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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Crystal Deposition in Hidradenitis Suppurativa

No abstract available

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Decreased T-Cell Programmed Death Receptor-1 Expression in Pregnancy-Associated Melanoma

Introduction: Pregnancy depends on tolerance of an immunologically foreign fetus through type 1 T-cell suppression. Worse melanoma outcomes have been described within 1 year of childbirth. We assessed immunopathologic factors that may account for the observed negative impact of pregnancy on outcome. Materials and Methods: Women of child-bearing age with ≥24 months follow-up were identified from our Institutional Melanoma Registry. Women with available primary tumor blocks were compared [history of childbirth within 1 year of diagnosis (CB1Y) (n = 18) vs. nonpregnant age-matched controls (n = 13)]. Immunohistochemical staining with quantification of immune infiltrates: CD68+ tumor-associated macrophages, CD3+ tumor-infiltrating T cells, and PD-1+ activated/exhausted T cells; and hematolymphangiogenesis: CD31+/D2-40− blood vessels and D2-40+ lymphatics was performed by 2 blinded dermatopathologists. Results: CB1Y tumors showed decreased CD3+ tumor-infiltrating T cells (P

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Progressive Cutaneous Lesions in a Young Girl: Answer

No abstract available

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CyclinD1 Is Useful to Differentiate Langerhans Cell Histiocytosis From Reactive Langerhans Cells

Abstract: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by clonal proliferation of neoplastic Langerhans cells (LCs). LC proliferation can also be seen in different reactive dermatosis. CyclinD1 is a downstream marker of mitogen-activated protein (MAP) kinase pathway, which is often activated in LCH. This study aimed to evaluate the role of cyclinD1 to differentiate reactive LC proliferation from LCH. All cases of cutaneous LCH diagnosed by biopsy in the past 3 years (n = 13) were immunostained with CD1a, p53, CD31, and cyclinD1. Seven cases each of discoid lupus erythematosus (DLE) and lichen planus (LP) were taken as control. Presence of p53, CD31, and cyclinD1-positive LCs (CD1a-positive) were compared in the dermis. In all LCH cases, dermal neoplastic LCs showed diffuse CD1a positivity and 12 cases (92.3%) showed variable (30%–70%) cyclinD1 expression. Weak p53 and CD31 expression were seen in 61.5% and 46.1% of LCH cases, respectively. In the control group, 5 cases of LP and 4 cases of DLE showed variable LC proliferation, highlighted by CD1a positivity. However, no case of reactive dermatosis showed cyclinD1 or p53 expression by the reactive LCs. Weak and patchy CD31 expression by the reactive LCs were found in 1 (25%) and 2 (40%) cases of DLE and LP, respectively. To conclude, cyclinD1 is frequently expressed in neoplastic LCs in LCH. It is an efficient marker to differentiate neoplastic from reactive LC proliferation, and can be used as a surrogate marker in LCH.

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Widespread Erythematous and Bullous Plaques Associated With Nasolabial Fold Ulceration: Challenge

No abstract available

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Galectin-1 and Galectin-3 and Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues

Abstract: Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules. Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3). Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered. Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells. We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening. We suggest that Gal-1 and Gal-3, in concert with some of the ECM molecules produced by fibroblasts and by immune cells, counteract the inflammatory response in keloids. We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.

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Widespread Erythematous and Bullous Plaques Associated With Nasolabial Fold Ulceration: Answer

No abstract available

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High-Risk Human Papillomavirus E6/E7 mRNA Is Rarely Detected in Nonanogenital Cutaneous Squamous Cell Carcinoma: An RNA In Situ Hybridization–Based Tissue Microarray Study

Abstract: High-risk human papillomavirus (HR-HPV) is known to play an oncogenic role in squamous cell carcinoma (SCC) at certain anatomical sites, namely the uterine cervix, oropharynx, and anogenital skin. However, the association between HR-HPV and nonanogenital cutaneous SCC (CSCC) remains controversial. In this study, we addressed this controversy by performing HR-HPV E6/E7 mRNA in situ hybridization (ISH) on 243 CSCC samples. A cocktail of E6/E7 mRNA ISH probes, recognizing 18 HR-HPV genotypes, was applied to a tissue microarray of paraffin-embedded sections of 154 invasive and 89 in situ CSCC specimens. The anatomical sites of CSCC included the head and neck (n = 100), extremities (n = 100), trunk (n = 25), and anogenitalia (n = 18). We also investigated the correlation between the p16 expression and HR-HPV status by immunohistochemistry. The results of HR-HPV E6/E7 mRNA ISH showed that 5.8% (14/243) of all CSCC samples were positive for HR-HPV, including 66.7% (12/18) of the anogenital and only 0.9% (2/225) of the nonanogenital CSCC samples (P

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Progressive Cutaneous Lesions in a Young Girl: Challenge

No abstract available

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Borderline Lepromatous Leprosy: Uncommon Clinical Presentation

No abstract available

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Melanoma With Loss of BAP1 Expression in Patients With No Family History of BAP1-Associated Cancer Susceptibility Syndrome: A Case Series

Abstract: The presence of multiple BAP1-negative melanocytic neoplasms is a hallmark of familial cancer susceptibility syndrome caused by germline mutations in BAP1. Melanocytic tumors lacking BAP1 expression may also present as sporadic lesions in patients lacking a germline BAP1 mutation. Here, we report histomorphologic and clinical characteristics of cutaneous melanomas with loss of BAP1 expression in 4 patients with no known history of BAP1-associated cancer susceptibility syndrome. The lesions were nodular melanomas composed predominantly of intradermal large epithelioid (Spitzoid) melanocytes with nuclear pseudoinclusions as well as scattered multinucleated cells, arising in association with a typical intradermal nevus. Of the 4 patients, only 1 had recurrence. This patient had multiple recurrences with in-transit and regional lymph node metastases. To the best of our knowledge, this is the first reported series of cutaneous melanomas with loss of BAP1 expression arising in patients without a family history of cancer.

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BRAF Inhibitor–Associated Granulomatous Dermatitis: A Report of 3 Cases

Abstract: Cutaneous toxicities associated with BRAF inhibitor treatment in patients with metastatic melanoma have been well described. We present a rare association of granulomatous dermatitis in association with the BRAF inhibitor vemurafenib. Three patients with metastatic melanoma all presented with asymptomatic papular eruptions 8–21 months into vemurafenib therapy. Skin biopsies confirmed the diagnosis of granulomatous dermatitis. Other causes of granulomatous dermatitis including infectious agents and sarcoid were excluded. Treatment with potent topical and oral steroids improved the eruptions, but only after the cessation of vemurafenib did all 3 cases of granulomatous dermatitis completely resolve within 2 weeks. It is important to recognize that this association, unlike most other BRAF inhibitor–related skin toxicities, can occur many months after commencement of therapy and that vemurafenib treatment can be continued without clinically significant adverse effects.

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Exophytic Mass Arising Within Hidradenitis Suppurativa: Answer

No abstract available

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Alveolar Soft-Part Sarcoma of the Tongue

Abstract: Alveolar soft-part sarcoma is a rare neoplasm of unknown histogenesis that accounts for less than 1% of all soft-tissue sarcomas. The tumor is highly vascularized with small vascular spaces separating nests of cells, and from cytogenetic point of view, is characterized by chromosome rearrangement der(17)t(X:17)(p11:q25) that results in the ASPL-TFE3 translocation. It can occur at any age, but it is most common between 15 and 35 years of age. The prognosis is poor, despite the relatively slow growth of the tumor. We present here an atypical case of alveolar soft-part sarcoma in which the age of the patient, the location, and the histopathologic characteristics of the lesion represented a diagnostic challenge.

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Comment on “Bullous Erythema Nodosum Leprosum as the First Manifestation of Multibacillary Leprosy: A Rare Phenomenon”

No abstract available

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Undifferentiated Sarcoma as Intermediate Step in the Progression of Malignant Melanoma to Rhabdomyosarcoma: Histologic, Immunohistochemical, and Molecular Studies of a New Case of Malignant Melanoma With Rhabdomyosarcomatous Differentiation

Abstract: Malignant melanoma (MM) may display highly variable phenotypic diversity, sometimes associated with loss of immunohistochemical melanocytic markers and acquisition of nonmelanocytic lineage of differentiation. Primary cutaneous MM with rhabdomyosarcomatous differentiation is extremely rare with only 5 reported cases in the literature. To date, a chronological progression of a MM to rhabdomyosarcoma has not been conclusively documented. A 96-year-old man underwent a re-excision of an "atypical fibroxanthoma" of the forearm, which revealed a small lentigo maligna melanoma associated with a dominant dermal high-grade spindle cell nodule admixed with a population of malignant polygonal epithelioid cells. On immunohistochemical studies, the spindle cells were completely negative for all melanocytic markers, whereas a small population of polygonal neoplastic cells at the periphery was positive for Desmin and Myo-D1, supporting early rhabdomyosarcomatous transformation. Several subsequent re-excisions demonstrated merely nodules of malignant pleomorphic epithelioid cells with rhabdomyosarcomatous differentiation and devoid of melanocytic markers. In addition, both rhabdomyosarcomatous component and original MM displayed identical mutations. Therefore, the histologic, immunohistochemical, and molecular findings documented for the first time a chronological progression from an invasive MM to a pleomorphic rhabdomyosarcoma through an intermediate stage of undifferentiated sarcoma/atypical fibroxanthoma. Interestingly, subsequent recurrences of pure rhabdomyosarcomatous component displayed skip lesions/microsatellitosis, marked tumor-infiltrative lymphocytes, and rare junctional nests of rhabdomyosarcomatous cells in the epidermis, histologic features that were not described in primary cutaneous rhabdomyosarcoma and therefore could serve as morphologic clues to the diagnosis of rhabdomyosarcomatous transformation in an MM.

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Disseminated Warty Papules and Plaques: Challenge

No abstract available

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Traumatic Neuroma With Melanoma Perineural Invasion

Abstract: Traumatic neuroma is a reactive non-neoplastic neural proliferation that results from trauma. Although such type of lesions found surgical scars due to different reasons, its involvement by residual or recurrent malignancies is rarely reported. In this article, we describe an unusual case of traumatic neuroma with perineural invasion by invasive melanoma.

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Exophytic Mass Arising Within Hidradenitis Suppurativa: Challenge

No abstract available

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Disseminated Warty Papules and Plaques: Answer

No abstract available

https://ift.tt/2Nse2IX

Progression of Albuminuria Among Patients with Type 1 Diabetes Mellitus: A Long Term Observational Follow-up Study

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0848-8076

Background The purpose of the present study was to determine whether patients with DM1 have shown improvement, stabilization or deterioration of their urine albumin excretion levels during a close follow-up. Patients and Methods A cohort of 84 patients, 18–76 years of age, a median duration of diabetes of 24 years (1–50 years) and a median follow-up duration of 12 years (1–37 years) were included in the study. Results Among the 84 patients for whom we had UAE levels at the beginning and by the end of the study, mean glycosylated hemoglobin was statistically significantly decreased during the follow-up period, from 8.02±2.04–7.06±1.05% (p=0.036). Normoalbuminuria was present in 66 patients and remained so in 56 patients while 9 patients progressed to microalbuminuria and one patient to macroalbuminuria by the end of the study. Microalbuminuria was present in 15 patients: regression was observed in 8 patients, and progression in one patient. Regression of macroalbuminuria to microalbuminuria was noted in one patient and to normoalbuminuria was noted in one participant, too. Conclusions Improvement of glycemic control with close monitoring of DM1 patients together with the appropriate use ACE or AT2 inhibitors and statins, seems to exert nephron-protective potential and to delay or even reverse the presence of micro/macroalbuminuria. This long term follow-up study has demonstrated a statistically significant increase in serum HDLcholesterol levels. The study also revealed that intensively treated diabetes patients may show reductions in serum ALP levels. Whether this finding is related to diabetic nephropathy, NAFLD, or diabetic hepatosclerosis remains to be assessed in future trials.
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© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Long-term effectiveness and safety of metreleptin in the treatment of patients with partial lipodystrophy

Abstract

Purpose

To evaluate the effects of metreleptin in patients with partial lipodystrophy (PL).

Methods

Patients aged ≥ 6 months with PL, circulating leptin < 12.0 ng/mL, and diabetes mellitus, insulin resistance, or hypertriglyceridemia received metreleptin doses (once or twice daily) titrated to a mean of 0.124 mg/kg/day. Changes from baseline to month 12 in glycated hemoglobin (HbA1c) and fasting serum triglycerides (TGs; co-primary endpoints), fasting plasma glucose (FPG), and liver volume were evaluated. Additional assessments included the proportions of patients achieving target decreases in HbA1c or fasting TGs at month 12, long-term treatment effects, and treatment-emergent adverse events (TEAEs).

Results

Significant (p < 0.05) reductions in HbA1c (−0.6%), fasting TGs (−20.8%), FPG (−1.2 mmol/L), and liver volume (−13.4%) were observed in the overall PL population at month 12. In a subgroup of patients with baseline HbA1c ≥ 6.5% or TGs ≥ 5.65 mmol/L, significant (p < 0.05) reductions were seen in HbA1c (−0.9%), fasting TGs (−37.4%), FPG (−1.9 mmol/L), and liver volume (−12.4%). In this subgroup, 67.9% of patients had a ≥ 1% decrease in HbA1c or ≥ 30% decrease in fasting TGs, and 42.9% had a ≥ 2% decrease in HbA1c or ≥ 40% decrease in fasting TGs. Long-term treatment in this subgroup led to significant (p < 0.05) reductions at months 12, 24, and 36 in HbA1c, fasting TGs, and FPG. Metreleptin was well tolerated with no unexpected safety signals. The most common TEAEs were abdominal pain, hypoglycemia, and nausea.

Conclusions

In patients with PL, treatment with metreleptin was well tolerated and resulted in improvements in glycemic control, hypertriglyceridemia, and liver volume.

https://ift.tt/2Snc1Pb

Primary hyperparathyroidism due to ectopic parathyroid adenoma in an adolescent: a case report and review of the literature

Abstract

Purpose

Primary hyperparathyroidism (PHPT) is a common endocrine disorder and is usually diagnosed in adults. PHPT due to ectopic parathyroid adenoma in adolescents is rare.

Methods

We describe the case of a 15-year-old boy with PHPT due to ectopic parathyroid adenoma. A review of the literature of PHPT in adolescents was performed, focusing on etiology, clinical presentation, preoperative localization methods, pathology, and treatment.

Results

The patient was successfully treated with surgery and was followed up for 5 years with no signs or symptoms of hyperparathyroidism. By reviewing the literature, only seven cases of PHPT associated with ectopic parathyroid lesions in adolescents have been reported. Parathyroidectomy is the only known curative treatment. Accurate preoperative localization of the target lesion is critical.

Conclusions

This study should raise awareness of the diagnosis and treatment of PHPT due to ectopic parathyroid adenoma/carcinoma in adolescents.

https://ift.tt/2Xnh9GU

Long-term effectiveness and safety of metreleptin in the treatment of patients with partial lipodystrophy

Abstract

Purpose

To evaluate the effects of metreleptin in patients with partial lipodystrophy (PL).

Methods

Patients aged ≥ 6 months with PL, circulating leptin < 12.0 ng/mL, and diabetes mellitus, insulin resistance, or hypertriglyceridemia received metreleptin doses (once or twice daily) titrated to a mean of 0.124 mg/kg/day. Changes from baseline to month 12 in glycated hemoglobin (HbA1c) and fasting serum triglycerides (TGs; co-primary endpoints), fasting plasma glucose (FPG), and liver volume were evaluated. Additional assessments included the proportions of patients achieving target decreases in HbA1c or fasting TGs at month 12, long-term treatment effects, and treatment-emergent adverse events (TEAEs).

Results

Significant (p < 0.05) reductions in HbA1c (−0.6%), fasting TGs (−20.8%), FPG (−1.2 mmol/L), and liver volume (−13.4%) were observed in the overall PL population at month 12. In a subgroup of patients with baseline HbA1c ≥ 6.5% or TGs ≥ 5.65 mmol/L, significant (p < 0.05) reductions were seen in HbA1c (−0.9%), fasting TGs (−37.4%), FPG (−1.9 mmol/L), and liver volume (−12.4%). In this subgroup, 67.9% of patients had a ≥ 1% decrease in HbA1c or ≥ 30% decrease in fasting TGs, and 42.9% had a ≥ 2% decrease in HbA1c or ≥ 40% decrease in fasting TGs. Long-term treatment in this subgroup led to significant (p < 0.05) reductions at months 12, 24, and 36 in HbA1c, fasting TGs, and FPG. Metreleptin was well tolerated with no unexpected safety signals. The most common TEAEs were abdominal pain, hypoglycemia, and nausea.

Conclusions

In patients with PL, treatment with metreleptin was well tolerated and resulted in improvements in glycemic control, hypertriglyceridemia, and liver volume.

https://ift.tt/2Snc1Pb

Primary hyperparathyroidism due to ectopic parathyroid adenoma in an adolescent: a case report and review of the literature

Abstract

Purpose

Primary hyperparathyroidism (PHPT) is a common endocrine disorder and is usually diagnosed in adults. PHPT due to ectopic parathyroid adenoma in adolescents is rare.

Methods

We describe the case of a 15-year-old boy with PHPT due to ectopic parathyroid adenoma. A review of the literature of PHPT in adolescents was performed, focusing on etiology, clinical presentation, preoperative localization methods, pathology, and treatment.

Results

The patient was successfully treated with surgery and was followed up for 5 years with no signs or symptoms of hyperparathyroidism. By reviewing the literature, only seven cases of PHPT associated with ectopic parathyroid lesions in adolescents have been reported. Parathyroidectomy is the only known curative treatment. Accurate preoperative localization of the target lesion is critical.

Conclusions

This study should raise awareness of the diagnosis and treatment of PHPT due to ectopic parathyroid adenoma/carcinoma in adolescents.

https://ift.tt/2Xnh9GU

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

https://ift.tt/2TeK4xp

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

https://ift.tt/2Iz6Mwc

A mnemonic to assist patients with topical steroid application

Publication date: Available online 23 February 2019

Source: Journal of the American Academy of Dermatology

Author(s): Brett C. Neill, Spyros M. Siscos, Edward W. Seger, Daniel J. Aires

https://ift.tt/2VhNRrd

Corrigendum to Objective volumetric grading of postacne scarring J Am Acad Dermatol Volume 75 (2016) 229–231

Publication date: Available online 23 February 2019

Source: Journal of the American Academy of Dermatology

Author(s):

https://ift.tt/2EuKgjT

Feasibility of quantitative MR-perfusion imaging to monitor treatment response after uterine artery embolization (UAE) in symptomatic uterus fibroids

Publication date: Available online 23 February 2019

Source: Magnetic Resonance Imaging

Author(s): Maliha Sadick, Jakob Richers, Benjamin Tuschy, Lothar R. Schad, Stefan O. Schoenberg, Frank G. Zöllner

Abstract

Introduction

In 25% of women, symptomatic uterus myomas are diagnosed with clinical and functional impairment ranging from abdominal and pelvic pain to dys- and hypermenorrhea, dyspareunia, pollakiuria and infertility. Women undergoing a treatment increasingly prefer nowadays minimal invasive, uterus preserving therapies like uterine artery embolization (UAE) over surgical hysterectomy, nowadays. To emphasize the efficacy of UAE as a uterus preserving treatment with targeted therapy of myomas only, analysis of tissue perfusion pre and post embolization is required. The purpose of this study was to assess treatment response in UAE in females with symptomatic uterus myomas by quantitative magnetic resonance perfusion imaging.

Methods

Seven females scheduled for uterus myoma embolization underwent three MRI examinations (pre, post, follow-up) including morphological and dynamic contrast enhanced perfusion imaging at 3 T. To measure tumor volume, regions-of-interest covering the tumor and the uterus were drawn by two readers in consensus. Blood flow, blood volume, and mean transit time were calculated by a pixel-by-pixel deconvolution approach. Kruskal-Wallis/Friedman test was employed to test whether the group medians differ significantly with correction for multiple comparisons using Bonferroni method.

Results

Change of volume could be observed in all patients after embolization but was significantly different only between pre/post and follow-up time point. Measured differences in all perfusion parameters were significant between pre-intervention and post-intervention/follow-up in the myomas, no significant differences could be detected for the uterus tissue.

Conclusions

Our results demonstrate devascularization of symptomatic myomas which correlates with cessation of hypermenorrhea in all treated patients without affecting healthy uterus tissue. Supplementing UAE with perfusion imaging to monitor early treatment response is feasible and might provide valuable information for the follow-up of patients and contribute to providing confidence for the patients in treatment success.

https://ift.tt/2BQASWq

Performance and emission characteristics analysis of thermal barrier coated diesel engine using palm biodiesel

Abstract

Various research works are being undertaken around the world on the subject of thermal efficiency improvisation and emission reduction from diesel engines. This research work analyzes the performance and emission characteristics of a thermal barrier coated diesel engine which used palm biodiesel. The piston and cylinder liners were coated with equal percentages of alumina (Al₂O₃) and yittria-stabilized zirconia (YSZ) powder using plasma spraying coating method. The piston was coated with 100 μm thickness and the two cylinder liners were coated with 150 and 200 μm thicknesses and were used to analyze the performance and emission characteristics. Test results of the thermal barrier coated engine using palm biodiesel were compared with the results derived from the base engine. The tests revealed an increase of 3.8% specific fuel consumption (SFC) as an average when neat palm biodiesel was used in the base engine. Interestingly, the palm biodiesel used in the 150- and 200-μm thick thermal barrier coated engine was responsible for a significant decrease of the SFC by an average of 4.18% and 8.05% respectively. The brake thermal efficiency was found to decrease on an average of 1.02% when tests were run using the neat palm biodiesel in the base engine. But an average proportionate increase of 0.72% and 2.19% was visible when palm biodiesel was used in the tests conducted on the 150- and 200-μm thick thermal barrier coated engine. There was also an understandable brake specific reduction of 0.991 g/kWh carbon monoxide (CO) emission and 0.025 g/kWh unburned hydrocarbon (HC) levels. The nitrogen oxide (NO_x) emission was observed as 14.06 g/kWh in the 200-μm thick thermal barrier coated engine which was slightly higher when the results were compared with that of the uncoated engine. The novelty of this research investigation is based on the usage of yttrium-stabilized zirconia and alumina thermal barrier coating on the cylinder liner and piston head of engine. This is justified due to the fact that most of the previous investigations undertaken focused on the thermal barrier coating in the piston, valve, and cylinder head alone. The utility factor of the palm biodiesel (B 100) in the low heat rejection engine has also proved to be another significant and novel factor in the present investigation outlined in this paper. This is mainly due to the fact that the ongoing investigations in this realm concentrated only on blends of 20 to 30% of palm biodiesel with diesel fuel in the low heat rejection diesel engine.

https://ift.tt/2E9w8LL

Stability and uptake of methylphenidate and ritalinic acid in nine-spine stickleback ( Pungitius pungitius ) and water louse ( Asellus aquaticus )

Abstract

The presence of human pharmaceuticals in the environment has garnered significant research attention because these compounds may exert therapeutic effects on exposed wildlife. Yet, for many compounds, there is still little research documenting their stability in the water column and uptake in organism tissues. Here, we measured the uptake and stability of methylphenidate (Ritalin®, a frequently prescribed central nervous system stimulant) and its primary metabolite, ritalinic acid, in (1) water only or (2) with nine-spine stickleback and water louse. Methylphenidate degraded to ritalinic acid in both studies faster at a higher temperature (20 °C versus 10 °C), with concentrations of ritalinic acid surpassing methylphenidate after 48–100 h, depending on temperature. The concentration of methylphenidate in stickleback was highest at the first sampling point (60 min), while the concentration in water louse tissues reached comparatively higher levels and peaked after ~ 6 days. Neither stickleback nor water louse took up ritalinic acid in tissues despite being present in the water column. Our findings provide valuable data for use in future risk assessment of methylphenidate and will aid in the design of studies aimed at measuring any ecotoxicological effects on, for example, the behaviour or physiology of aquatic organisms.

https://ift.tt/2T2IBvb

Antioxidant and cytoprotective effects of N -acetylcysteine against subchronic oral glyphosate-based herbicide-induced oxidative stress in rats

Abstract

It is claimed that oxidative stress has a prominent role in the mechanism of toxic effects formed by glyphosate-based herbicide (GBH) in living systems. A strong thiol compound, N-acetylcysteine (NAC), has antioxidative and cytoprotective properties. The objective in this subchronic toxicity study was to identify the prophylactic effect of NAC over histopathological changes and oxidative stress induced by GBH in blood, renal, liver, cardiac, and brain tissues. A sum of 28 male Wistar rats were divided into four equal groups, each containing 7 rats. During the study, group I (control group) was supplied with normal rodent bait and tap water ad libitum. The applied agents were 160 mg/kg NAC to group II, 375 mg/kg as equivalent to 1/10 of lethal dose 50% (LD50) of GBH to group III, and 160 mg/kg of NAC and 375 mg/kg of GBH together once per day as oral gavage to group IV for 8 weeks. While GBH decreased the levels of GSH in blood, liver, kidney, and brain tissues, it considerably increased malondialdehyde levels. On the contrary, these parameters happened to improve in the group supplied with NAC. Besides, it was seen that NAC was observed to improve the histopathologic changes in rat tissues induced by GBH. It was concluded that NAC protects oxidative stress and tissue damage induced by GBH in blood and tissue and this prophylactic effect could be attributed to its antioxidant and free radical sweeper character.

https://ift.tt/2E8R7hB

Investigating the perceived timing of sensory events triggering actions in patients with Parkinson’s disease and the effects of dopaminergic therapy

Publication date: Available online 23 February 2019

Source: Cortex

Author(s): Yoshiko Yabe, Melvyn A. Goodale, Penny A. MacDonald

Abstract

Few studies have investigated if Parkinson's disease (PD), advancing age, or exogenous dopamine therapy affect the perceived timing of past events. Here we show a phenomenon of 'temporal repulsion' of a sensory event relative to an action decision in patients with PD. In these patients, the timing of a sensory event triggering an action was perceived to have occurred earlier in time than it really did. In other words, the event appeared to be pushed away in time from the performance of the action. This finding stands in sharp contrast to the 'temporal binding' we have observed here and elsewhere (Yabe and Goodale, 2015; Yabe et al., 2017) in young healthy participants for whom the perceived onset of a sensory event triggering an action is typically delayed, as if it were pulled towards the action in time. In elderly patients, sensory events were neither repulsed nor pulled toward the action decision event. Exogenous dopamine alleviated the temporal repulsion in PD patients and normalized the temporal binding in healthy elderly controls. In contrast, dopaminergic therapy worsened temporal binding in healthy young participants. We discuss this pattern of findings, relating temporal binding processes to dopaminergic and striatal mechanisms.

https://ift.tt/2EdOSKd

Continuous efficient removal and inactivation mechanism of E. coli by bismuth-doped SnO 2 /C electrocatalytic membrane

Abstract

The Bi-SnO₂/C electrocatalytic membrane was fabricated via a simple electrochemical reduction and hydrothermal method. Under the action of electric field, the Sn²⁺ and Bi³⁺ were firstly adsorbed and reduced to metallic Sn and Bi on the carbon membrane surface by cathodic reduction reaction, and the Bi-SnO₂/C membrane was obtained subsequently through hydrothermal oxidation process. Confirmed by SEM, TEM, XRD, and XPS characterizations, the nano-Bi-SnO₂ is homogeneously distributed on the membrane surface and is firmly attached to the carbon membrane via C–O–Sn chemical bond. Through CV, LSV, and EIS electrochemical analysis, the Bi-SnO₂/C membrane possesses the higher electrocatalytic activity and stability than carbon membrane. Therefore, the Bi-SnO₂/C membrane could continuously efficiently remove and inactivate Escherichia coli in water through flow-through mode. As a result, the sterilization efficiency can reach more than 99.99% under the conditions of cell voltage 4 V, flow rate 1.4 mL/min, and E. coli initial concentration 1.0 × 10⁴ CFU/mL, owing to the synergistic effect of the membrane separation and electrocatalytic oxidation. Moreover, it was found that the oxidation groups of ⋅OH radicals generated by Bi-SnO₂/C membrane play the crucial role for bactericidal performance. This work presents a low-cost, highly active, and stable electrocatalytic membrane towards continuous bacterial inactivation, which exhibits promising potential in water disinfection and is beneficial for practical large-scale applications.

https://ift.tt/2BREYNH

Thyroid dysfunction induced by nivolumab: searching for disease patterns and outcomes

Abstract

Purpose

Nivolumab is a monoclonal antibody that blocks the activation of programmed death-1 receptor, promoting T-cell activation against cancer cells. Thyroid dysfunction (TD) is a common immune-related adverse event (irAE) induced by nivolumab. We report the prevalence, patterns and outcomes of nivolumab-induced TD among cancer patients in our center.

Methods

All patients treated with nivolumab during 2016 were included. We assessed thyroid function tests, thyroid autoimmunity, thyroid imaging, and clinical outcome during nivolumab therapy as well as overall survival (OS).

Results

Seventy-three patients (55 with non-small-cell lung cancer [NSCLC], 9 with melanoma and 9 with Hodgkin lymphoma) were included. Median of follow up: 390.5 days. Seventeen patients (23.3%) developed TD during treatment. Thyrotoxicosis was reported in seven patients. Serum thyroid-stimulating hormone (TSH) nadir occurred after a median of 51 days (95% CI: 35–71). Thyroid antibodies were positive in three of the seven patients. Five of the seven hyperthyroid patients became hypothyroid later, and four of them required levothyroxine treatment. Primary hypothyroidism occurred in ten patients. Serum TSH peak occurred after a median of 110 days [95% CI: 85.2–197]. Thyroid autoimmunity was positive in one patient. In patients with NSCLC, TD was associated with better OS (HR = 0.4 [95% CI: 0.17–0.94]; p = 0.035).

Conclusions

TD induced by nivolumab is a common and heterogeneous irAE. Thyrotoxicosis develops earlier than hypothyroidism. A pattern consistent with a transient thyroiditis followed by hypothyroidism was observed in one-third of patients. Our results suggest that patients with NSCLC and nivolumab-induced TD might have better survival.

https://ift.tt/2XoXJBd

Thyroid dysfunction induced by nivolumab: searching for disease patterns and outcomes

Abstract

Purpose

Nivolumab is a monoclonal antibody that blocks the activation of programmed death-1 receptor, promoting T-cell activation against cancer cells. Thyroid dysfunction (TD) is a common immune-related adverse event (irAE) induced by nivolumab. We report the prevalence, patterns and outcomes of nivolumab-induced TD among cancer patients in our center.

Methods

All patients treated with nivolumab during 2016 were included. We assessed thyroid function tests, thyroid autoimmunity, thyroid imaging, and clinical outcome during nivolumab therapy as well as overall survival (OS).

Results

Seventy-three patients (55 with non-small-cell lung cancer [NSCLC], 9 with melanoma and 9 with Hodgkin lymphoma) were included. Median of follow up: 390.5 days. Seventeen patients (23.3%) developed TD during treatment. Thyrotoxicosis was reported in seven patients. Serum thyroid-stimulating hormone (TSH) nadir occurred after a median of 51 days (95% CI: 35–71). Thyroid antibodies were positive in three of the seven patients. Five of the seven hyperthyroid patients became hypothyroid later, and four of them required levothyroxine treatment. Primary hypothyroidism occurred in ten patients. Serum TSH peak occurred after a median of 110 days [95% CI: 85.2–197]. Thyroid autoimmunity was positive in one patient. In patients with NSCLC, TD was associated with better OS (HR = 0.4 [95% CI: 0.17–0.94]; p = 0.035).

Conclusions

TD induced by nivolumab is a common and heterogeneous irAE. Thyrotoxicosis develops earlier than hypothyroidism. A pattern consistent with a transient thyroiditis followed by hypothyroidism was observed in one-third of patients. Our results suggest that patients with NSCLC and nivolumab-induced TD might have better survival.

https://ift.tt/2XoXJBd

Characterization and risk assessment of heavy metals in road dust from a developing city with good air quality and from Shanghai, China

Abstract

To investigate the differences in characteristics of heavy metals associated with different levels of ambient air quality, we collected road dust samples from Beihai (BH) and Shanghai (SH). The mean concentrations of Ni, Cr, Zn, and Cu in BH samples were one to four times the background concentrations in soil, whereas the concentrations of Cd, Cr, Mn, Zn, Cu, and Pb in SH were one to three times the background concentrations. The geo-accumulation index (I_geo) indicated widespread moderate contamination by Zn and high contamination near industrial areas by Ni and Cr in BH, whereas in SH was partly moderately contaminated by Pb, Cu, and Zn. The potential ecological risk index ( \( {E}_r^i \) ) indicated the low risk posed by all metals in both BH and SH. However, special attention should be given to the maximal \( {E}_r^i \) values, such as considerable risk for Hg ( \( {E}_r^i \)  = 148.7) and high risk for Ni (254.1) in BH, respectively. According to the health risk assessment results, there were no non-carcinogenic or carcinogenic risks (CR) posed by heavy metals in road dust collected from BH and SH. Non-carcinogenic risks due to Cr for children in both BH (0.36) and SH (0.24) were relatively high compared to other metals, and a maximal CR value for Cr (2.7 × 10⁻⁶) was found to pose a potential carcinogenic risk near the industrial area in BH. Compared with those in developed cities, the health risks in BH related to Cu, Pb, and Zn from motor vehicle emissions were relatively low, but those related to Ni and Cr from local industrial activity in road dust were relatively high.

https://ift.tt/2EtquW0

The effects of particulate matters on allergic rhinitis in Nanjing, China

Abstract

Particulate matter pollution is a serious environmental problem. Individuals exposed to particulate matters have an increased prevalence to diseases. In the present study, we performed an epidemiological study to investigate the effects of particulate matter less than 10 μm in aerodynamic diameter (PM₁₀) and particulate matter less than 2.5 μm in aerodynamic diameter (PM_2.5) on allergic rhinitis in Nanjing, China. Daily numbers of allergic rhinitis patients (33,063 patients), PM₁₀, PM_2.5, and weather data were collected from January 2014 to December 2016 in Nanjing, China. Generalized additive models (GAM) were used to evaluate the effects of PM₁₀ and PM_2.5 on allergic rhinitis. We found that the interquartile range (IQR) increases in PM₁₀ (difference of estimates, 5.86%; 95% CI, 3.00–8.81%; P = 4.72 × 10⁻⁵) and PM_2.5 (difference of estimates, 5.39%; 95% CI, 2.73–8.12%; P = 5.67 × 10⁻⁵) concentrations were associated with the higher increased numbers of allergic rhinitis patients with 3-day cumulative effects in single-pollutant model. In addition, we found that the IQR increase in PM₁₀ (age ≥ 18 years: 7.37%, 3.91–10.96%, 2.14 × 10⁻⁵; 0–17 years: 0.83%, − 4.00–5.91%, 0.740) and PM_2.5 (age ≥ 18 years: 7.00%, 3.78–10.32%, 1.40 × 10⁻⁵; 0–17 years: 0.40%, − 4.10–5.10%, 0.866) increased the number of allergic rhinitis patients in adults, but not in children. In summary, our findings suggested that exposure to PM₁₀ and PM_2.5 was associated with the risk of allergic rhinitis.

https://ift.tt/2U7Ua0e

Development of magnetic porous coordination polymer adsorbent for the removal and preconcentration of Pb(II) from environmental water samples

Abstract

A novel porous coordination polymer adsorbent (BTCA-P-Cu-CP) based on a piperazine(P) as a ligand and 1,2,4,5-benzenetetracarboxylic acid (BTCA) as a linker was synthesized and magnetized to form magnetic porous coordination polymer (BTCA-P-Cu-MCP). Fourier transform infrared (FTIR), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), field emission scanning electron microscope(FESEM), energy-dispersive X-ray spectroscopy(EDS), CHN, and Brunauer–Emmett–Teller(BET) analysis were used to characterize the synthesized adsorbent. BTCA-P-Cu-MCP was used for removal and preconcentration of Pb(II) ions from environmental water samples prior to flame atomic absorption spectrometry(FAAS) analysis. The maximum adsorption capacity of BTCA-P-Cu-MCP was 582 mg g⁻¹. Adsorption isotherm, kinetic, and thermodynamic parameters were investigated for Pb(II) ions adsorption. Magnetic solid phase extraction (MSPE) method was used for preconcentration of Pb(II) ions and the parameters influencing the preconcentration process have been examined. The linearity range of proposed method was 0.1–100 μg L⁻¹ with a preconcentration factor of 100. The limits of detection and limits of quantification for lead were 0.03 μg L⁻¹ and 0.11 μg L⁻¹, respectively. The intra-day (n = 7) and inter-day (n = 3) relative standard deviations (RSDs) were 1.54 and 3.43% respectively. The recoveries from 94.75 ± 4 to 100.93 ± 1.9% were obtained for rapid extraction of trace levels of Pb(II) ions in different water samples. The results showed that the BTCA-P-Cu-MCP was steady and effective adsorbent for the decontamination and preconcentration of lead ions from the aqueous environment.

https://ift.tt/2EuFvae