Cancer Stem Cells and Macrophages: Implications in Tumor Biology and Therapeutic Strategies

Cancer stem cells (CSCs) are a unique subset of cells within tumors with stemlike properties that have been proposed to be key drivers of tumor initiation and progression. CSCs are functionally defined by their unlimited self-renewal capacity and their ability to initiate tumor formation in vivo. Like normal stem cells, CSCs exist in a cellular niche comprised of numerous cell types including tumor-associated macrophages (TAMs) which provides a unique microenvironment to protect and promote CSC functions. TAMs provide pivotal signals to promote CSC survival, self-renewal, maintenance, and migratory ability, and in turn, CSCs deliver tumor-promoting cues to TAMs that further enhance tumorigenesis. Studies in the last decade have aimed to understand the molecular mediators of CSCs and TAMs, and recent advances have begun to elucidate the complex cross talk that occurs between these two cell types. In this review, we discuss the molecular interactions that define CSC-TAM cross talk at each stage of tumor progression and examine the clinical implications of targeting these interactions.

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Evaluation of SCUBE-1 and sCD40L biomarkers in patients with hypothyroidism due to Hashimoto’s thyroiditis: a single-blind, controlled clinical study

OBJECTIVE: This study was performed to investigate the levels of platelet activation marker SCUBE-1 and sCD40L which plays some role in the progression of atherosclerosis, in patients with hypothyroidism due to Hashimoto's thyroiditis.

PATIENTS AND METHODS: The cohort of this study includes 90 patients and 35 healthy volunteers, who admitted to the internal medicine out-patient. Simultaneously in the same samples; SCUBE-1 and sCD40L measurements were accomplished by enzyme-linked immunosorbent assay (ELISA). The data obtained were analyzed statistically.

RESULTS: Hypothyroidism due to Hashimoto's thyroiditis in comparison to the control group that includes healthy volunteers; SCUBE-1 and sCD40L, were increased. And these results were statistically significant (p < 0.05).

CONCLUSIONS: SCUBE-1 and sCD40L levels were increased in Hashimoto's hypothyroidism patients. This may indicate an increased endothelial dysfunction, platelet activation and cardiovascular risk in hypothyroidism. SCUBE-1 and sCD40L may be helpful in cardiovascular risk assessment of hypothyroid patients.

L'articolo Evaluation of SCUBE-1 and sCD40L biomarkers in patients with hypothyroidism due to Hashimoto's thyroiditis: a single-blind, controlled clinical study sembra essere il primo su European Review.

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Inhalation of ambroxol inhibits cigarette smoke-induced acute lung injury in a mouse model by inhibiting the Erk pathway

Publication date: April 2016
Source:International Immunopharmacology, Volume 33
Author(s): Ling-tian Ge, Ya-nan Liu, Xi-xi Lin, Hui-juan Shen, Yong-liang Jia, Xin-wei Dong, Yun Sun, Qiang-min Xie
Oral and injection administration of ambroxol has been clinically used to treat airway disease. However, little is known about its potentials in inhalation therapy. In present studies, we tested the effects of ambroxol by inhalation with intravenous administration, and explored the underlying working mechanism. The mice received 10 cigarettes exposure every day for 4days. Inhaled solution of ambroxol was aerosolized 20min before the exposure of cigarette smoke (CS). The effect of ambroxol on the expression of mucoprotein 5AC (MUC5AC) and proinflammatory cytokines in NCI-H292 cells stimulated with cigarette smoke extract (CSE). Four days of daily inhalation of ambroxol at 3.75 or 7.5mg/ml for 20min suppressed the accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) and lung tissues, and inhibited increases in the mRNA and protein levels of tumor necrosis factor (TNF)-α, CCL-2 and KC, but not interleukin (IL)-1β in the CS-exposed mice. Moreover, ambroxol at 3.75 or 7.5mg/ml facilitated airway mucosa cilia clearance, reduced glycosaminoglycans level in BALF and MUC5AC mRNA levels in lung tissues. The effects of ambroxol by inhalation at 7.5mg/ml was comparable to that of ambroxol at 20mg/kg i.v. and dexamethasone at 0.5mg/kg i.p. Using cultured lung epithelial cells, we demonstrated that pretreatment with ambroxol at 2 or 20μM inhibited the CSE-induced up-regulation of MUC5AC, TNF-α, IL-1β mRNA levels, which was through inhibiting Erk signaling pathway. Our results demonstrate the beneficial effects of ambroxol as an inhalation replace systemic administration for COPD therapy.



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Metabolic signaling of insulin secretion by pancreatic β-cell and its derangement in type 2 diabetes

The article "Metabolic signaling of insulin secretion by pancreatic β-cell and its derangement in type 2 diabetes" by C.-Y. Zou, Y. Gong, J. Liang, published in Eur Rev Med Pharmacol Sci 2014; 18 (15): 2215-2227 has been withdrawn.

L'articolo Metabolic signaling of insulin secretion by pancreatic β-cell and its derangement in type 2 diabetes sembra essere il primo su European Review.

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Use of Statins to Augment Progenitor Cell Function in Preclinical and Clinical Studies of Regenerative Therapy: a Systematic Review.

Use of Statins to Augment Progenitor Cell Function in Preclinical and Clinical Studies of Regenerative Therapy: a Systematic Review.

Stem Cell Rev. 2016 Feb 12;

Authors: Park A, Barrera-Ramirez J, Ranasinghe I, Pilon S, Sy R, Fergusson D, Allan DS

Abstract
BACKGROUND: Mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) are used in cell-based regenerative therapy. HMG CoA reductase inhibitors (statins) appear promising in blocking apoptosis, prolonging progenitor cell survival and improving their capacity to repair organ function.
METHODS: We performed a systematic review of preclinical and clinical studies to clarify whether statins can improve cell-based repair of organ injury. MEDLINE, EMBASE, and PUBMED databases were searched (1947 to June 25, 2013). Controlled clinical and pre-clinical studies were included that evaluated statin therapy used alone or in combination with MSCs or EPCs in patients or animals with organ injury.
RESULTS: After screening 771 citations, 100 records underwent full eligibility screening of which 38 studies met eligibility and were included in the review: Studies were grouped into pre-clinical studies that involved statin treatment in combination with cell therapy (18 studies), preclinical studies of statin therapy alone (13 studies) and clinical studies of statin therapy (7 studies). Studies addressed cardiac injury (14 studies), vascular disorders (15 studies), neurologic conditions (8 studies) and bone fractures (1 study). Pre-clinical studies of statins in combination with MSC infusion (15 studies) or EPC therapy (3 studies) were described and despite marked heterogeneity in reporting outcomes of cellular analysis and organ function, all of these cell-based pre-clinical studies reported improved organ recovery with the addition of statin therapy. Moreover, 13 pre-clinical studies involved the administration of a statin drug alone to animals. An increase in EPC number and/or function (no studies of MSCs) was reported in 11 of these studies (85 %) and improved organ function in 12 studies (92 %). We also identified 7 clinical studies and none involved the administration of cells but described an increased number and/or function of EPCs (no studies of MSCs) and improved organ function with statin therapy (1.2-fold to 35-fold improvement over controls) in all 7 studies.
CONCLUSION: Our systematic review provides a foundation of encouraging results that support further study of statins in regenerative therapy to augment the number and/or function of MSCs used in cell-based repair and to augment the number and function of EPCs in vivo to repair damaged tissues. Larger studies are needed to ensure safety and confirm clinical benefits.

PMID: 26873165 [PubMed - as supplied by publisher]

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Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: an arterial spin-labeling fMRI study

Publication date: May 2016
Source:Magnetic Resonance Imaging, Volume 34, Issue 4
Author(s): Jeff Boissoneault, Janelle Letzen, Song Lai, Andrew O'Shea, Jason Craggs, Michael E. Robinson, Roland Staud
BackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by severe fatigue and neurocognitive dysfunction. Recent work from our laboratory and others utilizing arterial spin labeling functional magnetic resonance imaging (ASL) indicated that ME/CFS patients have lower resting state regional cerebral blood flow (rCBF) in several brain areas associated with memory, cognitive, affective, and motor function. This hypoperfusion may underlie ME/CFS pathogenesis and may result in alterations of functional relationships between brain regions. The current report used ASL to compare functional connectivity of regions implicated in ME/CFS between patients and healthy controls (HC).MethodsParticipants were 17 ME/CFS patients (Mage=48.88years, SD=12) fulfilling the 1994 CDC criteria and 17 age/sex matched HC (Mage=49.82years, SD=11.32). All participants underwent T1-weighted structural MRI as well as a 6-min pseudo-continuous arterial spin labeling (pCASL) sequence, which quantifies CBF by magnetically labeling blood as it enters the brain. Imaging data were preprocessed using SPM 12 and ASL tbx, and seed-to-voxel functional connectivity analysis was conducted using the CONN toolbox. All effects noted below are significant at p<0.05 with cluster-wise FDR correction for multiple comparisons.ResultsME/CFS patients demonstrated greater functional connectivity relative to HC in bilateral superior frontal gyrus, ACC, precuneus, and right angular gyrus to regions including precuneus, right postcentral gyrus, supplementary motor area, posterior cingulate gyrus, and thalamus. In contrast, HC patients had greater functional connectivity than ME/CFS in ACC, left parahippocampal gyrus, and bilateral pallidum to regions including right insula, right precentral gyrus, and hippocampus. Connectivity of the left parahippocampal gyrus correlated strongly with overall clinical fatigue of ME/CFS patients.ConclusionThis is the first ASL based connectivity analysis of patients with ME/CFS. Our results demonstrate altered functional connectivity of several regions associated with cognitive, affective, memory, and higher cognitive function in ME/CFS patients. Connectivity to memory related brain areas (parahippocampal gyrus) was correlated with clinical fatigue ratings, providing supporting evidence that brain network abnormalities may contribute to ME/CFS pathogenesis.



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New Claims for Wild Carrot (Daucus carota subsp. carota) Essential Oil

The essential oil of Daucus carota subsp. carota from Portugal, with high amounts of geranyl acetate (29.0%), α-pinene (27.2%), and 11αH-himachal-4-en-1β-ol (9.2%), was assessed for its biological potential. The antimicrobial activity was evaluated against several Gram-positive and Gram-negative bacteria, yeasts, dermatophytes, and Aspergillus strains. The minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) were evaluated showing a significant activity towards Gram-positive bacteria (MIC = 0.32–0.64 μL/mL), Cryptococcus neoformans (0.16 μL/mL), and dermatophytes (0.32–0.64 μL/mL). The inhibition of the germ tube formation and the effect of the oil on Candida albicans biofilms were also unveiled. The oil inhibited more than 50% of filamentation at concentrations as low as 0.04 μL/mL (MIC/128) and decreased both biofilm mass and cell viability. The antioxidant capacity of the oil, as assessed by two in chemico methods, was not relevant. Still, it seems to exhibit some anti-inflammatory potential by decreasing nitric oxide production around 20% in LPS-stimulated macrophages, without decreasing macrophages viability. Moreover, the oils safety profile was assessed on keratinocytes, alveolar epithelial cells, macrophages, and hepatocytes. Overall, the oil demonstrated a safety profile at concentrations below 0.64 μL/mL. The present work highlights the bioactive potential of D. carota subsp. carota suggesting its industrial exploitation.

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Polyarteritis Nodosa: A contemporary overview

Publication date: Available online 13 February 2016
Source:Autoimmunity Reviews
Author(s): Armando De Virgilio, Antonio Greco, Giuseppe Magliulo, Andrea Gallo, Giovanni Ruoppolo, Michela Conte, Salvatore Martellucci, Marco de Vincentiis
Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis predominantly targeting medium-sized arteries. PAN is a rare form of vasculitis, and the precise frequency of this disease is difficult to determine. The major environmental factor associated with PAN is HBV infection.The pathogenesis of "idiopathic PAN" remains enigmatic, although the clinical responses to immunosuppressive therapy support the concept that immunological mechanisms play an active pathogenic role.The spectrum of disease ranges from involving a single organ to polyvisceral failure. Any organ might be affected; however, for reasons that are not understood, PAN does not affect the lungs. In addition to the systemic idiopathic form, called "idiopathic generalized PAN", there are 2 clinical variants of this disease: "cutaneous PAN" and "hepatitis B virus (HBV)-associated PAN".Diagnosis requires the integration of clinical, angiographic, and biopsy findings. The overall prognosis of this disease has been improved in recent decades, primarily reflecting early diagnosis and more effective treatments.Idiopathic generalized PAN should be treated with a combination of glucocorticoids and cyclophosphamide. The treatment of HBV-associated PAN involves a different approach, centred on the use of an antiviral agent to control the infection. The therapy for cutaneous PAN requires a less aggressive approach based on the administration of non-steroidal anti-inflammatory drugs over short periods of time.



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Automatic tracking of laparoscopic instruments for autonomous control of a cameraman robot.

Automatic tracking of laparoscopic instruments for autonomous control of a cameraman robot.

Minim Invasive Ther Allied Technol. 2016 Feb 12;:1-8

Authors: Amini Khoiy K, Mirbagheri A, Farahmand F

Abstract
Background An automated instrument tracking procedure was designed and developed for autonomous control of a cameraman robot during laparoscopic surgery. Material and methods The procedure was based on an innovative marker-free segmentation algorithm for detecting the tip of the surgical instruments in laparoscopic images. A compound measure of Saturation and Value components of HSV color space was incorporated that was enhanced further using the Hue component and some essential characteristics of the instrument segment, e.g., crossing the image boundaries. The procedure was then integrated into the controlling system of the RoboLens cameraman robot, within a triple-thread parallel processing scheme, such that the tip is always kept at the center of the image. Results Assessment of the performance of the system on prerecorded real surgery movies revealed an accuracy rate of 97% for high quality images and about 80% for those suffering from poor lighting and/or blood, water and smoke noises. A reasonably satisfying performance was also observed when employing the system for autonomous control of the robot in a laparoscopic surgery phantom, with a mean time delay of 200ms. Conclusion It was concluded that with further developments, the proposed procedure can provide a practical solution for autonomous control of cameraman robots during laparoscopic surgery operations.

PMID: 26872883 [PubMed - as supplied by publisher]

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Analysis of the predictive efficiency of S100P on adverse prognosis and the pathogenesis of S100P-mediated invasion and metastasis of colon adenocarcinoma

Publication date: Available online 13 February 2016
Source:Cancer Genetics
Author(s): Zhi-Yong Shen, Yuan Fang, Li Zhen, Xian-Jun Zhu, Hao Chen, Hao Liu, Bo Jiang, Guo-Xin Li, Hai-Jun Deng
Elevated expression of S100P has been detected in several tumor types. To analyze the potential use of S100P for the prediction of colorectal cancer (CRC) metastasis and prognosis, S100P expression was detected in 125 patients with colon adenocarcinoma by immunohistochemistry, followed by correlation and survival analysis. High S100P expression was correlated with metastasis, as demonstrated by clinically relevant data, and predicted poor survival more effectively than preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels in colon adenocarcinoma. Stable S100P knockdown CRC cell lines were established to elucidate the relationship between S100P expression and tumor progression in vitro and in vivo. S100P knockdown resulted in reductions in the invasiveness and metastasis of CRC cells. Xenograft growth in nude mice also demonstrated that down-regulated S100P dramatically inhibited peritoneal metastasis of CRC cells. S100P promoted the invasion and metastasis of CRC by activating RAGE/ERK signaling and promoting the epithelial-mesenchymal transition (EMT). RAGE was found to be crucial for S100P-mediated EMT in colon cancer. Knockdown of RAGE in S100P-overexpressing colon cancer cells dramatically suppressed EMT process. Our results indicate that overexpression of S100P is related with an invasive and metastatic phenotype of CRC which is EMT-involved and RAGE dependent.



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High throughput approaches for controlled stem cell differentiation

Publication date: Available online 13 February 2016
Source:Acta Biomaterialia
Author(s): Hwan D. Kim, Eunjee A. Lee, Young Hwan Choi, Young Hyeon An, Rachel H. Koh, Seunghyun L. Kim, Nathaniel S. Hwang
Stem cells have unique ability to undergo self-renewal indefinitely in culture and potential to differentiate into almost all cell types in the human body. However, the developing a method for efficiently differentiating or manipulating these stem cells for therapeutic purposes remains a challenging problem. Pluripotent stem cells, as well as adult stem cells, require biological cues for their proliferation and differentiation. These cues are largely controlled by cell-cell, cell–insoluble factors (such as extracellular matrix), and cell–soluble factors (such as cytokine or growth factors) interactions. In this review, we describe a state of research on various stem cell–based tissue engineering applications and high throughput strategies for developing synthetic or biosynthetic microenvironments to allow efficient commitments in stem cells.Statement of SignificanceNowadays, pluripotency of stem cells have received much attention to use therapeutic purpose. However, a major difficulty with stem cell therapy is to control its differentiation through desired cells or tissues. In other words, various microenvironment factors are involved during stem cell differentiation, including dimensionality, growth factors, cell junctions, nutritional status, matrix stiffness, matrix composition, mechanical stress, and cellmatrix adhesion. Therefore, researchers have engineered a variety of platforms to enable controlling and monitoring bioactive factors to induce stem cell commitment. In this review, we report on recent advancements in a novel technology based on high-throughput strategies for stem cell–based tissue engineering applications.

Graphical abstract

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Hierarchical self-assembly of magnetic nanoclusters for theranostics: Tunable size, enhanced magnetic resonance imagability, and controlled and targeted drug delivery

Publication date: Available online 13 February 2016
Source:Acta Biomaterialia
Author(s): Dai Hai Nguyen, Jung Seok Lee, Jong Hoon Choi, Kyung Min Park, Yunki Lee, Ki Dong Park
Nanoparticle-based imaging and therapy are of interest for theranostic nanomedicine. In particular, superparamagnetic iron oxide (SPIO) nanoparticles (NPs) have attracted much attention in cancer imaging, diagnostics, and treatment because of their superior imagability and biocompatibility (approved by the Food and Drug Administration). Here, we developed SPIO nanoparticles (NPs) that self-assembled into magnetic nanoclusters (SAMNs) in aqueous environments as a theranostic nano-system. To generate multi-functional SPIO NPs, we covalently conjugated β-cyclodextrin (β-CD) to SPIO NPs using metal-adhesive dopamine groups. Polyethylene glycol (PEG) and paclitaxel (PTX) were hosted in the β-CD cavity through high affinity complexation. The core-shell structure of the magnetic nanoclusters was elucidated based on the condensed SPIO core and a PEG shell using electron microscopy and the composition was analyzed by thermogravimetric analysis (TGA). Our results indicate that nanocluster size could be readily controlled by changing the SPIO/PEG ratio in the assemblies. Interestingly, we observed a significant enhancement in magnetic resonance contrast due to the large cluster size and dense iron oxide core. In addition, tethering a tumor-targeting peptide to the SAMNs enhanced their uptake into tumor cells. PTX was efficiently loaded into β-CDs and released in a controlled manner when exposed to competitive guest molecules. These results strongly indicate that the SAMNs developed in this study possess great potential for application in image-guided cancer chemotherapy.Statement of SignificanceIn this study, we developed multi-functional SPIO NPs that self-assembled into magnetic nanoclusters (SAMNs) in aqueous conditions as a theranostic nano-system. The beta-cyclodextrin (β-CD) was immobilized on the surfaces of SPIO NPs and RGD-conjugated polyethylene glycol (PEG) and paclitaxel (PTX) were hosted in the β-CD cavity through high affinity complexation. We found that nanocluster size could be readily controlled by varying the SPIO/PEG ratio in the assemblies, and also demonstrated significant improvement of the functional nanoparticles for theranostic systems; enhanced magnetic resonance, improved cellular uptake, and efficient PTX loading and sustained release at the desired time point. These results strongly indicate that the SAMNs developed in this study possess great potential for application in image-guided cancer chemotherapy.

Graphical abstract

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Elucidating the role of free polycations in gene knockdown by siRNA polyplexes

Publication date: Available online 13 February 2016
Source:Acta Biomaterialia
Author(s): Thomas C.B. Klauber, Rikke V. Søndergaard, Rupa R. Sawant, Vladimir P. Torchilin, Thomas L. Andresen
Future improvements of non-viral vectors for siRNA delivery require better understanding of intracellular processing and vector interactions with target cells. Here, we have compared the siRNA delivery properties of a lipid derivative of bPEI 1.8kDa (DOPE-PEI) with branched polyethyleneimine (bPEI) with average molecular weights of 1.8kDa (bPEI 1.8kDa) and 25 kDa (bPEI 25kDa). We find mechanistic differences between the DOPE-PEI conjugate and bPEI regarding siRNA condensation and intracellular processing. bPEI 1.8kDa and bPEI 25kDa have similar properties with respect to condensation capability, but are very different regarding siRNA decondensation, cellular internalization and induction of reporter gene knockdown. Lipid conjugation of bPEI 1.8kDa improves the siRNA delivery properties, but with markedly different formulation requirements and mechanisms of action compared to conventional PEIs. Interestingly, strong knockdown using bPEI 25kDa is dependent on the presence of a free vector fraction which does not increase siRNA uptake. Finally, we have investigated the effect on lysosomal pH induced by these vectors to elucidate the differences in the proton sponge effect between lipid conjugated PEI and conventional PEI: Neither DOPE-PEI nor bPEI 25kDa affected lysosomal pH as a function of time, underlining that the possible proton sponge effect is not associated with changes in lysosomal pH.Statement of significanceGene silencing therapy has the potential to treat diseases which are beyond the reach of current small molecule-based medicines. However, delivery of the small interfering RNAs (siRNAs) remains a bottleneck to clinical implementation, and the development of safe and efficient delivery systems would be one of the most important achievements in medicine today.A major reason for the lack of progress is insufficient understanding of cell-polyplex interaction. We investigate siRNA delivery using polyethyleneimine (PEI) based vectors and examine how crucial formulation parameters determines the challenges associated with PEI as a delivery vector. We further evaluate how lipid conjugation of PEI influences formulation, cytotoxicity and polymer interaction with cells and cargo as well as the proton sponge capabilities of the vectors.

Graphical abstract

Highlights

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Glial progenitor cell migration promotes CNS axon growth on functionalized electroconducting microfibers

Publication date: Available online 13 February 2016
Source:Acta Biomaterialia
Author(s): Jorge E. Collazos-Castro, Concepción García-Rama, Alexandra Alves-Sampaio
Electroactive systems that promote directional axonal growth and migration of glial progenitor cells (GPC) are needed for the treatment of neurological injuries. We report the functionalization of electroconducting microfibers with multiple biomolecules that synergistically stimulate the proliferation and migration of GPC, which in turn induce axonal elongation from embryonic cerebral cortex neurons. PEDOT doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)] was synthesized on carbon microfibers and used for covalent attachment of molecules to the electroactive surface. The molecular complexes that promoted GPC proliferation and migration, followed by axonal extension, were composed of polylysine, heparin, basic fibroblast growth factor (bFGF), and matricellular proteins; the combination of bFGF with vitronectin or fibronectin being indispensable for sustained glial and axonal growth. The rate of glial-induced axonal elongation was about threefold that of axons growing directly on microfibers functionalized with polylysine alone. Electrical stimuli applied through the microfibers released bFGF and fibronectin from the polymer surface, consequently reducing GPC proliferation and promoting their differentiation into astrocytes, without causing cell detachment or toxicity. These results suggest that functionalized electroactive microfibers may provide a multifunctional tool for controlling neuron-glia interactions and enhancing neural repair.Statement of SignificanceWe report a multiple surface functionalization strategy for electroconducting microfibers (MFs), in order to promote proliferation and guided migration of glial precursor cells (GPC) and consequently create a permissive substrate for elongation of central nervous system (CNS) axons. GPC divided and migrated extensively on the functionalized MFs, leading to fast elongation of embryonic cerebral cortex axons. The application of electric pulses thorough the MFs controlled glial cell division and differentiation. The functionalized MFs provide an advanced tool for neural tissue engineering and for controlling neuron-glial interactions. CNS axonal growth associated to migratory glial precursors, together with the possibility of directing glial differentiation by electrical stimuli applied through the MFs, open a new research avenue to explore for CNS repair.

Graphical abstract

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Robustness Quantification Methods Comparison in Volumetric-Modulated Arc Therapy to treat Head and Neck Cancer

Publication date: Available online 13 February 2016
Source:Practical Radiation Oncology
Author(s): Wei Liu, Samir H. Patel, Jiajian (Jason) Shen, Yanle Hu, Daniel P. Harrington, Xiaoning Ding, Michele Y. Halyard, Steven E. Schild, William W. Wong, Gary A. Ezzell, Martin Bues
BackgroundTo compare plan robustness of volumetric-modulated arc therapy (VMAT) with intensity-modulated radiation therapy (IMRT) and to compare the effectiveness of 3 plan robustness quantification methods.MethodsVMAT and IMRT plans were created for 9 head and neck cancer patients. For each plan, 6 new perturbed dose distributions were computed using ±3mm setup deviations along each of the 3 orientations. Worst-case analysis (WCA), dose-volume histogram (DVH) band (DVHB), and root-mean-square-dose (RMSD) volume histogram (RVH) were used to quantify plan robustness. In WCA a shaded area in the DVH plot bounded by the DVHs from the lowest and highest dose per voxel was displayed. In DVHB we displayed the envelope of all DVHs in band graphs of all the 7 dose distributions. RVH represents the relative volume on the vertical axis and the RMSD on the horizontal axis. The width from the first two methods at different target DVH indices (such as D95% and D5%) and the area under the RVH curves (AUC) for the target were used to indicate plan robustness. Results were compared using Wilcoxon signed-rank test.ResultsDVHB showed that the width at D95% of IMRT was larger than that of VMAT (unit Gy) [1.59 vs 1.18] and the width at D5% of IMRT was comparable to that of VMAT [0.59 vs 0.54]. WCA showed similar results between IMRT and VMAT plans [D95%: 3.28 vs 3.00; D5%: 1.68 vs 1.95]. RVH showed the AUC of IMRT was comparable to that of VMAT [1.13 vs 1.15]. No statistical significance was found in plan robustness between IMRT and VMAT.ConclusionsVMAT is comparable to IMRT in terms of plan robustness. For the 3 quantification methods, WCA and DVHB are DVH-parameter dependent whereas RVH captures the overall effect of uncertainties.



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A Prospective Evaluation of Open Face Masks for Head and Neck Radiotherapy

Publication date: Available online 13 February 2016
Source:Practical Radiation Oncology
Author(s): David Wiant, Sarah Squire, Han Liu, Jacqueline Maurer, T. Lane Hayes, Benjamin Sintay
PurposeHead and neck radiotherapy patients (HN) are typically immobilized with closed thermoplastic masks that cover the face and may cause discomfort for patients. In this work we examine the use of open-masks for HN radiotherapy.Methods and MaterialsFifty HN patients were prospectively randomized into two groups (25 closed-masks, 25 open-masks). The open-mask group was monitored with surface imaging to evaluate intra-fraction motion. Both groups underwent daily volumetric imaging. All daily images were rigidly registered to their respective planning images to evaluate spinal canal and mandible position as a check for inter-fraction posture change. Posture changes were determined by the amount the spinal canal and mandible contours from the planning images had to be expanded to cover the structures on each daily image set. The vector length (VL) of the intra-fraction linear translations, spine, and mandible positions for each open-mask patient were checked for correlation with fraction number using Pearson's r value. All patients were given a weekly survey ranking anxiety and claustrophobia from 0 to 10 (0 = no issue, 10 = extreme issue).ResultsThe mean VL for all open-mask patients was 0.9 mm +/- 0.5 mm (1 SD). Only 1 patient showed significant correlation between VL and fraction number. The mean contour expansions to cover the spine and mandible were 1.5 mm +/- 0.9 mm and 1.8 mm +/- 1.3 mm for the closed-mask group, and 1.6 mm +/- 0.8 mm and 1.8 mm +/- 1.1 mm for the open-mask group. Both groups showed similar behavior relative to fraction number. The mean anxiety and claustrophobia scores were 1.63 and 1.44 for the closed-mask group, and 0.81 and 0.63 for the open-mask group. The groups were not significantly different.ConclusionsOpen-masks provide comparable immobilization and posture preservation to closed-masks for HN radiotherapy.



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The impact of different cone beam computed tomography and multi-slice computed tomography scan parameters on virtual three-dimensional model accuracy using a highly precise ex vivo evaluation method

Publication date: Available online 13 February 2016
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Ragai-Edward Matta, Cornelius von Wilmowsky, Winfried Neuhuber, Michael Lell, Friedrich W. Neukam, Werner Adler, Manfred Wichmann, Bastian Bergauer
ObjectivesMulti-slice computed tomography (MSCT) and cone beam computed tomography (CBCT) are indispensable imaging techniques in advanced medicine. The possibility of creating virtual and corporal three-dimensional (3D) models enables detailed planning in craniofacial and oral surgery. The objective of this study was to evaluate the impact of different scan protocols for CBCT and MSCT on virtual 3D model accuracy using a software-based evaluation method that excludes human measurement errors.Material and MethodsMSCT and CBCT scans with different manufacturers' predefined scan protocols were obtained from a human lower jaw and were superimposed with a master model generated by an optical scan of an industrial noncontact scanner. To determine the accuracy, the mean and standard deviations were calculated, and t-tests were used for comparisons between the different settings.ResultsAveraged over 10 repeated x-ray scans per method and 19 measurement points per scan (n = 190), it was found that the MSCT scan protocol 140 kV delivered the most accurate virtual 3D model, with a mean deviation of 0.106 mm compared to the master model. Only the CBCT scans with 0.2-voxel resolution delivered a similar accurate 3D model (mean deviation 0.119 mm).ConclusionWithin the limitations of this study, it was demonstrated that the accuracy of a 3D model of the lower jaw depends on the protocol used for MSCT and CBCT scans.



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Stable fixation with absorbable sutures in craniofacial surgery

Publication date: Available online 13 February 2016
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): C. Linz, F. Kunz, J. Krauß, H. Böhm, C. Wirth, S. Hartmann, J. Wirbelauer, T. Schweitzer
The present study analyses the exclusive use of absorbable suture material (Vicryl®, Ethicon, Germany) in the fixation of transposed bone segments in craniofacial surgery without modification of the osteotomy design.Among 129 children up to 24 months of age, osteosynthesis was conducted exclusively with Vicryl® sutures. The stability of postoperative results was evaluated and possible foreign body reactions were examined within the framework of clinical and radiological routine checks.All examined children exhibited stable postoperative conditions while the length of hospital stay was not affected. X-ray examinations of the skull in two planes demonstrated good bony union in all cases. Relevant foreign body reactions were not observed.The exclusive application of absorbable suture material enables stable and cost effective osteosynthesis. Significant foreign body reactions were not observed. The exclusive use of absorbable sutures did not alter the osteotomy design.



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Trends in anemia treatment among patients with five non-myeloid malignancies treated with chemotherapy in a large integrated health care delivery system in California, 2000-2013.

Trends in anemia treatment among patients with five non-myeloid malignancies treated with chemotherapy in a large integrated health care delivery system in California, 2000-2013.

Support Care Cancer. 2016 Feb 12;

Authors: Xu L, Xu H, Cannavale K, Sattayapiwat O, Rodriguez R, Page JH, Chao C

Abstract
PURPOSE: The aim of this study is to examine treatment patterns for chemotherapy-induced anemia (CIA) between calendar periods when the changes in the US prescribing information, for erythropoiesis-stimulating agents (ESAs) took place.
METHODS: Patients diagnosed with breast, lung, colorectal, ovarian, or gastric cancer (2000-2012) who developed grade 2+ CIA (hemoglobin (Hb) <10 g/dl) were identified from Kaiser Permanente Southern California Health Plan. We estimated the proportions of CIA episodes with ESA use, red blood cell (RBC) transfusion, or prescription nutritional supplements in three calendar periods: January 1, 2000-December 31, 2006 (P1), January 1, 2007-March 24, 2010 (P2), and March 25, 2010-June 30, 2013 (P3). Multivariable regressions were used to test the differences of CIA treatment approaches and Hb concentration prior to CIA treatment across these calendar periods.
RESULTS: The proportions of CIA episodes with ESA use were 28 % in P1, 21 % in P2, and 3 % in P3. For RBC transfusion, they were 8 % in P1, 14 % in P2 and 16 % in P3. The trend of decreasing ESA use and increasing transfusion use were statistically significant. Relative to P1, the odds ratio (OR) was 0.69 (95% CI: 0.55, 0.86) for P2 and 0.08 (0.30, 0.88) for P3 for ESA use. For RBC transfusion, OR was 2.00 (1.56, 2.56) for P2 and 2.37 (1.88, 3.00) for P3. Use of prescription nutritional supplement was rare across calendar periods. There was a decreasing trend of Hb concentration prior to ESA use (p value <0.01), but no difference in Hb concentrations prior to transfusion.
CONCLUSION: In the management of CIA, use of ESA has decreased over time, while use of RBC transfusion has increased.

PMID: 26872791 [PubMed - as supplied by publisher]

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Cancer Related Fatigue and Quality of Life in Patients with Advanced Prostate Cancer Undergoing Chemotherapy

Cancer related fatigue (CRF) is a common and debilitating symptom that can influence quality of life (QoL) in cancer patients. The increase in survival times stresses for a better understanding of how CRF affects patients' QoL. This was a cross-sectional descriptive study with 148 randomly recruited prostate cancer patients aiming to explore CRF and its impact on QoL. Assessments included the Cancer Fatigue Scale, EORTC QLQ-C30, and EORTC QLQ-PR25. Additionally, 15 in-depth structured interviews were performed. Quantitative data were analyzed with simple and multiple regression analysis and independent samples -test. Qualitative data were analyzed with the use of thematic content analysis. The 66.9% of the patients experienced CRF with higher levels being recorded for the affective subscale. Statistically significant differences were found between the patients reporting CRF and lower levels of QoL (mean = 49.1) and those that did not report fatigue and had higher levels of QoL (mean = 72.1). The interviews emphasized CRF's profound impact on the patients' lives that was reflected on the following themes: "dependency on others," "loss of power over decision making," and "daily living disruption." Cancer related fatigue is a significant problem for patients with advanced prostate cancer and one that affects their QoL in various ways.

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Optimized Biotransformation of Icariin into Icariside II by β-Glucosidase from Trichoderma viride Using Central Composite Design Method

A crude -glucosidase has been produced from Trichoderma viride and used to explore a simple method to prepare icariside II from icariin. The crude enzyme has been studied by zymography method and used for hydrolysis of ICA. To achieve a high conversion rate of ICA, various factors have been studied including pH, reaction time, temperature, initial concentration of enzyme, and initial concentration of ICA through central composite design experiments. In the condition of the optimum hydrolysis parameters with pH 4.0, 41°C, 1.0 mg/mL ICA, and 9.8 U/mL crude -glucosidase, the conversion rate of ICA reached 95.03% at 1 h. Moreover, the cytotoxicity test showed that ICA II performed inhibition effects on proliferation of A549 cell, while ICA has no cytotoxicity. It indicated that the hydrolysis transformation study of ICA is valuable for exploration of active new drugs.

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Could In-Home Sensors Surpass Human Observation of People with Parkinson’s at High Risk of Falling? An Ethnographic Study

Self-report underpins our understanding of falls among people with Parkinson's (PwP) as they largely happen unwitnessed at home. In this qualitative study, we used an ethnographic approach to investigate which in-home sensors, in which locations, could gather useful data about fall risk. Over six weeks, we observed five independently mobile PwP at high risk of falling, at home. We made field notes about falls (prior events and concerns) and recorded movement with video, Kinect, and wearable sensors. The three women and two men (aged 71 to 79 years) having moderate or severe Parkinson's were dependent on others and highly sedentary. We most commonly noted balance protection, loss, and restoration during chair transfers, walks across open spaces and through gaps, turns, steps up and down, and tasks in standing (all evident walking between chair and stairs, e.g.). Our unobtrusive sensors were acceptable to participants: they could detect instability during everyday activity at home and potentially guide intervention. Monitoring the route between chair and stairs is likely to give information without invading the privacy of people at high risk of falling, with very limited mobility, who spend most of the day in their sitting rooms.

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"Angiotensin II memory" contributes to the development of hypertension and vascular injury via activation of NADPH oxidase.

"Angiotensin II memory" contributes to the development of hypertension and vascular injury via activation of NADPH oxidase.

Life Sci. 2016 Feb 10;

Authors: Li WJ, Liu Y, Wang JJ, Zhang YL, Lai S, Xia YL, Wang HX, Li HH

Abstract
AIMS: Activation of the rennin-angiotensin system plays a critical role in the development of hypertension and its complication. Our previous study has demonstrated that a cellular "memory" is involved in angiotensin II (Ang II)-induced cardiac hypertrophy. The aim of this study is to investigate the effect of reversal of high Ang II to normal condition on hypertension and vascular damage.
MAIN METHODS: Wild-type male mice were randomly divided into five groups. The vascular function, inflammation, oxidative stress and angiogenesis were examined by aortic ring relaxation studies, histological analysis, real-time PCR and Western blot analysis.
KEY FINDINGS: We found that continuous high Ang II infusion for 3weeks (Ang II 3w) significantly elevated blood pressure, increased aortic wall thickness, collagen deposition, inflammation, oxidative stress, vascular function and activation of p38 MAPK, JNK1/2, STAT3 and NF-κB pathways in mouse aorta compared with saline group. High Ang II exposure for 2weeks followed by saline for 1week (Ang II 2+1w) failed to reverse these alterations. This phenomenon was named "metabolic memory" (or persistent effect). However, addition of NADPH oxidase inhibitor apocynin during saline infusion (Ang II 2+1w+Apo) markedly ameliorated such deleterious effects.
SIGNIFICANCE: These results showed that we report the first that persistent effect or "metabolic memory" of angiotensin II through NADPH oxidase-mediated oxidative stress plays important roles in hypertension and vascular injury.

PMID: 26874025 [PubMed - as supplied by publisher]

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Expression and clinical significance of MAGE and NY-ESO-1 cancer-testis antigens in adenoid cystic carcinoma of the head and neck.

Expression and clinical significance of MAGE and NY-ESO-1 cancer-testis antigens in adenoid cystic carcinoma of the head and neck.

Head Neck. 2016 Feb 13;

Authors: Veit JA, Heine D, Thierauf J, Lennerz J, Shetty S, Schuler PJ, Whiteside T, Beutner D, Meyer M, Grünewald I, Ritter G, Gnjatic S, Sikora AG, Hoffmann TK, Laban S

Abstract
BACKGROUND: Adenoid cystic carcinoma (ACC) of the head and neck is a rare but highly malignant tumor. Cancer-testis antigens (CTAs) represent an immunogenic family of cancer-specific proteins and thus represent an attractive target for immunotherapy.
METHODS: Eighty-four cases of ACC were identified, the CTAs pan-Melanoma antigen (pan-MAGE; M3H67) and New York esophageal squamous cell carcinoma (NY-ESO-1; E978) were detected immunohistochemically (IHC) and correlated with clinical data.
RESULTS: Expression of NY-ESO-1 was found in 48 of 84 patients (57.1%) and of pan-MAGE in 28 of 84 patients (31.2%). Median overall survival (OS) in NY-ESO-1 positive versus negative patients was 130.8 and 282.0 months (p = .223), respectively. OS in pan-MAGE positive versus negative patients was 105.3 and 190.5 months, respectively (p = .096). Patients expressing both NY-ESO-1 and pan-MAGE simultaneously had significantly reduced OS with a median of 90.5 months compared with 282.0 months in negative patients (p = .047).
CONCLUSION: A significant fraction of patients with ACC show expression of the CTAs NY-ESO-1 and/or pan-MAGE with promising immunotherapeutic implications. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 26874246 [PubMed - as supplied by publisher]

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Impact of neck failure on survival in older patients with differentiated thyroid cancer.

Impact of neck failure on survival in older patients with differentiated thyroid cancer.

Head Neck. 2016 Feb 13;

Authors: Marcus DM, Jiang R, Ward KC, Higgins KA, Saba NF, Wadsworth JT, Beitler JJ

Abstract
BACKGROUND: Regional recurrence of differentiated thyroid cancer (DTC) is often salvaged with neck dissection without survival penalty. It is unknown whether recurrence may be associated with inferior survival in older patients.
METHODS: Surveillance, Epidemiology, and End Results (SEER) and Medicare data were linked to identify patients age ≥65 with nonmetastatic DTC. Patients undergoing neck dissection >6 months after their initial diagnosis were considered to have regional recurrent disease. We compared overall survival (OS) and cause-specific survival (CSS) for patients with recurrent disease versus a matched cohort of patients with non-recurrent DTC.
RESULTS: Of 6235 patients, 143 had treatment-defined recurrent disease. Patients with recurrent disease had inferior OS (p < .01) and CSS (p < .01). Multivariate analysis demonstrated that recurrent disease was independently associated with inferior 10-year OS (hazard ratio [HR] = 1.75; p < .01) and CSS (HR = 3.05; p < .01).
CONCLUSION: Regional recurrence of DTC may negatively impact OS and CSS in patients ≥65 years old. © 2015 Wiley Periodicals, Inc. Head Neck, 2015.

PMID: 26874073 [PubMed - as supplied by publisher]

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Survival and overall treatment time after postoperative radio(chemo)therapy in patients with head and neck cancer.

Survival and overall treatment time after postoperative radio(chemo)therapy in patients with head and neck cancer.

Head Neck. 2016 Feb 13;

Authors: Tribius S, Donner J, Pazdyka H, Münscher A, Gröbe A, Petersen C, Krüll A, Tennstedt P

Abstract
BACKGROUND: Generally, overall treatment time for patients with locally advanced head and neck cancer should be as short as reasonably possible. This analysis was undertaken to determine at what overall treatment time additional survival/locoregional control benefits could be achieved compared to a 100-day cutoff.
METHODS: Clinical impact of overall treatment time was assessed in 272 patients by multivariable Cox regression and Kaplan-Meier analyses using the historical 100-day cutoff and the optimal overall treatment time, determined using recursive partitioning analysis. Survival endpoints were determined for the 100-day and optimal overall treatment times validated using bootstrap resampling.
RESULTS: Recursive partitioning determined the optimal overall treatment time as 87 days. In the 87-day multivariable analysis, adverse factors for overall survival (OS) and disease-free survival (DFS) were overall treatment time ≥87 days and extracapsular spread, and overall treatment time and R1 status, respectively.
CONCLUSION: Overall treatment time is important for survival in patients with head and neck cancer. Completing treatment within as short a timeframe as possible may be associated with longer OS and DFS. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 26873810 [PubMed - as supplied by publisher]

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Prophylactic neck dissection for low-risk differentiated thyroid cancers: Risk-benefit analysis.

Prophylactic neck dissection for low-risk differentiated thyroid cancers: Risk-benefit analysis.

Head Neck. 2016 Feb 13;

Authors: Dubernard X, Dabakuyo S, Ouedraogo S, Amroun K, Kere D, Nasser T, Deguelte S, Pochart JM, Merol JC, Makeieff M, Chays A, Schvartz C

Abstract
BACKGROUND: The benefit of neck dissection is the subject of debate in differentiated thyroid cancer (DTC). We analyze the risk-benefit of neck dissection for low-risk DTC without detectable lymph nodes.
METHODS: We conducted a retrospective study from 1983 to 2003; which included 295 patients without detectable lymph nodes who were treated by thyroidectomy with (C+) or without (C-) neck dissection. All patients had iodine131 therapy. We compared the frequency of remission, disease progression, and permanent complications between groups.
RESULTS: Two hundred twelve patients comprised the C+ group, and 83 patients the C- group. Respectively for C+ versus C-, remission rates were 92% versus 89.2% (p = .40), and progressive disease observed was 3.3% versus 7.2% (p = .10). Permanent hypoparathyroidism occurred in 15.1% in C+ versus 3.6% in C- (p = .006).
CONCLUSION: The risk-benefit analysis of neck dissection in patients with low-risk DTC shows no benefit in terms of complete remission or occurrence of progression. However, risk of complications seems to be higher in patients with neck dissection. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 26873677 [PubMed - as supplied by publisher]

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Functional benefits of implants placed during ablative surgery: A 5-year prospective study on the prosthodontic rehabilitation of 56 edentulous oral cancer patients.

Functional benefits of implants placed during ablative surgery: A 5-year prospective study on the prosthodontic rehabilitation of 56 edentulous oral cancer patients.

Head Neck. 2016 Feb 13;

Authors: Wetzels JG, Koole R, Meijer GJ, de Haan AF, Merkx MA, Speksnijder CM

Abstract
BACKGROUND: The timing of placement as well as the functional benefit of interforaminal implants in edentulous patients treated for oral cancer is unclear.
METHODS: Fifty-six patients were recruited at 2 institutions. In 1 institution, interforaminal implants were placed during ablative surgery, the other institution used conventional prosthodontics with optional placement of implants postsurgery (postponed-placement). Masticatory performance, bite force, and subjective masticatory function were assessed before and 6 months, 1 year, and 5 years after surgery.
RESULTS: Implant-retained overdentures (IODs) demonstrated the highest bite force and the least problems with solid food and food choice. Masticatory performance was equal for IODs and conventional dentures. After 5 years, IODs from patients in the during-ablative-surgery cohort tend to have higher bite force and masticatory performance than those from patients in the postponed-placement cohort.
CONCLUSION: IODs produce the highest overall masticatory function. Implant placement during ablative surgery seems to be functionally beneficial. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 26873437 [PubMed - as supplied by publisher]

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Mechanisms of immune escape in central nervous system infection with neurotropic JC virus variant.

Mechanisms of immune escape in central nervous system infection with neurotropic JC virus variant.

Ann Neurol. 2016 Feb 13;

Authors: Jelcic I, Jelcic I, Kempf C, Largey F, Planas R, Schippling S, Budka H, Sospedra M, Martin R

Abstract
OBJECTIVE: Symptomatic infections of the central nervous system (CNS) with JC polyomavirus (JCV) usually occur as a result of immunocompromise and manifest as progressive multifocal leukoencephalopathy (PML) or granule cell neuronopathy (GCN). After immune reconstitution, some of these cases may show long-term persistence of JCV and delayed clinical improvement despite inflammation.
METHODS: We followed 4 patients with multiple sclerosis, who developed natalizumab-associated PML or GCN with regard to JC viral load and JCV-specific T-cell responses in the CNS. All of them experienced immune reconstitution inflammatory syndrome (IRIS), but in 2 cases JCV persisted > 21 months after IRIS accompanied by delayed clinical improvement.
RESULTS: Persistence of JCV was associated with a lack of JCV VP1-specific T-cell responses during immune reconstitution in 1 of the patients. Detailed analysis of the brain infiltrate in another patient with neuronal persistence of JCV revealed strong infiltration of CD8(+) T cells and clonal expansion of activated CD8(+) effector T cells with a CD4(dim) CD8(+) phenotype, both exhibiting exquisite specificity for conserved epitopes of JCV large T antigen. However, clearance of JCV was not efficient, because mutations in the major capsid protein VP1 caused reduced CD4(+) T-cell responses against the identified JCV variant and subsequently resulted in a decline of CD8(+) T-cell responses after IRIS.
INTERPRETATION: Our findings suggest that efficient CD4(+) T-cell recognition of neurotropic JCV variants is crucial to support CD8(+) T cells in combating JCV infection of the CNS. Ann Neurol 2016.

PMID: 26874214 [PubMed - as supplied by publisher]

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First translational 'Think Tank' on cerebrovascular disease, cognitive impairment and dementia.

First translational 'Think Tank' on cerebrovascular disease, cognitive impairment and dementia.

J Transl Med. 2016;14(1):50

Authors: Barone FC, Gustafson D, Crystal HA, Moreno H, Adamski MG, Arai K, Baird AE, Balucani C, Brickman AM, Cechetto D, Gorelick P, Biessels GJ, Kiliaan A, Launer L, Schneider J, Sorond FA, Whitmer R, Wright C, Zhang ZG

Abstract
As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and dementia. Thus with our more recent recognition of these relationships and our need to understand and more positively impact on this world health problem, "The Leo and Anne Albert Charitable Trust" (Gene Pranzo, Trustee with significant support from Susan Brogan, Meeting Planner) provided generous support for this inaugural international workshop that was held from April 13-16, 2015 at the beautiful Ritz Carlton Golf Resort in North Naples, Florida. Researchers from SUNY Downstate Medical Center, Brooklyn, NY organized the event by selecting the present group of translationally inclined preclinical, clinical and population scientists focused on cerebrovascular disease (CVD) risk and its progression to vascular cognitive impairment (VCI) and dementia. Participants at the workshop addressed important issues related to aging, cognition and dementia by: (1) sharing new data, information and perspectives that intersect vascular, metabolic and neurodegenerative diseases, (2) discussing gaps in translating population risk, clinical and preclinical information to the progression of cognitive loss, and (3) debating new approaches and methods to fill these gaps that can translate into future therapeutic interventions. Participants agreed on topics for group discussion prior to the meeting and focused on specific translational goals that included promoting better understanding of dementia mechanisms, the identification of potential therapeutic targets for intervention, and discussed/debated the potential utility of diagnostic/prognostic markers. Below summarizes the new data-presentations, concepts, novel directions and specific discussion topics addressed by this international translational team at our "First Leo and Anne Albert Charitable Trust 'Think Tank' VCI workshop".

PMID: 26873444 [PubMed - as supplied by publisher]

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Chemerin in peritoneal sepsis and its associations with glucose metabolism and prognosis: a translational cross-sectional study.

Chemerin in peritoneal sepsis and its associations with glucose metabolism and prognosis: a translational cross-sectional study.

Crit Care. 2016;20(1):39

Authors: Horn P, Metzing UB, Steidl R, Romeike B, Rauchfuß F, Sponholz C, Thomas-Rüddel D, Ludewig K, Birkenfeld AL, Settmacher U, Bauer M, Claus RA, von Loeffelholz C

Abstract
BACKGROUND: Stress hyperglycaemia (SHG) is a common complication in sepsis associated with poor outcome. Chemerin is an adipocytokine associated with inflammation and impaired glucose homeostasis in metabolic diseases such as type 2 diabetes (T2D). We aimed to investigate how alterations of circulating chemerin levels and corresponding visceral adipose tissue (VAT) expression are linked to glucose metabolism and prognosis in sepsis.
METHODS: Clinical data and tissue samples were taken from a cross-sectional study including control, T2D and sepsis patients, all undergoing laparotomy. A second independent patient cohort of patients with sepsis was included to evaluate associations with prognosis. This was complemented by a murine model of peritoneal infection and a high-fat diet. We analysed circulating chemerin by enzyme-linked immunosorbent assay and VAT messenger RNA (mRNA) expression by real-time polymerase chain reaction.
RESULTS: Circulating chemerin was increased in sepsis 1.69-fold compared with controls (p = 0.012) and 1.47-fold compared with T2D (p = 0.03). Otherwise, chemerin VAT mRNA expression was decreased in patients with sepsis (p = 0.006) and in septic diabetic animals (p = 0.009). Circulating chemerin correlated significantly with intra-operative glucose (r = 0.662; p = 0.01) and in trend with fasting glucose (r = 0.528; p = 0.052). After adjusting for body mass index or haemoglobin A1c, chemerin correlated in trend with insulin resistance evaluated using the logarithmised homeostasis model assessment of insulin resistance (r = 0.539, p = 0.071; r = 0.553, p = 0.062). Chemerin was positively associated with Acute Physiology and Chronic Health Evaluation II score in patients with sepsis (p = 0.036) and with clinical severity in septic mice (p = 0.031). In an independent study population, we confirmed association of chemerin with glucose levels in multivariate linear regression analysis (β = 0.556, p = 0.013). In patients with sepsis with SHG, non-survivors had significantly lower chemerin levels than survivors (0.38-fold, p = 0.006), while in patients without SHG, non-survivors had higher chemerin levels, not reaching significance (1.64-fold, p = 0.089). No difference was apparent in patients with pre-existing T2D (p = 0.44).
CONCLUSIONS: We show, for the first time to our knowledge, that chemerin is increased in sepsis and that it associates with impaired glucose metabolism and survival in these patients. It could be further evaluated as a biomarker to stratify mortality risk of patients with SHG.

PMID: 26873079 [PubMed - as supplied by publisher]

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Expression of Peroxisome Proliferator-Activated Receptor alpha (PPARα) in somatotropinomas: Relationship with Aryl hydrocarbon receptor Interacting Protein (AIP) and in vitro effects of fenofibrate in GH3 cells.

Expression of Peroxisome Proliferator-Activated Receptor alpha (PPARα) in somatotropinomas: Relationship with Aryl hydrocarbon receptor Interacting Protein (AIP) and in vitro effects of fenofibrate in GH3 cells.

Mol Cell Endocrinol. 2016 Feb 9;

Authors: Rotondi S, Modarelli A, Oliva MA, Rostomyan L, Sanita P, Ventura L, Daly AF, Esposito V, Angelucci A, Arcella A, Giangaspero F, Beckers A, Jaffrain-Rea ML

Abstract
PURPOSE: To search for a possible role of Peroxisome Proliferator-Activated Receptor α (PPARα), a molecular partner of the Aryl hydrocarbon receptor Interacting Protein (AIP), in somatotropinomas.
METHODS: Tumours from 51 acromegalic patients were characterized for PPARα and AIP expression by immunohistochemistry (IHC) and/or Real Time RT-PCR. Data were analysed according to tumour characteristics and pre-operative treatment with somatostatin analogues (SSA). The effects of fenofibrate were studied in GH3 cells in vitro.
RESULTS: PPARα was expressed in most somatotropinomas. A modest relationship was found between PPARα and AIP expression, both being significantly higher in the presence of pre-operative SSA. However, only AIP expression was influenced by the response to treatment. Dual effects of fenofibrate were observed in GH3 cells, consisting of cell growth inhibition and an increase in GH secretion inhibited by octreotide.
CONCLUSIONS: PPARα is a new player in somatotropinomas. Potential interactions between PPARα agonists and SSA may deserve further investigation.

PMID: 26872613 [PubMed - as supplied by publisher]

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Development and validation of quantitative PCR for detection of Terrapene herpesvirus 1 utilizing free-ranging eastern box turtles (Terrapene carolina carolina).

Development and validation of quantitative PCR for detection of Terrapene herpesvirus 1 utilizing free-ranging eastern box turtles (Terrapene carolina carolina).

J Virol Methods. 2016 Feb 10;

Authors: Kane LP, Bunick D, Abd-Eldaim M, Dzhaman E, Allender MC

Abstract
Diseases that affect the upper respiratory tract (URT) in chelonians have been well described as a significant contributor of morbidity and mortality. Specifically, herpesviruses are common pathogens in captive chelonians worldwide, but their importance on free-ranging populations is less well known. Historical methods for the diagnosis of herpesvirus infections include virus isolation and conventional PCR. Real-time PCR has become an essential tool for detection and quantitation of many pathogens, but has not yet been developed for herpesviruses in box turtles. Two quantitative real-time TaqMan PCR assays, TerHV58 and TerHV64, were developed targeting the DNA polymerase gene of Terrapene herpesvirus 1 (TerHV1). The assay detected a viral DNA segment cloned within a plasmid with 10-fold serial dilutions from 1.04×10(7) to 1.04×10(1) viral copies per reaction. Even though both primers had acceptable levels of efficiency and variation, TerHV58 was utilized to test clinical samples based on less variation and increased efficiency. This assay detected as few as 10 viral copies per reaction and should be utilized in free-ranging and captive box turtles to aid in the characterization of the epidemiology of this disease.

PMID: 26874287 [PubMed - as supplied by publisher]

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Population-based epidemiology of Staphylococcus aureus bloodstream infection: clonal complex 30 genotype is associated with mortality.

Population-based epidemiology of Staphylococcus aureus bloodstream infection: clonal complex 30 genotype is associated with mortality.

Eur J Clin Microbiol Infect Dis. 2016 Feb 12;

Authors: Blomfeldt A, Eskesen AN, Aamot HV, Leegaard TM, Bjørnholt JV

Abstract
Staphylococcus aureus bloodstream infections (SABSI) are associated with a high burden of morbidity and mortality. The impact of specific S. aureus genotypes on outcome is unclear. The aim of this study was to evaluate the epidemiology and outcome of SABSI, with a special emphasis on the impact of bacterial clonal lineage on mortality. We conducted a 3-year population-based prospective study between 2011 and 2014, including 303 consecutive adult patients. Clinical data were obtained from interviews and medical records. S. aureus isolates were genotyped using DNA microarrays. The incidence rate of SABSI was 27.6 per 100,000 inhabitants [95 % confidence interval (CI) 24.6-31.0]. The median age of the patients was 71 years (interquartile range 56-81 years) and 61.4 % were male. Most SABSI (70.6 %) occurred in hospitals or associated to healthcare, and 34.1 % of these were associated with intravascular catheters. Only five (1.6 %) SABSI were caused by methicillin-resistant S. aureus (MRSA). The 30-day case fatality rate was 20.8 % (95 % CI 16.6-25.7). S. aureus clonal complex 30 [hazard ratio (HR) 3.9; 95 % CI 1.8-8.5, p = 0.001], unknown focus of infection (HR 4.5; 95 % CI 1.9-10.8, p = 0.001) and respiratory tract infection (HR 12.7; 95 % CI 4.6-34.6, p < 0.001) were independent predictors of mortality in a Cox regression analysis after adjusting for age, sex and underlying conditions. A high proportion of potential preventable SABSI calls for effective infection control measures. S. aureus clonal complex 30 genotype was associated with mortality in patients with bloodstream infections. The genetic basis underlying this association remains to be demonstrated.

PMID: 26873380 [PubMed - as supplied by publisher]

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[Efficacy of Maxing Shigan Decoction combined with Western medicine for pneumonia in children: a systematic review and meta-analysis].

Related Articles

[Efficacy of Maxing Shigan Decoction combined with Western medicine for pneumonia in children: a systematic review and meta-analysis].

Zhong Xi Yi Jie He Xue Bao. 2009 Sep;7(9):809-13

Authors: Li L, Lu FG, He QH

Abstract
OBJECTIVE: To systematically evaluate the clinical effects of Maxing Shigan Decoction (MXSGD), a compound traditional Chinese herbal medicine, combined with Western medicine on pneumonia in children.
METHODS: In this study, the relative trials published from 1994 to 2008 were searched in Chongqing Weipu Database, Chinese Journal Full-text Database, Wanfang database, Chinese Biomedical Literature Database and other electronic database by using the method of Cochrane systematic review. At the same time the information from related journals, professional data and network were hand-searched. The methodological quality of the included trials was assessed by two evaluators, and homogeneous evaluation by meta-analysis was performed. Statistical analysis of clinical data was performed by using RevMan 4.2.7 software provided by the Cochrane Collaboration.
RESULTS: A total of 146 reports were found, while only eight randomized controlled trials met the inclusion criteria. The methodology quality of the reports included in the study was evaluated by the Jadad scale, and the specific random method, allocation concealment, blinding and intention-to-treat analysis were not described in all of the eight trial reports. As MXSGD combined with Western medicine group (treatment group) was compared with Western medicine group (control group), the meta-analysis indicated that the odds ratio for the total effective rate was 4.06, and the 95% confidence interval was from 2.63 to 6.27. MXSGD combined with Western medicine was good at increasing the total effective rate as compared with Western medicine, and the difference was statistically significant (P<0.000 01).
CONCLUSION: MXSGD combined with Western medicine can improve clinical symptoms and increase the total effective rate of the patients with pneumonia in children. However, its clinical effects should be further identified by high quality, multicenter and randomized controlled trials with large-scale design.

PMID: 19747433 [PubMed - indexed for MEDLINE]

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Intratympanic corticosteroid for sudden hearing loss: does it really work?

Intratympanic corticosteroid for sudden hearing loss: does it really work?

Braz J Otorhinolaryngol. 2015 Nov 6;

Authors: Barreto MA, Ledesma AL, de Oliveira CA, Bahmad F

Abstract
INTRODUCTION: Sudden deafness is characterized by an abrupt hearing loss of at least 30dB in three sequential frequencies in the standard pure tone audiogram over three days or less. Treatment is based on its etiology, and oral corticosteroids are widely used. Intratympanic corticosteroids are included as primary or secondary treatment when there is no improvement with the use of oral corticosteroids.
OBJECTIVE: To determine the effectiveness of therapy with intratympanic steroids in sudden deafness.
METHODS: A systematic review was performed of publications on the topic in the databases of PubMed/MEDLINE, with the keywords: sudden deafness, sudden hearing loss, and corticosteroids.
RESULTS: Thirty scientific studies were analyzed. As to the objectives of the study analyzed, 76.7% sought to evaluate the use of intratympanic therapy salvage after failure to conventional treatment, and intratympanic therapy was used as the primary treatment 23.3% of the studies.
CONCLUSION: Intratympanic corticosteroid therapy is prescribed primarily when there is failure of conventional therapy and when it is limited to use systemic corticosteroids, such as the diabetic patient.

PMID: 26873148 [PubMed - as supplied by publisher]

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Prevalence of mitochondrial DNA mutations in sporadic patients with nonsyndromic sensorineural hearing loss.

Prevalence of mitochondrial DNA mutations in sporadic patients with nonsyndromic sensorineural hearing loss.

Braz J Otorhinolaryngol. 2015 Nov 5;

Authors: Jiang H, Chen J, Li Y, Lin PF, He JG, Yang BB

Abstract
INTRODUCTION: Several mitochondrial DNA mutations have been reported to be associated with nonsyndromic hearing loss in several families. However, little is known about the prevalence of these mutations in sporadic patients with nonsyndromic sensorineural hearing loss.
OBJECTIVE: The purpose of our study was to investigate the incidence of these mitochondrial DNA mutations in such population.
METHODS: A total of 178 sporadic patients with nonsyndromic sensorineural hearing loss were enrolled in this study. Genomic DNA was extracted from the peripheral blood sample. We employed the SNaPshot(®) sequencing method to detect five mitochondrial DNA mutations, including A1555G and A827G in 12S rRNA gene and A7445G, 7472insC, and T7511C in tRNA(Ser(UCN)) gene. Meanwhile, we used polymerase chain reaction and sequenced the products to screen GJB2 gene mutations in patients carrying mitochondrial DNA mutations.
RESULTS: We failed to detect the presence of A1555G mutation in 12S rRNA gene, and of A7445G, 7472insC, T7511C mutations in tRNA(Ser(UCN)) gene in our population. However, we found that 6 patients (3.37%) were carriers of a homozygous A827G mutation and one of them also carried homozygous GJB2 235delC mutation.
CONCLUSION: Our findings in the present study indicate that even in sporadic patients with nonsyndromic sensorineural hearing loss, mitochondrial DNA mutations might also contribute to the clinical phenotype.

PMID: 26873147 [PubMed - as supplied by publisher]

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The 100 Most Influential Manuscripts in Gastric Cancer: A Bibliometric Analysis.

The 100 Most Influential Manuscripts in Gastric Cancer: A Bibliometric Analysis.

Int J Surg. 2016 Feb 9;

Authors: Powell AG, Hughes DL, Wheat JR, Lewis WG

Abstract
BACKGROUND: Bibliometric analysis highlights the key topics and publications which have shaped the understanding and management of Gastric cancer. Here the 100 most cited manuscripts in the field of gastric cancer (GC) are analyzed.
METHODS: The Thomson Reuters Web of Science database with the search terms 'gastric cancer' or 'gastric carcinoma' or 'stomach cancer' or 'stomach carcinoma' or 'gastroscopy' was used to identify all English language full manuscripts for the study. The 100 most cited papers were further analysed by topic, journal, author, year and institution.
RESULTS: 122,616 eligible papers were returned and the median (range) citation number was 417 (2893 to 299). The most cited paper (by Parsonnet) focused on H.Pylori risk and gastric cancer (2893 citations). Cancer Research published the highest number of papers (n=13, 6901 citations) and The New England Journal of Medicine (NEJM) had the most citations (n=8, 9358 citations). The country and year with the greatest number of publications were the USA (n=29), and 1998 (n=10). The most ubiquitous topic was the pathology of gastric cancer (n=57) followed by aetiology of gastric cancer (n=47), and basic science of gastric cancer (n=44).
CONCLUSION: The most cited manuscripts highlighted in this study describe the science related to the pathogenesis of GC including surgery and regimens that have resulted in the contemporary understanding and treatment of GC. This work provides the most influential references related to GC and serves as a guide as to what makes a citable paper.

PMID: 26873521 [PubMed - as supplied by publisher]

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Clinical evaluation of percutaneous kyphoplasty in the treatment of osteolytic and osteoblastic metastatic vertebral lesions.

Clinical evaluation of percutaneous kyphoplasty in the treatment of osteolytic and osteoblastic metastatic vertebral lesions.

Int J Surg. 2016 Feb 9;

Authors: Wang Y, Liu H, Pi B, Yang H, Qian Z, Zhu X

Abstract
Percutaneous vertebral augmentation (Percutaneous vertebroplasty, PVP and Percutaeous kyphoplasty, PKP) for the treatment of metastatic spinal lesions has been considered as a preferred alternative to relieve pain and rebuild spinal stabilization relying on minimally invasive procedure. However, there have been few reports on clinical outcomes of percutaneous kyphoplasty in the treatment of osteolytic and osteoblastic metastatic vertebral fracture. We report our experience for 81 kyphoplasty procedures performed in 45 patients with thoracic and lumbar vertebral lesions caused by metastases. 4 out of the 45 patients were withdrawn at 1-year follow-up. 41 patients demonstrated good clinical result. The osteoblastic group performed a better pain relief in visual analog scale (VAS) score after the treatment than the osteoclastic goup 3 days, 1 month, 3 months and 1 year after the KP. And the Oswestry Disability Index (ODI) scores of the osteoblastic group is lower than that of the osteoclastic group just in 3 days after the KP. And there were no significant difference between the two groups of ODI scores 1 month, 3 month and 1 year after the KP. And there were no statistical differences of the radiographic parameters including VB height variation and local kyphosis angle(LKA) between the two groups. Kyphoplasty results in an effective, minimally invasive procedure for the stabilization of thoracic and lumbar metastatic vertebral lesions, including both osteoblastic and osteoclastic types, which achieves statictically significant pain relief, function improvement, preventing further local kyphotic deformity, and VB height.

PMID: 26873520 [PubMed - as supplied by publisher]

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Editor's perspectives - February 2016.

Editor's perspectives - February 2016.

Int J Surg. 2016 Feb;26:86-7

Authors: Rosin RD

PMID: 26873117 [PubMed - in process]

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Rwanda to use drones to deliver medical supplies

The unmanned aircraft will make deliveries to rural health facilities for less than it would cost to make the same deliveries by motorbike

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Diagnostic and Therapeutic Implications of Erectile Dysfunction in Patients with Cardiovascular Disease.

Diagnostic and Therapeutic Implications of Erectile Dysfunction in Patients with Cardiovascular Disease.

Eur Urol. 2016 Feb 9;

Authors: Gandaglia G, Briganti A, Montorsi P, Mottrie A, Salonia A, Montorsi F

Abstract
Erectile dysfunction (ED) and cardiovascular disease (CVD) share many common pathophysiologic pathways and might be regarded as two different clinical manifestations of the same systemic disease. Consequently, ED and CVD are pathologic conditions that often coexist in the same patient. The urologist plays an important role in the management of ED in patients with a history of cardiovascular events. Therapeutic measures aimed at improving sexual function in CVD patients should be considered only after careful evaluation of the underlying cardiologic condition and assessment of ability to exercise. Sexual activity and treatment of ED might trigger cardiac events in selected patients with preexisting CVD; therefore, proerectile therapies should be administered only to low-risk patients for whom subsequent risk of cardiac events would not be increased. Conversely, men at high risk of CVD should receive cardiologic reassessment and stabilization before attempting sexual activity and receiving ED treatment. Risk reduction and lifestyle changes, administration of phosphodiesterase type 5 inhibitors, and testosterone replacement therapy, as indicated, might provide benefits not only in terms of improving sexual function but also for reducing the risk of future cardiac events.
PATIENT SUMMARY: Erectile dysfunction (ED) and cardiovascular disease (CVD) share many pathophysiologic mechanisms and often coexist in the same patient. We evaluated the role of the urologist in the management of ED in patients with preexisting CVD and the impact of measures aimed at improving sexual function on the subsequent risk of cardiac events.

PMID: 26873841 [PubMed - as supplied by publisher]

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Hereditary cancer syndromes: utilizing DNA repair deficiency as therapeutic target.

Hereditary cancer syndromes: utilizing DNA repair deficiency as therapeutic target.

Fam Cancer. 2016 Feb 12;

Authors: Goyal G, Fan T, Silberstein PT

Abstract
Human cells have numerous repair mechanisms to counteract various insults incurred on the DNA. Any mutation in these repair mechanisms can lead to accumulation of DNA errors and carcinogenesis. This review aims to discuss the therapeutic options in the two most common DNA repair deficient cancer syndromes, namely Lynch syndrome (hereditary non-polyposis colorectal cancer) and breast cancer susceptibility gene (BRCA) associated ovarian and breast cancer. Deficiency in DNA repair mechanisms renders these tumors with increased sensitivity to platinum agents. There has been increasing amount of information on the utility of the defects in DNA repair as targets for cancer therapy in these syndromes. Novel therapies like poly (ADP-ribose) polymerase (PARP) inhibitors are one of such example where the induction of double stranded breaks in DNA leads to tumoricidal effect in patients with homologous DNA repair deficiency. Interestingly, patients with DNA repair deficiencies tend to have a more favorable prognosis than sporadic malignancies. In microsatellite high colorectal cancer patients, this has been attributed to increased recruitment of CD8+ T lymphocytes in tumor microenvironment. However, these tumors are able to limit the host immune response by activation of immune checkpoints that seem like attractive targets of therapy in the future.

PMID: 26873719 [PubMed - as supplied by publisher]

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Hyaluronidase: from clinical applications to molecular and cellular mechanisms.

Hyaluronidase: from clinical applications to molecular and cellular mechanisms.

Eur J Med Res. 2016;21(1):5

Authors: Buhren BA, Schrumpf H, Hoff NP, Bölke E, Hilton S, Gerber PA

Abstract
Over the past 60 years, hyaluronidase has been successfully utilized in ophthalmic surgery and is now being implemented in dermatosurgery as well as in other surgical disciplines. The enzyme is considered a "spreading factor" as it decomplexes hyaluronic acid (also called hyaluronan, HA), an essential component of the extracellular matrix (ECM). When applied as an adjuvant, hyaluronidase enhances the diffusion capacity and bioavailability of injected drugs. Therefore, the enzyme has been used as a local adjuvant to increase the diffusion capacity of local anesthetics, increasing the analgesic efficacy, and the anesthetized area particularly in the first minutes following injection, resulting in diminished intra- and postoperative pain. In aesthetic medicine, the off-label use of hyaluronidase is considered the gold standard for the management of HA-filler-associated complications. Here, we review the clinical use, underlying biological mechanisms, and future directions for the application of hyaluronidase in surgical and aesthetic medicine.

PMID: 26873038 [PubMed - as supplied by publisher]

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Comparison of acyclovir and famciclovir for the treatment of Bell's palsy.

Comparison of acyclovir and famciclovir for the treatment of Bell's palsy.

Eur Arch Otorhinolaryngol. 2016 Feb 12;

Authors: Kim HJ, Kim SH, Jung J, Kim SS, Byun JY, Park MS, Yeo SG

Abstract
The relative effectiveness of acyclovir and famciclovir in the treatment of Bell's palsy is unclear. This study therefore compared recovery outcomes in patients with Bell's palsy treated with acyclovir and famciclovir. The study cohort consisted of patients with facial palsy who visited the outpatient clinic between January 2006 and January 2014. Patients were treated with prednisolone plus either acyclovir (n = 457) or famciclovir (n = 245). Patient outcomes were measured using the House-Brackmann scale according to initial severity of disease and underlying disease. The overall recovery rate tended to be higher in the famciclovir than in the acyclovir group. The rate of recovery in patients with initially severe facial palsy (grades V and VI) was significantly higher in the famciclovir than in the acyclovir group (p = 0.01), whereas the rates of recovery in patients with initially moderate palsy (grade III-IV) were similar in the two groups. The overall recovery rates in patients without hypertension or diabetes mellitus were higher in the famciclovir than in the acyclovir group, but the difference was not statistically significant. Treatment with steroid plus famciclovir was more effective than treatment with steroid plus acyclovir in patients with severe facial palsy. Famciclovir may be the antiviral agent of choice in the treatment of patients with severe facial palsy.

PMID: 26873601 [PubMed - as supplied by publisher]

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Acromegaly - Diagnosis and Clinical Management.

Acromegaly - Diagnosis and Clinical Management.

QJM. 2016 Feb 12;

Authors: Dineen R, Stewart PM, Sherlock M

Abstract
Acromegaly is a rare, chronic, progressive disease characterized by excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) concentrations. It is caused by a pituitary adenoma in the vast majority of cases. The clinical diagnosis, based on symptoms related to GH excess, is often delayed due to the insidious nature of the disease. Consequently, patients often have established systemic complications at diagnosis with increased morbidity and premature mortality. Serum IGF-1 measurement is recommended as the initial screen for patients with suspected acromegaly. The gold standard diagnostic test remains the oral glucose tolerance test with concomitant GH measurement. Therapy for acromegaly is targeted at decreasing GH and IGF-1 levels, ameliorating patients' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, medical therapies (such as dopamine agonists, somatostatin receptor agonists and the GH receptor antagonist pegvisomant) and radiotherapy. A multidisciplinary approach is recommended with often a requirement for combined treatment modalities. With disease control, associated morbidity and mortality can be reduced. The recently published evidence-based guidelines by the Endocrine society addressed important clinical issues regarding the evaluation and management of acromegaly. This review discusses advances in our understanding of the pathophysiology of acromegaly, diagnosis of various forms of the disease, and focuses on current treatment modalities, and on future pharmacological therapies for patients with acromegaly.

PMID: 26873451 [PubMed - as supplied by publisher]

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Acromegaly presenting as cutis verticis gyrata.

Acromegaly presenting as cutis verticis gyrata.

QJM. 2016 Feb 12;

Authors: Yerawar C, Bandgar T, Lila A, Shah NS

PMID: 26873450 [PubMed - as supplied by publisher]

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Usefulness of standardized uptake value normalized by individual CT-based lean body mass in application of PET response criteria in solid tumors (PERCIST).

Usefulness of standardized uptake value normalized by individual CT-based lean body mass in application of PET response criteria in solid tumors (PERCIST).

Radiol Phys Technol. 2016 Feb 12;

Authors: Narita A, Shiomi S, Katayama Y, Yamanaga T, Daisaki H, Hamada K, Watanabe Y

Abstract
Our aim in this study was to verify the usefulness of the standardized uptake value (SUV) normalized by individual CT-based lean body mass (LBMCT) in application of PET response criteria in solid tumors (PERCIST).We retrospectively investigated 14 patients (4 male and 10 female) with malignant lymphoma who were undergoing chemotherapy. (18)F-FDG PET/CT examinations were performed before and after chemotherapy. The LBMCT was calculated by estimation of fat weight from CT data (from skull base to pelvis). The mean ± standard deviation (SD) and the Bland-Altman plot were used for comparison among body weight, LBMCT, and LBM derived from a predictive equation (LBMPE). Indices for FDG uptake in the liver were: SUV, SUV based on LBMPE (SULPE), and SUV based on LBMCT (SULCT). Overall differences between the uptake values were analyzed by one-way ANOVA. If the ANOVA showed significance, differences between uptake values were investigated further by use of the Tukey-Kramer test. The mean values of body weight, LBMPE, and LBMCT were: 55.4 ± 14.9 (39.0-112.0), 43.0 ± 10.5 (31.3-75.2), and 35.3 ± 9.8 (23.4-75.8) kg, respectively. There was a wide dispersion between LBMPE and LBMCT (differences, 7.6 ± 3.6 kg; 95 % CI, 6.42-8.85). LBMPE was higher than LBMCT in all the cases except in Case 11. The mean uptake values significantly differed among SUV, SULPE, and SULCT (F = 68.3, p < 0.05). Whereas SULPE deviated from PERCIST criteria in seven patients, SULCT satisfied the criteria except in one case. These results suggest that liver SULCT is useful for application of PERCIST.

PMID: 26873140 [PubMed - as supplied by publisher]

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Recent Advances and Perspective of Studies on Phlegm Syndrome in Chinese Medicine

This review paper summarized the current situation of studies on the essence of phlegm syndrome and relation between phlegm syndrome, diseases, and therapeutics based on published English articles. In studies on the essence of phlegm syndrome, omic technologies were used to explore the molecular basis of phlegm syndrome; in studies on relation between phlegm syndrome and diseases, discovery of markers of phlegm syndrome in diseases becomes a hotspot; the distribution of phlegm syndromes in some common chronic diseases was found; in the therapy of phlegm syndrome, two therapeutic models, treatment with CM formula and treatment with a combination of CM formula and Western medicine, were used most frequently. It is certainly that using one omic technology is not able to deal with the complexity of phlegm syndrome and that the use of a combination of multiple omic methods will be a trend in future studies. Meanwhile, for rapidly increasing clinical research quality of phlegm syndrome, a series of agreed criteria, such as syndrome diagnostic criteria and efficacy criteria clinical studies of phlegm syndrome, needed to be established urgently, and there was an urgent need of standardizing syndrome names in English.

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The Efficacy of Shen Shuaining Capsule on Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Objective. To evaluate the efficacy of Shen shuaining capsule on treating chronic kidney disease (CKD). Methods. All randomized controlled trials (RCTs) of Shen shuaining capsule in treating CKD were collected from CBM, CNKI, VIP, Wanfang, EMBASE, MEDLINE, PubMed, and Cochrane library clinical controlled trials database. Two reviewers independently performed analysis of the included trials according to the inclusion and exclusion criteria. The risk of bias tool was from the Cochrane Handbook version 5.1.0. The Review Manager 5.2 software was employed for data analysis. Funnel plot and Egger's test were applied to evaluate publication bias. Results. 20 studies including 1606 participants met the inclusion criteria, most of which were of low quality. Meta-analysis indicated that Shen shuaining capsule was effective for CKD in terms of SCR, BUN, Hb, and response rate and with less adverse effects, of which SCR and BUN decreased significantly (MD = −84.72, 95% CI: −107.36, −62.07, ) (MD = −4.30, 95% CI: −5.71, −2.89, ); Hb and response rate increased significantly (MD = 9.94, 95% CI: 9.24, 10.64, ) (OR = 4.25, 95% CI (3.32, 5.42), ). Conclusion. Shen shuaining capsule significantly reduced SCR and BUN, increased HB, and improved total efficiency of the symptoms and signs in patients with CKD. Subgroup analysis found that Shen shuaining capsule group was better than control group. Due to low quality of the methodology of included studies, further high-quality researches were needed to study its efficacy and safety.

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