We report a case of a patient with appendicular bone involvement of diffuse large B-cell lymphoma visualized by whole-body technetium-99m methylenediphosphonate bone scintigraphy (bone scan) and 18F-fluorodeoxygl...
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Δευτέρα 3 Απριλίου 2017
Distal appendicular skeletal involvement of diffuse large B-cell lymphoma on technetium-99m methylenediphosphonate bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: a case report
A large giant cell tumor of the larynx: case report and review of the literature
Giant cell tumors (GCTs) are typically found in the metaphyseal-epiphyseal area of long bones but can also occur in the head and neck region. GCT of the larynx is a rare entity with only 42 reported cases in t...
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The first Canadian experience with the Afirma® gene expression classifier test
Thyroid nodules are common and often benign, although prove to be malignant upon surgical pathology in 5–15% of cases. When assessed with ultrasound-guided fine-needle aspiration (USFNA), 15–30% of the nodules...
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Striae distensae: Immunohistochemical assessment of hormone receptors in multigravida and nulligravida
Summary
Background
Striae distensae (SD), a type of dermal scarring, are psychologically disappointing. To date, information and scientific research behind the role of hormonal factors in the development of SD are still unclear. It is vital to understand striae to offer patients the best therapeutic options.
Objectives
To investigate early alterations regarding the expression of estrogen, androgen, and glucocorticoid receptors (estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR) in skin samples of multigravida (MG) and nulligravida (NG) cases and to compare them with normal controls.
Methods
This study included 30 subjects (10 MG and 10 NG cases with early SD and 10 healthy controls). Biopsies from SD lesions, perilesional normal skin of cases and normal skin of controls were examined immunohistochemically for ER, AR, and GR expression using immune peroxidase technique.
Results
Comparing MG and NG with controls, ER expression appeared reduced in MG and NG (P-value<.001), AR was elevated in MG (P-value<.05) with no considerable difference in NG (P-value>.05), while GR was elevated in both MG and NG (P-value<.05). On comparing perilesional skin with SD lesions in each of MG and NG groups, SD lesions revealed reduced ER expression in both groups (P-value<.05), whereas in MG group: AR expression was elevated with no difference detected regarding GR (P-value˃.05); meanwhile in NG, elevated expression in both AR and GR expression was noted (P-Value<.001)
Conclusions
Striae distansae lesions demonstrated a significant increase in the expression of AR and GR and a declined expression of ER indicating their involvement in the development of early SD.
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Gratitude !
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
RNA isolation from alveolar bone and gene expression analysis of RANK, RANKL and OPG: A new tool to monitor bone remodeling and healing in different bone substitutes used for prosthetic rehabilitation
Source:Archives of Oral Biology, Volume 80
Author(s): Elena Canciani, Claudia Dellavia, Monica Gioia Marazzi, Davide Augusti, Daniela Carmagnola, Elena Vianello, Luigi Canullo, Emanuela Galliera
Objective(i) To validate a simple and efficient method for extracting high quality RNA from small samples of bone tissue, (ii) to test its application on limited amounts of grafted oral bone and (iii) to analyze the gene expression of the OPG/RANK/RANKL system and IL-6 in "spontaneous healing" and grafted tissue.Design26 patients in need of extraction of one lower molar tooth were divided in 3 groups. In group A (8 patients) the alveolar socket was left for spontaneous healing, in group B (8 patients) it was filled with a hydroxyapatite scaffold while in group C (10 patients) it was filled with hydroxyapatite granules. A small amount of bone was scraped from the alveolar site and sent for analysis. Four months later a new bone specimen was harvested during implant bed preparation.ResultsIL-6 increased over time in all groups and in particular to the grafted groups. RANK, RANKL and OPG increased over time in all groups, except for RANK in group B. The RANKL/OPG ratio showed a negative value in group A and even more in group B, while it was positive in group C.ConclusionsThe alveolar site grafted with a granular biomaterial behaved similar to the physiological healing group but displayed a slow remodeling process. RANK, RANKL, OPG and the RANKL/OPG ratio might be able to distinguish among different biomaterials and represent different healing patterns according to different clinical conditions.
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Multimodale Therapie des kleinzelligen Lungenkarzinoms
Zusammenfassung
Hintergrund
Zum Zeitpunkt der Diagnosestellung kleinzelliges Lungenkarzinom (SCLC) sind etwa 30 % der Patienten im Stadium „limited disease". Dies entspricht in der Maximalausbreitung dem befallenen Hemithorax, dem Mediastinum und den supraklavikulären Lymphknoten. Diese Patienten haben eine kurative Chance durch eine kombinierte thorakale Radiochemotherapie.
Ergebnisse
Die Gesamtbehandlungszeit und frühe thorakale Bestrahlung simultan zur Chemotherapie sind für den Therapieerfolg wichtig. Dagegen scheint eine Dosiseskalation über 45–50 Gy hinaus keinen eindeutigen Vorteil zu bieten. Weiterhin trägt als wichtige Säule auch die prophylaktische Bestrahlung des Gehirns (PCI) bei, die Rate intrakranieller Rezidive zu senken.
Schlussfolgerung
Eine abgestimmte interdisziplinäre, multimodale Radiochemotherapie konnte sich in den letzten Jahren fest etablieren und ist essenziell für den Behandlungserfolg des kleinzelligen Lungenkarzinoms.
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The vagal nerve stimulation outcome, and laryngeal effect: Otolaryngologists roles and perspective
Epilepsy is one of the most common neurologic disorders. Vagus nerve stimulation (VNS), first investigated in 1938 and subsequently studied as a potential therapy for epilepsy. The FDA approved the use of VNS in 1997 as an adjunctive non-pharmacologic symptomatic treatment option for refractory epilepsy for adults and adolescents over 12years.VNS can cause laryngeal and voice side effects that can be managed by otolaryngologists safely and effectively.
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Xylitol nasal irrigation in the treatment of chronic rhinosinusitis
To evaluate the efficacy of xylitol nasal irrigation (XNI) treatment on chronic rhinosinusitis (CRS) and to investigate the effect of XNI on nasal nitric oxide (NO) and inducible nitric oxide synthase (iNOS) mRNA in maxillary sinus.
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Prognostic factors in head and neck mucosal malignant melanoma
Primary mucosal malignant melanoma of the head and neck (HN-PMMM) is an aggressive and uncommon neoplasm. Herein, we present a series of 33 patients and the results of treatment, and aimed to determine prognostic factors in HN-PMMM.
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Reduction in N-methyl-D-aspartate Receptor-mediated Cell Death in Hippocampal Neurons by Glucose Reduction Preconditioning.
Background: Repeated episodes of reduced glucose availability can precondition the brain against damage caused by severe hypoglycemia. Because N-methyl-D-aspartate (NMDA) receptor activation may contribute to neuronal loss in the hippocampus following glucose deprivation, we tested the hypothesis that preconditioning with reduced glucose decreased NMDA receptor-mediated cell death in hippocampal neurons. Methods: Hippocampal slice cultures from 7-day old rats were used to study glucose reduction preconditioning and N-methyl-D-aspartate receptor (NMDAR)-mediated cell death. Preconditioning involved reductions in glucose to the following levels: 0.1 mM, 0.5, or 1.0 mM for 30 minutes, 60 minutes, or 90 minutes on 3 consecutive days. Cell death following 1-hour total glucose deprivation was measured with a vital dye technique (SYTOX fluorescence). As an index of NMDAR activity, cell death following application of 1 mM NMDA, was also measured. Results: A preconditioning protocol of 30 minutes of 0.1 mM glucose per day for 3 days reduced cell death following 1-hour total glucose by 65% to 70%, depending on cellular region. No reduction in NMDAR-mediated cell death was seen following any of the preconditioning treatments. However, when NMDAR-mediated cell death was assessed following preconditioning combined with subsequent total glucose deprivation, cell death was reduced in the cultures that had been preconditioned with 0.1 mM glucose for 30 minutesx3 days. Conclusions: We found that that glucose reduction preconditioning protects hippocampal neurons against severe glucose deprivation-induced neuronal damage. This preconditioning was not associated with reductions in NMDAR-mediated cell death except when the preconditioning was combined with an additional exposure to a period of total glucose deprivation. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved
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Intraoperative Neurological Monitoring With Evoked Potentials During Carotid Endarterectomy Versus Cooperative Patients Under General Anesthesia Technique: A Retrospective Study.
Introduction: The best technique to evaluate contralateral carotid flow during carotid endarterectomy (CEA) is still debated; an accurate detection of efficient contralateral blood flow can avoid unnecessary shunt placement and its complications. The aim of this retrospective observational study was to evaluate and compare the safety and efficacy of general anesthesia with motor-evoked potential and somatosensory-evoked potentials (mSSEP and tcMEP) versus cooperative patients under general anesthesia (CPGA) technique for CEA. Primary outcome was the rate of technical failure. The procedural time and shunt incidence between the 2 neuromonitoring strategies were also analyzed. Patients and Methods: A total of 331 patients who consecutively underwent CEA were included (100 patients in the CPGA group and 231 in the mSSEP+tcMEP group). The anesthesia technique was customized according to the cerebral monitoring needs. Comparison between groups was performed along with risk analysis. Results: Electrophysiological monitoring seems to be a safe and effective strategy of neuromonitoring during CEA. Compared with the CPGA technique, it ensures fewer technical failures, reduces surgical and anesthesiological time and, moreover, it may reduce shunt risk/incidence. The incidence of shunt between the CPGA group and mSSEP+tcMEP was statistically different (CPGA 12%, mSSEP+tcMEP 5.2%; P=0.02), and the relative risk reduction in the mSSEP+tcMEP group, compared with the CPGA group, was 0.57. Conclusions: mSSEP and tcMEP neuromonitoring was associated with less technical failure and procedural time than asleep-awake-asleep strategy. The evoked potential neuromonitoring may be an alternative technique to awake clinical assessment during CEA. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved
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Efficacy and safety of buprenorphine in peripheral nerve blocks: A meta-analysis of randomised controlled trials.
BACKGROUND: The duration of analgesia provided by nerve blocks is limited if local anaesthetics are administered alone. Therefore, a variety of additives to local anaesthetics have been investigated to prolong postoperative analgesia following single-shot nerve blocks. OBJECTIVE(S): The aims of the current meta-analysis were to assess the efficacy and safety of the addition of perineural buprenorphine to local anaesthetic compared with local anaesthetic alone, or combined with systemic administration of buprenorphine, or other perineural opioids for peripheral nerve blocks. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: The following data sources were systematically searched: MEDLINE, CENTRAL and EMBASE (till 03/2016). ELIGIBILITY CRITERIA: All RCTs focusing on the efficacy and safety of perineural buprenorphine combined with local anaesthetic compared with local anaesthetic alone, or in combination with systemic buprenorphine, or other perineural opioids for peripheral nerve blocks were included. RESULTS: We included 13 RCTs (685 patients). Participants treated with perineural buprenorphine combined with local anaesthetic showed a longer duration of analgesia compared with those receiving local anaesthetic alone [mean difference 8.64 h, 95% confidence interval (CI) (6.44 to 10.85); P
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Noninvasive mechanical ventilation during spontaneous breathing anaesthesia: Can electrical impedance tomography be a useful bedside tool to titrate PEEP level?
We read with great interest the study by Bordes et al. [1] recently published in the Journal of Clinical Anaesthesia. In this single-centre observational study the authors used electrical impedance tomography (EIT) to assess the effects of noninvasive mechanical ventilation (NIMV) on functional residual capacity (FRC) and ventilation distribution during spontaneous breathing general anaesthesia. A total of 18 patients undergoing gastrointestinal endoscopy (including gastric fibroscopy and colonoscopy) were studied.
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Antiparasitic Treatment Induces an Improved CD8+ T Cell Response in Chronic Chagasic Patients [INFECTIOUS DISEASE AND HOST RESPONSE]
Chagas disease is a chronic infection caused by Trypanosoma cruzi, an intracellular protozoan parasite. Chronic chagasic patients (CCPs) have dysfunctional CD8+ T cells that are characterized by impaired cytokine production, high coexpression of inhibitory receptors, and advanced cellular differentiation. Most patients diagnosed in the chronic phase of Chagas disease already exhibit heart involvement, and there is no vaccination that protects against the disease. Antiparasitic treatment is controversial as to its indication for this stage of the disease. There is a lack of biological markers to evaluate the effectiveness of antiparasitic treatment, and little is known about the effect of the treatment on CD8+ T cells. Thus, the aim of the current study was to analyze the early effects of antiparasitic treatment on CD8+ T cells from CCPs with asymptomatic clinical forms of disease. To evaluate the CD8+ T cell subsets, expression of inhibitory receptors, and functionality of T cells in CCPs, PBMCs were isolated. The results showed that treatment of CCPs with the asymptomatic form of the disease induces an increase in the frequency of CD8+ central memory T cells and terminal effector T cells, a decrease in the coexpression of inhibitory receptors, an improved Ag-specific CD8+ T cell response exhibited by the individual production of IFN- or IL-2, and a multifunctional CD8+ T cell profile of up to four functions (IFN-+IL-2+Perforin+Granzyme B+). These findings suggest that, in CCPs, antiparasitic treatment improved the quality of Ag-specific CD8+ T cell responses associated with a decrease in inhibitory receptor coexpression, which could serve as biomarkers for monitoring the effectiveness of antiparasitic treatment.
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A CEACAM6-High Airway Neutrophil Phenotype and CEACAM6-High Epithelial Cells Are Features of Severe Asthma [INNATE IMMUNITY AND INFLAMMATION]
Severe asthma represents a major unmet clinical need; understanding the pathophysiology is essential for the development of new therapies. Using microarray analysis, we previously found three immunological clusters in asthma: Th2-high, Th17-high, and Th2/17-low. Although new therapies are emerging for Th2-high disease, identifying molecular pathways in Th2-low disease remains an important goal. Further interrogation of our previously described microarray dataset revealed upregulation of gene expression for carcinoembryonic Ag cell adhesion molecule (CEACAM) family members in the bronchi of patients with severe asthma. Our aim was therefore to explore the distribution and cellular localization of CEACAM6 using immunohistochemistry on bronchial biopsy tissue obtained from patients with mild-to-severe asthma and healthy control subjects. Human bronchial epithelial cells were used to investigate cytokine and corticosteroid in vitro regulation of CEACAM6 gene expression. CEACAM6 protein expression in bronchial biopsies was increased in airway epithelial cells and lamina propria inflammatory cells in severe asthma compared with healthy control subjects. CEACAM6 in the lamina propria was localized to neutrophils predominantly. Neutrophil density in the bronchial mucosa was similar across health and the spectrum of asthma severity, but the percentage of neutrophils expressing CEACAM6 was significantly increased in severe asthma, suggesting the presence of an altered neutrophil phenotype. CEACAM6 gene expression in cultured epithelial cells was upregulated by wounding and neutrophil elastase. In summary, CEACAM6 expression is increased in severe asthma and primarily associated with airway epithelial cells and tissue neutrophils. CEACAM6 may contribute to the pathology of treatment-resistant asthma via neutrophil and airway epithelial cell–dependent pathways.
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T Cells in Celiac Disease [BRIEF REVIEWS]
Celiac disease is a human T cell–mediated autoimmune-like disorder caused by exposure to dietary gluten in genetically predisposed individuals. This review will discuss how CD4 T cell responses directed against an exogenous Ag can cause an autoreactive B cell response and participate in the licensing of intraepithelial lymphocytes to kill intestinal epithelial cells. Furthermore, this review will examine the mechanisms by which intraepithelial cytotoxic T cells mediate tissue destruction in celiac disease.
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Annexin A1 Is Involved in the Resolution of Inflammatory Responses during Leishmania braziliensis Infection [INFECTIOUS DISEASE AND HOST RESPONSE]
Leishmaniases are diseases caused by several Leishmania species. Leishmania (Viannia) braziliensis can cause localized cutaneous leishmaniasis (LCL), which heals spontaneously, or mucosal leishmaniasis (ML), characterized by chronic and intense inflammation and scanty parasitism. Annexin A1 (AnxA1) is a protein involved in modulation and resolution of inflammation through multiple mechanisms. In the present study, the role of AnxA1 was investigated in L. braziliensis–infected BALB/c mice. AnxA1 levels increased at the peak of tissue lesion and parasitism in infected mice. AnxA1 increased also after L. braziliensis infection of BALB/c (wild-type [WT]) bone marrow derived macrophages. Despite a lower parasite intake, parasite burden in bone marrow-derived macrophages from AnxA1–/– mice was similar to WT and associated with an early increase of TNF-α and, later, of IL-10. AnxA1–/– mice controlled tissue parasitism similarly to WT animals, but they developed significantly larger lesions at later stages of infection, with a more pronounced inflammatory infiltrate and increased specific production of IFN-, IL-4, and IL-10. AnxA1–/– mice also presented higher phosphorylation levels of ERK-1/2 and p65/RelA (NF-B) and inducible NO synthase expression, suggesting that AnxA1 may be involved in modulation of inflammation in this model of experimental leishmaniasis. Finally, assessment of AnxA1 levels in sera from patients with LCL or ML revealed that ML patients had higher levels of serum AnxA1 than did LCL patients or control subjects. Collectively, these data indicate that AnxA1 is actively expressed during L. braziliensis infection. In the absence of AnxA1, mice are fully able to control parasite replication, but they present more intense inflammatory responses and delayed ability to resolve their lesion size.
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Cutting Edge: Targeting Epithelial ORMDL3 Increases, Rather than Reduces, Airway Responsiveness and Is Associated with Increased Sphingosine-1-Phosphate [CUTTING EDGE]
In this study, we used cre-lox techniques to generate mice selectively deficient in ORMDL3 in airway epithelium (Ormdl32-3/2-3/CC10) to simulate an inhaled therapy that effectively inhibited ORMDL3 expression in the airway. In contrast to the anticipated reduction in airway hyperresponsiveness (AHR), OVA allergen–challenged Ormdl32-3/2-3/CC10 mice had a significant increase in AHR compared with wild-type mice. Levels of airway inflammation, mucus, fibrosis, and airway smooth muscle were no different in Ormdl32-3/2-3/CC10 and wild-type mice. However, levels of sphingosine-1-phosphate (S1P) were significantly increased in Ormdl32-3/2-3/CC10 mice as well as in airway epithelial cells in which ORMDL3 was inhibited with small interfering RNA. Incubation of S1P with airway smooth muscle cells significantly increased contractility. Overall, Ormdl32-3/2-3/CC10 mice exhibit increased allergen-induced AHR independent of inflammation and associated with increased S1P generation. These studies raise concerns for inhaled therapies that selectively and effectively inhibit ORMDL3 in airway epithelium in asthma.
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Tim-3 is a Marker of Plasmacytoid Dendritic Cell Dysfunction during HIV Infection and Is Associated with the Recruitment of IRF7 and p85 into Lysosomes and with the Submembrane Displacement of TLR9 [INFECTIOUS DISEASE AND HOST RESPONSE]
In chronic diseases, such as HIV infection, plasmacytoid dendritic cells (pDCs) are rendered dysfunctional, as measured by their decreased capacity to produce IFN-α. In this study, we identified elevated levels of T cell Ig and mucin-domain containing molecule-3 (Tim-3)–expressing pDCs in the blood of HIV-infected donors. The frequency of Tim-3–expressing pDCs correlated inversely with CD4 T cell counts and positively with HIV viral loads. A lower frequency of pDCs expressing Tim-3 produced IFN-α or TNF-α in response to the TLR7 agonists imiquimod and Sendai virus and to the TLR9 agonist CpG. Thus, Tim-3 may serve as a biomarker of pDC dysfunction in HIV infection. The source and function of Tim-3 was investigated on enriched pDC populations from donors not infected with HIV. Tim-3 induction was achieved in response to viral and artificial stimuli, as well as exogenous IFN-α, and was PI3K dependent. Potent pDC-activating stimuli, such as CpG, imiquimod, and Sendai virus, induced the most Tim-3 expression and subsequent dysfunction. Small interfering RNA knockdown of Tim-3 increased IFN-α secretion in response to activation. Intracellular Tim-3, as measured by confocal microscopy, was dispersed throughout the cytoplasm prior to activation. Postactivation, Tim-3 accumulated at the plasma membrane and associated with disrupted TLR9 at the submembrane. Tim-3–expressing pDCs had reduced IRF7 levels. Furthermore, intracellular Tim-3 colocalized with p85 and IRF7 within LAMP1+ lysosomes, suggestive of a role in degradation. We conclude that Tim-3 is a biomarker of dysfunctional pDCs and may negatively regulate IFN-α, possibly through interference with TLR signaling and recruitment of IRF7 and p85 into lysosomes, enhancing their degradation.
http://ift.tt/2ov01QR
Cutting Edge: Innate Immune Augmenting Vesicular Stomatitis Virus Expressing Zika Virus Proteins Confers Protective Immunity [CUTTING EDGE]
Zika virus (ZIKV) has become a serious public health concern because of its link to brain damage in developing human fetuses. Recombinant vesicular stomatitis virus (rVSV) was shown to be a highly effective and safe vector for the delivery of foreign immunogens for vaccine purposes. In this study, we generated rVSVs (wild-type and attenuated VSV with mutated matrix protein [VSVm] versions) that express either the full length ZIKV envelope protein (ZENV) alone or include the ZENV precursor to the membrane protein upstream of the envelope protein, and our rVSV-ZIKV constructs showed efficient immunogenicity in murine models. We also demonstrated maternal protective immunity in challenged newborn mice born to female mice vaccinated with VSVm-ZENV containing the transmembrane domain. Our data indicate that rVSVm may be a suitable strategy for the design of effective vaccines against ZIKV.
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The Cytokine Response to Lipopolysaccharide Does Not Predict the Host Response to Infection [INNATE IMMUNITY AND INFLAMMATION]
The magnitude of the LPS-elicited cytokine response is commonly used to assess immune function in critically ill patients. A suppressed response, known as endotoxin tolerance, is associated with worse outcomes, yet endotoxin tolerance-inducing TLR4 ligands are known to protect animals from infection. Thus, it remains unknown whether the magnitude of the LPS-elicited cytokine response provides an accurate assessment of antimicrobial immunity. To address this, the ability of diverse TLR ligands to modify the LPS-elicited cytokine response and resistance to infection were assessed. Priming of mice with LPS, monophosphoryl lipid A (MPLA), or poly(I:C) significantly reduced plasma LPS–elicited proinflammatory cytokines, reflecting endotoxin tolerance, whereas CpG-ODN–primed mice showed augmented cytokine production. In contrast, LPS, MPLA, and CpG-ODN, but not poly(I:C), improved the host response to a Pseudomonas aeruginosa infection. Mice primed with protective TLR ligands, including CpG-ODN, showed reduced plasma cytokines during P. aeruginosa infection. The protection imparted by TLR ligands persisted for up to 15 d yet was independent of the adaptive immune system. In bone marrow–derived macrophages, protective TLR ligands induced a persistent metabolic phenotype characterized by elevated glycolysis and oxidative metabolism as well as augmented size, granularity, phagocytosis, and respiratory burst. Sustained augmentation of glycolysis in TLR-primed cells was dependent, in part, on hypoxia-inducible factor 1-α and was essential for increased phagocytosis. In conclusion, the magnitude of LPS-elicited cytokine production is not indicative of antimicrobial immunity after exposure to TLR ligands. Additionally, protective TLR ligands induce sustained augmentation of phagocyte metabolism and antimicrobial function.
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Cutting Edge: Fetal/Placental Type I IFN Can Affect Maternal Survival and Fetal Viral Load during Viral Infection [CUTTING EDGE]
Pregnant women have greater mortality and complications associated with viral infections compared with the general population, but the reason for the increased susceptibility is not well defined. Placenta type I IFN is an important immune modulator and protects the pregnancy. We hypothesized that loss of placental IFN affects the regulation of the maternal immune system, resulting in the differential response to infections observed in pregnancy. Pregnant mice lacking the IFN-α/β receptor (IFNAR) became viremic and had higher mortality compared with nonpregnant animals. Notably, an embryo with functional IFN signaling alone was sufficient to rescue the pregnant IFNAR–/– dam from virus-associated demise. Placental IFN was also an important regulator of viral replication in placental tissue and significantly affected viral transmission to the fetus. These findings highlight the role of fetal/placental IFN in the modulation of viral infection in the mother and fetus.
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Systematic Analysis of Cell-Type Differences in the Epithelial Secretome Reveals Insights into the Pathogenesis of Respiratory Syncytial Virus-Induced Lower Respiratory Tract Infections [SYSTEMS IMMUNOLOGY]
Lower respiratory tract infections from respiratory syncytial virus (RSV) are due, in part, to secreted signals from lower airway cells that modify the immune response and trigger airway remodeling. To understand this process, we applied an unbiased quantitative proteomics analysis of the RSV-induced epithelial secretory response in cells representative of the trachea versus small airway bronchiolar cells. A workflow was established using telomerase-immortalized human epithelial cells that revealed highly reproducible cell type–specific differences in secreted proteins and nanoparticles (exosomes). Approximately one third of secretome proteins are exosomal; the remainder are from lysosomal and vacuolar compartments. We applied this workflow to three independently derived primary human cultures from trachea versus bronchioles. A total of 577 differentially expressed proteins from control supernatants and 966 differentially expressed proteins from RSV-infected cell supernatants were identified at a 1% false discovery rate. Fifteen proteins unique to RSV-infected primary human cultures from trachea were regulated by epithelial-specific ets homologous factor. A total of 106 proteins unique to RSV-infected human small airway epithelial cells was regulated by the transcription factor NF-B. In this latter group, we validated the differential expression of CCL20/macrophage-inducible protein 3α, thymic stromal lymphopoietin, and CCL3-like 1 because of their roles in Th2 polarization. CCL20/macrophage-inducible protein 3α was the most active mucin-inducing factor in the RSV-infected human small airway epithelial cell secretome and was differentially expressed in smaller airways in a mouse model of RSV infection. These studies provide insights into the complexity of innate responses and regional differences in the epithelial secretome participating in RSV lower respiratory tract infection–induced airway remodeling.
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Distinct Expression and Function of Fc{varepsilon}RII in Human B Cells and Monocytes [ALLERGY AND OTHER HYPERSENSITIVITIES]
FcRII is a multifunctional low-affinity IgER that is involved in the pathogenesis of allergic, inflammatory, and neoplastic diseases. Although discrepancies in FcRII-mediated functions are being increasingly recognized, the consequences of FcRII activation are not completely understood. In this study, we evaluated the expression of FcRII on human blood cells and found that it was primarily expressed on monocytes and B cells. Although IL-4 promoted expression of the FcRIIb isoform on B cells and monocytes, the expression of the FcRIIa isoform was not dependent on IL-4. Furthermore, FcRII predominantly bound allergen–IgE complexes on B cells but not on monocytes. FcRII-mediated allergen–IgE complex uptake by B cells directed Ags to MHC class II–rich compartments. FcRII-bearing monocytes and B cells expressed high levels of the FcRII sheddase a disintegrin and metalloproteinase 10, which implies that they are important sources of soluble FcRII. Moreover, we identified that IgE immune complex stimulation of FcRII activated intracellular tyrosine phosphorylation via Syk in B cells but not in monocytes. Importantly, FcRII-mediated signaling by allergen–IgE immune complexes increased IFN- production in B cells of allergic patients during the build-up phase of allergen-specific immunotherapy. Together, our results demonstrate that FcRII mediates cell type-dependent function in allergic reactions. In addition, the results identify a novel allergen–IgE complex/FcRII/Syk/IFN- pathway in allergic responses and suggest that FcRII may play a role in regulating allergic reactions via modulating IFN- production in B cells.
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Atg7 Deficiency Intensifies Inflammasome Activation and Pyroptosis in Pseudomonas Sepsis [INFECTIOUS DISEASE AND HOST RESPONSE]
Sepsis is a severe and complicated syndrome that is characterized by dysregulation of host inflammatory responses and organ failure, with high morbidity and mortality. The literature implies that autophagy is a crucial regulator of inflammation in sepsis. In this article, we report that autophagy-related protein 7 (Atg7) is involved in inflammasome activation in Pseudomonas aeruginosa abdominal infection. Following i.p. challenge with P. aeruginosa, atg7fl/fl mice showed impaired pathogen clearance, decreased survival, and widespread dissemination of bacteria into the blood and lung tissue compared with wild-type mice. The septic atg7fl/fl mice also exhibited elevated neutrophil infiltration and severe lung injury. Loss of Atg7 resulted in increased production of IL-1β and pyroptosis, consistent with enhanced inflammasome activation. Furthermore, we demonstrated that P. aeruginosa flagellin is a chief trigger of inflammasome activation in the sepsis model. Collectively, our results provide insight into innate immunity and inflammasome activation in sepsis.
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Novel Pattern Recognition Receptor Protects Shrimp by Preventing Bacterial Colonization and Promoting Phagocytosis [ANTIGEN RECOGNITION AND RESPONSES]
The recognition of pathogen-associated molecular patterns is accomplished by the recognition modules of pattern recognition receptors (PRRs). Leucine-rich repeats (LRRs) and C-type lectin-like domain (CTLD) represent the two most universal categories of recognition modules. In the current study, we identified a novel soluble and bacteria-inducible PRR comprising LRRs and a CTLD from the hepatopancreas of kuruma shrimp Marsupenaeus japonicus and named it Leulectin. The module arrangement of Leulectin is unique among all organisms. Both modules, together with the whole molecule, protected shrimp against Vibrio infection. By screening the pathogen-associated molecular patterns that shrimp might encounter, Leulectin was found to sense Vibrio flagellin through the LRRs and to recognize LPS through CTLD. The LRR–flagellin interaction was confirmed by pull-down and far-Western assays and was found to rely on the fourth LRR of Leulectin and the N terminus of flagellin. The recognition of LPS was determined by the long loop region of CTLD in a calcium-independent manner. By sensing the flagellin, LRRs could prevent its attachment to shrimp cells, thereby inhibiting Vibrio colonization. With the ability to recognize LPS, CTLD could agglutinate the bacteria and promote hemocytic phagocytosis. Our study clearly showed the division of labor and the synergy between different recognition modules and provided new insights into the concept of pattern recognition and the function of soluble PRRs in the antibacterial response.
http://ift.tt/2ouZtdI
Antibody-Independent Function of Human B Cells Contributes to Antifungal T Cell Responses [INFECTIOUS DISEASE AND HOST RESPONSE]
Fungal infections (e.g., Candida albicans) can manifest as serious medical illnesses, especially in the elderly and immune-compromised hosts. T cells are important for Candida control. Whether and how B cells are involved in antifungal immunity has been less clear. Although patients with agammaglobulinemia exhibit normal antifungal immunity, increased fungal infections are reported following B cell–depleting therapy, together pointing to Ab-independent roles of B cells in controlling such infections. To test how human B cells may contribute to fungal-associated human T cell responses, we developed a novel Ag-specific human T cell/B cell in vitro coculture system and found that human B cells could induce C. albicans–associated, MHC class II–restricted responses of naive T cells. Activated B cells significantly enhanced C. albicans–mediated Th1 and Th17 T cell responses, which were both strongly induced by CD80/CD86 costimulation. IL-6+GM-CSF+ B cells were the major responding B cell subpopulation to C. albicans and provided efficient costimulatory signals to the T cells. In vivo B cell depletion in humans resulted in reduced C. albicans–associated T responses. Of note, the decreased Th17, but not Th1, responses could be reversed by soluble factors from B cells prior to depletion, in an IL-6–dependent manner. Taken together, our results implicate an Ab-independent cytokine-defined B cell role in human antifungal T cell responses. These findings may be particularly relevant given the prospects of chronic B cell depletion therapy use in lymphoma and autoimmune disease, as patients age and are exposed to serial combination therapies.
http://ift.tt/2ouTpC2
Distinct and Overlapping Functions of TEC Kinase and BTK in B Cell Receptor Signaling [ANTIGEN RECOGNITION AND RESPONSES]
The Tec tyrosine kinase is expressed in many cell types, including hematopoietic cells, and is a member of the Tec kinase family that also includes Btk. Although the role of Btk in B cells has been extensively studied, the role of Tec kinase in B cells remains largely unclear. It was previously shown that Tec kinase has the ability to partly compensate for loss of Btk activity in B cell differentiation, although the underlying mechanism is unknown. In this study, we confirm that Tec kinase is not essential for normal B cell development when Btk is present, but we also found that Tec-deficient mature B cells showed increased activation, proliferation, and survival upon BCR stimulation, even in the presence of Btk. Whereas Tec deficiency did not affect phosphorylation of phospholipase C or Ca2+ influx, it was associated with significantly increased activation of the intracellular Akt/S6 kinase signaling pathway upon BCR and CD40 stimulation. The increased S6 kinase phosphorylation in Tec-deficient B cells was dependent on Btk kinase activity, as ibrutinib treatment restored pS6 to wild-type levels, although Btk protein and phosphorylation levels were comparable to controls. In Tec-deficient mice in vivo, B cell responses to model Ags and humoral immunity upon influenza infection were enhanced. Moreover, aged mice lacking Tec kinase developed a mild autoimmune phenotype. Taken together, these data indicate that in mature B cells, Tec and Btk may compete for activation of the Akt signaling pathway, whereby the activating capacity of Btk is limited by the presence of Tec kinase.
http://ift.tt/2nQgBrw
PPAR-{alpha} Activation Mediates Innate Host Defense through Induction of TFEB and Lipid Catabolism [INNATE IMMUNITY AND INFLAMMATION]
The role of peroxisome proliferator–activated receptor α (PPAR-α) in innate host defense is largely unknown. In this study, we show that PPAR-α is essential for antimycobacterial responses via activation of transcription factor EB (TFEB) transcription and inhibition of lipid body formation. PPAR-α deficiency resulted in an increased bacterial load and exaggerated inflammatory responses during mycobacterial infection. PPAR-α agonists promoted autophagy, lysosomal biogenesis, phagosomal maturation, and antimicrobial defense against Mycobacterium tuberculosis or M. bovis bacillus Calmette–Guérin. PPAR-α agonists regulated multiple genes involved in autophagy and lysosomal biogenesis, including Lamp2, Rab7, and Tfeb in bone marrow–derived macrophages. Silencing of TFEB reduced phagosomal maturation and antimicrobial responses, but increased macrophage inflammatory responses during mycobacterial infection. Moreover, PPAR-α activation promoted lipid catabolism and fatty acid β-oxidation in macrophages during mycobacterial infection. Taken together, our data indicate that PPAR-α mediates antimicrobial responses to mycobacterial infection by inducing TFEB and lipid catabolism.
http://ift.tt/2ov4dA8
Dimethyl Fumarate Selectively Reduces Memory T Cells and Shifts the Balance between Th1/Th17 and Th2 in Multiple Sclerosis Patients [CLINICAL AND HUMAN IMMUNOLOGY]
Dimethyl fumarate (DMF; trade name Tecfidera) is an oral formulation of the fumaric acid ester that is Food and Drug Administration approved for treatment of relapsing-remitting multiple sclerosis. To better understand the therapeutic effects of Tecfidera and its rare side effect of progressive multifocal leukoencephalopathy, we conducted cross-sectional and longitudinal studies by immunophenotyping cells from peripheral blood (particularly T lymphocytes) derived from untreated and 4–6 and 18–26 mo Tecfidera-treated stable relapsing-remitting multiple sclerosis patients using multiparametric flow cytometry. The absolute numbers of CD4 and CD8 T cells were significantly decreased and the CD4/CD8 ratio was increased with DMF treatment. The proportions of both effector memory T cells and central memory T cells were reduced, whereas naive T cells increased in treated patients. T cell activation was reduced with DMF treatment, especially among effector memory T cells and effector memory RA T cells. Th subsets Th1 (CXCR3+), Th17 (CCR6+), and particularly those expressing both CXCR3 and CD161 were reduced most significantly, whereas the anti-inflammatory Th2 subset (CCR3+) was increased after DMF treatment. A corresponding increase in IL-4 and decrease in IFN- and IL-17–expressing CD4+ T cells were observed in DMF-treated patients. DMF in vitro treatment also led to increased T cell apoptosis and decreased activation, proliferation, reactive oxygen species, and CCR7 expression. Our results suggest that DMF acts on specific memory and effector T cell subsets by limiting their survival, proliferation, activation, and cytokine production. Monitoring these subsets could help to evaluate the efficacy and safety of DMF treatment.
http://ift.tt/2ov87J7
Structural Implications for the Formation and Function of the Complement Effector Protein iC3b [MOLECULAR AND STRUCTURAL IMMUNOLOGY]
Complement-mediated opsonization, phagocytosis, and immune stimulation are critical processes in host defense and homeostasis, with the complement activation fragment iC3b playing a key effector role. To date, however, there is no high-resolution structure of iC3b, and some aspects of its structure-activity profile remain controversial. Here, we employed hydrogen–deuterium exchange mass spectrometry to describe the structure and dynamics of iC3b at a peptide resolution level in direct comparison with its parent protein C3b. In our hydrogen–deuterium exchange mass spectrometry study, 264 peptides were analyzed for their deuterium content, providing almost complete sequence coverage for this 173-kDa protein. Several peptides in iC3b showed significantly higher deuterium uptake when compared with C3b, revealing more dynamic, solvent-exposed regions. Most of them resided in the CUB domain, which contains the heptadecapeptide C3f that is liberated during the conversion of C3b to iC3b. Our data suggest a highly disordered CUB, which has acquired a state similar to that of intrinsically disordered proteins, resulting in a predominant form of iC3b that features high structural flexibility. The structure was further validated using an anti-iC3b mAb that was shown to target an epitope in the CUB region. The information obtained in this work allows us to elucidate determinants of iC3b specificity and activity and provide functional insights into the protein's recognition pattern with respect to regulators and receptors of the complement system.
http://ift.tt/2ov4cfy
Human Plasmacytoid Dendritic Cells Display and Shed B Cell Maturation Antigen upon TLR Engagement [CLINICAL AND HUMAN IMMUNOLOGY]
The BAFF-APRIL system is best known for its control of B cell homeostasis, and it is a target of therapeutic intervention in autoimmune diseases and lymphoma. By analyzing the expression of the three receptors of this system, B cell maturation Ag (BCMA), transmembrane activator and CAML interactor, and BAFF receptor, in sorted human immune cell subsets, we found that BCMA was transcribed in plasmacytoid dendritic cells (pDCs) in both blood and lymphoid tissue. Circulating human pDCs contained BCMA protein without displaying it on the cell surface. After engagement of TLR7/8 or TLR9, BCMA was detected also on the cell surface of pDCs. The display of BCMA on the surface of human pDCs was accompanied by release of soluble BCMA (sBCMA); inhibition of -secretase enhanced surface expression of BCMA and reduced the release of sBCMA by pDCs. In contrast with human pDCs, murine pDCs did not express BCMA, not even after TLR9 activation. In this study, we extend the spectrum of BCMA expression to human pDCs. sBCMA derived from pDCs might determine local availability of its high-affinity ligand APRIL, because sBCMA has been shown to function as an APRIL-specific decoy. Further, therapeutic trials targeting BCMA in patients with multiple myeloma should consider possible effects on pDCs.
http://ift.tt/2nQkhcU
Glucose-Dependent Insulinotropic Polypeptide Receptor Deficiency Leads to Impaired Bone Marrow Hematopoiesis [IMMUNE REGULATION]
The bone marrow (BM) contains controlled specialized microenvironments, or niches, that regulate the quiescence, proliferation, and differentiation of hematopoietic stem and progenitor cells (HSPC). The glucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin hormone that mediates postprandial insulin secretion and has anabolic effects on adipose tissue. Previous studies demonstrated altered bone microarchitecture in mice deficient for GIP receptor (Gipr–/–), as well as the expression of high-affinity GIP receptor by distinct cells constructing the BM HSPC niche. Nevertheless, the involvement of GIP in the process of BM hematopoiesis remains elusive. In this article, we show significantly reduced representation and proliferation of HSPC and myeloid progenitors in the BM of Gipr–/– mice. This was further manifested by reduced levels of BM and circulating differentiated immune cells in young and old adult mice. Moreover, GIP signaling was required for the establishment of supportive BM HSPC niches during HSPC repopulation in radioablated BM chimera mice. Finally, molecular profiling of various factors involved in retention, survival, and expansion of HSPC revealed significantly lower expression of the Notch-receptor ligands Jagged 1 and Jagged 2 in osteoblast-enriched bone extracts from Gipr–/– mice, which are important for HSPC expansion. In addition, there was increased expression of CXCL12, a factor important for HSPC retention and quiescence, in whole-BM extracts from Gipr–/– mice. Collectively, our data suggest that the metabolic hormone GIP plays an important role in BM hematopoiesis.
http://ift.tt/2ouW9zv
Diagnostic challenges, the evaluation of antibiotic allergy.
Purpose of review: Antibiotic allergy is commonly reported and often challenging to evaluate. This review highlights recent developments in our understanding of antibiotic allergy, primarily surrounding evaluation, and diagnosis of antibiotic allergy. We provide historical context to establish a framework, lending relevance to the latest studies. Recent findings: Clinicians have typically employed skin testing as a first step in the diagnosis of drug allergy, reserving drug provocation challenge, the gold standard for diagnosis, for those with negative skin tests. Although skin tests have a good negative predictive value, the positive predictive value has never been established. An increasing amount of research is demonstrating that drug provocation challenge is well tolerated as the initial evaluation in patients with non-life-threatening reactions to antibiotics. This research also calls into question the value of skin testing in these patients. Summary: Skin testing has long been used as the initial investigation in the diagnosis of drug allergy. New research supports that this may not be necessary in all patients, particularly those with non-life-threatening reactions. Further research into the validity of skin testing is required, along with the development of new diagnostic tests for antibiotic allergy. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2nUdjp3
http://ift.tt/2nUdjp3
Foamix's Acne Drug Misses Main Goal in Key Study
Foamix Pharmaceuticals Ltd said on Monday its experimental acne treatment failed to meet one of two main goals in a late-stage study.
Reuters Health Information
http://ift.tt/2nKC5Ie
Diagnostic challenges, the evaluation of antibiotic allergy.
Purpose of review: Antibiotic allergy is commonly reported and often challenging to evaluate. This review highlights recent developments in our understanding of antibiotic allergy, primarily surrounding evaluation, and diagnosis of antibiotic allergy. We provide historical context to establish a framework, lending relevance to the latest studies. Recent findings: Clinicians have typically employed skin testing as a first step in the diagnosis of drug allergy, reserving drug provocation challenge, the gold standard for diagnosis, for those with negative skin tests. Although skin tests have a good negative predictive value, the positive predictive value has never been established. An increasing amount of research is demonstrating that drug provocation challenge is well tolerated as the initial evaluation in patients with non-life-threatening reactions to antibiotics. This research also calls into question the value of skin testing in these patients. Summary: Skin testing has long been used as the initial investigation in the diagnosis of drug allergy. New research supports that this may not be necessary in all patients, particularly those with non-life-threatening reactions. Further research into the validity of skin testing is required, along with the development of new diagnostic tests for antibiotic allergy. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2nUdjp3
http://ift.tt/2nUdjp3
Predictive Significance of Tumor Depth and Budding for Late Lymph Node Metastases in Patients with Clinical N0 Early Oral Tongue Carcinoma
Abstract
In clinical N0 early oral tongue carcinoma, treatment of occult lymph node metastasis is controversial. The purpose of this study was to assess the histopathological risk factors for predicting late lymph node metastasis in early oral tongue carcinoma. We retrospectively reviewed 48 patients with early oral tongue squamous cell carcinoma. Associations between the histopathological factors (depth of tumor, differentiation, blood vessel invasion, lymphatic invasion, and tumor budding) and late lymph metastasis were analyzed. Although the univariate analysis identified blood vessel invasion, lymphatic invasion, and high-grade tumor budding as predictive factors for neck recurrence (p < 0.001), the Cox proportional hazards model identified high-grade tumor budding as an independent predictive factor (p < 0.01). The combination of a tumor depth ≥ 3 mm and high-grade tumor budding yielded high diagnostic accuracy. Tumor depth and budding grade were identified as histopathological risk factors for late neck recurrence in clinical N0 early oral tongue carcinoma.
http://ift.tt/2nPuzdq
Electric Nerve Stimulation Does Not Correctly Predict Needle-Nerve Distance and Potential Local Anesthetic Spread for Interscalene Brachial Plexus Blockade.
http://ift.tt/2nPXiP1
Closed-Loop Feedback Computer-Controlled Phenylephrine for Maintenance of Blood Pressure During Spinal Anesthesia for Cesarean Delivery: A Randomized Trial Comparing Automated Boluses Versus Infusion.
BACKGROUND: We previously described the use of closed-loop feedback computer-controlled infusion of phenylephrine for maintaining blood pressure (BP) during spinal anesthesia for cesarean delivery. In this study, we report a modified system in which phenylephrine is delivered by intermittent boluses rather than infusion. We hypothesized that the use of computer-controlled boluses would result in more precise control of BP compared with infusions. METHODS: Two hundred fourteen healthy patients having spinal anesthesia for elective cesarean delivery were randomized to have their systolic BP maintained by phenylephrine administered by computer-controlled continuous infusion or computer-controlled intermittent boluses. From induction of anesthesia until the time of uterine incision, a noninvasive BP monitor was set to cycle at 1-minute intervals. In the infusion group, the infusion rate was automatically adjusted after each BP measurement using a previously described algorithm. In the bolus group, the algorithm was modified so that the mass of drug that would have been delivered over 1 minute was instead injected as a rapid intravenous bolus after each BP measurement. The precision of BP control was assessed using performance error calculations and compared between groups, with the primary outcome defined as median absolute performance error, and the latter being a measure of inaccuracy showing an average of the magnitudes of the differences of measured BP values above or below the target values. RESULTS: The precision of BP control was greater, as shown by smaller values for median absolute performance error, in the bolus group (median 4.38 [quartiles 3.22, 6.25] %) versus the infusion group (5.39 [4.12, 7.04] %, P = .008). In the bolus group, phenylephrine consumption was smaller; this was associated with smaller values for median performance error compared with the continuous infusion group (P
http://ift.tt/2ouD6Fq
http://ift.tt/2ouD6Fq
Physician-Directed Versus Computerized Closed-Loop Control of Blood Pressure Using Phenylephrine in a Swine Model.
http://ift.tt/2nQ1VZA
Effect of Endotracheal Tube Cuff Shape on Postoperative Sore Throat After Endotracheal Intubation.
http://ift.tt/2ouLAMN
Application of the Novel Ventilation Mode FLow-Controlled EXpiration (FLEX): A Crossover Proof-of-Principle Study in Lung-Healthy Patients.
BACKGROUND: Traditionally, mechanical ventilation is achieved via active lung inflation during inspiration and passive lung emptying during expiration. By contrast, the novel FLEX (FLow-controlled EXpiration) ventilator mode actively decreases the rate of lung emptying. We investigated whether FLEX can be used during intraoperative mechanical ventilation of lung-healthy patients. METHODS: In 30 adult patients scheduled for neurosurgical procedures, we studied respiratory system mechanics, regional ventilation, oxygenation, and hemodynamics during ventilation with and without FLEX at positive end-expiratory pressure (PEEP) of 5 and 7 cm H2O. The FLEX system was integrated into the expiratory limb and modified the expiratory flow profile by continuously changing expiratory resistance according to a computer-controlled algorithm. RESULTS: Mean airway pressure increased with PEEP by 1.9 cm H2O and with FLEX by 1 cm H2O (all P
http://ift.tt/2nQ8zz7
http://ift.tt/2nQ8zz7
Determination of Perioperative Blood Loss: Accuracy or Approximation?.
BACKGROUND: Various different interventions can be used to reduce surgical blood loss; however, there is no "gold standard" for accurately measuring the volume of perioperative blood loss, and this makes it difficult to assess the efficacy of these interventions. METHODS: We used data from a previous multicenter double-blind randomized clinical trial in patients undergoing total hip arthroplasty in which we compared 2 regimens for administering tranexamic acid versus placebo. We assessed direct measures (external blood loss) and indirect estimates (using the formulas of Bourke, Gross, Mercuriali, and Camarasa and a new formula we have developed) using analysis of variance to compare estimated volumes of blood loss among the study groups. In addition, intraclass correlation coefficients (ICCs) and Bland-Altman diagrams were used to compare the estimated volumes of blood loss obtained with each formula. RESULTS: The mean estimated external blood loss was 909 +/- 324 mL, and the mean estimates of blood loss calculated using the formulas of Gross, Bourke and Smith, and Camarasa were 1308 +/- 555, 1091 +/- 454, and 1641 +/- 945 mL, respectively, whereas we obtained a value of 1511 +/- 919 mL with the new formula at day 2. In all cases, the results favored the use of tranexamic acid (P
http://ift.tt/2ouYL09
http://ift.tt/2ouYL09
Continuous Ropivacaine Subfascial Wound Infusion Compared With Intrathecal Morphine for Postcesarean Analgesia: A Prospective, Randomized Controlled, Double-Blind Study.
http://ift.tt/2nQ1DBL
Predictive Significance of Tumor Depth and Budding for Late Lymph Node Metastases in Patients with Clinical N0 Early Oral Tongue Carcinoma
Abstract
In clinical N0 early oral tongue carcinoma, treatment of occult lymph node metastasis is controversial. The purpose of this study was to assess the histopathological risk factors for predicting late lymph node metastasis in early oral tongue carcinoma. We retrospectively reviewed 48 patients with early oral tongue squamous cell carcinoma. Associations between the histopathological factors (depth of tumor, differentiation, blood vessel invasion, lymphatic invasion, and tumor budding) and late lymph metastasis were analyzed. Although the univariate analysis identified blood vessel invasion, lymphatic invasion, and high-grade tumor budding as predictive factors for neck recurrence (p < 0.001), the Cox proportional hazards model identified high-grade tumor budding as an independent predictive factor (p < 0.01). The combination of a tumor depth ≥ 3 mm and high-grade tumor budding yielded high diagnostic accuracy. Tumor depth and budding grade were identified as histopathological risk factors for late neck recurrence in clinical N0 early oral tongue carcinoma.
http://ift.tt/2nPuzdq
A Study of Clinicopathological Profile of Patients of Hoarseness of Voice Presenting to Tertiary Care hospital
Abstract
Hoarseness is subjective term used to describe abnormal voice quality which may occur due to many causes because it is just a symptom. Proper knowledge and clinicopathological profile is important to treat the underlying pathology. This prospective study was carried out in 100 patients presented in Department of ENT, Gandhi Medical College, Bhopal from April 2013 to September 2014 with complaint of hoarseness of voice for more than 15 days. Objective of this study is to study incidence, duration and sex predilection for hoarseness of voice. Also to study different etiological and predisposing factors for hoarseness of voice. After taking detailed history of the patient, complete examination of ear, nose and throat has been carried out. Indirect laryngoscopy, direct laryngoscopy, FOFE is done. Any suspicious tissue is sent for histopathological evaluation. X-ray soft tissue neck and if required CT SCAN larynx is done. Out of 100 patients maximum were from 50 to 70 years age group. 89% were males while only 11% were females. Labourers (37%) and farmers (32%) were the major groups affected. Smoking habit found in 60% of patients and tobacco chewing in 33% of patients and both, also having. Most common cause for hoarseness was found out to be laryngeal neoplasms of which supraglottic growth being commonest (37%) in our study. Hoarseness of voice may be present due to various underlying pathologies. So proper diagnosis, through detailed history, clinical examination and investigations is warranted to find out the cause and starting treatment.
http://ift.tt/2orqKOn
Predictive Significance of Tumor Depth and Budding for Late Lymph Node Metastases in Patients with Clinical N0 Early Oral Tongue Carcinoma
Abstract
In clinical N0 early oral tongue carcinoma, treatment of occult lymph node metastasis is controversial. The purpose of this study was to assess the histopathological risk factors for predicting late lymph node metastasis in early oral tongue carcinoma. We retrospectively reviewed 48 patients with early oral tongue squamous cell carcinoma. Associations between the histopathological factors (depth of tumor, differentiation, blood vessel invasion, lymphatic invasion, and tumor budding) and late lymph metastasis were analyzed. Although the univariate analysis identified blood vessel invasion, lymphatic invasion, and high-grade tumor budding as predictive factors for neck recurrence (p < 0.001), the Cox proportional hazards model identified high-grade tumor budding as an independent predictive factor (p < 0.01). The combination of a tumor depth ≥ 3 mm and high-grade tumor budding yielded high diagnostic accuracy. Tumor depth and budding grade were identified as histopathological risk factors for late neck recurrence in clinical N0 early oral tongue carcinoma.
http://ift.tt/2nPuzdq
Dual incarcerated internal hernias after laparoscopic total gastrectomy with Roux-en-Y reconstruction for gastric cancer
Internal hernia postgastrectomy is an exceedingly rare complication especially in the laparoscopic cohort of patients. Different types of internal hernias have been described, of which, Petersen's and jejunojejunostomy mesenteric defect hernias are the most commonly encountered followed by oesophageal defect and transverse colon mesocolic defect hernias. As the early presentation is always non-specific, late diagnosis of internal hernia has significant implication on morbidity and mortality. Here, we present a rare case of a patient with previous laparoscopy-assisted total gastrectomy presented with features of impending bowel obstruction and bowel ischaemia secondary to dual incarcerated internal hernias. We also reviewed the literature focusing on clinical features of internal hernia, essential CT findings and preventive measures.
http://ift.tt/2nwH4IQ
Cortical subarachnoid haemorrhage with reversible cerebral vasoconstriction syndrome in an elderly woman
Description
A woman aged 65 years had a sudden onset of severe headache after swimming. She had prolonged headache; therefore, she presented at the emergency department. During the examination in the emergency department, her physical and neurological examinations were unremarkable. Haematological findings were normal. The CT scan of the head revealed a cortical subarachnoid haemorrhage (cSAH) in the right frontal and left temporal lesion (figure 1A, B). The cerebrospinal fluid analysis revealed normal protein and cell counts. A brain MRI showed only high-intensity changes for cSAH with no findings of microbleeds (figure 1C, D). The magnetic resonance angiography (MRA) showed mild stenotic changes on the right posterior cerebral artery (PCA) (figure 2A). There was no evidence of any aneurysm. Based on the constriction findings, reversible cerebral vasoconstriction syndrome (RCVS) in conjunction with cSAH was suspected, and intravenous nicardipine was initiated followed by...
http://ift.tt/2otQp9x
“TuNa-saving” endoscopic medial maxillectomy: a surgical technique for maxillary inverted papilloma
Abstract
The maxillary sinus is the most common site of sinonasal inverted papilloma. Endoscopic sinus surgery, in particular endoscopic medial maxillectomy, is currently the gold standard for treatment of maxillary sinus papilloma. Although a common technique, complications such as stenosis of the lacrimal pathway and consequent development of epiphora are still possible. To avoid these problems, we propose a modification of this surgical technique that preserves the head of the inferior turbinate and the nasolacrimal duct. A retrospective analysis was performed on patients treated for maxillary inverted papilloma in three tertiary medical centres between 2006 and 2014. Pedicle-oriented endoscopic surgery principles were applied and, in select cases where the tumour pedicle was located on the anterior wall, a modified endoscopic medial maxillectomy was carried out as described in this paper. From 2006 to 2014 a total of 84 patients were treated. A standard endoscopic medial maxillectomy was performed in 55 patients (65.4%), while the remaining 29 (34.6%) had a modified technique performed. Three recurrences (3/84; 3.6%) were observed after a minimum follow-up of 24 months. A new surgical approach for select cases of maxillary sinus inverted papilloma is proposed in this paper. In this technique, the endoscopic medial maxillectomy was performed while preserving the head of the inferior turbinate and the nasolacrimal duct ("TuNa-saving"). This technique allowed for good visualization of the maxillary sinus, good oncological control and a reduction in the rate of complications.
http://ift.tt/2nSDmN4
The efficacy of extended Draf IIb procedure by partial nasal septectomy: long-term follow up
Abstract
Draf IIb procedure is mostly used in a very narrow frontal recess and in a revision frontal sinus surgery. In most cases, the contralateral sinus is not involved. In order to avoid Draf III procedure's reported disadvantages we have commenced the use of the extended Draf IIb procedures in our center. Patients treated with extended Draf IIb procedure at our center between the years 1997 and 2012 were retrospectively evaluated. This procedure includes further widening of the frontal ostium and recces by excising the adjacent most superior nasal septum. Included in our study were patients who have failed previous Draf IIb procedure or had a small and narrow frontal sinus. Collected data included demographics, prior sinus pathology, previous surgical treatment, surgical complications and further treatment if required. All were evaluated by the SNOT-22 questioner pre and post-operatively and all were endoscopically evaluated during the follow up period. 15 patients and 18 frontal sinuses were included in our study, eight males and seven females with a mean age of 50.3 years. The mean pre-operative SNOT-22 fell from 46 to 24 and all patients improved clinically. No surgical complications were reported except for one case of postoperative maxillary sinusitis. Only one patient required further surgical intervention. In most cases the patients had a patent frontal sinus ostium after a follow up of 3–8 years. Extended Draf IIb procedure is less traumatic, safe and effective in the treatment of persistent frontal sinus disease, without surgically involving the healthy contralateral frontal sinus, and may obviate the need for Draf III procedure.
http://ift.tt/2nAEthP
Check and recheck ETT placement: Do it for Drew
The family of a teen who died after an esophageal intubation has started the 'Do It For Drew' foundation to prevent another tragic death
http://ift.tt/2nAI4fO
The Complexity of Pain Management in Children Affected by Mucopolysaccharidoses
Mucopolysaccharidoses (MPSs) are a group of rare, genetic lysosomal storage disorders. They are caused by deficiencies of the lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Pain is a common feature in mucopolysaccharidoses. However, the pathophysiology of pain in this group of diseases is still unclear and genesis of pain is multifactorial. Currently, poor data about pain management in these patients are available. Here, we present our clinical experience in complex pain management in three children with MPS.
http://ift.tt/2osWoeL
Effect of an oral healthcare programme on care staff knowledge and attitude regarding oral health: a non-randomised intervention trial
Abstract
Objectives
The objective of the study was to evaluate the effect of an oral healthcare programme in nursing homes on care staff knowledge and attitude regarding oral health.
Methods
The study sample consisted of the nurses and nurses' aides from 63 nursing homes, which either received an oral healthcare programme including mobile dental care or were on a waiting list to receive this programme. A validated questionnaire completed at baseline and again after the study period assessed the care staff knowledge and attitude. Paired t test, independent t test, general linear and linear mixed models were used to examine the changes in attitude and knowledge scores.
Results
In total, 546 questionnaires were completed by the same people from 36 nursing homes at baseline and on completion of the study. After the intervention period, knowledge significantly improved in both study groups (I p < 0.001; C p < 0.001), the intervention group significantly showing the largest increase (p < 0.001). The outcome variable attitude only showed a significant improvement in the intervention group (p < 0.001). The mixed models confirmed the impact of some aspects of the intervention on the attitude and the knowledge of the caregivers.
Conclusions
The oral healthcare programme including a mobile dental team resulted in a significant increase of the care staff knowledge and attitude regarding oral health.
Clinical relevance
The integration of a dental professional team in nursing home organisations should be encouraged because it could be valuable to tackle barriers for the provision of daily oral hygiene and to support the continuous integration of oral health care into general care.
http://ift.tt/2nSbvwF
Isolated right ventricular infarction following aortic valve replacement
Description
A woman aged 64 years, with a history of hypertension, symptomatic severe aortic stenosis and normal coronary arteries (figure 1), was submitted to aortic valve replacement with bioprosthesis Perimount Magna 21 mm and enlargement of the aortic root. Apart from atrial fibrillation, no electrocardiographic changes occurred in the postoperative period. She was discharged 7 days after surgery taking warfarin. Fifteen days later, she was readmitted in emergency department with oppressive chest pain radiating to back, hypotension, sweating and cold limbs. The 12-lead ECG showed junctional rhythm and mild ST segment elevation in V1–V3 leads, ST segment depression in inferolateral leads and an unequivocal ST segment elevation in right leads (figure 2A, B). Transthoracic echocardiogram disclosed dilation of right chambers, severe right ventricular dysfunction with akinesia of free wall and preserved left systolic function. On the blood sample, mild anaemia, hyperlactacidemia, INR 2.1 and normal values...
http://ift.tt/2oQ7OFg
Possible utility of contrast-enhanced ultrasonography for detecting spread of local anesthetic in nerve block
Abstract
Purpose
This study demonstrated the effects of perfluorobutane (Sonazoid®) with contrast-enhanced ultrasonography (CEUS) to identify the spread of local anesthetics in ultrasound-guided nerve block.
Methods
This study consists of simulation, cadaveric, and animal studies. In a simulation study, 1% lidocaine with 10- to 1000-fold diluted Sonazoid®, a US-specific contrast agent to diagnose hepatic and breast cancers (0.5 mL), was injected into a resin-based phantom to determine the optimal concentration for ultrasound-guided peripheral nerve block. The enhanced area was measured by direct observation and ultrasonography (US). In the cadaver study, ultrasound-guided sciatic nerve block was performed at the popliteal fossa in the 9 extremities, and 5 mL of the optimally diluted Sonazoid® defined in the simulation study with X-ray contrast medium and blue dye was injected. Longitudinal spread of the solution was measured by CEUS, X-ray imaging and anatomical dissection. In the animal study, the optimally diluted Sonazoid® was injected around the sciatic nerve of rats (n = 6), and neuronal function and toxicity were evaluated by behavioral and histological estimation.
Results
The simulation study proved that 100-fold diluted Sonazoid® was the optimal concentration. In the cadaver study, CEUS and anatomical dissection (r = 0.90, P = 0.0020) or radiography (r = 0.84, P = 0.0072) showed high agreement and correlation with the longitudinal spread. CEUS clearly showed a fine intraneuronal injection image compared to the usual B-mode imaging. The animal study suggested no adverse effects by co-administration of lidocaine and Sonazoid®.
Conclusions
CEUS with 100-fold diluted Sonazoid® could identify the spread of local anesthetic as well as radiography and anatomical dissection, and distinguish between intra- and extraneuronal injections without neurodegeneration.
http://ift.tt/2osFzjD
Acute Onset Ocular Hypotony after Coronary Artery Bypass Surgery
Importance: The purpose of this case report is to evaluate risk factors associated with post-coronary artery bypass graft (CABG) ocular hypotony compared to post-CABG ischemic optic neuropathy. Observations: The patient described here is a single case at the University of California, Irvine Medical Center, from July 2016. This case demonstrates the rare incidence of acute post-CABG ocular hypotony and vision loss in a patient with prior history of optic atrophy. Both vision loss and hypotony resolved completely to baseline without intervention within 3 days postoperatively. Conclusions and Relevance: Severe anemia and large fluctuations in central venous pressure and blood pressure can occur in any patient undergoing CABG surgery. These hemodynamic shifts can cause transient ischemia to pressure controlling systems such as the ciliary body and reduce episcleral venous pressure. Other risk factors for acute hypotony in the setting of CABG surgery also include the use of hypertonic agents, cardiopulmonary bypass, and intravenous anesthesia.
Case Rep Ophthalmol 2017;8:200–207
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Case Rep Ophthalmol 2017;8:200–207
http://ift.tt/2nRpnY2
Early childhood risk factors for rhinoconjunctivitis in adolescence: a prospective birth cohort study
Rhinoconjunctivitis is a global health problem and one of the most common chronic conditions in children. Development of rhinoconjunctivitis depends on both genetic and environmental factors. Many studies have...
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Anatomic distribution of cervicofacial lymphatic malformations based on lymph node groups
Source:International Journal of Pediatric Otorhinolaryngology, Volume 97
Author(s): Phayvanh P. Sjogren, Ryan W. Arnold, Jonathan R. Skirko, Johannes F. Grimmer
ObjectivesTo evaluate radiographic characteristics and to identify locations of cervicofacial lymphatic malformations in children based on known lymph node groupings.MethodsRetrospective chart review of pediatric patients with cervicofacial lymphatic malformations who underwent imaging with magnetic resonance imaging (MRI), computed tomography (CT) or ultrasonography (US). Ninety charts were reviewed from November 2005 to June 2015. Demographic information and imaging characteristics were evaluated.ResultsNinety children were included. The average age at presentation was 52 months (range, 1 day to 170 months). Imaging modalities were MRI in 73 (81%), CT in 7 (8%), US in 6 (7%), and multimodality imaging in 4 (4%) cases. Nearly half (49%) of lesions were found in the parotid and submandibular nodal group, 32% in the cervical group, and 19% in the midline face and oral cavity group. The lymphatic malformations were found on the left in 39 (43%) of cases, on the right in 30 (33%) of cases, and were bilateral in 21 (23%) cases. Nineteen (21%) lesions were macrocystic, twenty-two (24%) were microcystic, and forty-nine (49%) had mixed features. Mixed lesions were more likely to be extensive and involve multiple lymph node groups (P = 0.0005). Adjacent lymphadenopathy was present in 20 (22%) among all subjects, with an average size of 1.22 (± 1.92) cm in the short-axis.ConclusionThe results of this study demonstrate three lymph node groupings in which LM are commonly identified. The midline face and oral cavity lesions are predominantly microcystic, the parotid and submandibular lesions are predominately of mixed morphology, and the cervical lesions are predominately macrocystic and mixed. Further studies are needed to determine if such a classification system demonstrates clinically significant difference in disease progression and response to therapy.
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Hepatitis B virus induced cytoplasmic antineutrophil cytoplasmic antibody-mediated vasculitis causing subarachnoid hemorrhage, acute transverse myelitis, and nephropathy: a case report
Transverse myelitis, subarachnoid hemorrhage, and nephropathy are established but rare complications of hepatitis B virus infection that can potentially be triggered by an antibody-mediated vasculitis as a res...
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