Portosystemic Shunts for "Small for Size Syndrome" Following Liver Transplantation: A Philosopher's Stone?
World J Surg. 2016 Jul 28;
Authors: Rammohan A, Govil S, Rela M
PMID: 27468740 [PubMed - as supplied by publisher]
Cytomegalovirus Colitis: An Uncommon Mimicker of Common Colitides.
Arch Pathol Lab Med. 2016 Aug;140(8):854-858
Authors: Baniak N, Kanthan R
Abstract
Cytomegalovirus latency, though ubiquitous in the human population, is known to cause colitis in both immunocompromised and immunocompetent hosts. Furthermore, the clinical, endoscopic, and histologic appearance of cytomegalovirus colitis can mimic that of inflammatory bowel disease, an extremely well-documented disease. In this context, though many reports have looked at inflammatory bowel disease with superimposed cytomegalovirus infection, less attention has been paid to cytomegalovirus as a primary cause of isolated colitis. Owing to the rarity of this phenomenon, it is important to consider this diagnosis and implement proper testing to avoid misdiagnosis and mismanagement.
PMID: 27472242 [PubMed - as supplied by publisher]
Pleuroparenchymal Fibroelastosis of the Lung: A Review.
Arch Pathol Lab Med. 2016 Aug;140(8):849-853
Authors: Cheng SK, Chuah KL
Abstract
Described in Japan by Amitani et al in 1992, the entity of idiopathic upper lobe fibrosis was subsequently given the name pleuroparenchymal fibroelastosis (PPFE) in the English-speaking world. Pleuroparenchymal fibroelastosis is believed to be a rare disease characterized by a fibrosing process affecting the pleura and the subpleural lung parenchyma, with a predilection for the upper lobes. Uniquely, the fibrosing process is elastotic in nature, being associated with intra-alveolar fibrosis. The etiology of PPFE is unclear at this juncture, with many cases being considered as idiopathic forms of the disease. Conditions associated with PPFE include infections, bone marrow transplantation, and autoimmunity. In this review, we explore the clinical, radiologic, and pathologic features associated with PPFE in light of current understanding of the disease. Recent studies implicated that PPFE may not be as uncommon as claimed. The various differential diagnoses and implications of diagnosing PPFE are discussed.
PMID: 27472241 [PubMed - as supplied by publisher]
Molecular Testing in Breast Cancer: A Guide to Current Practices.
Arch Pathol Lab Med. 2016 Aug;140(8):815-824
Authors: Hagemann IS
Abstract
CONTEXT: -Molecular diagnostics play a role in the management of many cancers, including breast cancer.
OBJECTIVE: -To provide an update on molecular testing in current clinical practice, targeted at practicing pathologists who are not breast cancer specialists.
DATA SOURCES: -This study is a narrative literature review.
CONCLUSIONS: -In addition to routine hormone (estrogen and progesterone) receptor testing, new and recurrent tumors are tested for HER2 amplification by in situ hybridization or overexpression by immunohistochemistry. Intrinsic subtyping of tumors represents a fundamental advance in our understanding of breast cancer biology, but currently it has an indirect role in patient management. Clinical next-generation sequencing (tumor profiling) is increasingly used to identify potentially actionable mutations in tumor tissue. Multianalyte assays with algorithmic analysis, including MammaPrint, Oncotype DX, and Prosigna, play a larger role in breast cancer than in many other malignancies. Given that a proportion of breast cancers are familial, testing of nontumor tissue for cancer predisposition mutations also plays a role in breast cancer care.
PMID: 27472240 [PubMed - as supplied by publisher]
Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update.
Arch Pathol Lab Med. 2016 Aug;140(8):806-814
Authors: Tang P, Tse GM
Abstract
CONTEXT: -The pioneering works on molecular classification (MC) by Perou and Sorlie et al in the early 2000s using global gene expression profiling identified 5 intrinsic subtypes of invasive breast cancers (IBCs): luminal A, luminal B, normal breast-like, HER2-enriched, and basal-like subtypes, each unique in incidence, survival, and response to therapy. Because the application of gene expression profiling in daily practice is not economical or practical at the present time, many investigators have studied the use of immunohistochemical (IHC) surrogates as a substitute for determining the MC of IBC.
OBJECTIVE: -To discuss the continuing efforts that have been made to develop clinically significant and readily available IHC surrogates for the MC of IBC.
DATA SOURCES: -Data were obtained from pertinent peer-reviewed English-language literature.
CONCLUSIONS: -The most commonly used IHC surrogates are estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2), dividing IBC into luminal, HER2, and triple-negative subtypes. The addition of Ki-67, cytokeratin 5, and epidermal growth factor receptor (EGFR) separates luminal B from luminal A subtypes, and basal-like subtype from triple-negative breast cancer. More recently, biomarkers such as androgen receptor and p53 have been shown to further stratify these molecular subtypes. Although many studies of IHC-based MC have shown clinical significance similar to gene expression profiling-defined MC, its critical limitations are: (1) a lack of standardization in terminology, (2) a lack of standardization in biomarkers used for each subtype, and (3) the lack of a uniform cutoff for each biomarker. A panel of IHC surrogates for each subtype of IBC is proposed.
PMID: 27472239 [PubMed - as supplied by publisher]
Invasive Micropapillary Carcinoma of the Breast: An Update.
Arch Pathol Lab Med. 2016 Aug;140(8):799-805
Authors: Yang YL, Liu BB, Zhang X, Fu L
Abstract
CONTEXT: -Invasive micropapillary carcinoma (IMPC) is a distinct variant of mammary carcinoma in which tumor cells are arranged in morulelike clusters devoid of fibrovascular cores and situated within empty stromal spaces. Identification of IMPC can be achieved by the assessment of morphologic features in conjunction with the characteristic "inside-out" staining pattern of epithelial membrane antigen and sialyl Lewis X highlighted by immunohistochemical analysis. Although recognizing micropapillary architecture is often not challenging, the criteria for distinguishing between mixed and pure IMPC remain imprecise. Some mucin-producing carcinomas can also have micropapillary histology, but there is no consensus on whether these tumors are variants of IMPC or mucinous carcinomas. The molecular genetic studies demonstrate that IMPCs have distinct molecular genetic profiles, supporting the theory that they constitute distinct pathologic entities. However, genomic analyses have not identified any specific genomic aberration that may explain the distinctive morphology and clinical behavior of IMPC.
OBJECTIVE: -To provide an overview on the current concepts in the diagnosis and pathogenesis of IMPC of the breast, incorporating recent molecular genetic advances and prognosis-based reclassification.
DATA SOURCES: -PubMed search and the cited references were reviewed.
CONCLUSIONS: -The recent evolution of prognosis-based reclassification and molecular genetic advances has enhanced our knowledge of the pathogenesis of IMPC of the breast. Additional studies might reveal consistent molecular alterations that underlie the formation of the inside-out growth pattern, and they might elucidate the molecular mechanisms responsible for the unfavorable clinical behavior of IMPC.
PMID: 27472238 [PubMed - as supplied by publisher]
Sentinel Lymph Nodes for Breast Carcinoma: A Paradigm Shift.
Arch Pathol Lab Med. 2016 Aug;140(8):791-798
Authors: Maguire A, Brogi E
Abstract
CONTEXT: -Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes.
OBJECTIVE: -To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes.
DATA SOURCES: -Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network.
CONCLUSIONS: -The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin-stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non-sentinel lymph node involvement. This information is important to decide on further axillary treatment.
PMID: 27472237 [PubMed - as supplied by publisher]
Practical Considerations in Breast Papillary Lesions: A Review of the Literature.
Arch Pathol Lab Med. 2016 Aug;140(8):770-790
Authors: Agoumi M, Giambattista J, Hayes MM
Abstract
CONTEXT: -Diagnosis of papillary breast lesions, especially in core biopsies, is challenging for most pathologists, and these lesions pose problems for patient management. Distinction between benign, premalignant, and malignant components of papillary lesions is challenging, and the diagnosis of invasion is problematic in lesions that have circumscribed margins. Obtaining a balance between overtreatment and undertreatment of these lesions is also challenging.
OBJECTIVES: -To provide a classification and a description of the histologic and immunohistochemical features and the differential diagnosis of papillary breast lesions, to provide an update on the molecular pathology of papillary breast lesions, and to discuss the recommendations for further investigation and management of papillary breast lesions. This review provides a concise description of the histologic and immunohistochemical features of the different papillary lesions of the breast.
DATA SOURCES: -The standard pathology text books on breast pathology and literature on papillary breast lesions were reviewed with the assistance of the PubMed database ( http://ift.tt/INqSxj ).
CONCLUSIONS: -Knowledge of the clinical presentation, histology, immunoprofile, and behavior of papillary breast lesions will assist pathologists with the diagnosis and optimal management of patients with papillary breast lesions.
PMID: 27472236 [PubMed - as supplied by publisher]
Immunohistochemistry as a Practical Tool in Molecular Pathology.
Arch Pathol Lab Med. 2016 Aug;140(8):766-769
Authors: Sheffield BS
Abstract
CONTEXT: -Molecular genetics is playing an increasingly important role in patient care and pathology practice. Immunohistochemistry (IHC) is a valuable and practical tool employed by most pathologists on a regular basis.
OBJECTIVE: -To highlight select examples of how IHC may be used in the realm of molecular diagnostics.
DATA SOURCES: -Select sources on IHC relating to tumor subtyping, hereditary cancer screening, and treatment-response prediction are reviewed. These represent some of the areas in which IHC can be employed by anatomic pathologists to optimize patient care and further inform molecular testing.
CONCLUSION: -In the emerging era of personalized medicine, IHC continues to serve a valuable function, complementing and enhancing other molecular techniques.
PMID: 27472235 [PubMed - as supplied by publisher]
Practical Strategies to Improve the Clinical Utility of the Dermatopathology Report.
Arch Pathol Lab Med. 2016 Aug;140(8):759-765
Authors: Trotter MJ, Au S, Naert KA
Abstract
CONTEXT: -Dermatologists and subspecialty dermatopathologists, working together over many years, develop a common understanding of clinical information provided on the requisition and of terminology used in the pathology report. Challenges arise for pathologists without additional subspecialty training in dermatology/dermatopathology, and for any pathologist reporting skin biopsies for nondermatologists such as general practitioners or surgeons.
OBJECTIVE: -To provide practical strategies to improve efficiency of dermatopathology sign-out, at the same time providing the clinician with clear diagnostic and prognostic information to guide patient management.
DATA SOURCES: -The information outlined in this review is based on our own experiences with routine dermatopathology and dermatology practice, and review of English-language articles related to the selected topics discussed.
CONCLUSIONS: -Using generic diagnoses for some benign lesions, listing pertinent negatives in the pathology report, and using logical risk management strategies when reporting on basal cell carcinoma, partial biopsies, or specimens with incomplete clinical information allow the pathologist to convey relevant and useful diagnostic information to the treating clinician.
PMID: 27472234 [PubMed - as supplied by publisher]
The Ever-Changing Landscape of Drug-Induced Injury of the Lower Gastrointestinal Tract.
Arch Pathol Lab Med. 2016 Aug;140(8):748-758
Authors: Marginean EC
Abstract
CONTEXT: -There is an ever-growing armamentarium of pharmacologic agents that can cause gastrointestinal (GI) mucosal injury, the most common symptoms being diarrhea, constipation, nausea, and vomiting. These are often self-limiting and without serious sequelae, but some symptoms are of greater concern, like drug-induced mucosal ulceration that can manifest as GI hemorrhage, stricture formation, and even perforation. Histologically, there is significant overlap between drug-induced injuries and various disease entities. A single type of medication may cause multiple patterns of injury, which can involve the entire GI tract or just some parts of it.
OBJECTIVE: -To review the most common drug-induced injury patterns affecting the colon, which may be recognized by the surgical pathologist on colonic mucosal biopsies. This review does not address the injuries occurring in the upper GI tract.
DATA SOURCES: -A PubMed review of English-language literature, up to December 2015, on drug-induced injury of GI tract was performed.
CONCLUSIONS: -There are numerous drugs that damage the colonic mucosa. The most common drugs are included in this review according to their histologic pattern of injury. It is important for the pathologist to keep in mind that a single drug type can induce many histologic patterns of mucosal injury that can mimic many disease entities. Although there are some histologic clues helpful in the diagnosis of drug-induced colonic injury, correlation with clinical history and especially medication history is essential to improve diagnostic accuracy.
PMID: 27472233 [PubMed - as supplied by publisher]
Insights on the "Why, When, and How" of Integrating Molecular Testing in Anatomic Pathology Practice: Dedicated to the Memory of Gregory J. Naus, MD (1951-2015).
Arch Pathol Lab Med. 2016 Aug;140(8):746-747
Authors: Ionescu DN
PMID: 27472232 [PubMed - as supplied by publisher]
Reports of the Death of the Microscope Have Been Greatly Exaggerated.
Arch Pathol Lab Med. 2016 Aug;140(8):744-745
Authors: Granter SR
PMID: 27472231 [PubMed - as supplied by publisher]
HER2 Immunohistochemistry-Guided Targeted Fluorescence In Situ Hybridization Analysis Does Not Help Identify Intratumoral Heterogeneity in Breast Cancer.
Arch Pathol Lab Med. 2016 Aug;140(8):741
Authors: Gulbahce HE, Factor R, Geiersbach K, Downs-Kelly E
PMID: 27472230 [PubMed - as supplied by publisher]
First-Line Immune Therapy-Implications for Pathologists.
Arch Pathol Lab Med. 2016 Aug;140(8):739-740
Authors: Miller RA, Cagle PT, Bernicker EH
PMID: 27472228 [PubMed - as supplied by publisher]
hTERT gene polymorphism correlates with the risk and the prognosis of thyroid cancer.
Cancer Biomark. 2016 Jul 8;
Authors: Gong L, Xu Y, Hu YQ, Ding QJ, Yi CH, Huang W, Zhou M
Abstract
OBJECTIVES: The study explored the association between rs10069690C/T and rs2736100G/T of human telomerase reverse transcriptase (hTERT) gene, and the prognosis of thyroid cancer.
METHODS: The study had 452 thyroid cancer patients recruited as case group who hospitalized in Jingzhou Central Hospital from January 2001 to June 2004 and 452 healthy people recruited as control group at the same area. The hTERT gene polymorphisms at rs10069690 C/T and rs2736100 G/T were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between patients' life quality and hTERT gene polymorphisms six months after surgery was evaluated based on the Cancer patients' quality of life index rating scale.
RESULTS: There were statistical differences in genotype and allele frequencies of rs10069690 C/T between the case group and control group (both P < 0.05). An association between rs10069690C/T polymorphism and an increased risk of thyroid cancer was shown by logistic regression analysis (CT vs. CC, OR = 1.333, 95%CI = 1.006-1.766, P = 0.045; TT vs. CC, OR = 1.910, 95%CI = 1.084-3.367, P = 0.023; CT + TT vs. CC, OR = 2.246, 95%CI = 1.078-1.840, P = 0.006; T vs. C, OR = 1.376, 95%CI = 1.104-1.715, P = 0.004). Genotype frequency of rs2736100G/T between the two groups had no statistical differences (P > 0.05). After stratification according to age, T stage, tumor size and tumor node metastasis (TNM) stage, the distribution frequencies of CC genotype and CT + TT genotype of rs10069690C/T showed significant difference (P < 0.05). The life quality of patients with CC genotype was better than that of patients with CT $+$ TT genotype. The results of Cox regression model multifactor analysis showed that age, T stage, tumor size and rs10069690C/T were independent risk factors of thyroid cancer prognosis.
CONCLUSIONS: hTERT gene polymorphism at rs10069690C/T is associated with the risk and prognosis of thyroid cancer, but hTERT gene polymorphism at rs2736100G/T is not.
PMID: 27472887 [PubMed - as supplied by publisher]
48 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2016/07/30
PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
upper respiratory tract infection
These pubmed results were generated on 2016/07/30
PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
"Zhonghua Yi Xue Za Zhi"[jour]
These pubmed results were generated on 2016/07/30
PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Increased frequency of hormone negative and polyhormonal endocrine cells in lean individuals with type 2 diabetes.
J Clin Endocrinol Metab. 2016 Jul 29;:jc20162496
Authors: Saleh Md Moin A, Dhawan S, Cory M, Butler PC, Rizza RA, Butler AE
Abstract
CONTEXT: It has been suggested that beta cell loss in type 2 diabetes (T2D) may be due to beta cell degranulation and/or altered cell identity. While shown to have a minor role in obese T2D, this has not been evaluated in lean T2D.
OBJECTIVE: To establish the contribution of altered beta cell identity in lean T2D and, using a rodent model of lean T2D, whether changes in beta cell identity precede hyperglycemia.
DESIGN, SETTING AND PARTICIPANTS: We investigated the frequency of chromogranin A positive hormone negative (CPHN) and polyhormonal endocrine cells in pancreas from 10 lean non diabetic (LND) and 10 lean T2D (LT2D) subjects and in pancreas from wild type (WT) and human IAPP transgenic (HIP) rats at the pre-diabetic and diabetic stage.
RESULTS: CPHN cells and polyhormonal expressing cells were comparably increased in lean T2D and HIP rats, in the latter both before and at onset of diabetes. However, the extent of these cells could only account for ∼2% of beta cell loss.
CONCLUSION: Degranulation and altered identity play at most a minor role in the beta cell deficit in lean T2D. Since the increase in CPHN and polyhormonal cells precede diabetes onset, these changes are likely a response to stress rather than hyperglycemia, and may reflect attempted regeneration.
PMID: 27472443 [PubMed - as supplied by publisher]
Altered Concentrations in Dyslipidemia Evidence a Role for ANGPTL8/Betatrophin in Lipid Metabolism in Humans.
J Clin Endocrinol Metab. 2016 Jul 29;:jc20162084
Authors: Gómez-Ambrosi J, Pascual-Corrales E, Catalán V, Rodríguez A, Ramírez B, Romero S, Vila N, Ibáñez P, Margall MA, Silva C, Gil MJ, Salvador J, Frühbeck G
Abstract
CONTEXT: ANGPTL8/betatrophin is a secreted protein initially involved in β-cell replication. Recent data in humans and mice models suggest that ANGPTL8/betatrophin is more related to lipid metabolism.
OBJECTIVE: The aim of the present study was to compare the circulating concentrations of ANGPTL8/betatrophin in individuals with dyslipidemia defined as having high or low levels of HDL-cholesterol or triglycerides, respectively.
DESIGN, SETTING, AND PARTICIPANTS: Serum concentrations of ANGPTL8/betatrophin were measured by ELISA in 177 subjects. We studied two different selected case-control dyslipidemic cohorts including individuals with high (n=43) or low (n=46) circulating concentrations of HDL-cholesterol or with low (n=48) or high (n=40) levels of triglycerides.
RESULTS: Circulating concentrations of ANGPTL8/betatrophin were significantly lower in individuals with dyslipidemia P<0.001 in both males (C 27.8 ± 15.2 vs DL 17.0 ± 11.2 ng/mL) and females (C 50.0 ± 22.2 vs DL 27.0 ± 16.5 ng/mL). The magnitude of the differences was higher in dyslipidemic patients with low HDL-cholesterol than in those with high TG concentrations. ANGPTL8/betatrophin levels were lower in subjects with T2D (P<0.001) but the impact of T2D vanished (P=0.257) when the effect of dyslipidemia was included in the analysis.
CONCLUSIONS: We conclude that serum ANGPTL8/betatrophin concentrations are altered in human dyslipidemia. ANGPTL8/betatrophin emerges as a potential player in dyslipidemia with a strong association with HDL-C and a potential therapeutic tool for the treatment of dyslipidemia.
PMID: 27472196 [PubMed - as supplied by publisher]
Menopause, reproductive life, hormone replacement therapy and bone phenotype at age 60-64: a British birth cohort.
J Clin Endocrinol Metab. 2016 Jul 29;:jc20161828
Authors: Kuh D, Muthuri S, Cooper R, Moore A, MacKinnon K, Cooper C, Adams JE, Hardy R, Ward KA
Abstract
CONTEXT: Previous studies of menopausal age and length of reproductive life on bone are limited by retrospective reproductive histories, being cross sectional, or lacking gold standard bone technologies, or information on hormone replacement therapy (HRT) or surgical treatment.
OBJECTIVE: To investigate age at menopause, length of reproductive life and HRT use in relation to volumetric and areal bone mineral density (vBMD, aBMD), bone size and strength in women aged 60-64.
DESIGN: A birth cohort study followed for 64 years with prospective measures of age at menarche and menopause and monthly HRT histories.
SETTING: England, Scotland, Wales Participants: 848 women with known type of menopause and bone measures at 60-64 years Main outcome measures: Peripheral quantitative computed tomography (pQCT) measurements of the distal radius total and trabecular vBMD; diaphyseal radius total and medullary cross sectional area, cortical vBMD and polar strength strain index (SSI); dual energy x-ray absorptiometry (DXA) measurments of aBMD at the lumbar spine and total hip.
RESULTS: A ten year increase in age at natural (but not surgical) menopause was associated with 8.2% (95% CI: 1.3,15.1%, p=.02) greater trabecular vBMD and a 6.0% (95% CI 0.51,11.5%, p=.03) greater total vBMD; findings were similar for length of reproductive life. A ten year difference in HRT use was associated with a 6.0% (95% CI 2.6%,9.3%, p<.001) greater polar SSI and a 0.9% (95% CI 0.4%, 1.5%, p=.001) greater cortical vBMD. These estimates changed little on adjustment. Estimates for aBMD were consistent with those for pQCT.
CONCLUSIONS: The positive effects on trabecular vBMD of later natural menopause and longer reproductive life persisted into early old age. HRT use was associated with greater radius cortical vBMD and polar SSI, and spine aBMD.
PMID: 27472291 [PubMed - as supplied by publisher]
Memo interacts with c-Src to control Estrogen Receptor alpha sub-cellular localization.
Oncotarget. 2016 Jul 26;
Authors: Frei A, MacDonald G, Lund I, Gustafsson JÅ, Hynes NE, Nalvarte I
Abstract
Understanding the complex interaction between growth factor and steroid hormone signaling pathways in breast cancer is key to identifying suitable therapeutic strategies to avoid progression and therapy resistance. The interaction between these two pathways is of paramount importance for the development of endocrine resistance. Nevertheless, the molecular mechanisms behind their crosstalk are still largely obscure. We previously reported that Memo is a small redox-active protein that controls heregulin-mediated migration of breast cancer cells. Here we report that Memo sits at the intersection between heregulin and estrogen signaling, and that Memo controls Estrogen Receptor alpha (ERα) sub-cellular localization, phosphorylation, and function downstream of heregulin and estrogen in breast cancer cells. Memo facilitates ERα and c-Src interaction, ERα Y537 phosphorylation, and has the ability to control ERα extra-nuclear localization. Thus, we identify Memo as an important key mediator between the heregulin and estrogen signaling pathways, which affects both breast cancer cell migration and proliferation.
PMID: 27472465 [PubMed - as supplied by publisher]
Inhibition of heat shock protein 90 improves pulmonary arteriole remodeling in pulmonary arterial hypertension.
Oncotarget. 2016 Jul 26;
Authors: Wang GK, Li SH, Zhao ZM, Liu SX, Zhang GX, Yang F, Wang Y, Wu F, Zhao XX, Xu ZY
Abstract
While the molecular chaperone heat shock protein 90 (HSP90) is involved in a multitude of physiological and pathological processes, its role relating to pulmonary arterial hypertension (PAH) remains unclear. In the present study, we investigated the effect in which HSP90 improves pulmonary arteriole remodeling, and explored the therapeutic utility of targeting HSP90 as therapeutic drug for PAH. By Elisa and immunohistochemistry, HSP90 was found to be increased in both plasma and membrane walls of pulmonary arterioles from PAH patients. Moreover, plasma HSP90 levels positively correlated with mean pulmonary arterial pressure and C-reactive protein. In a monocrotaline-induced rat model of PH, we found that 17-AAG, a HSP90-inhibitor, alleviated the progress of PH, demonstrated by lower pulmonary arterial pressure and absence of right ventricular hypertrophy. Immunohistochemical staining demonstrated that 17-AAG improved pulmonary arteriole remodeling on the basis of reduced wall thickness and wall area. The inflammatory response attributed to PH could be attenuated by 17-AAG through reduction of NF-κB signaling. Moreover, 17-AAG was found to suppress PDGF-stimulated proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through induction of cell cycle arrest in the G1 phase. In conclusion, HSP90 inhibitor 17-AAG could improve pulmonary arteriole remodeling via inhibiting the excessive proliferation of PASMCs, and inhibition of HSP90 may represent a therapeutic avenue for the treatment of PAH.
PMID: 27472464 [PubMed - as supplied by publisher]
Royal jelly promotes DAF-16-mediated proteostasis to tolerate β-amyloid toxicity in C. elegans model of Alzheimer's disease.
Oncotarget. 2016 Jul 26;
Authors: Wang X, Cao M, Dong Y
Abstract
Numerous studies have demonstrated that dietary intervention may promote health and help prevent Alzheimer's disease (AD). We recently reported that bee products of royal jelly (RJ) and enzyme-treated royal jelly (eRJ) were potent to promote healthy aging in C. elegans. Here, we examined whether RJ/eRJ consumption may benefit to mitigate the AD symptom in the disease model of C. elegans. Our results showed that RJ/eRJ supplementation significantly delayed the body paralysis in AD worms, suggesting the β-amyloid (Aβ) toxicity attenuation effects of RJ/eRJ. Genetic analyses suggested that RJ/eRJ-mediated alleviation of Aβ toxicity in AD worms required DAF-16, rather than HSF-1 and SKN-1, in an insulin/IGF signaling dependent manner. Moreover, RJ/eRJ modulated the transactivity of DAF-16 and dramatically improved the protein solubility in aged worms. Given protein solubility is a hallmark of healthy proteostasis, our findings demonstrated that RJ/eRJ supplementation improved proteostasis, and this promotion depended on the transactivity of DAF-16. Collectively, the present study not only elucidated the possible anti-AD mechanism of RJ/eRJ, but also provided evidence from a practical point of view to shed light on the extensive correlation of proteostasis and the prevention of neurodegenerative disorders.
PMID: 27472466 [PubMed - as supplied by publisher]
Activation of proinflammatory signaling by 4-hydroxynonenal-Src adducts in aged kidneys.
Oncotarget. 2016 Jul 26;
Authors: Jang EJ, Kim DH, Lee B, Lee EK, Chung KW, Moon KM, Kim MJ, An HJ, Jeong JW, Kim YR, Yu BP, Chung HY
Abstract
In our previous study, reactive 4-hydroxy-2-nonenal (4-HNE) was shown to activate Src (a non-receptor tyrosine kinase) by forming an adduct on binding with a specific residue of Src, leading to the activation of proinflammatory signaling pathways in cultured cells. However, to date, the deleterious roles of 4-HNE in inflammatory signaling activation in kidneys during aging have not been explored. The purpose of the present study was to document the mechanisms by which 4-HNE induces inflammation in the kidney during aging. Initial experiments revealed that activated nuclear factor-κB (NF-κB) expression was caused by 4-HNE activation, which suppressed transcriptional activity in the aged kidney. Treatment of human umbilical vein endothelial cells with 4-HNE revealed that Src caused senescence via NF-κB activation. Furthermore, our immunohistochemistry data showed that 4-HNE-adducted Src significantly increased in aged kidney tissues. The data showed age-related upregulation of downstream signaling molecules such as mitogen activated protein kinases (MAPKs), activator protein-1 (AP-1), NF-κB, and COX-2 in a cell culture cell system.Taken together, the results of this study show that the formation of adducts between 4-HNE and Src activates inflammatory signaling pathways in the aged kidney, contributing to age-related nephropathy.
PMID: 27472463 [PubMed - as supplied by publisher]
Effective combination therapies in preclinical endocrine resistant breast cancer models harboring ER mutations.
Oncotarget. 2016 Jul 26;
Authors: Ladd B, Mazzola AM, Bihani T, Lai Z, Bradford J, Collins M, Barry E, Goeppert AU, Weir HM, Hearne K, Renshaw JG, Mohseni M, Hurt E, Jalla S, Bao H, Hollingsworth R, Reimer C, Zinda M, Fawell S, D'Cruz CM
Abstract
Although endocrine therapy is successfully used to treat patients with estrogen receptor (ER) positive breast cancer, a substantial proportion of this population will relapse. Several mechanisms of acquired resistance have been described including activation of the mTOR pathway, increased activity of CDK4 and activating mutations in ER. Using a patient derived xenograft model harboring a common activating ER ligand binding domain mutation (D538G), we evaluated several combinatorial strategies using the selective estrogen receptor degrader (SERD) fulvestrant in combination with chromatin modifying agents, and CDK4/6 and mTOR inhibitors. In this model, fulvestrant binds WT and MT ER, reduces ER protein levels, and downregulated ER target gene expression. Addition of JQ1 or vorinostat to fulvestrant resulted in tumor regression (41% and 22% regression, respectively) though no efficacy was seen when either agent was given alone. Interestingly, although the CDK4/6 inhibitor palbociclib and mTOR inhibitor everolimus were efficacious as monotherapies, long-term delayed tumor growth was only observed when co-administered with fulvestrant. This observation was consistent with a greater inhibition of compensatory signaling when palbociclib and everolimus were co-dosed with fulvestrant. The addition of fulvestrant to JQ1, vorinostat, everolimus and palbociclib also significantly reduced lung metastatic burden as compared to monotherapy. The combination potential of fulvestrant with palbociclib or everolimus were confirmed in an MCF7 CRISPR model harboring the Y537S ER activating mutation. Taken together, these data suggest that fulvestrant may have an important role in the treatment of ER positive breast cancer with acquired ER mutations.
PMID: 27472462 [PubMed - as supplied by publisher]
Novel function of MDA-9/Syntenin (SDCBP) as a regulator of survival and stemness in glioma stem cells.
Oncotarget. 2016 Jul 26;
Authors: Talukdar S, Das SK, Pradhan AK, Emdad L, Shen XN, Windle JJ, Sarkar D, Fisher PB
Abstract
Glioblastoma multiforme (GBM) is an aggressive cancer with current therapies only marginally impacting on patient survival. Glioma stem cells (GSCs), a subpopulation of highly tumorigenic cells, are considered major contributors to glioma progression and play seminal roles in therapy resistance, immune evasion and increased invasion. Despite clinical relevance, effective/selective therapeutic targeting strategies for GSCs do not exist, potentially due to the lack of a definitive understanding of key regulators of GSCs. Consequently, there is a pressing need to identify therapeutic targets and novel options to effectively target this therapy-resistant cell population. The precise roles of GSCs in governing GBM development, progression and prognosis are under intense scrutiny, but key upstream regulatory genes remain speculative. MDA-9/Syntenin (SDCBP), a scaffold protein, regulates tumor pathogenesis in multiple cancers. Highly aggressive cancers like GBM express elevated levels of MDA-9 and contain increased populations of GSCs. We now uncover a unique function of MDA-9 as a facilitator and determinant of glioma stemness and survival. Mechanistically, MDA-9 regulates multiple stemness genes (Nanog, Oct4 and Sox2) through activation of STAT3. MDA-9 controls survival of GSCs by activating the NOTCH1 pathway through phospho-Src and DLL1. Once activated, cleaved NOTCH1 regulates C-Myc expression through RBPJK, thereby facilitating GSC growth and proliferation. Knockdown of MDA-9 affects the NOTCH1/C-Myc and p-STAT3/Nanog pathways causing a loss of stemness and initiation of apoptosis in GSCs. Our data uncover a previously unidentified relationship between MDA-9 and GSCs, reinforcing relevance of this gene as a potential therapeutic target in GBM.
PMID: 27472461 [PubMed - as supplied by publisher]
EZH2-mediated Puma gene repression regulates non-small cell lung cancer cell proliferation and cisplatin-induced apoptosis.
Oncotarget. 2016 Jul 26;
Authors: Liu H, Li W, Yu X, Gao F, Duan Z, Ma X, Tan S, Yuan Y, Liu L, Wang J, Zhou X, Yang Y
Abstract
Polycomb group (PcG) proteins are highly conserved epigenetic effectors that maintain the silenced state of genes. EZH2 is the catalytic core and one of the most important components of the polycomb repressive complex 2 (PRC2). In non-small cell lung cancer (NSCLC) cells and primary lung tumors, we found that PRC2 components, including EZH2, are overexpressed. High levels of EZH2 protein were associated with worse overall survival rate in NSCLC patients. RNA interference mediated attenuation of EZH2 expression blunted the malignant phenotype in this setting, exerting inhibitory effects on cell proliferation, anchorage-independent growth, and tumor development in a xenograft mouse model. Unexpectedly, we discovered that, in the suppression of EZH2, p53 upregulated modulator of apoptosis (PUMA) expression was concomitantly induced. This is achieved through EZH2 directly binds to the Puma promoter thus epigenetic repression of PUMA expression. Furthermore, cisplatin-induced apoptosis of EZH2-knocking down NSCLC cells was elevated as a consequence of increased PUMA expression. Our work reveals a novel epigenetic regulatory mechanism controlling PUMA expression and suggests that EZH2 offers a candidate molecular target for NSCLC therapy and EZH2-regulated PUMA induction would synergistically increase the sensitivity to platinum agents in non-small cell lung cancers.
PMID: 27472460 [PubMed - as supplied by publisher]
Crosstalk among the proteome, lysine phosphorylation, and acetylation in romidepsin-treated colon cancer cells.
Oncotarget. 2016 Jul 26;
Authors: Wang TY, Chai YR, Jia YL, Gao JH, Peng XJ, Han HF
Abstract
Romidepsin (FK228) is one of the most promising histone-deacetylase inhibitors due to its potent antitumor activity, and has been used as a practical option for cancer therapy. However, FK228-induced changes in protein modifications and the crosstalk between different modifications has not been reported. To better understand the underlying mechanisms of FK228-related cancer therapy, we investigated the acetylome, phosphorylation, and crosstalk between modification datasets in colon cancer cells treated with FK228 by using stable-isotope labeling with amino acids in cell culture and affinity enrichment, followed by high-resolution liquid chromatography tandem mass spectrometry analysis. In total, 2728 protein groups, 1175 lysine-acetylation sites, and 4119 lysine-phosphorylation sites were quantified. When the quantification ratio thresholds were set to > 2.0 and < 0.5, respectively, a total of 115 and 38 lysine-acetylation sites in 85 and 32 proteins were quantified as increased and decreased targets, respectively, and 889 and 370 lysine-phosphorylation sites in 599 and 289 proteins were quantified as increased and decreased targets, respectively. Furthermore, we identified 274 proteins exhibiting both acetylation and phosphorylation modifications. These findings indicated possible involvement of these proteins in FK228-related treatment of colon cancer, and provided insight for further analysis of their biological function.
PMID: 27472459 [PubMed - as supplied by publisher]
Targeting XBP1-mediated β-catenin expression associated with bladder cancer with newly synthetic Oridonin analogues.
Oncotarget. 2016 Jul 27;
Authors: Chen W, Zhou J, Wu K, Huang J, Ding Y, Yun EJ, Wang B, Ding C, Hernandez E, Santoyo J, Chen H, Lin H, Sagalowsky A, He D, Zhou J, Hsieh JT
Abstract
Conventional chemotherapy is commonly used for advanced stages of transitional cell carcinoma (TCC) with modest success and high morbidity; however, TCC eventually develops resistance. Muscle invasive bladder cancer (MIBC) is recognized as a lethal disease due to its poor response to traditional chemotherapy. Numerous studies have implicated β-catenin, a critical effector in Wnt-mediated pathway associated with epithelial-mesenchymal transition and cancer stem cell, is involved in TCC progression, and furthermore closely associated with chemo-resistance. In this study, we discovered a novel natural product analogue CYD 6-17 that has a potent inhibitory effect on TCC cells exhibiting drug resistance to various chemotherapeutics, with an IC50 at nM range. Delivery of CYD 6-17 significantly inhibited the tumor growth using xenograft model but without detectable side effects. Mechanistically, it targeted β-catenin gene transcription by decreasing the binding of XBP1 to the promoter region, which appeared to be a new regulatory mechanism for β-catenin gene expression. Clinically, XBP1 expression correlated with the poor overall survival of patients. Overall, this study unveils unique mechanism of β-catenin gene regulation in advanced TCC and also offers a potential rational therapeutic regimen to MIBC.
PMID: 27472396 [PubMed - as supplied by publisher]
IGF-1R inhibition sensitizes breast cancer cells to ATM-Related Kinase (ATR) inhibitor and cisplatin.
Oncotarget. 2016 Jul 27;
Authors: O'Flanagan CH, O'Shea S, Lyons A, Fogarty FM, McCabe N, Kennedy RD, O'Connor R
Abstract
The complexity of the IGF-1 signalling axis is clearly a roadblock in targeting this receptor in cancer therapy. Here, we sought to identify mediators of resistance, and potential co-targets for IGF-1R inhibition. By using an siRNA functional screen with the IGF-1R tyrosine kinase inhibitor (TKI) BMS-754807 in MCF-7 cells we identified several genes encoding components of the DNA damage response (DDR) pathways as mediators of resistance to IGF-1R kinase inhibition. These included ATM and Ataxia Telangiectasia and RAD3-related kinase (ATR). We also observed a clear induction of DDR in cells that were exposed to IGF-1R TKIs (BMS-754807 and OSI-906) as indicated by accumulation of γ-H2AX, and phosphorylated Chk1. Combination of the IGF-1R/IR TKIs with an ATR kinase inhibitor VE-821 resulted in additive to synergistic cytotoxicity compared to either drug alone. In MCF-7 cells with stably acquired resistance to the IGF-1R TKI (MCF-7-R), DNA damage was also observed, and again, dual inhibition of the ATR kinase and IGF-1R/IR kinase resulted in synergistic cytotoxicity. Interestingly, dual inhibition of ATR and IGF-1R was more effective in MCF-7-R cells than parental cells. IGF-1R TKIs also potentiated the effects of cisplatin in a panel of breast cancer cell lines. Overall, our findings identify induction of DDR by IGF-1R kinase inhibition as a rationale for co-targeting the IGF-1R with ATR kinase inhibitors or cisplatin, particularly in cells with acquired resistance to TKIs.
PMID: 27472395 [PubMed - as supplied by publisher]
Role of SATB2 in human pancreatic cancer: Implications in transformation and a promising biomarker.
Oncotarget. 2016 Jul 27;
Authors: Yu W, Ma Y, Shankar S, Srivastava RK
Abstract
SATB2 (special AT-rich binding protein-2), a transcription factor and chromatin modulator, regulates the expression of genes required for maintaining pluripotency and self-renewal. The molecular mechanisms by which human pancreatic normal ductal epithelial cells are transformed to cancer cells are not well understood. The main goal of the paper is to examine the molecular mechanisms by which SATB2 regulates transformation of human pancreatic normal ductal epithelial (HPNE) cells, and assess whether transformed HPNE cells gained the phenotypes of cancer stem cells (CSCs). The results demonstrate that SATB2 is highly expressed in pancreatic CSCs, primary tissues and cell lines, but not in HPNE cells. SATB2 induces cellular transformation, stemness and epithelial to mesenchymal transition in HPNE cells, and inhibition of its expression suppresses these activities. Overexpression of SATB2 in HPNE cells resulted in induction of stem cell markers (CD44, CD24 and CD133), and transcription factors (Oct4, Sox2 and Nanog). SATB2 can directly bind to promoters of Bcl-2, Bsp, Nanog, c-Myc, XIAP, Klf4 and Hoxa2, suggesting the role of SATB2 in pluripotency, cell survival and proliferation. SATB2-overexpressing HPNE cells (HPNE/SATB2) formed tumors in Balb C nude mice, whereas HPNE/Empty vector cells did not form any tumor. Since SATB2 is highly expressed in human pancreatic cancer tissues and cell lines, but not in HPNE cells and normal pancreatic tissue, it can drive pancreatic cancer growth and metastasis. Our findings suggest that SATB2 can induce dedifferentiation by inducing stemness and may have a role in pancreatic carcinogenesis, and can be used as a diagnostic biomarker.
PMID: 27472393 [PubMed - as supplied by publisher]
c-CBL regulates melanoma proliferation, migration, invasion and the FAK-SRC-GRB2 nexus.
Oncotarget. 2016 Jul 27;
Authors: Nihal M, Wood GS
Abstract
Melanoma is one of the most aggressive and lethal forms of skin cancer. Despite recent improvements in targeted therapies, many patients with advanced disease fail to achieve lasting tumor regression. Therefore, it is important to develop novel druggable targets that can be exploited to improve clinical outcome. Here, we studied the role of Casitas B-lineage lymphoma (c-CBL), an E3 ubiquitin ligase, in human melanoma. Employing quantitative real-time PCR and Western blot analysis in a panel of human melanoma cell lines (A375, G361, Hs-294T, SK-Mel-2, SK-Mel-28 and 451Lu), we found that c-CBL is strongly expressed in human melanoma cells at the mRNA and protein levels. Further, we determined c-CBL levels in clinical samples of melanomas and benign melanocytic nevi, using quantitative Nuance multispectral imaging. Compared to benign nevi, melanomas showed an overlapping range of c-CBL immunoreactivity. Small interfering RNA (siRNA)-mediated knockdown of c-CBL resulted in decreased proliferation, clonogenic survival and migration of melanoma cells. Furthermore, it also resulted in decreased cellular invasion in a 3D spheroid assay system. C-CBL and FAK are regulated by SRC, and FAK binds SRC and GRB2. C-CBL E3 ligase domain regulates receptor tyrosine kinase internalization through ubiquitination and its ring finger domain stabilizes the FAK-SRC-actin cytoskeleton thereby promoting cellular motility. C-CBL knockdown was associated with decreased protein and/or mRNA levels of SRC, FAK and GRB2. Taken together, we have provided evidence that c-CBL plays a role in melanoma cell proliferation, migration and invasion as well as inhibition of the FAK-GRB2-SRC nexus. Our findings indicate that additional studies are warranted to further dissect the role of c-CBL in melanoma and determine the therapeutic potential of its inhibition.
PMID: 27472394 [PubMed - as supplied by publisher]
TRPC1/TRPC3 channels mediate lysophosphatidylcholine-induced apoptosis in cultured human coronary artery smooth muscles cells.
Oncotarget. 2016 Jul 26;
Authors: Wang Y, Wang Y, Li GR
Abstract
The earlier study showed that lysophosphatidylcholine (lysoPC) induced apoptosis in human coronary artery smooth muscle cells (SMCs); however, the related molecular mechanisms are not fully understood. The present study investigated how lysoPC induces apoptosis in cultured human coronary artery SMCs using cell viability assay, flow cytometry, confocal microscopy, and molecular biological approaches. We found that lysoPC reduced cell viability in human coronary artery SMCs by eliciting a remarkable Ca2+ influx. The effect was antagonized by La3+, SKF-96365, or Pyr3 as well as by silencing TRPC1 or TRPC3. Co-immunoprecipitation revealed that TRPC1 and TRPC3 had protein-protein interaction. Silencing TRPC1 or TRPC3 countered the lysoPC-induced increase of Ca2+ influx and apoptosis, and the pro-apoptotic proteins Bax and cleaved caspase-3 and decrease of the anti-apoptotic protein Bcl-2 and the survival kinase pAkt. These results demonstrate the novel information that TRPC1/TRPC3 channels mediate lysoPC-induced Ca2+ influx and apoptosis via activating the pro-apoptotic proteins Bax and cleaved caspase-3 and inhibiting the anti-apoptotic protein Bcl-2 and the survival kinase pAkt in human coronary artery SMCs, which implies that TRPC1/TRC3 channels may be the therapeutic target of lysoPC-induced disorders such as atherosclerosis.
PMID: 27472391 [PubMed - as supplied by publisher]
Acquired savolitinib resistance in non-small cell lung cancer arises via multiple mechanisms that converge on MET-independent mTOR and MYC activation.
Oncotarget. 2016 Jul 26;
Authors: Henry RE, Barry ER, Castriotta L, Ladd B, Markovets A, Beran G, Ren Y, Zhou F, Adam A, Zinda M, Reimer C, Qing W, Su W, Clark E, D'Cruz CM, Schuller AG
Abstract
Lung cancer is the most common cause of cancer death globally with a significant, unmet need for more efficacious treatments. The receptor tyrosine kinase MET has been implicated as an oncogene in numerous cancer subtypes, including non-small cell lung cancer (NSCLC). Here we explore the therapeutic potential of savolitinib (volitinib, AZD6094, HMPL-504), a potent and selective MET inhibitor, in NSCLC. In vitro, savolitinib inhibits MET phosphorylation with nanomolar potency, which correlates with blockade of PI3K/AKT and MAPK signaling as well as MYC down-regulation. In vivo, savolitinib causes inhibition of these pathways and significantly decreases growth of MET-dependent xenografts. To understand resistance mechanisms, we generated savolitinib resistance in MET-amplified NSCLC cell lines and analyzed individual clones. We found that upregulation of MYC and constitutive mTOR pathway activation is a conserved feature of resistant clones that can be overcome by knockdown of MYC or dual mTORC1/2 inhibition. Lastly, we demonstrate that mechanisms of resistance are heterogeneous, arising via a switch to EGFR dependence or by a requirement for PIM signaling. This work demonstrates the efficacy of savolitinib in NSCLC and characterizes acquired resistance, identifying both known and novel mechanisms that may inform combination strategies in the clinic.
PMID: 27472392 [PubMed - as supplied by publisher]
Prognostic significance of preoperative aspartate aminotransferase to neutrophil ratio index in patients with hepatocellular carcinoma after hepatic resection.
Oncotarget. 2016 Jul 26;
Authors: Ji F, Fu S, Guo Z, Pang H, Chen D, Wang X, Ju W, Wang D, He X, Hua Y, Peng B
Abstract
OBJECTIVES: Various inflammation-based prognostic scores have been associated with poor survival in patients with hepatocellular carcinoma (HCC), and neutrophils display important roles. However, few studies have illuminated the relationship between preoperative aspartate aminotransferase (AST) to neutrophil ratio index (ANRI) and poor prognosis of HCC. We aimed to clarify the prognostic value of ANRI and evaluate the ability of different inflammation-based prognostic scores such as ANRI, AST to lymphocyte ratio index (ALRI), AST to platelet count ratio index (APRI), neutrophil-lymphocyte ratio index (NLR), and platelet-lymphocyte ratio index (PLR).
METHODS: Data were collected retrospectively from 303 patients who underwent curative resection for HCC. Preoperative ANRI, ALRI, APRI, NLR, PLR and clinico-pathological variables were analyzed. Univariate, multivariate and Kaplan-Meier analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS).
RESULTS: ANRI was correlated with presence of HBsAg, AST, presence of cirrhosis, tumor size, PVTT, cancer of the liver Italian program (CLIP) score ,recurrence. Univariate analysis showed ANRI, ALRI, APRI, NLR, PLR were significantly associated with DFS and OS in HCC patients with curative resection. After multivariate analysis, ANRI was demonstrated to be superior to ALRI, APRI, NLR, PLR, which were independently correlated with DFS and OS. Survival analysis showed that preoperative ANRI > 7.8 predicted poor prognosis of patients with HCC after hepatectomy. preoperative ANRI also showed different prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of ANRI and NLR.
CONCLUSIONS: preoperative ANRI is an independent effective predictor of prognosis for patients with HCC, higher levels of ANRI predict poorer outcomes and the combining ANRI and NLR increases the prognostic accuracy of testing.
PMID: 27472390 [PubMed - as supplied by publisher]
Estimating Risk of Venous-Thromboembolic Events in Hospitalized Medical Patients: Comparison between 2008 and 2012 Guidelines.
Isr Med Assoc J. 2016 Jun;18(6):346-9
Authors: Oz N, Alon D, Chezar-Azerrad C, Cooper L, Levi Y, Fuchs S, Stein GY
Abstract
BACKGROUND: Prophylaxis for hospitalized venous-thromboembolic events (VTEs) is frequently underutilized, in part due to lack of a simple risk assessment model (RAM).
OBJECTIVES: To compare patient selection and administration of VTE prophylaxis according to the American College of Chest Physicians (ACCP) 2008 guidelines versus the newer 2012 guidelines, and assess the feasibility of developing simpler local RAMs.
METHODS: We conducted a prospective assessment of VTE risk among 300 unselected consecutive patients admitted to a medical hospital ward, using the 2008 and 2012 ACCP guidelines. The frequency and relative weight of each risk factor in the 2012 ACCP guidelines were used to develop a local VTE RAM.
RESULTS: VTE prophylaxis was indicated by the 2008 and 2012 ACCP guidelines in 40% and 42% of the cohort respectively, and was administered in 28% and 26% of eligible patients, respectively. Contraindication to VTE prophylaxis was found in 29% of patients according to both guidelines. In comparison to the 2008 guidelines, sensitivity and specificity of the 2012 guidelines were 96% and 88%, respectively. A local RAM based on the following concise score, comprising age, malignancy and immobility, correctly identified 99% of at-risk patients based on the 2012 guidelines, with a sensitivity and specificity of 98% and 95%, respectively.
CONCLUSIONS: Both guidelines performed to a similar degree and were poorly implemented in daily practice. A simplified RAM accurately identified the vast majority of these eligible patients. The development of local RAMs is feasible and may result in higher utilization rates.
PMID: 27468528 [PubMed - in process]
Using Advanced Imaging Methods to Study Neurolathyrism.
Isr Med Assoc J. 2016 Jun;18(6):341-5
Authors: Bick AS, Meiner Z, Gotkine M, Levin N
Abstract
BACKGROUND: Neurolathyrism is a toxic nutritional disorder caused by consumption of the grass pea, Lathyrus sativus. The disease, which manifests as an acute or insidiously evolving spastic paraparesis, continues to occur throughout Africa and Asia. Research on this disease is limited, and to our knowledge no imaging studies of patients with neurolathyrism have been published.
OBJECTIVES: To better localize the site of damage in neurolathyrism using advanced imaging methods.
METHODS: Three male patients, immigrants from Ethiopia, were included in the study. All had a history of arrested spastic paraparesis that had evolved before their emigration from Ethiopia, and a past history of exposure to grass pea without any other cause. Functional magnetic resonance imaging (fMRI) included simple motor tasks to evaluate cortical motor areas. Anatomic scans included diffusion tensor imaging (DTI) to evaluate the corticospinal tracts.
RESULTS: In all patients clear activation was found in motor regions, and the patients' activity pattern was qualitatively similar to that in control sublects. In one patient in whom clinical symptoms were asymmetric, an asymmetric activity pattern in Ml was identified. DTI analysis identified intact corticospinal tracts connecting the pons and the primary motor regions, similar to control subjects.
CONCLUSIONS: Advanced neuroimaging clearly identified well-functioning motor regions and tracts in neurolathyrism patients, suggesting a spinal etiology.
PMID: 27468527 [PubMed - in process]
'Open access' and the International Journal of Audiology.
Int J Audiol. 2016 Jul 29;:1-2
Authors:
PMID: 27472297 [PubMed - as supplied by publisher]
Gastrostomy Tube Weaning and Treatment of Severe Selective Eating in Childhood: Experience in Israel Using an Intensive Three Week Program.
Isr Med Assoc J. 2016 Jun;18(6):331-5
Authors: Shalem T, Fradkin A, Dunitz-Scheer M, Sadeh-Kon T, Goz-Gulik T, Fishler Y, Weiss B
Abstract
BACKGROUND: Children dependent on gastrostomy tube feeding and those with extremely selective eating comprise the most challenging groups of early childhood eating disorders. We established, for the first time in Israel, a 3 week intensive weaning and treatment program for these patients based on the "Graz model."
OBJECTIVES: To investigate the Graz model for tube weaning and for treating severe selective eating disorders in one center in Israel.
METHODS: Pre-program assessment of patients' suitability to participate was performed 3 months prior to the study, and a treatment goal was set for each patient. The program included a multidisciplinary outpatient or inpatient 3 week treatment course. The major outcome measures were achievement of the target goal of complete or partial tube weaning for those with tube dependency, and expansion of the child's nutritional diversity for those with selective eating.
RESULTS: Thirty-four children, 28 with tube dependency and 6 with selective eating, participated in four programs conducted over 24 months. Their mean age was 4.3 ± 0.37 years. Of all patients, 29 (85%) achieved the target goal (24 who were tube-dependent and 5 selective eaters). One patient was excluded due to aspiration pneumonia. After 6 months follow-up, 24 of 26 available patients (92%) maintained their target or improved.
CONCLUSIONS: This intensive 3 week program was highly effective in weaning children with gastrostomy tube dependency and ameliorating severe selective eating. Preliminary evaluation of the family is necessary for completion of the program and achieving the child's personal goal, as are an experienced multidisciplinary team and the appropriate hospital setup, i.e., inpatient or outpatient.
PMID: 27468525 [PubMed - in process]
Down-Regulation of Cardiac Erythropoietin Receptor and its Downstream Activated Signal Transducer Phospho-STAT-5 in a Rat Model of Chronic Kidney Disease.
Isr Med Assoc J. 2016 Jun;18(6):326-30
Authors: Hertzberg-Bigelman E, Barashi R, Levy R, Cohen L, Ben-Shoshan J, Keren G, Entin-Meer M
Abstract
BACKGROUND: Chronic kidney disease (CKD) is often accompanied by impairment of cardiac function that may lead to major cardiac events. Erythropoietin (EPO), a kidney-produced protein, was shown to be beneficial to heart function. It was suggested that reduced EPO secretion in CKD may play a role in the initiation of heart damage.
OBJECTIVES: To investigate molecular changes in the EPO/ erythropoietin receptor (EPO-R) axis in rat cardiomyocytes using a rat model for CKD.
METHODS: We established a rat model for CKD by kidney resection. Cardiac tissue sections were stained with Masson's trichrome to assess interstitial fibrosis indicating cardiac damage. To evaluate changes in the EPO/EPO-R signaling cascade in the myocardium we measured cardiac EPO and EPO-R as well as the phosphorylation levels of STAT-5, a downstream element in this cascade.
RESULTS: At 11 weeks after resection, animals presented severe renal failure reflected by reduced creatinine clearance, elevated blood urea nitrogen and presence of anemia. Histological analysis revealed enhanced fibrosis in cardiac sections of CKD animals compared to the sham controls. Parallel to these changes, we found that although cardiac EPO levels were similar in both groups, the expression of EPO-R and the activated form of its downstream protein STAT-5 were significantly lower in CKD animals.
CONCLUSIONS: CKD results in molecular changes in the EPO/EPO-R axis. These changes may play a role in early cardiac damage observed in the cardiorenal syndrome.
PMID: 27468524 [PubMed - in process]
Post-Infectious Glomerulonephritis in Pediatric Patients over Two Decades: Severity-Associated Features.
Isr Med Assoc J. 2016 Jun;18(6):336-40
Authors: Dagan R, Cleper R, Davidovits M, Sinai-Trieman L, Krause I
Abstract
BACKGROUND: The incidence of post-infectious glomerulonephritis (PIGN) has decreased over the last decades. As a result, recent epidemiological data from industrialized countries are scarce.
OBJECTIVES: To evaluate patterns of PIGN in children and detect possible predictors of disease severity.
METHODS: We collected clinical and laboratory data of patients with PIGN admitted to Schneider Children's Medical Center during 1994-2011. Diagnostic criteria included presence of hematuria with/without other features of nephritic syndrome along with hypocomplementemia and/or microbiological/serological evidence of streptococcal infection. Patients with other diseases (systemic lupus erythematosus, vasculitis, etc.) were excluded from the study.
RESULTS: A total of 125 patients with a mean age of 5.8 ± 3.3 years (range 1.5-17.6), of whom 16% were < 3 years, matched the study criteria. Presenting features included hypertension in 103 (82.4%) patients, azotemia in 87 (70.2%), fever in 49 (40/6), and elevated C-reactive protein in 75 (81.5%). Isolated macrohematuria was found in 21 (16%). Full-blown nephritic syndrome was diagnosed in 51 patients (41.1%) and 28 (22.9%) had nephritic syndrome with nephrotic-range proteinuria. Depressed C3 complement levels were associated with the presence of nephritic syndrome (OR 0.73, 95% CI 0.60-0.88, P = 0.001) as well as older age (OR 1.24, Cl 1.08-1.43, P = 0.001). At last follow-up (mean 42 months) all examined patients (100 of 125) had normal renal function, 6 had hypertension, and 1 had proteinuria.
CONCLUSIONS: PIGN remains an important cause of glomerular disease in children and may affect very young patients. Nephrotic-range proteinuria with hypoalbuminemia seems to be more frequent than previously reported. Hypocomplementemia is associated with a more severe disease course, namely, azotemia and nephritic syndrome.
PMID: 27468526 [PubMed - in process]
Standardised surveillance of Clostridium difficile infection in European acute care hospitals: a pilot study, 2013.
Euro Surveill. 2016 Jul 21;21(29)
Authors: van Dorp SM, Kinross P, Gastmeier P, Behnke M, Kola A, Delmée M, Pavelkovich A, Mentula S, Barbut F, Hajdu A, Ingebretsen A, Pituch H, Macovei IS, Jovanović M, Wiuff C, Schmid D, Olsen KE, Wilcox MH, Suetens C, Kuijper EJ, European Clostridium difficile Infection Surveillance Network (ECDIS-Net) on behalf of all participants
Abstract
Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a 'minimal' option (aggregated hospital data), a 'light' option (including patient data for CDI cases) and an 'enhanced' option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe.
PMID: 27472820 [PubMed - as supplied by publisher]
Do 18F-FDG PET/CT findings have a relationship with histopathological and immunohistochemical factors of breast cancer in men?
Nucl Med Commun. 2016 Jul 28;
Authors: Vatankulu B, Işik G, Kocael P, Kuyumcu S, Ilvan Ş, Sağer S, Halaç M, Türkmen C, Sönmezoğlu K
Abstract
PURPOSE: We aimed to investigate the relationship between histopathological and immunohistochemical features of male breast cancer (MBC) and comprehensive fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) parameters.
METHODS: Fifteen male patients with newly diagnosed breast cancer who underwent F-FDG PET/CT were included in the study. Maximum and average standardized uptake value (SUVmax and SUVavg), metabolic total volume, and total lesion glycolysis (TLG) were compared with the histopathological and immunohistochemical findings of patients. In addition, metabolic tumor-node-metastases (TNM) staging was performed following the determination of metastatic axillary lymph nodes and tumor size by F-FDG PET/CT and verified by histopathological evaluation.
RESULTS: There were no significant differences between all groups classified on the basis of histopathological and immunohistochemical parameters for SUVmax, SUVavg, TLG, and metabolic total volume. The only difference was found in patients with distant metastases and stage IV. SUVmax, SUVavg, and TLG were higher in patients with distant metastases compared with patients without distant metastases (P: 0.005, 0.011, and 0.042, respectively). Strong correlations were found between metabolic TNM staging and histopathological TNM staging (for T stage; r: 0.590, P: 0.021, N stage; r: 0.694, P: 0.002, TNM stage; r: 0.835, P: 0.002). In addition, no differences were found with any metabolic F-FDG PET/CT parameters in survival.
CONCLUSION: Although no correlation was found between metabolic parameters and groups categorized on the basis of histopathological or immunohistochemical features, F-FDG PET/CT is a reliable imaging modality to determine tumor size, axillary lymph node involvement, and metabolic TNM staging of MBC. In addition, none of those metabolic F-FDG PET/CT parameters predicted survival in MBC.
PMID: 27472037 [PubMed - as supplied by publisher]
Advances in Digitalized Preoperative Templating in Orthopedic Surgery.
Isr Med Assoc J. 2016 Jun;18(6):365
Authors: Robinson D
PMID: 27468533 [PubMed - in process]
Olfactory Impairment in Chronic Rhinosinusitis Using Threshold, Discrimination, and Identification Scores.
Chem Senses. 2016 Jul 28;
Authors: Soler ZM, Kohli P, Storck KA, Schlosser RJ
Abstract
Differences in testing modalities and cut-points used to define olfactory dysfunction contribute to the wide variability in estimating the prevalence of olfactory dysfunction in chronic rhinosinusitis (CRS). The aim of this study is to report the prevalence of olfactory impairment using each component of the Sniffin' Sticks test (threshold, discrimination, identification, and total score) with age-adjusted and ideal cut-points from normative populations. Patients meeting diagnostic criteria for CRS were enrolled from rhinology clinics at a tertiary academic center. Olfaction was assessed using the Sniffin' Sticks test. The study population consisted of 110 patients. The prevalence of normosmia, hyposmia, and anosmia using total Sniffin' Sticks score was 41.8%, 20.0%, and 38.2% using age-appropriate cut-points and 20.9%, 40.9%, and 38.2% using ideal cut-points. Olfactory impairment estimates for each dimension mirrored these findings, with threshold yielding the highest values. Threshold, discrimination, and identification were also found to be significantly correlated to each other (P < 0.001). In addition, computed tomography scores, asthma, allergy, and diabetes were found to be associated with olfactory dysfunction. In conclusion, the prevalence of olfactory dysfunction is dependent upon olfactory dimension and if age-adjusted cut-points are used. The method of olfactory testing should be chosen based upon specific clinical and research goals.
PMID: 27469973 [PubMed - as supplied by publisher]
This study investigated chewing function in elderly individuals with Alzheimer’s disease (AD) and correlated chewing function with cognitive status.
Sixteen elderly individuals with mild AD (mean age 76.7 ± 6.3 years; 8 men, 8 women) and 16 age and gender-matched healthy controls (mean age 75.23 ± 4.4 years; 8 men, 8 women) were included in this study. All volunteers wore removable prostheses: 11 were totally edentulous and five were partially edentulous in each group. Chewing function was evaluated via masticatory performance (MP) using Optocal chewable test material and a sieve fractionation method. Cognitive functioning was assessed by the Mini Mental State Exam (MMSE), administered by a trained examiner. Data were analyzed by non-paired t test and Pearson’s correlation with α = 0.05.
Compared to controls, mild AD patients had decreased MP (P < 0.01) and MMSE (P = 0.01). MP showed a moderate negative correlation with MMSE (r = −0.69).
Mild AD was associated with impaired chewing function.
Knowledge that mild AD has an impact on chewing is important for dental professionals in decision-making related to prosthetics and general dental treatment.
This study investigated chewing function in elderly individuals with Alzheimer's disease (AD) and correlated chewing function with cognitive status.
Sixteen elderly individuals with mild AD (mean age 76.7 ± 6.3 years; 8 men, 8 women) and 16 age and gender-matched healthy controls (mean age 75.23 ± 4.4 years; 8 men, 8 women) were included in this study. All volunteers wore removable prostheses: 11 were totally edentulous and five were partially edentulous in each group. Chewing function was evaluated via masticatory performance (MP) using Optocal chewable test material and a sieve fractionation method. Cognitive functioning was assessed by the Mini Mental State Exam (MMSE), administered by a trained examiner. Data were analyzed by non-paired t test and Pearson's correlation with α = 0.05.
Compared to controls, mild AD patients had decreased MP (P < 0.01) and MMSE (P = 0.01). MP showed a moderate negative correlation with MMSE (r = −0.69).
Mild AD was associated with impaired chewing function.
Knowledge that mild AD has an impact on chewing is important for dental professionals in decision-making related to prosthetics and general dental treatment.
| Related Articles |
Microscopic Chain Motion in Polymer Nanocomposites with Dynamically Asymmetric Interphases.
Sci Rep. 2016;6:29326
Authors: Senses E, Faraone A, Akcora P
Abstract
Dynamics of the interphase region between matrix and bound polymers on nanoparticles is important to understand the macroscopic rheological properties of nanocomposites. Here, we present neutron scattering investigations on nanocomposites with dynamically asymmetric interphases formed by a high-glass transition temperature polymer, poly(methyl methacrylate), adsorbed on nanoparticles and a low-glass transition temperature miscible matrix, poly(ethylene oxide). By taking advantage of selective isotope labeling of the chains, we studied the role of interfacial polymer on segmental and collective dynamics of the matrix chains from subnanoseconds to 100 nanoseconds. Our results show that the Rouse relaxation remains unchanged in a weakly attractive composite system while the dynamics significantly slows down in a strongly attractive composite. More importantly, the chains disentangle with a remarkable increase of the reptation tube size when the bound polymer is vitreous. The glassy and rubbery states of the bound polymer as temperature changes underpin the macroscopic stiffening of nanocomposites.
PMID: 27457056 [PubMed - in process]
Spindle cell hemangioma (SCH) is an uncommon benign vascular tumor that rarely occurs in the mouth.
We present an SCH arising in the tongue of a 52-year-old otherwise healthy woman. SCH should be considered in the differential diagnosis of vascular tumors in the oral cavity and not misinterpreted as a more aggressive vascular tumor. We describe the clinical presentation, investigation, differential diagnosis and management of this condition and a literature search showing published case reports.
Although SCH rarely presents in the oral cavity it needs to be considered in the differential diagnosis of oral cavity tumors.
We report the case of patient with fungal skull base osteomyelitis cured by sustained antifungal therapy after 16 months of debilitating illness. Due to medical complications, a strong clinical rationale was needed to justify long‐term antifungal therapy. The offending fungus was identified by experimental molecular technology (Ibis T5000 universal biosensor); invasive fungal disease was corroborated by biochemical assays. Our discussion will help familiarize the otolaryngologist with existing biochemical and molecular diagnostics for invasive fungal disease. We encourage future investigators to study their application in cases of skull base osteomyelitis. Laryngoscope, 2016 (Source: The Laryngoscope)
http://ift.tt/2a1aCLj
http://ift.tt/2aihVOa
Hand, Foot, and Mouth Disease (HFMD) is a contagious illness most commonly occurring in children 5 years old or younger. The most common cause of HFMD in the United States is Coxsackievirus A16. HFMD is uncommon in adults, and may show other atypical features including a broader spectrum of cutaneous involvement and a greater degree of severity.
We evaluated the clinical, histopathologic, and molecular features of three cases of atypical HFMD occurring in adults.
All three cases showed clinical features that were worrisome for erythema multiforme or a disseminated herpesvirus infection. The histopathologic findings were quite uniform, and showed intraepidermal vesiculation with a predominantly neutrophil-rich infiltrate. A characteristic feature was the specific involvement of the upper stratum spinosum and stratum granulosum, with relative sparing of the stratum corneum. In none of the cases was there evidence of herpesvirus. Molecular analysis performed on two of the cases showed involvement by Coxsackievirus A6, an uncommon serotype in HFMD. All three cases resolved spontaneously.
Atypical Hand, Foot, and Mouth Disease associated with Coxsackievirus A6 represents an uncommon and potentially diagnostically challenging cutaneous eruption. Its recognition is critical to avoid unneeded therapy and to establish accurate prognostic expectations.
| Related Articles |
Comparison of microendoscopic discectomy system and anterior open approach in treatment of unstable odontoid fracture with cannulated screw internal fixation.
Acta Orthop Belg. 2014 Dec;80(4):529-36
Authors: Lin B, Lu C, Yu H, Zhang W, Yang W
Abstract
This study intended to investigate the safety and efficacy of microendoscopic discectomy system compared with anterior open approach in the treatment of odontoid fracture with cannulated screw internal fiation. Thirty-two patients (25 male and 7 female) were enrolled and randomly assigned to different treatments. 15 patients were treated with microendoscopic discectomy system (Group MED) and 17 patients were treated with anterior open approach (Group AOA). The operating time, volume of blood loss, occurrence of complications, and fracture healing rate were compared. In Group MED, the mean operating time and blood loss volume were significant lower than those in Group AOA (P < 0.05). Nevertheless, all patients in both groups obtained bony union and cervical range of motion without significant difference statistically (P > 0.05). Three patients in Group AOA complained of transient dysphagia. We concluded that microendoscopic discectomy system for odontoid fracture treatment with cannulated screw is a safe, reliable and minimal invasive procedure compared with traditional open surgery.
PMID: 26280726 [PubMed - indexed for MEDLINE]
Spindle cell hemangioma (SCH) is an uncommon benign vascular tumor that rarely occurs in the mouth.
We present an SCH arising in the tongue of a 52-year-old otherwise healthy woman. SCH should be considered in the differential diagnosis of vascular tumors in the oral cavity and not misinterpreted as a more aggressive vascular tumor. We describe the clinical presentation, investigation, differential diagnosis and management of this condition and a literature search showing published case reports.
Although SCH rarely presents in the oral cavity it needs to be considered in the differential diagnosis of oral cavity tumors.
British Dental Journal 221, 71 (2016). doi:10.1038/sj.bdj.2016.526
Authors: T. Renton & W. Sabbah
British Dental Journal 221, 49 (2016). doi:10.1038/sj.bdj.2016.512
Author: A. Holden
British Dental Journal 221, 49 (2016). doi:10.1038/sj.bdj.2016.513
Authors: P. V. Mc Crory & A. V. Jacobs
British Dental Journal 221, 94 (2016). doi:10.1038/sj.bdj.2016.534
British Dental Journal 221, 93 (2016). doi:10.1038/sj.bdj.2016.530
British Dental Journal 221, 50 (2016). doi:10.1038/sj.bdj.2016.514
Authors: K Kukuła & P Plakwicz
British Dental Journal 221, 95 (2016). doi:10.1038/sj.bdj.2016.538
British Dental Journal 221, 87 (2016). doi:10.1038/sj.bdj.2016.528
Authors: M. Bifulco, M. Amato, G. Gangemi, M. Marasco, M. Caggiano, A. Amato & S. Pisanti
British Dental Journal 221, 51 (2016). doi:10.1038/sj.bdj.2016.515
Author: H. Nazir
British Dental Journal 221, 53 (2016). doi:10.1038/sj.bdj.2016.516
British Dental Journal 221, 94 (2016). doi:10.1038/sj.bdj.2016.532
British Dental Journal 221, 53 (2016). doi:10.1038/sj.bdj.2016.517
British Dental Journal 221, 95 (2016). doi:10.1038/sj.bdj.2016.536
British Dental Journal 221, 53 (2016). doi:10.1038/sj.bdj.2016.518
| Related Articles |
Do probiotics have a role in the treatment of allergic rhinitis?: A comprehensive systematic review and meta analysis.
Am J Rhinol Allergy. 2016 Jul 20;
Authors: Guvenc IA, Muluk NB, Mutlu FS, Eski E, Altintoprak N, Oktemer T, Cingi C
Abstract
OBJECTIVE: To investigate clinical evidence for the efficacy of probiotics in the treatment of allergic rhinitis (AR).
METHODS: A systematic search was conducted to review the results of all randomized, double-blind, placebo-controlled trials by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. Primary outcome measurements were total nasal and ocular symptom scores (SS) and quality of life (QoL) questionnaires. Secondary outcome measurements were individual nasal SS and immunologic parameters.
RESULTS: Twenty-two randomized, double-blind, placebo-controlled studies were included. Seventeen trials showed significant benefit of probiotics clinically, whereas eight trials showed significant improvement in immunologic parameters compared with placebo. All five studies with Lactobacillus paracasei (LP) strains demonstrated clinically significant improvements compared with placebo. Probiotics showed significant reduction in nasal and ocular SS (standardized mean difference [SMD], -1.23, p < 0.001; and SMD, -1.84, p < 0.001; respectively), total, nasal, and ocular QoL scores compared with placebo (SMD, -1.84, p < 0.001; SMD, -2.30, p = 0.006; and SMD, -3.11, p = 0.005; respectively). Although heterogeneity was high, in subgroup analysis, SMD for total nasal and ocular symptoms with patients with seasonal AR and for nasal QoL scores for studies with LP-33 strain were significant and homogenous. Scores of nasal blockage, rhinorrhea, and nasal itching were significantly lower in the probiotic group compared with placebo. The meta-analysis studies SS the Japanese guidelines revealed a significant, homogenous SMD score of -0.34 for individual nasal SS, above the minimal important clinical difference value of 0.3. The T-helper 1 to T-helper 2 ratio was significantly lower in the probiotic group compared with placebo (SMD,-0.78; p = 0.045).
CONCLUSION: Despite high variability among the studies, synthesis of available data provided significant evidence of beneficial clinical and immunologic effects of probiotics in the treatment of AR, especially with seasonal AR and LP-33 strains. With the rising pool of studies, the most promising strains in specific allergies can be revealed and adjuvant therapy with probiotics can be recommended for the treatment of AR.
PMID: 27442711 [PubMed - as supplied by publisher]
