tbuckley/cabot-search huggingface dataset:
Abstract 11089: Hepatic Abnormalities are Present Before and Early After the Fontan Operation
Authors: Matthew Schwartz, Andrew C Glatz, Kaitlyn Daniels, David J Goldberg, Elizabeth Rand, Monica Epelman, Meryl S Cohen
Journal: Circulation (2014)

Objectives: Progressive hepatic fibrosis is common after the Fontan operation, but little is known about its onset. We sought to determine if there is non-invasive evidence of hepatic injury prior to the Fontan operation, and if further injury is seen soon after the procedure. Methods: Patients undergoing the Fontan operation at our institution were prospectively enrolled and underwent hepatic ultrasound with Doppler and serum testing immediately before and 3 to 6 months after the operation. Results: Thirty patients were enrolled at a median age at time of the Fontan operation of 3.1 yrs (range: 2.2-8.1 yrs). An extracardiac Fontan operation was performed in 67% and nearly all (97%) underwent fenestration. Three patients (10%) had abnormal hepatic echotexture prior to the Fontan operation. At the post-Fontan study, mean liver length increased (9.9 vs. 10.9 cm, p&lt;0.0001) and mean hepatic artery end diastolic velocity decreased (18.8 vs. 14.5 cm/sec, p=0.03). One patient showed new, abnormal hepatic echotexture after surgery. Among serum indices, mean aspartate aminotransferase (56.7 vs. 60.7 IU, p=0.04), mean alanine transaminase (ALT) (18.9 vs. 33.9 IU, p=0.0002), and mean gamma-glutamyl transferase (GGT) (18.7 vs. 46.1 IU, p=0.002) increased at the post-Fontan assessment compared to the pre-operative values. By linear regression, hospital length of stay and duration with chest tube after Fontan operation were both significantly associated with an increase in GGT (p&lt; 0.001 for both) and ALT (p=0.008, p=0.04) 3 to 6 months after surgery. There were no associations found between change in ultrasound or serum markers of liver function and pre-Fontan hemodynamic variables as measured by echocardiogram, catheterization, and/or magnetic resonance imaging. Conclusions: Hepatic ultrasound abnormalities were seen prior to the Fontan operation in some patients. Early after the Fontan operation, liver length and serum hepatic markers were increased relative to pre-Fontan values. Post-operative morbidity was associated with an increase in these serum markers. In total, these findings suggest that liver insult may occur prior to the Fontan operation and further insult likely begins soon after the Fontan circulation is created.
Patients offered choices about psychological treatment have better outcomes, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Patients given a choice about the timing, location, type, or provider of the psychological treatment they are offered show better outcomes than those whose preferences are not met, a survey of NHS services in England and Wales has found.1

Services that provide psychological therapies are encouraged to offer people a choice about their treatment. Evidence has shown that giving people a choice between drug and talking treatments affects their outcomes, but little information existed on patients’ preferences for psychological therapies and …
Abstract 19075: TEVAR Remodels the Thoracic and Abdominal Aorta in Acute DeBakey 3 Dissection: Early Results
Authors: Bradley G Leshnower, Chun Li, Yazan M Duwayri, Travis S Henry, Edward P Chen, Ravi K Veeraswamy
Journal: Circulation (2014)

Introduction: The objective of this study was to determine the remodeling impact of TEVAR on different segments of the aorta in acute DeBakey 3 aortic dissections. Methods: Between January 2012 and June 2014, 136 patients underwent TEVAR at a US academic institution. 32 (24%) patients underwent TEVAR for acute complicated DeBakey 3 (3a n=3, 3b n=29) aortic dissections. Volumetric measurements of the true and false lumens of the descending thoracic and abdominal aorta were performed upon pre and postoperative CT scans using Osirix Imaging Software. Aortic volumes were measured for the stented, stent end to celiac artery, celiac to renals, and infrarenal aortic segments. True lumen (TLR= true lumen (TL)/total aortic volume) and false lumen ratios (FLR=false lumen(FL)/total aortic volume) were calculated using total aortic volumes. Results: The mean age was 56 ± 12 years. The mean length of aortic coverage was 197±29 mm. Operative mortality was 3.1%. The incidence of stroke and transient paraperesis were 3.1...
A role for human sulfiredoxin in stress response and redox regulation of protein glutathionylation
Authors: Victoria J. Findlay, Taylor E. Morris, Danyelle M. Townsend, Kenneth D. Tew
Journal: Cancer Research (2005)

2640  Either directly or indirectly, many cancer drugs cause oxidative stress. Modification of protein cysteine residues by disulfide formation with free glutathione (glutathionylation) is a post-translational modification of critical importance in controlling cell-signaling events following such stress. Sulfiredoxin (SRX) has recently been identified in S. cerevisiae as a redox protein directly involved in cysteine residue homeostasis, suggesting a role(s) in regulation of cell signaling events brought on by oxidative or nitrosative stress. We cloned the human homologue of sulfiredoxin (hSrx1) and showed a 33% identity and 54% homology with the yeast sulfiredoxin gene, with conservation of the critical cysteine residue located at position 99 in the human sequence (Cys 84 in yeast). Transfection of hSrx1 into HEK293 (human embryonic kidney) cells generated a stable over-expressing cell line (HEK293/SRX1), confirmed by RT-PCR and immunoblot with a polyclonal antibody generated in rabbits. HEK/SRX1 cells were resistant to hydrogen peroxide (H2O2) -induced cytotoxicity and demonstrated an elevated proliferation rate when compared to a mock-transfected control cell line. Moreover, hSrx1 had a role in regulating pathways of glutathionylation. The over-expression of hSrx1 resulted in a lower level of total cellular cysteine glutathionylation following treatment with nitric oxide releasing drugs (nitrosative stress). In addition, in vitro assays using recombinant E. coli expressed hSrx1 and protein tyrosine phosphatase 1B (PTP1B) showed a reversal of glutathionylation in a time and concentration dependent manner. Further in vitro studies suggested that the cysteine mutant (Cys99 to Ser) blocked glutathionylation, but did not remove the moiety. This suggested that the cysteine residue is not critical for the binding function of Srx, but is important for the catalytic function of the enzyme. Our studies also showed that the Srx protein did not itself become glutathionylated during this process. Using two-dimensional gel electrophoresis and mass spectrometry we are characterizing those approximately 20 proteins, the post-translational modifications of which are regulated by hSRX.
SSRP1 Contributes to the Malignancy of Hepatocellular Carcinoma and Is Negatively Regulated by miR-497
Authors: Qianshan Ding, Ke He, Tao Luo, Yunchao Deng, Hanning Wang, Hao Liu, Jinqian Zhang, Kaiyun Chen, Jinfeng Xiao, Xiaopeng Duan, Rui Huang, Zhenglin Xia, Wenjie Zhou, Jinliang He, Honggang Yu, Xingyuan Jiao, Guoan Xiang
Journal: Molecular Therapy (2016)

The aim of this study is to clarify the clinical implication and functional role of structure specific recognition protein 1 (SSRP1) in hepatocellular carcinoma (HCC) and explore the underlying mechanism of aberrant high expression of SSRP1 in cancers. In the present investigation, we validated that SSRP1 was upregulated in HCC samples. We also demonstrated that its upregulation was associated with several clinicopathologic features such as higher serum AFP level, larger tumor size, and higher T stage of HCC patients; and its high expression indicated shorter overall survival and faster recurrence. To investigate the role of SSRP1 in HCC progression, both loss- and gain-function models were established. We demonstrated that SSPR1 modulated both proliferation and metastasis of HCC cells in vitro and vivo. Furthermore, we demonstrated that SSRP1-modulated apoptosis process and its knockdown increased the sensitivity of HCC cells to doxorubicin, 5-Fluorouracil, and cisplatin. We also identified microRNA-497 (miR-497) as a posttranscriptional regulator of SSRP1. Ectopic expression of miR-497 inhibited 3'-untranslated-region–coupled luciferase activity and suppressed endogenous SSRP1 expression at both messenger RNA and protein levels. For the first time, we proved that SSRP1 upregulation contributed to HCC development and the tumor-suppressive miR-497 served as its negative regulator. The aim of this study is to clarify the clinical implication and functional role of structure specific recognition protein 1 (SSRP1) in hepatocellular carcinoma (HCC) and explore the underlying mechanism of aberrant high expression of SSRP1 in cancers. In the present investigation, we validated that SSRP1 was upregulated in HCC samples. We also demonstrated that its upregulation was associated with several clinicopathologic features such as higher serum AFP level, larger tumor size, and higher T stage of HCC patients; and its high expression indicated shorter overall survival and faster recurrence. To investigate the role of SSRP1 in HCC progression, both loss- and gain-function models were established. We demonstrated that SSPR1 modulated both proliferation and metastasis of HCC cells in vitro and vivo. Furthermore, we demonstrated that SSRP1-modulated apoptosis process and its knockdown increased the sensitivity of HCC cells to doxorubicin, 5-Fluorouracil, and cisplatin. We also identified microRNA-497 (miR-497) as a posttranscriptional regulator of SSRP1. Ectopic expression of miR-497 inhibited 3'-untranslated-region–coupled luciferase activity and suppressed endogenous SSRP1 expression at both messenger RNA and protein levels. For the first time, we proved that SSRP1 upregulation contributed to HCC development and the tumor-suppressive miR-497 served as its negative regulator.
Abstract 4295: INT230-6, a novel intratumoral anticancer agent, is able to eradicate large established tumors and stimulate potent anti tumor immunity
Authors: Ian B. Walters, Lewis H. Bender, Masaki Terabe, Jay A. Berzofsky
Journal: Cancer Research (2015)

Abstract Historically, intratumoral (IT) administered chemotherapy has not been shown to provide better efficacy than the same drugs delivered intravenously. This is postulated to be due to poor drug diffusion and dispersion throughout the tumor. Intensity has developed a novel formulation of cytotoxic chemotherapy plus a penetration enhancer which improves drug diffusion and uptake into the cancer cell. INT230-6 is a combination of low dose cisplatin, vinblastine and a cell penetration excipient. This technology enables more rapid and improved penetration throughout the tumor including hypoxic and un-vascularized areas. Cohorts of 10 BALB/c mice were inoculated with 1×106 CT26 cells subcutaneously (SC). Tumors were grown to a mean of 325mm3 and then treatment with INT230-6 was administered IT daily for a single cycle of 5 days. Control arms using comparable size tumors pre-dose included no treatment, IV cisplatin and vinblastine, and IT injection of these drugs without the enhancer. INT230-6 treatment resulted in regression from baseline in all animals with a complete regression of the large tumors in 20%. Many tumors continued to shrink in size well beyond multiple half-lives of the chemotherapy and excipient implying an anti-tumor effect not due to direct cytotoxicity from the drugs. INT230-6 administration resulted in a significant extension of overall survival compared to all controls. Notably complete responders with this treatment were resistant to 3 separate attempts at re-inoculation with 1×106 CT26 cells by SC or IV administration without retreatment of drug, while control animals rapidly developed metastatic tumors and died. This apparent tumor immunity persisted for &amp;gt; 440 days suggesting permanent immunity. In a follow-on study, tumors of some animals receiving INT230-6 were shown to be 75% necrotic on day 3 of treatment with an observed increase in the density of CD4 positive cells and CD11c positive cells in the treated tumors on day 10 versus controls. These changes might be involved in the induction of immunity. These results suggest that intratumoral administration of INT230-6 creates the proper tumor cell apoptosis kinetics and antigen presentation to enable a personalized adaptive immune response to develop. Further work is being done to look at repeat dosing and combinations with other immunomodulating agents. Citation Format: Ian B. Walters, Lewis H. Bender, Masaki Terabe, Jay A. Berzofsky. INT230-6, a novel intratumoral anticancer agent, is able to eradicate large established tumors and stimulate potent anti tumor immunity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4295. doi:10.1158/1538-7445.AM2015-4295
Bronchoscopic Lung Volume Reduction in COPD
Authors: Frank C. Sciurba, Divay Chandra, Jessica Bon
Journal: JAMA (2016)

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Coils implanted into lungs show promise for emphysema
Authors: Jacqui Wise
Journal: BMJ (2016)

Implanting tiny coils in the lungs of patients with severe emphysema improves exercise capacity at six months, although the short term costs of treatment are high, researchers have reported in JAMA .1

Management of emphysema, a key component of chronic obstructive pulmonary disease, is challenging because of the limited efficacy of currently available treatments. For example, lung volume reduction surgery, although it improves outcomes in some groups of patients, is associated with significant morbidity and mortality.

French researchers …
Screening MRI in Women With a Personal History of Breast Cancer
Authors: Constance D. Lehman, Janie M. Lee, Wendy B. DeMartini, Daniel S. Hippe, Mara H. Rendi, Grace Kalish, Peggy Porter, Julie Gralow, Savannah C. Partridge
Journal: JNCI Journal of the National Cancer Institute (2016)

Screening MRI is recommended for individuals at high risk for breast cancer, based on genetic risk or family history (GFH); however, there is insufficient evidence to support screening MRI for women with a personal history (PH) of breast cancer. We compared screening MRI performance in women with PH vs GFH of breast cancer. We analyzed case-series registry data, collected at time of MRI and at 12-month follow-up, from our regional Clinical Oncology Data Integration project. MRI performance was compared in women with PH with those with GFH. Chi-square testing was used to identify associations between age, prior history of MRI, and clinical indication with MRI performance; logistic regression was used to determine the combined contribution of these variables in predicting risk of a false-positive exam. All statistical tests were two-sided. Of 1521 women who underwent screening MRI from July 2004 to November 2011, 915 had PH and 606 had GFH of breast cancer. Overall, MRI sensitivity was 79.4% for all cancers and 88.5% for invasive cancers. False-positive exams were lower in the PH vs GFH groups (12.3% vs 21.6%, P < .001), specificity was higher (94.0% vs 86.0%, P < .001), and sensitivity and cancer detection rate were not statistically different (P > .99). Age (P < .001), prior MRI (P < .001), and clinical indication (P < .001) were individually associated with initial false-positive rate; age and prior MRI remained statistically significant in multivariable modeling (P = .001 and P < .001, respectively). MRI performance is superior in women with PH compared with women with GFH. Screening MRI warrants consideration as an adjunct to mammography in women with a PH of breast cancer.
Seven day opening of GP surgeries may not work everywhere, minister tells MPs
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Not every part of England may want seven day routine access to GP surgeries depending on what ongoing pilot schemes find, a minister has told MPs.

Alistair Burt, minister for community and social care, appearing before the parliamentary health committee on 12 January for the final evidence session of its inquiry into primary care, seemed to say that the same level of service may not be available universally if a local population does not want it.

MPs asked about the government’s intention to have the same level of services available seven days a week, after the Prime Minister’s Challenge Fund pilots in primary care had shown poor uptake of Sunday appointments made available to patients.

Burt said that he was not surprised at the different levels of uptake across the pilot schemes. “The truth about whether or …
Preemptive therapy of spontaneous fungal peritonitis
Authors: Marco Fiore, Lorenzo Andreana, Sebastiano Leone
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. To the Editor: In a recent study on the empirical antimicrobial treatment of nosocomial spontaneous bacterial peritonitis the authors designed a protocol in which patients with a new diagnosis of nosocomial spontaneous bacterial peritonitis were randomized to receive ceftazidime or meropenem plus daptomycin and patients without response after 48 hours of treatment received fluconazole as systemic antifungal therapy.1 Hassan et al. screened for invasive fungal infection in 46 end‐stage liver disease (ESLD) patients from the intensive care unit: both blood and ascitic fluid samples were collected for fungal culture and polymerase chain reaction.2 Seven patients had isolated invasive fungal infection (four had spontaneous fungal peritonitis [SFP], two had fungemia, and one had a disseminated fungal infection), and five cases had combined fungal and bacterial infections. SFP was attributed to Candida species. The authors concluded that patients with ESLD had a low frequency of invasive fungal infection; however, in patients with these infections, delayed diagnosis and treatment may contribute to a high fatality rate. More recently, Bremmer et al. published the results of a retrospective cohort study using the primary outcome of all‐cause mortality at 28 days: 25 patients were included, and Candida species were the causative pathogen in all cases.3 At the onset of SFP, patients were critically ill, with median Acute Physiology and Chronic Health Evaluation II (APACHE II) and Model for End‐Stage Liver Disease scores of 22 and 30.3, respectively. The 28‐day mortality rate was 56%; six patients died prior to culture positivity. In conclusion, SFP develops among critically ill patients with ESLD and is associated with high rates of death. Considering the high mortality rate of Candida‐related peritonitis and given the poor outcome that could result from inadequate systemic antifungal therapy for patients with nosocomially acquired SFP and for critically ill patients with community‐acquired SFP, the use of echinocandins is recommended.4 Once a susceptibility report is available, in patients with fluconazole‐susceptible infection of the ascitic fluid, deescalation from echinocandins to fluconazole is advised.5 The deescalation approach led to significant saving in antifungal drug costs and prevention of the emerging phenomenon of antifungal resistance. In conclusion, echinocandins, instead of fluconazole,1 should be considered as empirical or preemptive systemic antifungal therapy for ESLD patients with suspected SFP.
Barriers to an early switch from intravenous to oral antibiotic therapy in hospitalised patients with CAP
Authors: Madelon F. Engel, Douwe F. Postma, Marlies E.J.L. Hulscher, Ferdinand Teding van Berkhout, Marielle H. Emmelot-Vonk, Sanjay Sankatsing, Carlo A.J.M. Gaillard, Anke H.W. Bruns, Andy I.M. Hoepelman, Jan Jelrik Oosterheert
Journal: European Respiratory Journal (2012)

Do physicians apply an early-switch strategy (from intravenous to oral antibiotics) in clinically stable patients hospitalised with community-acquired pneumonia (CAP)? If not, why not? In a multicentre prospective cohort study, adult patients admitted for i.v. CAP treatment were included. On day 3 of antibiotic treatment, clinical stability was assessed and treating resident physicians were interviewed on their switch strategies. Additionally, treating physicians were interviewed to evaluate their knowledge of and adherence to guideline advice. 149 (92%) out of 162 patients were included and 97 (91%) out of 107 physicians were interviewed. A switch to oral antibiotics was possible in 68 (46%) out of 149 patients on day 3 of treatment but not performed in 27 (40%) out of 68. Patient factors delaying the switch were high CURB-65 (confusion of new onset, urea &gt;7 mmol·L −1 , respiratory rate of ≥30 breaths·min −1 , blood pressure &lt;90 mmHg or diastolic blood pressure ≤60 mmHg, and age ≥65 yrs) score (on admission) (p=0.04) and oxygen treatment (p=0.04), high temperature (p=0.00) and high respiration rate (p=0.04) (day 3). Physicians' barriers to an early switch in clinically stable patients included misconceptions (26 (55%) out of 47), practical considerations (13 (28%) out of 47) and organisational factors (eight (17%) out of 47). Strikingly, 91 (94%) out of 97 interviewed physicians were not aware of guideline advice. The switch from i.v. to oral antibiotics is often unnecessarily delayed in patients hospitalised with CAP due to different types of barriers.
Panel’s questions will delay large cigarette packet warnings, says expert
Authors: Cheryl Travasso
Journal: BMJ (2016)

An Indian parliamentary panel has raised questions about whether the health ministry’s move to increase the size of health warnings on cigarette packaging would reduce tobacco use, Reuters has reported.

The panel also raised concerns about whether this move would affect the livelihood of farmers who cultivated tobacco or increase its illegal trade and asked the ministry to state which tobacco ingredients were harmful and could cause cancer and how many cancers were linked to tobacco use.1

Health …
Nerve Regeneration: A Silk Sericin/Silicone Nerve Guidance Conduit Promotes Regeneration of a Transected Sciatic Nerve (Adv. Healthcare Mater. 15/2015)
Authors: Hongjian Xie, Wen Yang, Jianghai Chen, Jinxiang Zhang, Xiaochen Lu, Xiaobo Zhao, Kun Huang, Huili Li, Panpan Chang, Zheng Wang, Lin Wang
Journal: Advanced Healthcare Materials (2015)

A novel sericin nerve guidance conduit for the repair of peripheral nerve injury is designed and fabricated by L. Wang and Z. Wang's research team. On p. 2195, the authors show how this conduit, with physical properties optimized towards nerve regeneration, can increase the expression of neurotrophic factors and effectively promote the regeneration of the sciatic nerve, leading to functional recovery comparable to that resulted from nerve autograft.