tbuckley/cabot-search huggingface dataset:
PTU-077 Unplanned hospital readmission within 30 days after liver and pancreatic resection
Authors: E L Neo, E Viñuela, S R Bramhall, J Isaac, R Marudanayagam, D Mayer, D F Mirza, P Muiesan, R P Sutcliffe
Journal: Gut (2012)

<h3>Introduction</h3> Due to limited resources within the NHS, clinicians in the UK are under constant pressure to discharge patients rapidly, even after major surgery. There is a concern that premature discharge may lead to high readmission rates and worsen clinical outcomes. The aim of this study was to evaluate the incidence and outcome of unplanned hospital readmission after liver and pancreatic resection. <h3>Methods</h3> Patients who underwent liver or pancreatic resection between January and December 2010 were identified from a prospective database. Potential risk factors for unplanned readmission within 30 days of discharge from hospital were evaluated. Complications (Clavien grade) and 90-day mortality were also assessed. <h3>Results</h3> The median lengths of hospital stay after liver and pancreatic resections were 6 (range 4–66) and 9 days (range 5–225), respectively. 14/174 (8%) patients were readmitted after hepatic resection. Type of liver resection was significantly associated with readmission (major 12.5% vs minor 3%; p=0.03). Of the readmitted patients, 7 (50%) had grade 3 complications, including four patients who had an uncomplicated index admission, and two patients died due to sepsis. 10/100 (10%) patients were readmitted after pancreatic resection. Readmission was more likely in patients with a pancreatic fistula (30% vs 8%, p=0.06) and a white cell count &gt;16×10<sup>9</sup>/L at the time of discharge (50% vs 6%, p&lt;0.001). Of the readmitted patients, 4 (40%) had grade 3 complications, including three patients who needed embolisation to control bleeding (two patients in this group died within 24 h). <h3>Conclusion</h3> Hospital readmission rates after hepatic and pancreatic resection are acceptable. However, readmitted patients have a very high morbidity, often requiring urgent intervention only available at a specialist centre. Efficient communication and rapid transfer of patients to a centre with the available expertise is vital to prevent delayed deaths after major surgery. <h3>Competing interests</h3> None declared.
Problems in the Management of Attention-Deficit–Hyperactivity Disorder
Authors: Alan J. Zametkin, Monique Ernst
Journal: New England Journal of Medicine (1999)

Despite several name changes over the past 50 years, the current diagnosis of attention-deficit–hyperactivity disorder (ADHD) shares the core group of symptoms — impulsivity, inattention, and motor restlessness — with earlier terms such as minimal brain dysfunction, hyperactive child syndrome, and attention-deficit disorder with or without hyperactivity. The disorder is extremely common, affecting approximately 4 percent of all children, although estimates vary widely, from 3 to 11 percent or more.1,2 The cause of ADHD remains unknown.The presentation, although highly variable, is captured in the following vignettes:The parents of a nine-year-old boy are seeking help because their son . . .
Abstract 1249: Modulation of epidermal growth factor induction of migration by integrin-linked kinase
Authors: Lina Dagnino, Ernest Ho
Journal: Cancer Research (2012)

Abstract Epidermal growth factor (EGF) signaling is central for proliferation, survival and motility in epithelial cells. Cell migration is an obligatory prerequisite for metastasis and requires the development of front-rear polarity. EGF stimulation in various epithelial cell types induces formation of protrusions and migration via RhoG and Rac1 activation. We now demonstrate that treatment of primary epidermal keratinocytes with EGF, but not with other growth factors that promote cell migration, induces cell polarization mediated by complexes containing RhoG, integrin-linked kinase (ILK) and “Engulfment and Cell Motility-2” (ELMO2). This process requires the tyrosine kinase activity of the EGF receptor. Further, ELMO2, ILK, Rac1 and integrin beta1 are obligatory effectors in this pathway, as inactivation or knockdown of the genes or mRNA encoding these proteins abrogates the stimulatory effect of EGF. Thus, we have identified a novel pathway that links EGF receptor stimulation with RhoG/ELMO2/ILK complexes and activation of Rac1 in the acquisition of front-rear polarity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1249. doi:1538-7445.AM2012-1249
Abstract 2213: Identification of novel cancer mutations in sarcomas
Authors: Ogan D. Abaan, Princy Francis, Marbin Pineda, Robert L. Walker, Sven Bilke, Sean R. Davis, Paul S. Meltzer
Journal: Cancer Research (2010)

Abstract Understanding of how cancer initiates and progresses is the fundamental of cancer research. Identification of cancer mutations is of profound importance for both understanding of the disease and for developing novel therapies. To search novel cancer mutations, we have utilized a “targeted resequencing” approach to resequence coding exons from about 1300 genes in a panel of various sarcoma patient samples. We used the previously published method of “In-solution capture” to enrich for regions of interest and resequenced the enriched population on an Illumina GAII platform using single-ended or paired ended reads. The performance and depth of the enrichment and resequencing was adequate for variant calling. We obtained roughly 70% on genome reads and about 30% of the reads fall on target while about 40% of the reads fall on target±500bp. An in house variant calling script was used for SNP/variant calling. Each sample yielded multiple genes with novel variations some of which are either missense or nonsense and in a highly conserved residue that were also previously identified in other cancers as well. Preliminary results from samples resequenced so far demonstrate that these sarcoma samples have variations in a variety of genes with diverse functions, including but not limited to signaling pathway intermediates. In conclusion, our work will be important in cataloging novel cancer mutations in rare sarcomas, with potential implications for understanding their biology and the development of new therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2213.
Collision Lung Cancer on F-18 FDG PET/CT
Authors: Motohiro Sato, Takashi Abe, Yuta Ito, Ken Koyama, Yasutaka Hayashi
Journal: Clinical Nuclear Medicine (2011)

We report a case of a primary collision lung cancer consisting of squamous cell carcinoma and adenocarcinoma. A 73-year-old man with an abnormality found on chest radiograph in the right lower lobe was examined by FDG PET/CT (F-18 fluorodeoxyglucose positron emission tomography/computed tomography). The tumor was composed of 2 different morphologic and FDG accumulation portions and a collision tumor was suspected. Histopathologically, this tumor was composed of squamous cell carcinoma and adenocarcinoma. Each element was clearly distinguished but touched. FDG PET/CT is a useful tool to diagnose collision tumor as it shows morphologic and metabolic differences between 2 distinct tumor components.
A Simple Test for the Diagnosis of Absorptive, Resorptive and Renal Hypercalciurias
Authors: Charles Y.C. Pak, Roy Kaplan, Henry Bone, Judith Townsend, Oralee Waters
Journal: New England Journal of Medicine (1975)

A test was developed to diagnose various forms of hypercalciuria. A two-hour urine sample after an overnight fast and a four-hour urine sample after 1 g of calcium by mouth were tested for calcium, cyclic AMP and creatinine. The 24 patients with absorptive hypercalciuria had normocalcemia and normal fasting urinary calcium (< 0.11 mg per milligram of urinary creatinine). Urinary calcium was high (≥ 0.2 mg per milligram of creatinine) after a calcium load. Of the 28 patients with primary hyperparathyroidism (resorptive hypercalciuria), 25 had hypercalcemia and 21 had high fasting urinary calcium. Urinary cyclic AMP, elevated in 30 per cent of fasting patients, was high (> 4.60 μ moles per gram of creatinine) in 82 per cent of cases after calcium load. Six patients with renal hypercalciuria had normocalcemia, high fasting urinary calcium, and high (> 6.86 μ moles per gram of creatinine) or high-normal fasting urinary cyclic AMP. After a calcium load, urinary cyclic AMP was normal. This simple test should facilitate the differentiation of various causes of hypercalciuria. (N Engl J Med 292:497–500, 1975)
Indole Metabolism in the Malabsorption Syndrome
Authors: Bernard J. Haverback, Barbara Dyce, Heriberto V. Thomas
Journal: New England Journal of Medicine (1960)

PREVIOUS studies have demonstrated that the excretion of the serotonin metabolite, 5-hydroxyindoleacetic acid, is elevated in patients with nontropical sprue.1 , 2 Other studies have shown that when a patient with nontropical sprue is placed on a gluten-free diet and remission occurs, excretion reverts to normal levels.3 When urinary extracts from a patient with nontropical sprue were subjected to paper chromatography for assay of 5-hydroxyindoleacetic acid large amounts of another indole compound were discovered. It was determined that this substance was indole-3-acetic acid, and the daily urinary excretion of this substance was in the order of 200 mg. daily — a marked . . .
Case 18-2014
Authors: Susan Burgin, John H. Stone, Anuradha S. Shenoy-Bhangle, Declan McGuone
Journal: New England Journal of Medicine (2014)

A 32-year-old man was admitted to this hospital because of a violaceous eruption that was followed by muscle pain and weakness, leading to respiratory failure. New papules with white centers developed. A diagnostic procedure was performed.
Comparison of cetuximab (Cmab) with panitumumab (Pmab) monotherapy in salvage line against <i>KRAS</i> wild-type patients with metastatic colorectal cancer (mCRC): Analysis of HGCSG0901 and 1002.
Authors: Akira Ueda, Satoshi Yuki, Takahide Sasaki, Yoshimitsu Kobayashi, Ayumu Hosokawa, Ayako Doi, Yasushi Tsuji, Hiroyuki Okuda, Takashi Kato, Yutaka Watanabe, Takuto Miyagishima, Kazunori Eto, Tomoyuki Ohta, Takenori Takahata, Shinichiro Ikeda, Hiroshi Nakatsumi, Kazuhiro Iwai, Kanji Kato, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2014)

663 Background: Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) such as Cmab and Pmab have antitumor activity and acceptable safety profiles in patients (pts) with mCRC. Monotherapy with Cmab or Pmab demonstrated the effectiveness in salvage-line, and the direct comparison was reported in ESMO 2013 (ASPECCT trial). Methods: Data of 31 pts with mCRC treated by monotherapy with Cmab (HGCSG0901) and 51 pts by monotherapy with Pmab (HGCSG1002) registered from 27 institutions in Japan. Comparison of Cmab with Pmab was retrospectively analyzed. All patients with KRAS wild type were refractory to or intolerant for 5-FU/irinotecan/oxaliplatin and also were never administered anti-EGFR-antibodies. Survival analyses were performed with Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Patient characteristics were as below (Cmab vs. Pmab); male/female 20/11 vs. 27/24, median age (range) 65(44-76) vs. 64(44-81), PS 0-1/2-3 21/10 vs. 46/5, number of metastatic organs 1-2/3- 22/9 vs. 25/16. Skin toxicity was common adverse events and was generally similar in two groups. MST was 8.4 months in the Cmab and 8.1 months in the Pmab (p = 0.32). PFS was 3.8 months in the Cmab, as compared with 3.1 months in the Pmab (p = 0.60); the corresponding response rate was 19.4% and 13.7% (p = 0.54). After adjusting other prognostic factors with Cox proportional hazard model, the administration of Cmab/Pmab made significant difference neither for OS (HR 0.939, 95% CI 0.783-1.128, p = 0.503), nor PFS (HR 0.972, 95% CI 0.823-1.148, p = 0.735). Conclusions: In this integration analysis of two studies, there were no significant difference in efficacy between Cmab and Pmab monotherapy in the salvage-line treatment of pts with mCRC.
A Sweet Source of Abdominal Pain
Authors: Shari S. Rogal, Chinweike Ukomadu, Bruce D. Levy, Joseph Loscalzo
Journal: New England Journal of Medicine (2011)

A 25-year old woman presented for evaluation of abdominal pain. Her discomfort had begun 6 months earlier and was localized to the right upper quadrant. She described a constant pressure unrelated to food intake and associated with intermittent nausea and vomiting.
AB0911 Hip involvement in patients with ankylosing spondylitis
Authors: I.-H. Sung, T.-H. Kim, Y.-S. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing spondylitis(AS) is characterized by inflammation of the sacroiliac joints and spine, resulting in narrowing, sclerosis, erosions and ankylosis. Hip joint involvement in ankylosing spodylitis patients is clearly related to restricted body function due to the important and central function of the hip. However, it seems that limited data are available regarding the epidemiology, and the pathophysiological nature of hip joint involvement. <h3>Objectives</h3> Therefore, we described the epidemiology of hip joint involvement in patients with AS, association of hip joint involvement, factors associated with severe hip destruction, leading to the replacement surgery. <h3>Methods</h3> 1198 patients with AS (1029 men, 169 women, mean age 33.4 years) were recruited for this study. Radiographs of pelvis and hips were scored by using the Bath Ankylosing Spondylitis Radiology Index (BASRI), and the involvement of hip was determined when the score was above 2. Frequency of hip involvement by age, sex, duration of disease, age at onset of AS symptoms, history of uveitis, peripheral arthritis, enthesitis, and HLA-B27 carrier status was analyzed. Statistical analyses were performed using t-tests for continuous measures, and χ2 tests for categorical measures. <h3>Results</h3> The mean age (SD) of the AS patients was 33.4 (9.9) years. The mean onset age (SD) was 22.7 (8.9) years. The mean disease duration (SD) was 10.7 (7.7) years. The male was 1029 (85.9%) patients. 474 patients (39.6%) were found to have a history of peripheral arthritis. 367 (30.6%) patients were found to have a history of radiographic hip joint involvement. 257 (21.5%) patients was found to have JoAS. 1150 (96.0%) patients were HLA-B27 carrier. 332 (27.7%) patients were found to have a history of uveitis. 317 (26.5%) patients were found to have an evidence of enthesitis around pelvic bone and trochanteric areas. The hip involvement was observed more frequently in male patients. The mean age (SD) of hip joint involvement group was 34.7 (9.7) years, and that was significantly higher than that of control group. The patients of hip joint involvement had an earlier disease onset and a longer disease duration. History of uveitis, enthesitis, and HLA-B27 carrier state were more frequent in the hip involvement group. However, there was no significant difference of peripheral arthritis between two groups. <h3>Conclusions</h3> In conclusion, the hip involvement is a common disease manifestation of AS. Long-term studies are needed to evaluate the effect of therapeutic strategies that can prevent hip involvement and the need for hip replacement surgery. <h3>Disclosure of Interest</h3> None Declared
Overwhelming Pulmonary Blastomycosis Associated with the Adult Respiratory Distress Syndrome
Authors: Keith C. Meyer, Edward J. McManus, Dennis G. Maki
Journal: New England Journal of Medicine (1993)

Few cases of overwhelming pulmonary blastomycosis associated with the adult respiratory distress syndrome have been reported. We describe 10 patients with this condition who were treated at one center in Wisconsin.All 10 patients presented with fever, cough, and dyspnea; radiographic evidence of diffuse pulmonary infiltrates; and marked impairment of oxygenation. The mean alveolar-arterial oxygen gradient was 616 mm Hg. Six of the patients had no underlying disease associated with altered immunity, and two had no recent exposure to environmental reservoirs of Blastomyces dermatitidis. In all 10 patients, large numbers of broad-based budding yeasts were seen on microscopical examination of tracheal secretions. All patients were treated with intravenous amphotericin B (0.7 to 1.0 mg per kilogram per day). Of the five survivors, four received full doses of amphotericin B in the first 24 hours, and four required mechanical ventilatory support for 7 to 151 days. Long-term follow-up of three survivors showed good recovery of pulmonary function.Overwhelming infection with B. dermatitidis can cause diffuse pneumonitis and the adult respiratory distress syndrome, even in immunocompetent hosts. With prompt diagnosis by microscopical examination of tracheal secretions, intensive therapy with amphotericin B, and ventilatory support, good recovery of pulmonary function is possible.
P2-07-02: Germline Genetic Variants Disturbing the Let-7/LIN28 Double-Negative Feedback Loop Alter Breast Cancer Susceptibility.
Authors: K-D Yu, Z-M Shao, A-X Chen
Journal: Cancer Research (2011)

Abstract Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28, in turn, could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP) located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7-induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn downregulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300) demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR) of 1.25 (P = 0.0091), which was successfully replicated in a second independent study (n = 1,156) with community-based controls. The combined P-value of the two studies was 8.0 × 10−5. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-07-02.
SP0067 Osteocytes and Osteoclasts: Crosstalk in Osteoimmunology
Authors: H. Takayanagi
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The immune and skeletal systems share various molecules, including cytokines, transcription factors, signaling molecules and membrane receptors(1). RANKL is a key cytokine for osteoclast differentation expressed by msenchymal cells including osteoblastic cells as well as hematopoietic cells like T cell, thus it has been difficult to precisely characterize RANKL-expressing cells under physiological and pathological settings (2). The source of RANKL in bone has been thought to be osteoblasts or bone marrow stromal cells, but osteocyte-specific RANKL knockout mice revealed the crucial role of osteocytes in supporting osteoclastogenesis in adult bone remodeling (3). In autoimmune arthritis, RANKL is expressed by joint mesenchymal cells like synovial fibroblasts stimulated with IL-17 and other inflammatory cytokines. RANKL signal transduction is mediated by numerous immune-related molecules including NFATc1 and ITAM, which shed light on the mechanisms shared by the bone and the immune systems (2). Here I will review the history of osteoimmunology and discuss the emerging topics in osteoimmunology including bone cell communication factors in the regulation of bone formation by osteoclast-derived Sema4D (4) and osteoprotection by osteoblast-derived Sema3A (5). <h3>References</h3> Nat Rev Immunol 7, 292-304, 2007 Nat Rev Rheumatol 5, 667-76, 2009 Nat Med 17, 1231-34, 2011 Nat Med. 17, 1473-80, 2011 Nature 485, 69-74, 2012 <h3>Disclosure of Interest</h3> None Declared
Abstract 3112: The homeoprotein DLX4 induces topoisomerase IIα expression but reduces sensitivity of tumor cells to topoisomerase II poisons.
Authors: Bon Q. Trinh, Song Yi Ko, Nicolas Barengo, Shiaw-Yih Lin, Honami Naora
Journal: Cancer Research (2013)

Abstract Chemotherapeutic drugs such as anthracyclines and etoposide that target topoisomerase II (TOP2) induce tumor cell death by causing accumulation of DNA double-strand breaks (DSBs). Experimental studies have shown that overexpression of topoisomerase IIα (TOP2A) increases sensitivity to TOP2 poisons. However, the clinical value of TOP2A in predicting responsiveness to TOP2 poisons has been controversial and it is not known why some TOP2A-overexpressing tumors respond poorly to these drugs. We identified that expression of TOP2A, the gene encoding TOP2, is induced by DLX4, a homeoprotein that is overexpressed in breast and ovarian cancers. Analysis of breast cancer datasets revealed that TOP2A-High cases that expressed DLX4 at low levels responded more favorably to anthracycline-based chemotherapy than TOP2A-High cases that also highly expressed DLX4. Overexpression of TOP2A alone in tumor cells increased sensitivity to TOP2 poisons. However, DLX4 decreased sensitivity to these drugs irrespective of its induction of TOP2A. We identified that DLX4 stimulates repair of DSBs and interacts with Ku proteins that are components of the non-homologous end-joining machinery. DLX4 did not reduce levels of TOP2 poison-induced DSBs in Ku-deficient cells, but reduced the level of DSBs when Ku was reconstituted in these cells. Taken together, our findings indicate that DLX4 induces TOP2A expression, but reduces the sensitivity of tumor cells to TOP2 poisons by stimulating Ku-dependent repair of DSBs. These dual and opposing effects of DLX4 could explain why some tumors with elevated TOP2A levels are not highly sensitive to TOP2 poisons. Citation Format: Bon Q. Trinh, Song Yi Ko, Nicolas Barengo, Shiaw-Yih Lin, Honami Naora. The homeoprotein DLX4 induces topoisomerase IIα expression but reduces sensitivity of tumor cells to topoisomerase II poisons. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3112. doi:10.1158/1538-7445.AM2013-3112
Somatic <i>PIK3CA</i> mutations as a driver of sporadic venous malformations
Authors: Pau Castel, F. Javier Carmona, Joaquim Grego-Bessa, Michael F. Berger, Agnès Viale, Kathryn V. Anderson, Silvia Bague, Maurizio Scaltriti, Cristina R. Antonescu, Eulàlia Baselga, José Baselga
Journal: Science Translational Medicine (2016)

PIK3CA mutations induce venous malformations.