tbuckley/cabot-search huggingface dataset:
SPECT/CT Detection of a Communicating Arachnoid Cyst in a Patient With Normal Pressure Hydrocephalus
Authors: Lisa Walker, Ali Gholamrezanezhad, Daniel Bucklan, Peter F. Faulhaber, James K. O’Donnell
Journal: Clinical Nuclear Medicine (2017)

A 59-year-old man with history of multiple sclerosis and residual sensory and motor dysfunction presented with progressive lower-extremity weakness, ataxic gait, and intermittent urinary incontinence. Brain MRI demonstrated volume loss with disproportionate ventricular dilatation, but no evidence of infarction or abnormal enhancement. Radionuclide cisternography showed early and persistent ventricular reflux, poor progression of radiopharmaceutical over convexities, and delayed clearance in a pattern consistent with normal pressure hydrocephalus. Asymmetric activity in the right parietal region was also identified. Fused SPECT/CT, as well as fusion of the SPECT with a previous brain MRI, demonstrated a communicating arachnoidal cyst.
Bacteria-driven peribronchial lymphoid neogenesis in bronchiectasis and cystic fibrosis
Authors: Justine Frija-Masson, Clémence Martin, Lucile Regard, Marie-Noëlle Lothe, Lhousseine Touqui, Aurélie Durand, Bruno Lucas, Diane Damotte, Marco Alifano, Isabelle Fajac, Pierre-Régis Burgel
Journal: European Respiratory Journal (2017)

We aimed to characterise lymphoid neogenesis in bronchiectasis and cystic fibrosis (CF) lungs and to examine the role of bacterial infection. Lymphoid aggregates were examined using immunohistochemical staining and morphometric analysis in surgical lung sections obtained from nonsmokers and patients with bronchiectasis or CF. Sterile, Pseudomonas aeruginosa - or Staphylococcus aureus -coated agarose beads were instilled intratracheally in mice. Kinetics of lymphoid neogenesis and chemokine expression were examined over 14 days. Lymphoid aggregates were scarce in human lungs of nonsmokers, but numerous peribronchial lymphoid aggregates containing B-lymphocytes, T-lymphocytes, germinal centres and high endothelial venules were found in bronchiectasis and CF. Mouse lungs contained no lymphoid aggregate at baseline. During persistent P. aeruginosa or S. aureus airway infection peribronchial lymphoid neogenesis occurred. At day 14 after instillation, lymphoid aggregates expressed markers of tertiary lymphoid organs and the chemokines CXCL12 and CXCL13. The airway epithelium was an important site of CXCL12, CXCL13 and interleukin-17A expression, which began at day 1 after instillation. Peribronchial tertiary lymphoid organs are present in bronchiectasis and in CF, and persistent bacterial infection triggered peribronchial lymphoid neogenesis in mice. Peribronchial localisation of tertiary lymphoid organs and epithelial expression of chemokines suggest roles for airway epithelium in lymphoid neogenesis.
Reply
Authors: M De Vos
Journal: Gut (1993)

<h3>Background</h3> Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload. <h3>Methods</h3> To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged &gt;18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency &gt;3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging. <h3>Results</h3> The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake. <h3>Conclusions</h3> Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status. <h3>Clinical Trial registry name and registration number:</h3> The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.
Effect of Using the HEART Score in Patients With Chest Pain in the Emergency Department
Authors: Judith M. Poldervaart, Johannes B. Reitsma, Barbra E. Backus, Hendrik Koffijberg, Rolf F. Veldkamp, Monique E. ten Haaf, Yolande Appelman, Herman F.J. Mannaerts, Jan-Melle van Dantzig, Madelon van den Heuvel, Mohamed el Farissi, Bernard J.W.M. Rensing, Nicolette M.S.K.J. Ernst, Ineke M.C. Dekker, Frank R. den Hartog, Thomas Oosterhof, Ghizelda R. Lagerweij, Eugene M. Buijs, Maarten W.J. van Hessen, Marcel A.J. Landman, Roland R.J. van Kimmenade, Luc Cozijnsen, Jeroen J.J. Bucx, Clara E.E. van Ofwegen-Hanekamp, Maarten-Jan Cramer, A. Jacob Six, Pieter A. Doevendans, Arno W. Hoes
Journal: Annals of Internal Medicine (2017)

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: The HEART (History, Electrocardiogram, Age, Risk factors, and initial Troponin) score is an easy-to-apply instrument to stratify patients with chest pain according to their short-term risk for major adverse cardiac events (MACEs), but its effect on daily practice is unknown. Objective: To measure the effect of use of the HEART score on patient outcomes and use of health care resources. Design: Stepped-wedge, cluster randomized trial. (ClinicalTrials.gov: NCT01756846) Setting: Emergency departments in 9 Dutch hospitals. Patients: Unselected patients with chest pain presenting at emergency departments in 2013 and 2014. Intervention: All hospitals started with usual care. Every 6 weeks, 1 hospital was randomly assigned to switch to "HEART care," during which physicians calculated the HEART score to guide patient management. Measurements: For safety, a noninferiority margin of a 3.0% absolute increase in MACEs within 6 weeks was set. Other outcomes included use of health care resources, quality of life, and cost-effectiveness. Results: A total of 3648 patients were included (1827 receiving usual care and 1821 receiving HEART care). Six-week incidence of MACEs during HEART care was 1.3% lower than during usual care (upper limit of the 1-sided 95% CI, 2.1% [within the noninferiority margin of 3.0%]). In low-risk patients, incidence of MACEs was 2.0% (95% CI, 1.2% to 3.3%). No statistically significant differences in early discharge, readmissions, recurrent emergency department visits, outpatient visits, or visits to general practitioners were observed. Limitation: Physicians were hesitant to refrain from admission and diagnostic tests in patients classified as low risk by the HEART score. Conclusion: Using the HEART score during initial assessment of patients with chest pain is safe, but the effect on health care resources is limited, possibly due to nonadherence to management recommendations. Primary Funding Source: Netherlands Organisation for Health Research and Development.
Clinical characteristics of patients with low functional IL-6 production upon TLR/IL-1R stimulation
Authors: Glynis Frans, Jutte Van der Werff Ten Bosch, Leen Moens, Greet Wuyts, Heidi Schaballie, David Tuerlinckx, Mia De Bie, Francois Vermeulen, Rik Schrijvers, Wim Meert, Matthew S. Hestand, Joris Delanghe, Joris R. Vermeesch, Isabelle Meyts, Xavier Bossuyt
Journal: Journal of Allergy and Clinical Immunology (2017)
Patients told about muscle pain are more likely to report it, statin study finds
Authors: Nigel Hawkes
Journal: BMJ (2017)

Patients unaware that they are taking statins do not complain of muscle pains. But the same patients, once told that the drug they are taking is a statin, are much more likely to report such symptoms, shows a new analysis of data from a trial carried out more than a decade ago in the UK and Scandinavia.

The result, says Peter Sever of the National Heart and Lung Institute in London, is an example of the “nocebo effect,” where patients become more likely to report adverse effects of a drug once they are aware of them. “We all know of the placebo effect, where patients given placebo nevertheless get better,” he told a briefing at the Science Media Centre in London. “This is exactly the same, but in reverse. You only develop side effects when you know you are taking the drug.”

This is not the same as saying that the pains are “all in the mind,” he insisted. The pain is …
Renal recovery after acute kidney injury
Authors: L. G. Forni, M. Darmon, M. Ostermann, H. M. Oudemans-van Straaten, V. Pettilä, J. R. Prowle, M. Schetz, M. Joannidis
Journal: Intensive Care Medicine (2017)

Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality, chronic kidney disease (CKD) and cardiovascular events. The degree of renal recovery from AKI may substantially affect these long-term endpoints. Therefore maximising recovery of renal function should be the goal of any AKI prevention and treatment strategy. Defining renal recovery is far from straightforward due in part to the limitations of the tests available to assess renal function. Here, we discuss common pitfalls in the evaluation of renal recovery and provide suggestions for improved assessment in the future. We review the epidemiology of renal recovery and of the association between AKI and the development of CKD. Finally, we stress the importance of post-discharge follow-up of AKI patients and make suggestions for its incorporation into clinical practice. Summary key points are that risk factors for non-recovery of AKI are age, CKD, comorbidity, higher severity of AKI and acute disease scores. Second, AKI and CKD are mutually related and seem to have a common denominator. Third, despite its limitations full recovery of AKI may best be defined as the absence of AKI criteria, and partial recovery as a fall in AKI stage. Fourth, after an episode of AKI, serial follow-up measurements of serum creatinine and proteinuria are warranted to diagnose renal impairment and prevent further progression. Measures to promote recovery are similar to those preventing renal harm. Specific interventions promoting repair are still experimental.
Impact of the sterol 27-hydroxylase (CYP27A1) and 27-hydroxycholesterol on tumor-pathological features, prognosis and response to statin treatment in breast cancer
Authors: S. Kimbung, C.-Y. Chang, P.-O. Bendahl, L. Dubois, W.J. Thompson, D.P. McDonnell, S. Borgquist
Journal: Annals of Oncology (2017)
Recent advances in the use of nanoparticles for allergen‐specific immunotherapy
Authors: H. Pohlit, I. Bellinghausen, H. Frey, J. Saloga
Journal: Allergy (2017)

Abstract The number of patients suffering from allergic asthma and rhinoconjunctivitis has increased dramatically within the last decades. Allergen‐specific immunotherapy ( AIT ) is the only available cause‐oriented therapy so far. AIT reduces symptoms, but has also a disease‐modifying effect. Disadvantages are a long‐lasting procedure, and in a few cases potential systemic adverse reactions. Encapsulation of allergens or DNA vaccines into nanostructures may provide advantages compared to the conventional AIT with noncapsulated allergen extracts: The protein/ DNA molecule can be protected from degradation, higher local concentrations and targeted delivery to the site of action appear possible, and most importantly, recognition of encapsulated allergen by the immune system, especially by IgE antibodies, is prevented. AIT with nanoparticles ( NP s) may offer a safer and potentially more efficient way of treatment for allergic diseases. In this review, we summarize the use of biodegradable NP s consisting of synthetic or natural polymers, liposomes, and virus‐like particles as well as nonbiodegradable NP s like dendrimers, and carbon‐ or metal‐based NP s for AIT . More or less successful applications of these NP s in prophylactic as well as therapeutic vaccination approaches in rodents or other animals as well as first human clinical trials are discussed in detail.
Cholesterol Accumulation in Dendritic Cells Links the Inflammasome to Acquired Immunity
Authors: Marit Westerterp, Emmanuel L. Gautier, Anjali Ganda, Matthew M. Molusky, Wei Wang, Panagiotis Fotakis, Nan Wang, Gwendalyn J. Randolph, Vivette D. D'Agati, Laurent Yvan-Charvet, Alan R. Tall
Journal: Cell Metabolism (2017)
Phase I Trial of Intratumoral Injection of<i>CCL21</i>Gene–Modified Dendritic Cells in Lung Cancer Elicits Tumor-Specific Immune Responses and CD8+ T-cell Infiltration
Authors: Jay M. Lee, Mi-Heon Lee, Edward Garon, Jonathan W. Goldman, Ramin Salehi-Rad, Felicita E. Baratelli, Dörthe Schaue, Gerald Wang, Fran Rosen, Jane Yanagawa, Tonya C. Walser, Ying Lin, Stacy J. Park, Sharon Adams, Francesco M. Marincola, Paul C. Tumeh, Fereidoun Abtin, Robert Suh, Karen L. Reckamp, Gina Lee, William D. Wallace, Sarah Lee, Gang Zeng, David A. Elashoff, Sherven Sharma, Steven M. Dubinett
Journal: Clinical Cancer Research (2017)

Abstract Purpose: A phase I study was conducted to determine safety, clinical efficacy, and antitumor immune responses in patients with advanced non–small cell lung carcinoma (NSCLC) following intratumoral administration of autologous dendritic cells (DC) transduced with an adenoviral (Ad) vector expressing the CCL21 gene (Ad-CCL21-DC). We evaluated safety and tumor antigen–specific immune responses following in situ vaccination (ClinicalTrials.gov: NCT01574222). Experimental Design: Sixteen stage IIIB/IV NSCLC subjects received two vaccinations (1 × 106, 5 × 106, 1 × 107, or 3 × 107 DCs/injection) by CT- or bronchoscopic-guided intratumoral injections (days 0 and 7). Immune responses were assessed by tumor antigen–specific peripheral blood lymphocyte induction of IFNγ in ELISPOT assays. Tumor biopsies were evaluated for CD8+ T cells by IHC and for PD-L1 expression by IHC and real-time PCR (RT-PCR). Results: Twenty-five percent (4/16) of patients had stable disease at day 56. Median survival was 3.9 months. ELISPOT assays revealed 6 of 16 patients had systemic responses against tumor-associated antigens (TAA). Tumor CD8+ T-cell infiltration was induced in 54% of subjects (7/13; 3.4-fold average increase in the number of CD8+ T cells per mm2). Patients with increased CD8+ T cells following vaccination showed significantly increased PD-L1 mRNA expression. Conclusions: Intratumoral vaccination with Ad-CCL21-DC resulted in (i) induction of systemic tumor antigen–specific immune responses; (ii) enhanced tumor CD8+ T-cell infiltration; and (iii) increased tumor PD-L1 expression. Future studies will evaluate the role of combination therapies with PD-1/PD-L1 checkpoint inhibition combined with DC-CCL21 in situ vaccination. Clin Cancer Res; 23(16); 4556–68. ©2017 AACR.
A Rare Case of Urachal Carcinoma Metastatic to Thoracic Vertebra Detected by FDG PET/CT
Authors: Guangjie Yang, Zhenguang Wang, Simin Liu, Fengyu Wu, Dacheng Li
Journal: Clinical Nuclear Medicine (2017)

Both chest radiography and MRI scan showed compression fracture of the T6 vertebral body in a 33-year-old man who presented with back pain. Because of the absence of predisposing factors for compression fracture, a pathologic fracture was considered. For this reason, an FDG PET/CT was performed. The images revealed not only the abnormal activity in the known T6 vertebral body but also an additional activity immediately anterosuperior to the urinary bladder in a partially calcified soft tissue nodule. A mucinous adenocarcinoma of urachus with solitary bone metastasis was confirmed histopathologically.
Interobserver variability in ultrasound (US) guided fine needle aspiration cytology (FNAC) of sentinel nodes (SN): Experience in 1,000 melanoma patients.
Authors: Christiane A. Voit, Alexander Christopher Jonathan Van Akkooi, Saskia Gooskens, Petra Siegel, Gregor Schaefer, Alfred Schoengen, Wolfram Sterry, Joachim Roewert-Huber, Alexander M. Eggermont
Journal: Journal of Clinical Oncology (2014)

9097 Background: FNAC is used to determine nature of suspected lesions that are either clinically apparent (palpable) or discovered by imaging (non-palpable) with the same high sensitivity (Voit et al.JNCI 2011). However, there seems to be interobserver variability. Methods: Morphology criteria (Voit et al. JCO 2010) were tested in 3 pre-SLNB-US examiners. US criteria, FNAC results were collected in a prospective database.Positive cytology was confirmed by histopathology. Examiner #1 had a long US-FNAC experience, 2 others were learners, #2 with a long US, but not FNAC experience, #3 new to both. Results: In 1,000 consecutive prospective patients mean/median Breslow thickness was 2.58/1.57mm. Mean/median follow-up was 56 / 53 months (1 – 132). SN positivity rate was 21%. Overall US-FNAC sensitivity was 71%(US only) and 51%(US-FNAC). Sensitivity of US-FNAC was highest for T4 (76%) and ulcerated melanomas (63%). #1 performed 724(72%), #2 202(20%), #3 74(7%). US validation of #1 was 431/724(59.9%) benign, in 227/724(31.4%) suspicious and in 66/724(9.1%) malignant. #2 estimated in 144/202(71.3%) benign, in 50/202(24,7%) suspicious and in 8/202(4%) malignant; #3 in 57(77%) benign, in 8/75 (10.8%) suspicious and in 9/74 (12.2%) malignant (p<0.001). #1 detects early sign peripheral perfusion(PP) in 32%, #2 in 21% and #3 in 22%. #1 performed FNAC in 291(40%), #2 in 55(25%) and #3 in17(15%)(p<0.001). #1 had sensitivity of 86/157(55%), spec of 99%, PPV of 99% and NPV of 89% (p<0.001). #2 had 34%,100%,100% and 88%,#3 56%, 100%,100% and 89% respectively(p<0.001). Detected sentinel node Tuburden <1mm was successfully FNACed in 45% by #1 and in 20% by #2 and#3 respectively. Conclusions: This largest database covering FNACs in SN of melanoma patients showed no difference between ultrasonographists with regard to performing a FNAC if a late sign, baloonshape (BS) or loss of central echoes (LCE), was seen. An examiner experienced in both US and FNAC sees more PP, performs more FNACs and has more positive FNACs. Examiners not used to FNAC tend to not perform FNACS. Interobserver difference is due to a significantly lower detection rate of PP.
Lipid-oligonucleotide conjugates improve cellular uptake and efficiency of TCTP-antisense in castration-resistant prostate cancer
Authors: Sara Karaki, Sebastien Benizri, Raquel Mejías, Virginie Baylot, Nicolas Branger, Tan Nguyen, Brune Vialet, Khalid Oumzil, Philippe Barthélémy, Palma Rocchi
Journal: Journal of Controlled Release (2017)

Translationally controlled tumor protein (TCTP) has been implicated in a plethora of important cellular processes related to cell growth, cell cycle progression, malignant transformation and inhibition of apoptosis. Therefore, TCTP is now recognized as a potential therapeutic target in several cancers including prostate, breast and lung cancers. We previously showed that TCTP is overexpressed in castration-resistant prostate cancer (CRPC), and it has been implicated resistance to treatment. Recently, we developed TCTP antisense oligonucleotides (ASOs) to inhibit TCTP expression. However, the intracellular delivery and silencing activity of these oligonucleotides remains a challenge, and depend on the use of transfection agents and delivery systems. Here we show that lipid-modified ASO (LASOs) has improved penetration and efficiency in inhibiting TCTP expression in the absence of additional transfection agents, both in vitro and in vivo. Transfection with TCTP-LASO led to rapid and prolonged internalization via macropinocytosis, TCTP downregulation and significant decreased cell viability. We also show that lipid-modification led to delayed tumor progression in CRPC xenografts models, with no significant toxic effects observed.
Half of US physicians receive industry payments, study finds
Authors: Michael McCarthy
Journal: BMJ (2017)

Nearly half of US physicians receive payments from the drug, medical device, and related medical industries, and surgeons and male physicians are more likely to do so, a US study has found.1

The study leader, Jona A Hattangadi-Gluth, of the University of California, San Diego, based in La Jolla, said that most payments were relatively small but that many specialists receive more than $10 000 (£7750; $9160) a year from industry, including 11% of orthopedic surgeons, 12% of neurologists, and 13% of neurosurgeons.

She said, “The data suggest that these payments are much more pervasive than we thought and [that] there is much more money going directly to physicians than …
What would the experts do? Genetic testing, surveillance, and risk-reduction preferences for BRCA and Lynch syndrome.
Authors: Danielle C. Bonadies, Ellen T. Matloff, Karina L. Brierley, Anne Moyer
Journal: Journal of Clinical Oncology (2013)

e12542 Background: Extensive data and national guidelines are now available regarding surveillance and risk reduction options for BRCA and Lynch syndrome mutation carriers. However, most of these options are presented as choices to patients who will often ask their providers, “What would you do?” We surveyed providers from multiple specialties to learn what they would do if at 50% risk to carry a BRCA or Lynch syndrome mutation. Methods: In July of 2012 we surveyed providers from multiple specialties via internet- based surveys. Participants were obtained through the American Medical Association and the National Society of Genetic Counselors. All responses were anonymized. Results: 1,313 specialists completed the online questionnaire. Those providers who commonly treat breast, ovarian, colon and uterine cancers were grouped and compared to providers who are less likely to be the treating specialist. We found statistically significant differences in the percentage of cancer genetics specialists who would pursue BRCA and Lynch syndrome testing compared with providers in other specialties (p=0.000, 0.007, respectively). We found statistically significant differences in the percentage of providers who treat breast or ovarian cancer that would opt for prophylactic bilateral mastectomy or prophylactic oophorectomy if BRCA+ (p=0.000, p=0.004, respectively) compared to other providers. We found statistically significant differences in the percentage of providers who treat colon or uterine cancer that would have their colon or uterus removed if found to carry a Lynch syndrome mutation (p=0.000, p=0.04, respectively) compared to other specialists. Conclusions: Providers’ specialties and, possibly, disease-specific exposure to surveillance and treatment regimens impacted their personal choices with respect to cancer genetic testing, surveillance and prophylactic surgeries for BRCA and Lynch syndrome.