tbuckley/cabot-search huggingface dataset:
PTU-284 Linked primary care and hospital database analysis of trends in laparoscopy, short-term complications and recurrence following inguinal hernia repair in england
Authors: G Bouras, EM Burns, A Bottle, T Athanasiou, A Darzi
Journal: Gut (2015)

<h3>Introduction</h3> In September 2004, the National Institute for Health and Care Excellence (NICE) extended their recommendations for laparoscopic inguinal hernia repair to all patients from previous guidelines pertaining to bilateral and recurrent hernias. Despite these changes in policy little is known about short-term complications that are encountered in the primary care setting. <h3>Method</h3> Linked primary (Clinical Practice Research Datalink – CPRD) and secondary (Hospital Episode Statistics – HES) care records were used to evaluate outcomes from inguinal hernia repair in England. Patients undergoing primary inguinal hernia repair between 1997 and 2012 were evaluated. In-hospital complicaitons were measured in HES, out-of-hospital complications were measured in CPRD and reoperation for recurrence was measured in HES. <h3>Results</h3> From these datasets, 34400 primary hernia repairs performed in 32410 patients were evaluated. Of these repairs, 7.4% (2541/34400) were performed laparoscopically. The proportion of laparoscopic inguinal hernia repair increased after the introduction of guidelines in September 2004. Short-term complications were lower for laparoscopic (1.85% – 47/2541) compared with open (3.57% – 1138/31859) repair, but surgery for recurrence was more frequent following laparoscopic repair (laparoscopic 3.31% 84/2541, open 1.15% 366/31859) (p &lt; 0.001). There were no differences in the rate of short-term complications before (3.53% – 18405) and after (3.35% – 536/15995) the introduction of guidelines, while surgery for recurrence was more frequent after the introduction of guidelines (pre-guidelines 1.50% 240/15755, post-guidelines 1.14% 210/18405, p = 0.004). Independent predictors of short-term complications were age (OR = 1.01), body mass index (OR = 1.03), peptic ulcer disease (0.002), respiratory disease (OR = 1.26), bilateral repair (OR = 1.50), open surgery (OR = 1.38) and emergency surgery (OR = 2.13) (p &lt; 0.05). Independent predictors of surgery for recurrence included bilateral repair (OR = 3.67), laparoscopic repair (OR = 1.49), surgery after the introduction of guidelines (OR = 1.24) and wound infection (OR = 1.79) (p &lt; 0.05). <h3>Conclusion</h3> Laparoscopic inguinal hernia repair was associated with significantly lower short-term complication rates compared with open surgery, but significantly increasaed rates of surgery for recurrence. It is important that further dissemination of the technique is accompanied by adequate training to ensure longer term durability. <h3>Disclosure of interest</h3> None Declared.
Gut microbiota amplifies host-intrinsic conversion from the CD8 T cell lineage to CD4 T cells for induction of mucosal immune tolerance
Authors: Jen Bon Lui, Lander S McGinn, Zhibin Chen
Journal: Gut Microbes (2016)

Microbiota has been shown to promote tolerogenic differentiation of T lymphocytes. It remains unclear to what extent microbiota triggers de novo re-programming or amplify pre-existing plasticity intrinsic to T cells. In a study with mouse models to track the clonal fate of CD4 and CD8 T cells, we discovered that CD8 T cells converted to MHC class I-restricted CD4 T cells without regard to selfness of their antigen specificity. In mesenteric lymph nodes (MLN), CD8 T cells converted to CD4+Foxp3+ regulatory T (Treg) cells which were enriched in the large intestine lamina propria (LILP) and suppressed chemical- or immune-mediated inflammatory damage. In germ-free conditions, the converted CD4 populations were present in MLN, but absent in LILP. Therefore, an intrinsic plasticity in the host was amplified by the gut microbiota, leading to selfless tolerance induction in the intestinal mucosa. The findings may be relevant to HIV infection, cancer and autoimmune disorders.
Functional and Genetic Heterogeneity of Distinct Leukemic Stem Cell Populations in CD34- Human Acute Myeloid Leukemia
Authors: Lynn Quek, Georg Otto, Catherine Garnett, Ludovic Lhermitte, I-Jun Lau, Dimitris Karamitros, Jessica Doondeea, Batchimeg Usukhbayar, Nicolas Goardon, Adam Ivey, Yisu Gu, Christopher G Allen, Rosemary E Gale, Benjamin Davies, Alexander Sternberg, Sally Killick, Hannah Hunter, Paul Cahalin, Andrew Price, Andrew Carr, Mike Griffiths, Paul Virgo, Stephen Mackinnon, David Grimwade, Sylvie D Freeman, Nigel Russell, Charles Craddock, Adam Mead, Andrew Peniket, Catherine Porcher, Paresh Vyas
Journal: Blood (2014)
VAB-6 as initial treatment of patients with advanced seminoma.
Authors: G F Stanton, G J Bosl, W F Whitmore, H Herr, P Sogani, M Morse, R B Golbey
Journal: Journal of Clinical Oncology (1985)

Thirty patients with advanced seminoma were treated with VAB-6. Eighteen patients were previously untreated, eight had relapsed after radiation therapy, and four had persistent disease following chemotherapy and radiation therapy. Two patients had received prior high-dose cisplatin. Twenty-four (86%) of 28 evaluable patients achieved a complete remission. Four patients had relapsed. The median disease-free follow-up of patients achieving complete remission was 32+ months. VAB-6 is effective treatment for patients with advanced seminoma, and chemotherapy is recommended as the initial therapy in all patients with stage II seminoma with disease larger than 5 cm, extragonadal seminoma, and stage III seminoma.
Factors related to end-of-life (EOL) chemotherapy in solid tumor (ST) patients.
Authors: Maria Alma Rodriguez, Yvette A DeJesus, Lee Cheng, Aman Buzdar, Thomas W. Burke
Journal: Journal of Clinical Oncology (2013)

9538 Background: Oncologists will be required to report quality measures for cancer care, including use of chemotherapy in the last two-weeks of life. In this study, we evaluated how use of chemotherapy in ST patients (pts) within 14 days of EOL may be influenced by clinical factors. Methods: Adult pts (≥18 years) treated for ST at our institution, deceased December 01, 2010 through May 31, 2012, were retrospectively studied. Data on demographics, chemotherapy (excluded: hormones) within 14 days EOL, comorbidities, and cancer diagnoses were from tumor registry and administrative databases. Logistic regression analysis was performed for association of EOL chemotherapy with age, gender, ethnicity, comorbidities , cancer types, and metastatic status. Results: 5,607 pts met study criteria: median age 64 years; 48% female; 76% metastatic disease. EOL chemotherapy frequency was 3.9% overall, 4.6% in metastatic disease versus 1.7% in non-metastatic disease (p&lt;0.01). In 23 patients with non-metastatic disease who received chemotherapy, the diagnoses were: brain/other nerve system (34.8%, 8/23) and lung/bronchus (21.7%, 5/23).The top 10 frequencies in chemotherapy use by tumour sites were: melanoma (6.7%), female breast (5.5%), lung &amp; bronchus (4.9%), pancreas (4.2%), brain/other never system (3.9%), head &amp; neck (3.8%), female genital system, excluding ovary (3.4%), ovary (3.2%), liver/intrahepatic bile duct (3.0%), colon &amp; rectum (2.6%). By regression analysis, the factor statistically significantly associated with receiving chemotherapy was metastatic disease (odds ratio [OR], 3.29; 95% CI,1.96-5.54), while factors associated with significantly less treatment were age ≥ 65 (OR, 0.66; 95% CI, 0.49-0.90); and any co-morbid conditions (≥1 versus 0) (OR, 0.58; 95% CI, 0.38-0.89). Conclusions: A small portion of ST patients who died received EOL chemotherapy (3.9%). However, metastatic disease and diagnosis category influenced treatment. Melanoma and breast cancer patients had higher frequency of EOL treatment. Older age and comorbidities were associated with less treatment. Variation in EOL treatment of ST patients is thus influenced by several clinical factors, but did not seem influenced by gender or ethnicity factors.
Nasal Challenge with Ragweed Pollen Extract (RWPE) Increases the Level of Fortilin in Nasal Lavage Fluid from Subjects with Allergic Rhinitis
Authors: Julia W. Tripple, Koa Hosoki, Istvan Boldogh, David Rogers Redding, Sanjiv Sur, Ken Fujise
Journal: Journal of Allergy and Clinical Immunology (2016)
Need for evidence on telehealth providers: Table 1
Authors: Arnoupe S Jhass, Azeem Majeed
Journal: BMJ (2016)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Need for evidence on telehealth providers Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Scheme has been a disaster
Authors: J. A Gilley
Journal: BMJ (1996)

EDITOR,—Stephen Gillam and colleagues' editorial on the recording of health promotion activity arrives at a broadly correct conclusion by a route that ignores the present political context of the discredited banding scheme in general practice.1 General practitioners began to see the need to offer health promotion to their patients during the 1980s, and some exciting developments followed, in the best tradition of general practice. Unfortunately, 1990 saw the introduction of the “10 patients …
A malignant cellular network in gliomas: potential clinical implications
Authors: Matthias Osswald, Gergely Solecki, Wolfgang Wick, Frank Winkler
Journal: Neuro-Oncology (2016)

The recent discovery of distinct, ultra-long, and highly functional membrane protrusions in gliomas, particularly in astrocytomas, extends our understanding of how these tumors progress in the brain and how they resist therapies. In this article, we will focus on ideas on how to target these membrane protrusions, for which we have suggested the term "tumor microtubes" (TMs), and the malignant multicellular network they form. First, we discuss TM-specific features and their differential biological functions known so far. Second, the connection between 1p/19q codeletion and the inability to form functional TMs via certain neurodevelopmental pathways is presented; this could provide an explanation for the distinct clinical features of oligodendrogliomas. Third, the role of TMs for primary and potentially also adaptive resistance to cytotoxic therapies is highlighted. Fourth, avenues for therapeutic approaches to inhibit TM formation and/or function are discussed, with a focus on disruption (or exploitation) of network functionality. Finally, we propose ideas on how to use TMs as a biomarker in glioma patients. An increasing understanding of TMs in clinical and preclinical settings will show us whether they really are a long-sought-after Achilles' heel of treatment-resistant gliomas.
Clinical outcome assessment in malignant glioma trials: measuring signs, symptoms, and functional limitations
Authors: Jaishri O. Blakeley, Stephen Joel Coons, John R. Corboy, Nancy Kline Leidy, Tito R. Mendoza, Jeffrey S. Wefel
Journal: Neuro-Oncology (2016)

The shared goal of all parties developing therapeutics against malignant gliomas is to positively impact the lives of people affected by these cancers. Clinical outcome assessment (COA) tools, including measures of patient-reported outcome, performance outcome, clinician-reported outcome, and observer-reported outcome, allow patient-focused assessments to complement traditional efficacy measures such as overall survival and radiographic endpoints. This review examines the properties of various COA measures used in malignant glioma clinical trials to date and cross references their content to the priority signs, symptoms, and functional limitations defined through a community survey conducted by the National Brain Tumor Society. The overarching goal of this initiative is to identify COA measures that are feasible and have appropriate psychometric properties for use in this patient population as well as highlight where further development is needed.
Haptoglobin Types in Patients with Juvenile Rheumatoid Arthritis
Authors: A. C. Peacock, F. Paul Alepa
Journal: Annals of the Rheumatic Diseases (1966)

Howard and Ansell (1964) have recently reported the distribution of haptoglobin types among their patients with rheumatic disorders.The incidence of haptoglobin type 1-1 reported by these workers for patients with juvenile rheumatoid arthritis was three times that found in their normal population and twice that found in their adult rheumatoid arthritis patients.Since haptoglobin type is a geneticallycontrolled trait (Smithies and Walker, 1955), these findings suggest that genetic factors may be involved in juvenile rheumatoid arthritis, or that this disorder can modify the biochemical expression of the hapto- globin genotype.Studies designed to confirm and expand these findings would be of interest as it would add insight into the nature of juvenile rheumatoid arthritis, and perhaps provide evidence for selective advantage for the haptoglobin type 2 gene (Smithies, 1964) or alternatively provide evidence for the modification of genetic expression by disease.The present study reports the haptoglobin type distribution in fifty patients with juvenile rheuma- toid arthritis and in both parents of 29 of these patients.
Phase I-II study of irinotecan (CPT-11) and gefitinib in patients (pts) with gefitinib failure for non-small cell lung cancer (NSCLC)
Authors: A. Horiike, F. Ohyanagi, Y. Okano, K. Kudo, E. Miyauchi, K. Kasahara, T. Horai, M. Nishio
Journal: Journal of Clinical Oncology (2008)

19014 Background: Currently, there are no effective treatment options for NSCLC after failure of gefitinib. Pre-clinical studies demonstrated that gefitinib resistant NSCLC cells were more sensitive to CPT-11 than parental cells, and the combination of CPT-11 and gefitinib had a synergistic effect. We conducted a phase I-II study to evaluate the combination of CPT-11 and gefitinib as a therapeutic option in NSCLC patients with progressive disease after treatment with gefitinib. Methods: Eligibility criteria included histologically confirmed NSCLC, age 20–74 years, refractory to or relapsed after gefitinib, one or more prior chemotherapy regimens, ECOG performance status (PS) 0- 2, adequate organ function and informed consent. Pts were treated with CPT-11 on days 1 and 15 every 4 weeks, and daily gefitinib from day 2. The treatment was continued until disease progression. The Gefitinib dose was fixed at 250 mg. The starting dose of CPT-11 was 50 mg/m2, and then was escalated in different pts at 25 mg/m2 increments up to 150 mg/m2. Results: 25 pts were enrolled: Male/female =14/11; Median age = 60 (45–74); Histology, adeno/non-adeno= 23/2; PS 0–1/2= 19/6; Prior gefitinib response, PR/SD/PD = 19/2/4. Toxicities and efficacy for each dose level are shown in the table. Dose limiting toxicities were observed in only 2 pts at level 3, and the full dose of CPT-11 could be combined with the full dose of gefitinib. The disease control rate (DCR) and response rate (RR) for all 25 pts were 72.0% and 28.0%. For 10 pts at level 5, the DCR and RR were 80.0% and 60.0%. Conclusion: The combination of CPT-11 and gefitinib is highly effective and well tolerated in pts with gefitinib failure for NSCLC. Level CPT-11 (mg/m2) Gefitinib (mg) Number of Pts Total Grade 3/4 neutropenia Grade 3/4 diarrhea DLT PR SD 1 50 250 3 0 0 0 0 2 2 75 250 3 0 0 0 0 1 3 100 250 6 1 2 2 0 4 4 125 250 3 0 0 0 1 2 5 150 250 10 3 0 0 6 2 No significant financial relationships to disclose.
Measles, measles vaccination, and Crohn's disease
Authors: E. Miller, P. Waight, R G Pebody, M Paunio, P Ruutu, R. Lawrenson, R. Farmer
Journal: BMJ (1998)

Editor—Metcalf concludes that the scientific evidence does not support a causal link between measles virus and Crohn’s disease.1 Though few readers of the BMJ are likely to disagree with her appraisal of the science, parental concern about the safety of the vaccine remains high fuelled by continuing media interest in this controversial topic. More worrying is the recent decline in MMR vaccine coverage2 and evidence which suggests that most practice nurses would not give their own child a second dose of MMR vaccine because of concerns about vaccine safety.3

One of the claims made by the leading proponent of the hypothesis that measles vaccine causes Crohn’s disease is that there has been a “dramatic escalation” in paediatric cases in the wake of the 1994 national measles-rubella vaccination campaign targeted at school aged children.4 We have monitored hospital discharge diagnoses for Crohn’s disease (ICD-9 code 555 until March 1995, ICD-10 code K55 from April 1995) in children aged 5-16 years before and after the campaign using computerised hospital episode statistics from all districts in England (figure). Children with new cases of Crohn’s disease are almost always admitted to hospital, and this is a well established method of monitoring trends in incidence of the disease. Repeat admissions in the same child were identified by matching sex, date of birth, and postcode. 

No increase was evident in either first admissions or all admissions for Crohn’s disease since the campaign. Although the latent period between exposure to measles-rubella vaccine and alleged onset of Crohn’s disease was not stated by Wakefield, our data exclude an effect within the first 16 months. This technique can be reapplied annually, allowing the cohort immunised in the 1994 campaign to be followed longer term. 

We are not aware of any published evidence to support the hypothesis that re-exposure to measles vaccine can provoke the onset of Crohn’s disease. However, evidence which counters unsubstantiated allegations may help health professionals reassure themselves, as well as concerned parents, about the safety of measles vaccine given as a second dose in combination with another live viral vaccine.
Long-term survival differences for bronchioloalveolar carcinoma (BAC) patients with ipsilateral intrapulmonary metastasis at diagnosis
Authors: J. A. Zell, S. I. Ou, A. Ziogas, H. Anton-Culver
Journal: Journal of Clinical Oncology (2006)

7207 Background: It has been suggested that survival for BAC patients with stage IIIB disease due to multiple lesions in the same lobe is improved over other stage IIIB patients, and that patients with multicentric BAC have improved survival over BAC patients with distant metastasis. To determine the prognostic implications of these various subsets of advanced stage BAC patients, we compared survival rates using a large population-based cohort. Methods: A case-only analysis of data from the U.S. SEER database during 1998–2002 was conducted. The primary outcome measured was overall survival (OS). OS and lung cancer-specific survival (LCSS) univariate analyses were conducted using the Kaplan-Meier method; multivariate survival analyses were performed using Cox proportional hazards ratios. Results: 2653 incident cases of BAC were analyzed with a 5-year follow-up duration, including 831 patients with advanced (i.e. stage IIIB or IV) BAC. Patients with stage IIIB BAC due to multiple lesions in the same lobe (n = 96) had significantly improved median OS (46 months) and LCSS (not reached at &gt;58 months) compared to other stage IIIB BAC patients on univariate analysis (n = 133; OS = 8 months, LCSS = 9 months) (P &lt; 0.0001). Stage IV BAC patients with intrapulmonary metastasis (n = 320) had significantly improved median OS (13 months) and LCSS (15 months) compared to those with stage IV BAC due to distant spread on univariate analysis (n = 282; OS = 7 months, LCSS = 7 months) (P &lt; 0.0001). These observed survival differences remained after adjustment for age, gender, ethnicity, and surgical treatment status (Table). Conclusions: Patients with stage IIIB BAC due to tumors in the same lobe have significantly better outcomes than other stage IIIB BAC patients. Stage IV BAC patients due to intrapulmonary spread have significantly improved outcomes over stage IV BAC patients with distant metastasis. These results add further support for modification to the current NSCLC staging system. [Table: see text] No significant financial relationships to disclose.
Uridine triacetate: An orally administered, life-saving antidote for 5-FU overdose.
Authors: M. K. Bamat, R. Tremmel, J. D. O'Neil, R. von Borstel
Journal: Journal of Clinical Oncology (2010)

9084 Background: 5-fluorouracil (5-FU) is widely used to treat solid tumors and is often administered via infusion pump at or near its maximum tolerated dose. The common use of infusion pumps loaded with 5-FU for infusion over several days increases the possibility of potentially lethal overdoses due to pump malfunction or misprogramming. Uridine triacetate (vistonuridine) is an orally bioavailable prodrug of uridine, a direct biochemical antagonist of 5-FU toxicity. Uridine nucleotides derived from uridine triacetate dilute intracellular fluorouridine nucleotide anabolites of 5-FU, reducing their lethal incorporation into RNA. Successful outcomes for 17 5-FU overdose patients treated with uridine triacetate were reported at ASCO in 2009, along with 13 historical cases of comparable 5-FU overdoses treated with supportive care only. Consequent increased awareness of uridine triacetate as an antidote has resulted in a significant increase in the frequency of requests for emergency use of uridine triacetate. Methods: Uridine triacetate was provided under emergency IND provisions when requested by clinical sites following 5FU overdoses, most due to infusion pumps delivering 5FU faster than intended. Patients received uridine triacetate (10g q6h for 20 doses) beginning as soon as possible after overdose. Patient outcomes were monitored and compared to historical reports of 5-FU overdoses where uridine triacetate was not used. Results: More than 28 patients overdosed with 5-FU have now been treated with uridine triacetate as an antidote. All patients treated to date recovered fully, including an extreme case with a 5-FU dose 10-fold higher than intended (10,000 mg versus 1,000 mg, in 1 hour). Strong reductions in anticipated GI and hematologic toxicities were observed. A total of 43 historical cases of 5-FU overdoses not treated with uridine triacetate (39 fatal) have been identified, highlighting the potentially severe consequences of 5-FU overdoses and the need for an effective antidote. Conclusions: Uridine triacetate appears to be a safe and effective, life-saving antidote to 5-FU overdose. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Wellstat Therapeutics Corporation