tbuckley/cabot-search huggingface dataset:
Association Between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index
Authors: Christine E. Haugen, Mara McAdams-DeMarco, Elizabeth C. Verna, Robert S. Rahimi, Matthew R. Kappus, Michael A. Dunn, Michael L. Volk, Ahmet Gurakar, Andres Duarte-Rojo, Daniel R. Ganger, Jacqueline G. O’Leary, Daniela Ladner, Jacqueline Garonzik-Wang, Dorry L. Segev, Jennifer C. Lai
Journal: JAMA Surgery (2019)

Among liver transplant candidates, obesity and frailty are associated with increased risk of death while they are on the wait-list. However, use of body mass index (BMI) may not detect candidates at a higher risk of death owing to the fact that ascites and muscle wasting are seen across transplant candidates of all BMI measurements.To evaluate whether the association between wait-list mortality and frailty varied by BMI of liver transplant candidates.A prospective cohort study was conducted at 9 liver transplant centers in the United States from March 1, 2012, to May 1, 2018, among 1108 adult liver transplant candidates without hepatocellular carcinoma.At outpatient evaluation, the Liver Frailty Index score was calculated (grip strength, chair stands, and balance), with frailty defined as a Liver Frailty Index score of 4.5 or more. Candidates' BMI was categorized as nonobese (18.5-29.9), class 1 obesity (30.0-34.9), and class 2 or greater obesity (≥35.0).The risk of wait-list mortality was quantified using competing risks regression by candidate frailty, adjusting for age, sex, race/ethnicity, Model for End-stage Liver Disease Sodium score, cause of liver disease, and ascites, including an interaction with candidate BMI.Of 1108 liver transplant candidates (474 women and 634 men; mean [SD] age, 55 [10] years), 290 (26.2%) were frail; 170 of 670 nonobese candidates (25.4%), 64 of 246 candidates with class 1 obesity (26.0%), and 56 of 192 candidates with class 2 or greater obesity (29.2%) were frail (P = .57). Frail nonobese candidates and frail candidates with class 1 obesity had a higher risk of wait-list mortality compared with their nonfrail counterparts (nonobese candidates: adjusted subhazard ratio, 1.54; 95% CI, 1.02-2.33; P = .04; and candidates with class 1 obesity: adjusted subhazard ratio, 1.72; 95% CI, 0.99-2.99; P = .06; P = .75 for interaction). However, frail candidates with class 2 or greater obesity had a 3.19-fold higher adjusted risk of wait-list mortality compared with nonfrail candidates with class 2 or greater obesity (95% CI, 1.75-5.82; P < .001; P = .047 for interaction).This study's finding suggest that among nonobese liver transplant candidates and candidates with class 1 obesity, frailty was associated with a 2-fold higher risk of wait-list mortality. However, the mortality risk associated with frailty differed for candidates with class 2 or greater obesity, with frail candidates having a more than 3-fold higher risk of wait-list mortality compared with nonfrail patients. Frailty assessments may help to identify vulnerable patients, particularly those with a BMI of 35.0 or more, in whom a clinician's visual evaluation may be less reliable to assess muscle mass and nutritional status.
Novel data processing and image co-registration algorithm for region-specific lipid profiling in colorectal cancer tissue using DESI imaging mass spectrometry.
Authors: Reza Mirnezami, Kirill Veselkov, Nicole Strittmatter, James M Kinross, Robert D Goldin, Abigail Speller, Emrys A Jones, Elaine Holmes, Tigran Abramov, Jeremy K Nicholson, Ara W Darzi, Zoltan Takats
Journal: Journal of Clinical Oncology (2013)

e14620 Background: Imaging mass spectrometry (iMS) is a promising technique for cancer biomarker discovery. Clinical translation of iMS requires advanced data treatment methods and efficient co-registration of histology and iMS imaging modalities. In this study desorption electrospray ionisation (DESI) iMS has been used to address four aims: 1. To develop a data processing workflow to address current limitations; 2. To design an interactive software platform for image co-registration; 3. To investigate region-specific lipid biochemistry in colorectal cancer (CRC) tissue using the strategy outlined in aims 1-2; 4.To introduce an automated tissue recognition system based on multivariate molecular ion patterns (MIPs). Methods: Fresh CRC tissue sections (n=49) were subjected to DESI-iMS using a Thermo Exactive mass spectrometer coupled with a DESI ion source. Mass spectra were collected in the range m/z = 200-1000. Sections were then H&amp;E stained and scanned at high resolution. DESI-iMS data pre-processing involved peak detection, removal of noise/solvent related peaks and variance stabilising normalisation. An interactive image co-registration interface was developed using a feature-based image alignment algorithm for precise exploration of tissue region-specific biochemistry. A Recursive Maximum Margin Criterion (RMMC) algorithm was introduced for improved extraction of tissue specific MIPs. Results: CRC DESI-iMS profiles consisted mainly of complex lipids including phosphatidyl-inositols, phosphatidyl-serines, and phosphatidyl-ethanolamine plasmalogens. Different histological tissue regions showed characteristic lipid profiles. An automated tissue recognition system using multivariate MIPs derived by the proposed RMMC approach demonstrated highly accurate (classification accuracy &gt;98%) identification of pixels according to tissue type (cancer, healthy mucosa, smooth muscle, fibrous tissue, stroma). Conclusions: This workflow permits accurate tissue-specific lipidomic characterisation of the CRC tumor microenvironment and permits accurate reconstruction of different tissue types based on MIPs.
Comment on “Hypometabolic gliomas on FET-PET—is there an inverted U-curve for survival?”
Authors: Norbert Galldiks, Antoine Verger, Timothée Zaragori, Marcus Unterrainer, Bogdana Suchorska, Philipp Lohmann, Jörg C Tonn, Karl-Josef Langen, Nathalie L Albert
Journal: Neuro-Oncology (2019)
PACSIN2 rs2413739 Polymorphism and Thiopurine Pharmacokinetics: Validation Studies in Pediatric Patients
Authors: Gabriele Stocco, Raffaella Franca, Diego Favretto, Nagua Giurici, Alessandro Ventura, Giuliana Decorti, Luciana Vinti, Antonella Colombini, Erica Brivio, Laura Rachele Bettini, Ilaria Bini, Francesca Sismondi, Alessandra Mandese, Noelia Malusà, Stefano Martelossi, Marco Rabusin
Journal: Blood (2017)
Intradialytic Cerebral Hypoperfusion as Mechanism for Cognitive Impairment in Patients on Hemodialysis
Authors: Dawn F. Wolfgram
Journal: Journal of the American Society of Nephrology (2019)

The high frequency of cognitive impairment in individuals on hemodialysis is well characterized. In-center hemodialysis patients are disproportionately affected by cognitive impairment compared with other dialysis populations, identifying hemodialysis itself as a possible factor. The pathophysiology of cognitive impairment has multiple components, but vascular-mediated cerebral injury appears to contribute based on studies demonstrating increased cerebral ischemic lesions and atrophy in brain imaging of patients on hemodialysis. Patients on hemodialysis may be at increased risk for cerebral ischemic injury disease due to vasculopathy associated with ESKD and from their comorbid diseases, such as hypertension and diabetes. This review focuses on the intradialytic cerebral hypoperfusion that can occur during routine hemodialysis due to the circulatory stress of hemodialysis. This includes a review of current methods used to monitor intradialytic cerebral perfusion and the structural and functional cognitive outcomes that have been associated with changes in intradialytic cerebral perfusion. Monitoring of intradialytic cerebral perfusion may become clinically relevant as nephrologists try to avoid the cognitive complications seen with hemodialysis. Identifying the appropriate methods to assess risk for cerebral ischemic injury and the relationship of intradialytic cerebral hypoperfusion to cognitive outcomes will help inform the decision to use intradialytic cerebral perfusion monitoring in the clinical setting as part of a strategy to prevent cognitive decline.
Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-mediate gastrointestinal adverse events.
Authors: Vafa Shahabi, David Mark Berman, Scott D. Chasalow, Lisu Wang, Zenta Tsuchihashi, Beihong Hu, Lisa Panting, Maria Jure-Kunkel, Rui-Ru Ji
Journal: Journal of Clinical Oncology (2012)

8593 Background: Treatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for treatment of metastatic melanoma (MM), is associated with a number of immune-mediated Adverse Events (imAEs) such as colitis and skin rash. Predictive biomarkers that can help identify patients (pts) who might experience these imAEs could enhance the management of these toxicities. Methods: Gene expression profiling (using Affymetrix gene chip HT-HG-U133A) was performed on the whole blood samples from 162 MM pts at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and -007). Overall, 49 pts experienced Grade 2 or higher GI-imAE (G2+) during the course of treatment. A repeated measures ANOVA was used to evaluate the differences in mean expression levels between the two groups and at the three time points. Uncorrected p-value of 0.05 was used as a cutoff for this analysis. Results: In baseline samples, 27 probe sets showed differential mean expression (≥ 1.5 fold, p &lt; 0.05) between G2+ pts and others. Most of these genes belonged to three functional categories: immune system, cell cycle or intracellular trafficking. Changes in gene expression over time were also characterized. In the G2+ pts, 58 and 247 genes had a ≥ 1.5 fold (p &lt; 0.05) change in expression from baseline to week 3 and 11 post-treatment, respectively, compared to 17 and 73 in other pts. In particular, the on-treatment increases of the expression of CD177 and CEACAM1, two neutrophil activation markers, were closely associated with G2+ GI-imAE, suggesting a possible role of neutrophils in ipilimumab associated GI-imAEs. In addition, the expression of several Ig genes increased over time, with higher increases in the G2+ pts. These observations were reproduced in another ipilimumab monotherapy study in MM (CA184078). Conclusions: Gene expression profiling of peripheral blood resulted in the identification of a set of potential biomarkers that may be predictive of severe GI-imAEs before, or early in the course of treatment with ipilimumab. Further validation of these biomarkers in a larger patient cohort is warranted.
Analysis of Outcomes of Patients with Relapsed/Refractory Acute Myeloid Leukemia Treated in Randomized Clinical Trials
Authors: Raffi Tchekmedyian, Paul Elson, Aaron T. Gerds, Navneet Majhail, Hetty E. Carraway, Anjali S. Advani, Aziz Nazha, Jaroslaw P Maciejewski, Matt Kalaycio, Mikkael A. Sekeres, Sudipto Mukherjee
Journal: Blood (2016)
Spectrum of 18F-FDG Uptake in Bilateral Lung Parenchymal Diseases on PET/CT
Authors: Meghana Prabhu, Shobhana Raju, Dhritiman Chakraborty, Saurabh Arora, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2019)

Abstract Bilateral lung parenchymal involvement is seen in infective as well as noninfective conditions, appearing as focal or diffuse lung disease. PET/CT with FDG helps in characterization (increased glucose utilization is seen by both inflammatory and neoplastic cells). In this article, we describe the spectrum of patterns of FDG uptake and associated CT changes involving bilateral lung parenchyma. Benign conditions described are aspiration pneumonia; pulmonary toxicity by bleomycin; infections, namely, sarcoidosis, miliary pulmonary tuberculosis, and pulmonary nocardiosis; and inflammatory conditions such as pulmonary Langerhans cell histiocytosis and pulmonary alveolar proteinosis. Neoplastic conditions described are bilateral pulmonary metastases and lymphangitic carcinomatosis.
UK maternity services: audit finds wide variation in birth complications
Authors: Susan Mayor
Journal: BMJ (2019)

Birth complication rates and neonatal outcomes vary widely among maternity services around the UK, show clinical findings from the National Maternity and Perinatal Audit.1

Lesley Regan, president of the Royal College of Obstetricians and Gynaecologists, said, “National initiatives to improve maternal and neonatal care are making impressive headway to ensure services are as safe and personalised as possible for women. But this report highlights [that] marked variation in standards of care persist, particularly around birth complications, such as severe perineal tearing and obstetric haemorrhage.”

The audit analysed the clinical care and outcomes of …
Prospects for combining immune checkpoint blockade with PARP inhibition
Authors: Anping Li, Ming Yi, Shuang Qin, Qian Chu, Suxia Luo, Kongming Wu
Journal: Journal of Hematology & Oncology (2019)

Abstract The immunogenicity of a cancer cell is derived from accumulated somatic mutations. However, on the contrary to increased immunogenicity, anti-cancer immune response tends to be feeble. This impaired anti-cancer immunity could be attributed to multiple factors including loss of immunodominant epitopes, downregulation of major histocompatibility complex, and immunosuppressive microenvironment, as well as aberrant negative co-stimulatory signals. Immune checkpoint inhibitors block negative co-stimulatory signals such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, ultimately reactivating anti-cancer immunity. Immune checkpoint inhibitors elicit potent anti-cancer effect and have been approved for multiple cancers. Nevertheless, there still are significant potential improvements for the applications of checkpoint inhibitor, especially considering frequent resistance. Recent studies demonstrated that additional PARP inhibition could alleviate resistance and enhance efficacy of immune checkpoint blockade therapy via promoting cross-presentation and modifying immune microenvironment. We proposed that PARP inhibitors could enhance the priming and tumor-killing activities of T cell, boost the whole cancer-immunity cycle, and thereby improve the response to immune checkpoint blockade. In this review, we focused the latest understanding of the effect of PARP inhibitors on anti-cancer immunity and PARP inhibitors combining immune checkpoint blockade therapy. Moreover, we summarized the preclinical and clinical evidence and discussed the feasibility of this combination therapy in future clinical practice.
Unchecked immunity: a unique case of sequential immune-related adverse events with Pembrolizumab
Authors: N. Shah, J. Jacob, Z. Househ, E. Shiner, L. Baird, H. Soudy
Journal: Journal for ImmunoTherapy of Cancer (2019)

Background: Immune checkpoint inhibition has dramatically transformed the treatment of malignant melanoma.With increasing use, their unique spectrum of immune-mediated toxicity has become apparent.Case presentation: We describe a case of sequential immune-related adverse events (irAEs) in a patient with metastatic melanoma treated with single-agent anti-programmed cell death-1 (PD-1) therapy, pembrolizumab.Although numerous cases of irAEs have been reported, sequential multi-organ involvement, including progressive atopic dermatitis, vitiligo, autoimmune nephritis, autoimmune hepatitis, and autoimmune encephalitis after cessation of therapy, has not been previously documented.Conclusions: Immunosuppression resulted in clinical remission of each irAE, highlighting the importance of vigilance for autoimmune complications in patients treated with checkpoint inhibition, even after immunotherapy cessation.
Former GP partner who took images of patients in states of undress is struck off
Authors: Clare Dyer
Journal: BMJ (2019)

A GP partner who took covert mobile phone pictures of partly unclothed patients during examinations has been struck off the UK medical register.

Thair Altaii, 56, was convicted of three counts of voyeurism over six years and sentenced to 14 months’ imprisonment at Newcastle Crown Court in August 2018. He was also required to be on the register of sex …
Randomized Phase II Trial of Bevacizumab or Temsirolimus in Combination With Chemotherapy for First Relapse Rhabdomyosarcoma: A Report From the Children’s Oncology Group
Authors: Leo Mascarenhas, Yueh-Yun Chi, Pooja Hingorani, James R. Anderson, Elizabeth R. Lyden, David A. Rodeberg, Daniel J. Indelicato, Simon C. Kao, Roshni Dasgupta, Sheri L. Spunt, William H. Meyer, Douglas S. Hawkins
Journal: Journal of Clinical Oncology (2019)

The primary aim of this clinical trial was to prioritize bevacizumab or temsirolimus for additional investigation in rhabdomyosarcoma (RMS) when administered in combination with cytotoxic chemotherapy to patients with RMS in first relapse with unfavorable prognosis.Patients were randomly assigned to receive bevacizumab on day 1 or temsirolimus on days 1, 8, and 15 of each 21-day treatment cycle, together with vinorelbine on days 1 and 8, and cyclophosphamide on day 1 for a maximum of 12 cycles. Local tumor control with surgery and/or radiation therapy was permitted after 6 weeks of treatment. The primary end point was event-free survival (EFS). Radiographic response was assessed at 6 weeks. The study had a phase II selection that was design to detect a 15% difference between the two regimens (α = .2; 1-β = 0.8; two sided test).Eighty-seven of 100 planned patients were enrolled when the trial was closed after the second interim analysis after 46 events occurred in 68 patients with sufficient follow-up. The O'Brien Fleming boundary at this analysis corresponded to a two-sided P value of .058 with an observed two-sided P value of .003 favoring temsirolimus. The 6-month EFS for the bevacizumab arm was 54.6% (95% CI, 39.8% to 69.3%) and 69.1% (95% CI, 55.1% to 83%) for the temsirolimus arm. Objective response rates were 28% (95% CI, 13.7% to 41.3%) and 47% (95% CI, 31.5% to 63.2%) for the bevacizumab and temsirolimus arms, respectively (P = .12) and, 28% of patients on bevacizumab and 11% on temsirolimus had progressive disease at 6 weeks.Patients who received temsirolimus had a superior EFS compared with bevacizumab. Temsirolimus has been selected for additional investigation in newly diagnosed patients with intermediate-risk RMS.
Pituitary Adenoma on 18F-Fluciclovine PET/CT
Authors: Jiaqiong Wang, Mark Foley, Russ Kuker
Journal: Clinical Nuclear Medicine (2019)

Abstract A 69-year-old man presented with lower urinary tract symptoms and prostate biopsy showed prostate cancer. 18 F-Fluciclovine PET/CT revealed abnormal increased radiotracer uptake within the prostate gland, and multiple osseous structures, suspicious for tumoral involvement. Incidentally, an expansile soft tissue density mass arising from sella turcica demonstrated increased radiotracer activity. MRI showed a lobulated enhancing mass centered in the sella and eroding into the sphenoid sinus. The differential diagnosis includes pituitary macroadenoma versus prostate cancer metastasis. The tumor was resected and the pathological diagnosis was pituitary adenoma.
Population-level surveillance of antibiotic resistance in Escherichia coli through sewage analysis
Authors: Marion Hutinel, Patricia Maria Catharina Huijbers, Jerker Fick, Christina Åhrén, Dan Göran Joakim Larsson, Carl-Fredrik Flach
Journal: Eurosurveillance (2019)

IntroductionThe occurrence of antibiotic resistance in faecal bacteria in sewage is likely to reflect the current local clinical resistance situation.AimThis observational study investigated the relationship between Escherichia coli resistance rates in sewage and clinical samples representing the same human populations.MethodsE. coli were isolated from eight hospital (n = 721 isolates) and six municipal (n = 531 isolates) sewage samples, over 1 year in Gothenburg, Sweden. An inexpensive broth screening method was validated against disk diffusion and applied to determine resistance against 11 antibiotics in sewage isolates. Resistance data on E. coli isolated from clinical samples from corresponding local hospital and primary care patients were collected during the same year and compared with those of the sewage isolates by linear regression.ResultsE. coli resistance rates derived from hospital sewage and hospital patients strongly correlated (r2 = 0.95 for urine and 0.89 for blood samples), as did resistance rates in E. coli from municipal sewage and primary care urine samples (r2 = 0.82). Resistance rates in hospital sewage isolates were close to those in hospital clinical isolates while resistance rates in municipal sewage isolates were about half of those measured in primary care isolates. Resistance rates in municipal sewage isolates were more stable between sampling occasions than those from hospital sewage.ConclusionOur findings provide support for development of a low-cost, sewage-based surveillance system for antibiotic resistance in E. coli, which could complement current monitoring systems and provide clinically relevant antibiotic resistance data for countries and regions where surveillance is lacking.
A Prospective Study Identifying Predictive Factors of Cardiac Decompensation After Transjugular Intrahepatic Portosystemic Shunt: The Toulouse Algorithm
Authors: Chloé Billey, Sophie Billet, Marie Angèle Robic, Thomas Cognet, Maeva Guillaume, Jean Pierre Vinel, Jean Marie Péron, Olivier Lairez, Christophe Bureau
Journal: Hepatology (2019)

Background and Aims Transjugular intrahepatic portosystemic shunt (TIPS) is now a standard for the treatment of portal hypertension–related complications. After the TIPS procedure, incidence and risk factors of cardiac decompensation are poorly known. The main objectives were to measure the incidence of the onset of cardiac decompensation after TIPS and identify the predictive factors. Approach and Results All patients with cirrhosis treated with TIPS between May 2011 and June 2016 were considered for inclusion. They received a cardiac assessment by standard biological parameters, transthoracic echocardiography, and right heart catheterization. Patients were followed for 1 year after TIPS insertion. The main endpoint was the incidence of cardiac decompensation requiring hospitalization. One hundred seventy‐four patients were treated by TIPS during the period. One hundred patients who underwent a complete cardiac evaluation were included. A cardiac decompensation occurred in 20% of the patients. The parameters associated with the occurrence of severe cardiac decompensation were a prolonged QT interval corrected (462 vs. 443 ms; P = 0.05), an elevated pre‐TIPS brain natriuretic peptide (BNP) or N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) level, an elevated E/A ratio (1.5 vs. 1.0; P = 0.001) and E/e′ ratio (11 vs. 7; P &lt; 0.001), and a left atrial dilatation (40 vs. 29 mL/m 2 ; P = 0.011). The presence of aortic stenosis was also associated with cardiac decompensation. A level of BNP &lt;40 pg/mL and NT‐proBNP &lt;125 pg/mL allowed identifying patients without risk of cardiac decompensation. Additionally, absence of diastolic dysfunction criteria at echocardiography ruled out the risk of further cardiac decompensation. Conclusions Hospitalization for cardiac decompensation is observed in 20% of patients in the year after TIPS insertion. Combining BNP or NT‐proBNP levels and echocardiographic parameters should help improve patient selection.
Indirect Treatment Comparison (ITC) of Inotuzumab Ozogamicin (InO) and Blinatumomab (Blina) for Relapsed or Refractory (RR) Acute Lymphoblastic Leukemia (ALL)
Authors: Matthias Stelljes, Yun Su, Kyle Fahrbach, Erik Vandendries, Veronique Page, Uchenna Onyekwere, Yunyang Wang, Joseph C. Cappelleri, Irina Proskorovsky
Journal: Blood (2017)
Dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyposis: Pooled results from the SINUS-24 and SINUS-52 phase 3 studies
Authors: Claus Bachert, WJ Fokkens, R Jankowski, AU Cervin, TM Laidlaw, Se Lee, M Zhang, X Lu, N Amin, N Patel, Nmh Graham, M Ruddy, H Staudinger, LP Mannent
Journal: Allergy (2019)