tbuckley/cabot-search huggingface dataset:
PWE-438 Cholecystectomy audit: waiting time, readmissions and complications
Authors: MS Gill, C Doherty, J Veitch, M Brett
Journal: Gut (2015)

<h3>Introduction</h3> 15% of the UK adult population have gallstones. In those with symptomatic gallstone disease, laparoscopic cholecystectomy is the gold standard management.<sup>1</sup>There continues to be debate over whether patients should undergo definitive management at presentation or it should be delayed until inflammation has subsided. Guidelines suggest patients with acute cholecystitis should be offered cholecystectomy within 1 week<sup>1</sup>, while those with gallstone pancreatitis should receive therapeutic ERCP within 72 h followed by cholecystectomy within the same hospital admission, or within 2 weeks.<sup>2</sup> <h3>Method</h3> A retrospective audit of all cholecystectomies at the trust over a 1-year period was performed. Data extracted from electronic medical records (Medicorr) was collated using Microsoft Excel. Patient demographics, diagnosis at initial presentation, time to surgery, and rate and cause of readmission of those awaiting elective surgery were recorded. Chi-Squared analysis was performed to assess for a significant difference between elective and emergency lap-open conversion and complication rates. <h3>Results</h3> 477 patients were included. The median age was 51 years and 80% were female. The most common indications for cholecystectomy were biliary colic (69%) and cholecystitis (23%). The median wait for surgery was 81 days. The median wait for patients with acute cholecystits and gallstone pancreatitis was 69 and 62 days respectively. 8% of patients were readmitted while waiting. Those discharged after presenting with complicated gallstone disease (common bile duct stones or gallstone pancreatitis) were most likely to require readmission (27% and 24% respectively). Acute cholecystitis was the most common diagnosis on readmission (56%). 5 patients were readmitted with gallstone pancreatitis. The laparoscopic to open conversion rate was not significantly greater in emergency operations compared to elective (p &gt; 0.05). The complication rate of emergency operations, however, was significantly greater compared to elective (p &lt; 0.05). <h3>Conclusion</h3> Guidelines for performing urgent cholecystectomy for patients with gallstone pancreatitis and acute cholecystitis were not met for the majority of patients. A significant proportion were admitted to hospital while awaiting cholecystectomy, some with serious complications of gallstones. It appears that patients with complicated gallstones disease are more likely to be readmitted. We are continuing to collect data to attempt to identify high-risk patients. There may be a role for "elective-emergency" lists for such patients, to prevent complications developing. We plan to re-audit in one year to identify improvement. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> NICE Clinical Guidance 188 – Gallstone Disease British Society of Gastroenterology: UK guidelines for the management of acute pancreatitis. Gut 2005;54;1–9
Exploiting Mucosal Immunity for Antiviral Vaccines
Authors: Akiko Iwasaki
Journal: Annual Review of Immunology (2016)

Mucosal surfaces provide a remarkably effective barrier against potentially dangerous pathogens. Therefore, enhancing mucosal immunity through vaccines—strengthening that first line of defense—holds significant promise for reducing the burden of viral diseases. The large and varied class of viral pathogens, however, continues to present thorny challenges to vaccine development. Two primary difficulties exist: Viruses exhibit a stunning diversity of strategies for evading the host immune response, and even when we understand the nature of effective immune protection against a given virus, eliciting that protection is technically challenging. Only a few mucosal vaccines have surmounted these obstacles thus far. Recent developments, however, could greatly improve vaccine design. In this review, we first sketch out our understanding of mucosal immunity and then compare the herpes simplex virus, human immunodeficiency virus, and influenza virus to illustrate the distinct challenges of developing successful vaccines and to outline potential solutions.
Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study
Authors: N. Benito, M. Franco, A. Ribera, A. Soriano, D. Rodriguez-Pardo, L. Sorlí, G. Fresco, M. Fernández-Sampedro, M. Dolores del Toro, L. Guío, E. Sánchez-Rivas, A. Bahamonde, M. Riera, J. Esteban, J.M. Baraia-Etxaburu, J. Martínez-Alvarez, A. Jover-Sáenz, C. Dueñas, A. Ramos, B. Sobrino, G. Euba, L. Morata, C. Pigrau, P. Coll, I. Mur, J. Ariza, F. Barcenilla, F. Pérez-Villar, L. Prats-Gispert, R. Cisterna, S. Ibarra, Í. López, J.M. Santamaría, J. Cabo, D. García, J. Lora-Tamayo, O. Murillo, S. Pedrero, S. Álvarez-Parrondo, R. Muedra-Font, C. Raya-Fernández, C. Rodríguez-Alonso, A. Moreno, M.A. Blanco-Martínez-de-Morentin, R. Cabo-Magadan, A. Combalia, S. García, J.C. Martínez-Pastor, E. Tornero, J. Merino-Pérez, J.M. Montejo, A. Alier, J.P. Horcajada, V. Plasencia, L. Puig, Á. Auñon, A. Blanco, J. García-Cañete, E. Sandoval, M. Fakkas-Fernández, C. Garcés-Zarzalejo, C. Fariñas-Alvarez, M.C. Fariñas, L. Martinez-Martinez, C. Salas-Venero, J. Cobo, P. Ruiz-Carbajosa, M. Jordán, X. Crusi, C. Marinescu, F. Montaner, A. Ramírez, P.S. Corona, M. Lung, M.Á. Muniain-Ezcurra, C. Peñas-Espinar, A.I. Suárez, R. Álvarez, J.-A. Cordero, M. López-Pliego, J. Palomino, A. Puente
Journal: Clinical Microbiology and Infection (2016)
Treatment of clinically amyopathic dermatomyositis in adults: a systematic review
Authors: J. Callander, Y. Robson, J. Ingram, V. Piguet
Journal: British Journal of Dermatology (2016)

Clinically amyopathic dermatomyositis (CADM) affects a subset of 5-20% of patients with dermatomyositis and is defined as the presence of cutaneous features of dermatomyositis without clinical muscle weakness for ≥ 6 months. There is no consensus on first-line treatment for CADM and whether treatment should differ from treatment of classic dermatomyositis with muscle weakness. We carried out a systematic review of published literature about treatment of adult patients with CADM, via the Embase, Medline, CINAHL and ClinicalTrials.gov databases on 17 February 2015. The aim was to establish which treatments have been used for adult-onset CADM and what evidence is available regarding the efficacy of these treatments including topical treatments, dapsone, antimalarials, intravenous immunoglobulin (IVIG), nonsteroidal oral immunosuppressants and biological therapies. Eighteen cases series and 42 case reports were found. These provided data on 153 adult patients who met the inclusion criteria. No randomized controlled trials or robust observational studies were found. The majority of patients (60%) had tried more than one treatment due to side-effects or lack of efficacy. Antimalarial agents were the most commonly used treatment type. In the majority of patients (55%), antimalarial treatments were discontinued due to lack of improvement or inability to wean concomitant steroids. IVIG was the treatment that led to improvement or remission in the greatest proportion of patients. Further robust, high-quality studies are needed to assess treatment efficacy in CADM without bias.
FBXO11 inactivation leads to abnormal germinal-center formation and lymphoproliferative disease
Authors: Christof Schneider, Ning Kon, Letizia Amadori, Qiong Shen, Friederike H. Schwartz, Benjamin Tischler, Marion Bossennec, David Dominguez-Sola, Govind Bhagat, Wei Gu, Katia Basso, Riccardo Dalla-Favera
Journal: Blood (2016)
RT-15 * IMPACT OF CHANGING TRENDS OF TREATMENT ON OUTCOME OF GLIOSARCOMA: A TERTIARY CARE CENTER EXPERIENCE
Authors: N. Kumar, T. Bhattacharyya, K. Chanchalani, R. Kumar, P. Shalunke, B. D. Radotra, B. S. Yadav, S. Ghoshal
Journal: Neuro-Oncology (2014)

AIM: To assess the clinicopathological features and outcome in patients of primary gliosarcoma with changing trends of treatment. MATERIALS AND METHODS: Medical records were reviewed over a 5yearsperiod from 2009 to2013 of Gliosarcoma treated in the department. All patients who received 3D-Conformal Radiotherapy (3DCRT) with or without concurrent and adjuvant Temozolomide post surgery were included in the analysis. RESULTS: A total 27 patients were included in this study. Median age of presentation was 54 years (rang9-69 years), male to female ratio was 1.25:1, median KPS at presentation was 70. At presentation all patients had raised intracranial tension with motor symptoms in 48.1%, Memory impairment in 6 patients, Seizures and dimness of vision was seen in 18.5% and 11.1% cases respectively. Most common location of the tumour was temporal lobe (48.1%).About 60% (n = 16) patients underwent Gross total resection. On histopathological examination all patients showed biphasic pattern with glial fibrillary acidic protein positivity for (GFAP) glial component and vimentin positivity for mesenchymal component. Twenty three (80.8%) patients received radical radiotherapy i.e. 60 Gy/30#/6 weeks and 4 patients received hypo-fractionated radiotherapy 40 Gy in 15 fractions in 3 weeks. Eleven (42.3%) patients received Concurrent and adjuvant Temozolomide. Median overall survival of our patients was 9 months. Six months survival in the chemo-radiation arm was 82% as compared to 58% seen in patients who were treated with radiotherapy alone. CONCLUSION: Treating Gliosarcoma is a major therapeutic challenge to a clinician because of its poor prognosis, aggressive clinical behavior, rarity and limited clinical experience. Addition of Temozolomide has shown a better trend in survival though it is statistically not significant
Case 25-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Mark E. Molitch, Sara E. Kirkham
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 30-year-old man was admitted to the hospital because of hypogonadism.He was well until four years earlier, when diminished libido developed, followed by reduced volume of ejaculate and then by impotence. His muscle mass diminished, his strength decreased, and he noticed loss of body hair. On evaluation elsewhere x-ray films of the skull were normal. The prolactin was normal; basal and stimulated values of Cortisol, thyroxine, and human growth hormone were also normal; the testosterone, follicle-stimulating hormone, and luteinizing hormone were low and did not respond to stimulation. He was referred to this hospital.The patient . . .
Use and Costs of Disease Monitoring in Women With Metastatic Breast Cancer
Authors: Melissa K. Accordino, Jason D. Wright, Sowmya Vasan, Alfred I. Neugut, Grace C. Hillyer, Jim C. Hu, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2016)

Purpose The optimal frequency of monitoring patients with metastatic breast cancer (MBC) is unknown; however, data suggest that intensive monitoring does not improve outcomes. We performed a population-based analysis to evaluate patterns and predictors of extreme use of disease-monitoring tests (serum tumor markers [STMs] and radiographic imaging) among women with MBC. Methods The SEER-Medicare database was used to identify women with MBC diagnosed from 2002 to 2011 who underwent disease monitoring. Billing dates of STMs (carcinoembryonic antigen and/or cancer antigen 15-3/cancer antigen 27.29) and imaging tests (computed tomography and/or positron emission tomography) were recorded; if more than one STM or imaging test were completed on the same day, they were counted once. We defined extreme use as &gt; 12 STM and/or more than four radiographic imaging tests in a 12-month period. Multivariable analysis was used to identify factors associated with extreme use. In extreme users, total health care costs and end-of-life health care utilization were compared with the rest of the study population. Results We identified 2,460 eligible patients. Of these, 924 (37.6%) were extreme users of disease-monitoring tests. Factors significantly associated with extreme use were hormone receptor–negative MBC (odds ratio [OR], 1.63; 95% CI, 1.27 to 2.08), history of a positron emission tomography scan (OR, 2.92; 95% CI, 2.40 to 3.55), and more frequent oncology office visits (OR, 3.14; 95% CI, 2.49 to 3.96). Medical costs per year were 59.2% higher in extreme users. Extreme users were more likely to use emergency department and hospice services at the end of life. Conclusion Despite an unknown clinical benefit, approximately one third of elderly women with MBC were extreme users of disease-monitoring tests. Higher use of disease-monitoring tests was associated with higher total health care costs. Efforts to understand the optimal frequency of monitoring are needed to inform clinical practice.
OP0009 OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response
Authors: C. Jacquemin, N. Schmitt, C. Contin-Bordes, C. Richez, E. Lazaro, P. Duffau, M.-E. Truchetet, V. Pascual, H. Ueno, P. Blanco
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory autoimmune disease characterized by a breakdown of tolerance to nuclear antigens. Antigen-presenting cells including dendritic cells (DCs) are aberrantly activated in SLE patients, and promote the activation of autoreactive T and B cells. Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh responses in SLE remain elusive. <h3>Objectives</h3> To identify the mechanisms responsible for Tfh activation in human SLE. <h3>Methods</h3> Adult SLE patients (total 61: 53 females and 8 males) and pediatric SLE patients (total 38: 34 females and 4 males) who met the American College of Rheumatology revised criteria for SLE (Hochberg, 1997) were enrolled. All clinical and biologically relevant information were collected. For the analysis of OX40L expression, whole blood samples were stained with anti- CD14-PC5, CD16-FITC, CD11c-APC, HLA-DR-PC7, and OX40L-PE mAbs, and red blood cells were lysed with Versalyse. For the analysis of blood Tfh cells, whole blood samples were stained with anti-CXCR5-AF488, CCR6-PE, CXCR3- PC5, CCR4-PC7, CD3-AF700, CD8-APCH7, CD4-Pacific Blue CD45RA-ECD, ICOS-APC and CD45-Pacific Orange. Naïve and memory Th cells were sorted by flow cytometry, stimulated overnight in the presence or absence of sOX40L. Extensive phenotype and transcriptomic analysis was done. <h3>Results</h3> We show that the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid APCs, but not by B cells, in blood as well as in inflamed tissues in adult and pediatric active SLE patients. OX40L stimulation induced human CD4<sup>+</sup> helper T (Th) cells to express Tfh-associated molecules, and was sufficient to induce them to become functional B cell helpers. We found that OX40 signals promote the expression of Tfh molecules by enhancing TCR signals, in addition to the modulation of NF-kB pathway. Finally, we show that immune complexes (ICs) containing ribonucleoprotein (RNP) present in lupus sera induce OX40L expression by myeloid APCs through activation of TLR7. Thus, our study shows that the RNP IC-OX40L axis likely provides an amplification loop of the generation of autoantibodies in SLE. <h3>Conclusions</h3> Our study provides a rationale that therapeutic modalities targeting the RNP-containing IC-OX40L-OX40 axis and TLR7 could impact the development of autoantibodies and therefore be beneficial for human SLE. <h3>Acknowledgements</h3> This work was supported by grants from Arthritis fundation and Société Française de Rhumatologie. <h3>Disclosure of Interest</h3> None declared
Clinical Implications of Guanine Nucleotide–Binding Proteins as Receptor–Effector Couplers
Authors: Jeffrey S. Flier, Lisa H. Underhill, Allen M. Spiegel, Peter Gierschik, Michael A. Levine, Robert W. Downs
Journal: New England Journal of Medicine (1985)

IT has long been known that some cellular proteins bind guanine nucleotides such as guanosine tri-phosphate (GTP) with high affinity. These binding proteins are called G proteins and have been linked to such critical intracellular functions as protein synthesis.1 In the past decade three new G proteins have been discovered that reside in the plasma membrane and transmit information from the outside to the inside of the cell. Two of these new G proteins form part of the adenylate cyclase system, a membrane-bound enzyme complex found in virtually every cell, and the third G protein is found in the disk . . .
PTU-006 Glove port trans anal excision of rectal tumours
Authors: S Dharmavaram, M Nistor, K Badrinath
Journal: Gut (2015)

<h3>Introduction</h3> Transanal glove port excision is a safe minimally invasive procedure for excising rectal tumours that avoids major rectal surgeries and its complications. The aim of this study is to review a single Centre experience with Trans Anal Glove Port excision of rectal tumours. <h3>Method</h3> Between 2011–2014, 11 patients underwent resection of benign (N = 9) or Malignant (N = 2) rectal tumours, located above the dentate line to 14 cm. The mean follow up period was between 6–12 months. Glove port was constructed using circular anal dilator, standard surgical glove and a wound protector retractor. <h3>Results</h3> All the patients underwent Glove port transanal excision of rectal tumours. Male: Female ratio was 10:1. Average age of patients was 63 years. None of the patients in the series underwent conversion to radical surgery. Full thickness excision of the tumour was performed in 9 patients and the other two underwent submucosal excision. During the follow up period between 6–12 months, 1 patient had recurrent tubulo villous adenoma, which needed further excision of the adenoma. In two patients who had a planned glove port excision for a presumed benign rectal polyp (Tubulo villous adenoma), The final histology showed an adenocarcinoma on a background of Tubulo-villous adenoma. Both the Patients underwent further staging investigations, one patient had a further chemo-radiotherapy and the other patient did not need any further treatment. Both are under close surveillance with no recurrence. Post-operative complications were only mild which included bleeding and mucus discharge. <h3>Conclusion</h3> Glove port Trans anal excision is a safe, effective and cheap technique useful in excising rectal tumours with good clearance and full thickness excision of the rectal wall where necessary. It helps avoid major rectal resections with its attendant complications, in many cases. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Alessandro C, Daniela M, Michele M, <i>et al</i>. Glove port technique for transanal endoscopic microsurgery. <i>Int J Surg Oncol</i>. 2012;2012:Article ID 383025,1–4
NHS workforce planning is in disarray, MPs warn
Authors: Gareth Iacobucci
Journal: BMJ (2016)

MPs have urged the government to review levels of NHS clinical staffing in England after they found that there had been “no coherent attempt” to assess the headcount implications of the government’s proposal for seven day services.

In a new report published on Wednesday 11 May the House of Commons Committee of Public Accounts raised serious concerns about the NHS workforce with regards to supply, budgeting, agency costs, and leadership.1

The committee said that the Department of Health and other national bodies had failed to provide effective support to tackle current and future workforce pressures, and it urged them “to get a better grip” on the supply of medical and nursing staff.

The report criticised the health department for failing to provide separate costing for seven day services and other major policy initiatives and questioned whether the extra £10bn (€12.7bn; $14.4bn) in …
Identification of sentinel health events as indicators of environmental contamination.
Authors: C J Rothwell, C B Hamilton, P E Leaverton
Journal: Environmental Health Perspectives (1991)

The consensus process was applied to addressing a public health topic; this was a novel endeavor. The following question was addressed: What role, if any, should sentinel health events play in the decision-making process for identifying the effects of environmental exposure? The panel developed three levels of sentinel health events lists: those that are clearly identifiable, those that are potential signs, and those that are indicators of body burdens. Additionally, the panel developed several salient statements regarding the principles of environmental health surveillance and, especially, recommendations for future research.
Aging and Autophagy in the Heart
Authors: Akihiro Shirakabe, Yoshiyuki Ikeda, Sebastiano Sciarretta, Daniela K. Zablocki, Junichi Sadoshima
Journal: Circulation Research (2016)

The aging population is increasing in developed countries. Because the incidence of cardiac disease increases dramatically with age, it is important to understand the molecular mechanisms through which the heart becomes either more or less susceptible to stress. Cardiac aging is characterized by the presence of hypertrophy, fibrosis, and accumulation of misfolded proteins and dysfunctional mitochondria. Macroautophagy (hereafter referred to as autophagy) is a lysosome-dependent bulk degradation mechanism that is essential for intracellular protein and organelle quality control. Autophagy and autophagic flux are generally decreased in aging hearts, and murine autophagy loss-of-function models develop exacerbated cardiac dysfunction that is accompanied by the accumulation of misfolded proteins and dysfunctional organelles. On the contrary, stimulation of autophagy generally improves cardiac function in mouse models of protein aggregation by removing accumulated misfolded proteins, dysfunctional mitochondria, and damaged DNA, thereby improving the overall cellular environment and alleviating aging-associated pathology in the heart. Increasing lines of evidence suggest that autophagy is required for many mechanisms that mediate lifespan extension, such as caloric restriction, in various organisms. These results raise the exciting possibility that autophagy may play an important role in combating the adverse effects of aging in the heart. In this review, we discuss the role of autophagy in the heart during aging, how autophagy alleviates age-dependent changes in the heart, and how the level of autophagy in the aging heart can be restored.
Bipolar affective disorder and high achievement: a familial association
Authors: W Coryell, J Endicott, M Keller, N Andreasen, W Grove, R M Hirschfeld, W Scheftner
Journal: American Journal of Psychiatry (1989)

The authors studied 442 probands with nonbipolar major depression, 64 with bipolar II disorder, and 88 with bipolar I disorder. Although the proband groups did not differ in occupational or educational achievement, the first-degree relatives of probands with bipolar disorders had significantly higher mean levels of achievement than did those of probands with nonbipolar disorder. This pattern applied whether or not the relatives themselves had bipolar illness. The authors conclude that the socioeconomic advantage previously associated with affective disorder in general may be limited to the bipolar forms.