45 per 100 000/year for the two four-year periods after vaccine introduction. The incidence of CT-verified postseptal complication increased slightly from 1.51 to 2.34 and 2.74 per 100 000/year. The incidence of surgeries increased marginally but continued to be very low, from 0.22 to 0.54 and 1.03 per 100 000/year.

Conclusions

Complications due to acute rhinosinusitis in children living in Stockholm County continues to be very rare after the introduction of pneumococcal vaccine. Hospitalization has decreased for children under five years old after PCV introduction, but the incidence or postseptal complications and surgery in the same population increased slightly. Predominantly bacteria other than Streptococcus pneumoniae was found. There is a need of larger studies to determine trends, and a need of prospective studies to elucidate the bacterial etiology, of serious complications due to acute rhinosinusitis in children.

https://ift.tt/2GKz2dE

Polymorphism in GRHL2 gene may contribute to noise-induced hearing loss susceptibility: a meta-analysis

Publication date: Available online 23 February 2019

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Xin Li, Zhengping Zhu, Wei Li, Li Wei, Baocheng Zhao, Zheng Hao

Abstract

Instruction

Noise-induced hearing loss is a leading occupational disease caused by gene-environment interaction. The Grainy Like 2, GRHL2, is a candidate gene. In this regard, many studies have evaluated the association between GRHL2 and noise-induced hearing loss, although the results are ambiguous and conflicting.

Objective

The purpose of this study was to identify a precise estimation of the association between rs3735715 polymorphism in GRHL2 gene and susceptibility of noise-induced hearing loss.

Methods

A comprehensive search was performed to collect data up to July 8, 2018. Finally, 4 eligible articles were included in this meta-analysis comprising 2410 subjects. The pooled odds ratios with 95% confidence intervals were used to evaluate the strength of the association.

Results

Significant association was found in the overall population in the dominant model (GA/AA vs. GG, odds ratio = 0.707, 95% confidence interval = 0.594–0.841) and allele model (G allele vs. A allele, odds ratio = 1.189, 95% confidence interval = 1.062–1.333). When stratified by source of the subjects, we also found association between rs3735715 and noise-induced hearing loss risk in the dominant model (GA/AA vs. GG, odds ratio = 0.634, 95% confidence interval = 0.514–0.783) and allele model (G allele vs. A allele, odds ratio = 1.206, 95% confidence interval = 1.054–1.379).

Conclusion

Rs3735715 polymorphism in GRHL2 gene may influence the susceptibility of noise-induced hearing loss. Additional large, well-designed and functional studies are needed to confirm this association in different populations.

Resumo

Introdução

Perda auditiva induzida por ruído é uma das principais doenças ocupacionais causadas pela interação gene-ambiente. O Grainy Like 2, ou GRHL2 é um gene que tem sido considerado como candidato. Nesse sentido, muitos estudos avaliaram a associação entre o GRHL2 e perda auditiva induzida por ruído, embora os resultados sejam ambíguos e conflitantes.

Objetivo

O objetivo deste estudo foi identificar uma estimativa precisa da associação entre o polimorfismo rs3735715 no gene GRHL2 e a suscetibilidade à perda auditiva induzida por ruído.

Método

Uma pesquisa abrangente foi realizada para coletar dados até 8 de julho de 2018. No final, quatro artigos elegíveis foram incluídos nesta meta-análise, abrangendo 2410 indivíduos. Os odds ratios agrupados com intervalos de confiança de 95% foram utilizados para avaliar a força da associação.

Resultados

Uma associação significante foi encontrada na população geral no modelo de dominância (GA/AA vs. GG, odds ratio = 0,707, intervalo de confiança 95% = 0,594-0,841) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,189, intervalo de confiança 95% = 1,062 a 1,333). Quando estratificados pelo local de trabalho dos indivíduos, também encontramos associação entre rs3735715 e risco de perda auditiva induzida por ruído no modelo de dominância (GA/AA vs. GG, odds ratio = 0,634, intervalo de confiança 95% = 0,514 ± 0,783) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,206, intervalo de confiança 95% = 1,054- 1,379).

Conclusão

O polimorfismo Rs3735715 no gene GRHL2 pode influenciar a suscetibilidade à perda auditiva induzida por ruído. Estudos adicionais, amplos, bem desenhados e funcionais são necessários para confirmar essa associação em diferentes populações.

https://ift.tt/2NshMKF

Diagnosing acquired syphilis through oral lesions: the 12 year experience of an Oral Medicine Center

Publication date: Available online 23 February 2019

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Michelle Danielle Porto Matias, Alessandro Oliveira de Jesus, Renata Gonçalves Resende, Patrícia Carlos Caldeira, Maria Cássia Ferreira de Aguiar

Abstract

Introduction

A resurgence of syphilis in Brazil has been reported in recent years.

Objective

With this in mind, the present study sought to investigate the frequency, demographics, and clinical characteristics of patients with acquired syphilis with oral involvement who received medical care at an Oral Medicine Reference Center in a Brazilian Public Hospital.

Methods

A retrospective study, spanning a period of 12 years, was performed to identify changing trends in syphilis over time. Medical records from all patients diagnosed with acquired syphilis who received medical care at the Hospital's Oral Medicine Clinic from 2005 to 2016 were reviewed, and the demographic and clinical data were collected.

Results

A total of 85 patients had been diagnosed with acquired syphilis, with a significant increase in the number of cases over the past 5 years. Patients ranged from 16 to 76 years of age, with a peak in the third and fourth decades. Forty-eight cases affected males (56.5%), while 37 cases affected females (43.5%). Most of the oral lesions appeared as unique ulcers or plaques, with the lips and tongue representing the most affected sites. All cases were positive for Venereal Disease Research Laboratory or Fluorescent Treponemal Antibody Absorption, and treatment was performed with Penicillin G benzathine in most cases (84.7%).

Conclusion

The frequency of oral syphilis has been rising over time and oral lesions may well represent a diagnostic clue; therefore, oral health professionals must be made aware and properly trained in an attempt to develop a high degree of clinical suspicion in the diagnosis of syphilis.

Resumo

Introdução

Um ressurgimento da sífilis no Brasil tem sido relatado nos últimos anos.

Objetivo

Nesse sentido, o presente estudo buscou investigar a frequência, características demográficas e clínicas dos pacientes com sífilis adquirida com envolvimento oral que receberam atendimento médico em um centro de referência em medicina oral em um hospital público brasileiro.

Método

Trata-se de um estudo retrospectivo, abrangendo um período de 12 anos, realizado para identificar tendências de mudança na sífilis ao longo do tempo. Registros médicos de todos os pacientes diagnosticados com sífilis adquirida que receberam atendimento médico na clínica de medicina oral do hospital de 2005 a 2016 foram revisados, e os dados demográficos e clínicos foram coletados.

Resultados

Um total de 85 pacientes foi diagnosticado com sífilis adquirida, com um aumento significativo no número de casos nos últimos 5 anos. A idade dos pacientes variou de 16 a 76 anos de idade, com pico na terceira e quarta décadas. Quarenta e oito casos eram do sexo masculino (56,5%) e 37 casos do sexo feminino (43,5%). A maioria das lesões orais apareceu como úlceras ou placas únicas, com os lábios e a língua representando os locais mais afetados. Todos os casos foram positivos para Venereal Disease Research Laboratory e Fluorescent Treponemal Antibody Absorption Test, e o tratamento foi realizado com Penicilina G benzatina na maioria dos casos (84,7%).

Conclusão

A frequência da sífilis oral tem aumentado com o tempo e as lesões orais podem representar uma pista diagnóstica; portanto, os profissionais de saúde bucal devem ser conscientizados e devidamente treinados na tentativa de desenvolver um alto grau de suspeição clínica no diagnóstico da sífilis.

https://ift.tt/2GJOzKH

Marine Bromophenols as an effective inhibitor of virulent proteins (Peptidyl Arginine Deiminase, Gingipain R and Hemagglutinin A) in Porphyromas gingivalis

Publication date: Available online 23 February 2019

Source: Archives of Oral Biology

Author(s): Chikoo Cherian, J. Jannet Vennila, Leena Sharan

Abstract

Objectives

Porphyromonas gingivalis, is one of the major oral pathogen that produce virulent proteins which mediate periodontal tissue inflammation and infection. Marine algae have recently gained popularity for its bioactive molecules and their oral applications. Marine bromophenols (MBs) is abundant in red algae which are reported to have wide medicinal properties. The current research primarily focuses to elucidate the bioactivity of MBs against the virulent proteins produced by P. gingivalis.

Materials and methods

Potent MBs which effectively binds and inhibits the virulent proteins peptidyl arginine deiminase (PPAD), gingipain R (Rgp) and hemagglutinin A (HgA) was identified through molecular docking and molecular simulation approach. MBs were extracted from Kappaphycus alvarezii (KAB), marine red algae found in India. The efficacy of this MB was studied against P. gingivalis by employing antibacterial activity assays, gingipain assay, hemagglutination inhibition assay (HIA) and mRNA expression analysis (q RT PCR).

Results

MBs with benzene, methyl and glycosyl substitutions demonstrated significant docking score, with good stability and pharmacokinetic properties. In addition to the antibacterial activities against P. gingivalis, KAB was also found to inhibit the gingipain and hemagglutination activities. Exposure of KAB to the virulent genes in P. gingivalis resulted in low mRNA levels of these genes, which suggested the down regulation functions induced by the MBs

Conclusion

Biochemical investigations revealed that KAB is a potent natural metabolite that can inhibit and control the virulent proteins produced by P. gingivalis. This study recommends future research to direct towards applicability of MBs in commercial dental products.

Graphical abstract

https://ift.tt/2ViBKuc

Epidemiology of otorhinolaryngologic emergencies in a secondary hospital: analysis of 64,054 cases

Abstract

Purpose

To determine the incidence and distribution of care in relation to urgent otorhinolaryngologic pathologies by the different medical specialist units.

Methods

A descriptive, observational and retrospective study was conducted of patients seen by the Emergency Service at a secondary hospital over the course of 7 years (2011–2017).

Results

A total of 546,701 patients were seen during the period in question, of which 64,054 presented with otorhinolaryngologic symptoms. The attendance rate was 450/1000 inhabitants/year. The most frequent diagnoses were upper respiratory tract infection, with 13,639 cases (21.3%), tonsillopharyngitis, with 10,150 cases (15.8%) and vertigo/dizziness with 8761 cases (13.7%). Patients seen by the Hospital Emergency Service physicians and those referred to the Otorhinolaryngology or Paediatric Units were analysed both together and separately. The Hospital Emergency Service dealt with 77.1% of the cases, and referred 15.4% to the Otorhinolaryngology Unit and 7.5% to the Paediatrics Unit. Within the subgroup of patients referred to the Otorhinolaryngology Unit, the most frequent diagnoses were problems related to inflammatory ear disease (25.6%), followed by cervicofacial trauma (15.4%) and bleeding with otorhinolaryngologic symptoms (12.5%). The percentage of hospital admissions for the entire sample was 3%, while for patients referred to the Otorhinolaryngology Unit this figure was 6.8%.

Conclusions

A large percentage of patients presenting at the Hospital Emergency Service do so with otorhinolaryngologic symptoms, and the vast majority are treated effectively by the physicians in that service and are referred to the specialist services on the basis of sound criteria.

https://ift.tt/2H0Q46z

Depth of invasion alone as an indication for postoperative radiotherapy in small oral squamous cell carcinomas: An International Collaborative Study

Abstract

Background

We aimed to investigate whether depth of invasion (DOI) should be an independent indication for postoperative radiotherapy (PORT) in small oral squamous cell carcinomas (SCC).

Methods

Retrospective analysis of DOI (<5, 5 to <10, ≥10 mm) and disease‐specific survival (DSS) in a multi‐institutional international cohort of 1409 patients with oral SCC ≤4 cm in size treated between 1990‐2011.

Results

In patients without other adverse factors (nodal metastases; close [<5 mm] or involved margins), there was no association between DOI and DSS, with an excellent prognosis irrespective of depth. In the absence of PORT, the 5‐year disease‐specific mortality was 10% with DOI ≥10 mm, 8% with DOI 5‐10 mm, and 6% with DOI <5 mm (P = .169), yielding an absolute risk difference of only 4%.

Conclusion

The deterioration in prognosis with increasing DOI largely reflects an association with other adverse features. In the absence of these, depth alone should not be an indication for PORT outside a clinical trial.

https://ift.tt/2TlrgNm

Validation of web‐based thyroid imaging reporting and data system in atypia or follicular lesion of undetermined significance thyroid nodules

Abstract

Background

Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) show variable malignancy risk. We validated the web‐based predictive models and the scoring system by the American College of Radiology (ACR) for AUS/FLUS nodules to stratify the malignancy risk.

Methods

From January 2011 to November 2014, 275 consecutive nodules diagnosed as AUS/FLUS were enrolled. The discrimination and calibration ability of a web‐based scoring with inclusion of biopsy result and sonographic features, old web‐based scoring model without biopsy result, and ACR models were assessed.

Results

The areas under the receiver operating characteristic curve of the validation set were 0.670 for the new web‐based model, 0.710 for the old web‐based model, and 0.732 for the ACR scoring risk‐stratification model. All models were well calibrated.

Conclusion

The web‐based scoring risk‐stratification model using the combined information of ultrasonography features and biopsy result for AUS/FLUS nodules to stratify malignancy risk presents an acceptable predictive accuracy.

https://ift.tt/2XoCAXR