John Hopkins Medical Institutions
John Hopkins Medical Institutions
Weeks K.R.,University of Baltimore |
Goeschel C.A.,University of Baltimore |
Cosgrove S.E.,John Hopkins Medical Institutions |
Romig M.,University of Baltimore |
Berenholtz S.M.,University of Baltimore
Current Infectious Disease Reports | Year: 2011
Central line-associated blood stream infections (CLABSI) are among the most common, lethal, and costly health care-associated infections. Recent large collaborative quality improvement efforts have achieved unprecedented and sustained reductions in CLABSI rates and demonstrate that these infections are largely preventable, even for exceedingly ill patients. The broad acceptance that zero CLABSI rates are an achievable goal has motivated and stimulated diverse groups of stakeholders, including public and private groups to develop policy tools and to mobilize their local constituents toward achieving this goal. Nevertheless, attributing reductions in CLABSI rates achieved by multifaceted quality improvement efforts solely to the use of checklists to ensure adherence with appropriate infection control practices is an easily made but crucial mistake. National CLABSI prevention is a shared responsibility and creating novel partnerships between government agencies, health care industry, and consumers is critical to making and sustaining progress in achieving the goals toward eliminating CLABSI. © 2011 Springer Science+Business Media, LLC.
Arber D.A.,Stanford University |
Orazi A.,New York Medical College |
Hasserjian R.,Massachusetts General Hospital |
Thiele J.,University of Cologne |
And 5 more authors.
Blood | Year: 2016
The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. Since then, there have been numerous advances in the identification of unique biomarkers associated with some myeloid neoplasms and acute leukemias, largely derived from gene expression analysis and next-generation sequencing that can significantly improve the diagnostic criteria as well as the prognostic relevance of entities currently included in the WHO classification and that also suggest new entities that should be added. Therefore, there is a clear need for a revision to the current classification. The revisions to the categories of myeloid neoplasms and acute leukemia will be published in a monograph in 2016 and reflect a consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists. The 2016 edition represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. The major changes in the classification and their rationale are presented here. © 2016 by The American Society of Hematology.
PubMed | University of Cologne, University of Chicago, Stanford University, University of Pavia and 4 more.
Type: Journal Article | Journal: Blood | Year: 2016
The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. Since then, there have been numerous advances in the identification of unique biomarkers associated with some myeloid neoplasms and acute leukemias, largely derived from gene expression analysis and next-generation sequencing that can significantly improve the diagnostic criteria as well as the prognostic relevance of entities currently included in the WHO classification and that also suggest new entities that should be added. Therefore, there is a clear need for a revision to the current classification. The revisions to the categories of myeloid neoplasms and acute leukemia will be published in a monograph in 2016 and reflect a consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists. The 2016 edition represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. The major changes in the classification and their rationale are presented here.
Kaur J.,All India Institute of Medical Sciences |
Demokan S.,Johns Hopkins Medical Institutions |
Tripathi S.C.,All India Institute of Medical Sciences |
MacHa M.A.,All India Institute of Medical Sciences |
And 7 more authors.
International Journal of Cancer | Year: 2010
We evaluated promoter hypermethylation of a panel of tumor suppressor genes as a means to detect epigenetic alterations in oral squamous cell carcinomas (OSCC) of Indian-origin and compare with North-American head and neck squamous cell carcinomas (HNSCC). Quantitative-methylation-specific PCR was used to investigate the promoter methylation status of DCC, EDNRB, p16INK4a and KIF1A in 92 OSCC, and compared to 48 paired normal tissues and 30 saliva and sera samples from healthy control subjects. Aberrant methylation of at-least one of these genes was detected in 74/92 (80.4%) OSCC; 72.8% at EDNRB, 71.7% at KIF1A, 47.8% at p16INK4a and 58.7% at DCC; and in 5 of 48 (10.4%) normal oral tissues. None of the saliva and sera samples from controls exhibited DNA methylation in these four target genes. Thirty-two of 72 node positive cases harbored p16INK4a and DCC hypermethylation (p = 0.005). Thus, promoter hypermethylation in genes analyzed herein is a common event in Indian OSCC and may represent promising markers for the molecular staging of OSCC patients. We found higher frequency of p16INK4a methylation (47.8%) in this Indian cohort in comparison with a North-American cohort (37.5%). In conclusion, aberrant methylation of EDNRB, KIF1A, DCC and p16INK4a genes is a common event in Indian OSCC, suggesting that epigenetic alterations of these genes warrant validation in larger studies for their potential use as biomarkers. © 2010 UICC.
Streppel M.M.,Johns Hopkins Medical Institutions |
Streppel M.M.,University Utrecht |
Lata S.,Stanley Institute for Cognitive Genomics |
Delabastide M.,Stanley Institute for Cognitive Genomics |
And 13 more authors.
Oncogene | Year: 2014
The incidence of Barrett's esophagus (BE)-associated esophageal adenocarcinoma (EAC) is increasing. Next-generation sequencing (NGS) provides an unprecedented opportunity to uncover genomic alterations during BE pathogenesis and progression to EAC, but treatment-naive surgical specimens are scarce. The objective of this study was to establish the feasibility of using widely available endoscopic mucosal biopsies for successful NGS, using samples obtained from a BE 'progressor'. Paired-end whole-genome NGS was performed on the Illumina platform using libraries generated from mucosal biopsies of normal squamous epithelium (NSE), BE and EAC obtained from a patient who progressed to adenocarcinoma during endoscopic surveillance. Selective validation studies, including Sanger sequencing, immunohistochemistry and functional assays, were performed to confirm the NGS findings. NGS identified somatic nonsense mutations of AT-rich interactive domain 1A (SWI like) (ARID1A) and PPIE and an additional 37 missense mutations in BE and/or EAC, which were confirmed by Sanger sequencing. ARID1A mutations were detected in 15% (3/20) high-grade dysplasia (HGD)/EAC patients. Immunohistochemistry performed on an independent archival cohort demonstrated ARID1A protein loss in 0% (0/76), 4.9% (2/40), 14.3% (4/28), 16.0% (8/50) and 12.2% (12/98) of NSE, BE, low-grade dysplasia, HGD and EAC tissues, respectively, and was inversely associated with nuclear p53 accumulation (P=0.028). Enhanced cell growth, proliferation and invasion were observed on ARID1A knockdown in EAC cells. In addition, genes downstream of ARID1A that potentially contribute to the ARID1A knockdown phenotype were identified. Our studies establish the feasibility of using mucosal biopsies for NGS, which should enable the comparative analysis of larger 'progressor' versus 'non-progressor' cohorts. Further, we identify ARID1A as a novel tumor-suppressor gene in BE pathogenesis, reiterating the importance of aberrant chromatin in the metaplasia-dysplasia sequence. © 2014 Macmillan Publishers Limited.
Priyadarshini D.,National Institute of Virology |
Gadia R.R.,King Edward Memorial Hospital |
Tripathy A.,National Institute of Virology |
Gurukumar K.R.,National Institute of Virology |
And 6 more authors.
PLoS ONE | Year: 2010
Background:Descriptions of dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from Pune, Western India, with respect to clinical profile and pro-inflammatory cytokines. Methodology/Principal Findings:In 2005, 372 clinically suspected dengue cases were tested by MAC-ELISA and RT-PCR for dengue virus (DENV) aetiology. The clinical profile was recorded at the hospital. Circulating levels of IFN-γ, TNF-α, IL-6, and IL-8 were assessed by ELISA and secondary infections were defined by IgM to IgG ratio. Statistical analysis was carried out using the SPSS 11.0 version. Of the 372 individuals, 221 were confirmed to be dengue cases. Three serotypes, DENV-1, 2 and 3 were co-circulating and one case of dual infection was identified. Of 221 cases, 159 presented with Dengue fever (DF) and 62 with Dengue hemorrhagic fever (DHF) of which six had severe DHF and one died of shock. There was a strong association of rash, abdominal pain and conjunctival congestion with DHF. Levels of IFN-γ were higher in DF whereas IL-6 and IL-8 were higher in DHF cases (p<0.05). The mean levels of the three cytokines were higher in secondary compared to primary infections. Levels of IFN-γ and IL-8 were higher in early samples collected 2-5 days after onset than late samples collected 6-15 days after onset. IFN-γ showed significant decreasing time trend (p = 0.005) and IL-8 levels showed increasing trend towards significance in DHF cases (interaction p = 0.059). There was a significant association of IL-8 levels with thrombocytopenia and both IFN-γ and IL-8 were positively associated with alanine transaminase levels. Conclusions/Significance:Rash, abdominal pain and conjunctival congestion could be prognostic symptoms for DHF. High levels of IL-6 and IL-8 were shown to associate with DHF. The time trend of IFN-γ and IL-8 levels had greater significance than absolute values in DHF pathogenesis. © 2010 Priyadarshini et al.
Chen Z.,Wake forest University |
Greenwood C.,Lady Davis Institute for Medical Research |
Greenwood C.,McGill University |
Isaacs W.B.,John Hopkins Medical Institutions |
And 5 more authors.
Carcinogenesis | Year: 2013
A novel rare mutation, homeobox B13 (HOXB13) G84E, was reported to co-segregate with prostate cancer (PCa) in hereditary PCa families and associate with PCa risk in unrelated cases and controls. In this study, we aim to compare the G84E mutation frequency among subjects of different races/ethnicities from various geographic regions in the world and to assess its risk for developing PCa, in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial. All the 3508 subjects had initial negative prostate biopsy and were biopsied at Year 2 and 4 for detection of PCa. The G84E mutation was detected only in Caucasians, with the highest carrier frequency in Northern Europe (1.06%), followed by Western Europe (0.60%) and North America (0.31%). No mutation carrier was observed in Southern Europe, Eastern Europe, Latin America, Australia and South Africa. In Caucasians, the G84E mutation frequency was 0.99% and 0.24% in positive and negative biopsy subjects, respectively (P = 0.01). In positive biopsy subjects, the frequency was significantly higher in subjects with a positive family history than those without (4.31% versus 0.34%, P = 0.002). In the 4 year follow-up, the PCa detection rate was 53.8% among the 13 mutation carriers and 22.0% among 3186 non-carriers, relative risk = 2.45 (95% confidence interval: 1.48-4.07). All mutation carriers shared a common haplotype, suggesting a founder effect. In Finland, the G84E mutation was estimated to occur in the year 1792 (95% credible interval: 1735-1831). In conclusion, the G84E mutation of HOXB13, a relatively recent mutation that likely occurred in Northern Europe, significantly increases risk for PCa. © The Author 2013. Published by Oxford University Press. All rights reserved.
El-Naggar A.K.,University of Houston |
Westra W.H.,John Hopkins Medical Institutions
Head and Neck | Year: 2012
Recent studies of oropharyngeal carcinoma have reported remarkable correlation between integrated human papillomavirus (HPV) viral detection and p16 protein overexpression in tumor cells. These findings led to calls for the substitution of p16 expression for the more demanding HPV testing in clinical practice. The rationale for such practice is largely driven by the simplicity, low cost, and the feasibility of the immunohistochemical (IHC) analysis. There are, however, several caveats that need to be fully considered. These include the subjective nature of IHC evaluation, the variable mechanisms of p16 expression in head and neck squamous cell carcinoma, and the lack of scoring and interpretive criteria. This perspective addresses the conceptual and practical issues associated with the p16 expression analysis and provides a broad outline for its application and evaluation in patients with oropharyngeal carcinoma. Copyright © 2011 Wiley Periodicals, Inc.
Gemmete J.J.,University of Michigan |
Chaudhary N.,University of Michigan |
Pandey A.,University of Michigan |
Gandhi D.,John Hopkins Medical Institutions |
And 4 more authors.
American Journal of Neuroradiology | Year: 2010
BACKGROUND AND PURPOSE: Few reports have described the embolization of head and neck lesions by using direct percutaneous techniques. We report our preliminary experience in the direct percutaneous embolization of hypervascular head and neck tumors by using Onyx in conjunction with standard endovascular embolization techniques. We describe the technical aspects of the procedure and its efficacy in reducing intraoperative blood loss. MATERIALS AND METHODS: We retrospectively studied 14 patients (3 females and 11 males; mean age, 33.4 years; range, 11-56 years) with 15 hypervascular tumors of the head and neck that underwent direct percutaneous embolization with Onyx in conjunction with particulate embolization. Nine paragangliomas and 6 JNAs underwent treatment. Documented blood loss was obtained from operative reports in these 15 patients with surgical resection performed 24-48 hours after the embolization. RESULTS: Intratumoral penetration with progressive blood flow stasis was achieved during each injection. A mean of 3.1 needles (20-gauge, 3.5-inch spinal needle) were placed percutaneously into the lesion (range, 1-6). The mean intraoperative blood loss was 780 mL (range, <50-2200 mL). Near total angiographic devascularization was achieved in 13 of 15 tumors. There were no local complications or neurologic deficits from the percutaneous access or embolization of these hypervascular tumors. CONCLUSIONS: In this study, the use of percutaneous injected Onyx in conjunction with standard endovascular embolization techniques in patients with hypervascular head and neck tumors seemed to enhance the ability to devascularize these tumors before operative removal.
Epstein J.I.,John Hopkins Medical Institutions |
Egevad L.,Yale University |
Humphrey P.A.,Karolinska University Hospital |
Montironi R.,Marche Polytechnic University
American Journal of Surgical Pathology | Year: 2014
The following are the International Society of Urological Pathology (ISUP) recommendations for the use of immunohistochemistry (IHC) in prostate specimens. Either high-molecular weight cytokeratin (34βE12 or CK5/6 or others) or p63 or a combination of the 2 with AMACR either in a double or triple cocktail is recommended for the workup of small foci of atypical glands suspicious for adenocarcinoma of the prostate (PCa). ERG is optional as it is present in only 40% to 50% of prostate cancers and also positive in high-grade prostatic intraepithelial neoplasia. In the setting of obvious carcinoma or benign glands, there is no justification to do basal cell stains and AMACR. If there is a Gleason score of 3+4=7 or a higher-grade cancer on at least 1 part, the workup of other parts with an atypical focus suspicious for Gleason score 3+3=6 cancer is not recommended. In the setting of Gleason score 4+3 or 4+4=8 cancer on at least 1 part, the extent of high-grade cancer could affect clinical treatment such that workup of other atypical possible high-grade cancer foci is justified. In the setting of Gleason score 4+3 or higher-grade cancer on at least 1 part, given that intraductal carcinoma in the vast majority of cases is considered extension of high-grade cancer into prostatic ducts and acini, it is not recommended in the setting of definitive invasive high-grade cancer that workup of additional cribriform lesions be pursued. In the setting of Gleason score 3+3 on at least 1 part, the number of positive cores and/or their location could possibly affect subsequent therapy in terms of suitability for active surveillance or focal therapy, such that unless one knows with certainty that it would not affect therapy, it is justified to perform an IHC workup of additional atypical foci. In the differential diagnosis of high-grade PCa versus urothelial carcinoma (UC), the primary option is to use prostate-specific antigen (PSA) as a first test to identify PCa and GATA3 to identify UC. If GATA3 is not available, then HMWCK and p63 can be used. If the tumor is PSA positive with intense staining and HMWCK and p63 negative, the findings are diagnostic of PCa. If the tumor is equivocal/weak/negative for PSA and negative/focal for p63 and HMWCK, then one needs to perform staining for P501S, NKX3.1, and GATA3. Some experts also include PAP in this second round of staining. If the tumor is negative for PSA and diffusely strongly positive for p63 and HMWCK, the findings are diagnostic of UC. If the tumor is negative for PSA and moderately to strongly positive for GATA3, it is diagnostic of UC. Laboratories should be encouraged to use GATA3 for UC and add P501S and NKX3.1 as prostate markers in addition to PSA, p63, and HMWCK. If GATA3, p501S, and NKX3.1 are not available in equivocal cases, the case should be sent out for consultation to laboratories with these antibodies. The article also covers the use of IHC in: (1) high-grade PCa versus bladder adenocarcinoma; (2) prostatic small cell carcinoma versus high-grade PCa; (3) metastatic carcinoma of unknown primary: rule out PCa; (4) nonspecific granulomatous prostatitis/xanthoma versus high-grade PCa; (5) adult prostate sarcoma versus sarcomatoid PCa; (6) colorectal adenocarcinoma versus high-grade PCa; and (7) prognostic IHC markers. © 2014 by Lippincott Williams & Wilkins.