tbuckley/cabot-search huggingface dataset:
OC-005 Mortality following elective colorectal cancer resection: does size really matter?
Authors: K Edwards, C Ratcliff, A Sukha, M Clarke
Journal: Gut (2015)

<h3>Introduction</h3> Regional volume-outcome analysis of UK colorectal cancer registries has demonstrated survival benefit if major cancer resections are performed in high compared to low volume units. The Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the National Bowel Cancer Audit (NBCA) have published NHS Trust and individual surgeon outcomes, allowing the hypothesis to be tested against a more representative sample. Grouping individual hospital data under a Trust to reflect multidisciplinary team resources may over-estimate numbers of high volume colorectal units where surgeons operate in separate hospitals with different clinical teams. A hospital based volume-outcome analysis was conducted on the comprehensive dataset for patients treated by elective colorectal cancer resection with curative intent in England April 2010–March 2013. <h3>Method</h3> Number of procedures, deaths, adjusted 90-day mortality rate (DMR) and Trust for each surgeon was extracted. The DMR had been adjusted for age, sex, ASA grade, TNM stage, admission mode, cancer site, co-morbidities, interaction between age and metastases using multivariate logistic regression. Trusts with multiple hospitals providing colorectal surgical services were contacted to confirm if consultant surgeons were site-specific, unless detailed in Trust literature. Trusts with site-specific services were sub-divided into individual hospitals. Institutions were categorised as low (0–209 procedures; n = 54), medium (210–309; n = 55) or high volume (310–708; n = 54). <h3>Results</h3> 42,877 operations were performed in 163 centres at 143 NHS trusts. Procedures and surgeons per unit ranged from 30–708 (median 259) and 1–9 (median 4). 1,222 patients died within 90 days of resection, DMR 2.85. DMR for each volume group was: low 3.40, medium 2.93, high 2.61. 53.9% of surgeons experienced ≤1 death; 2.7% &gt;5 deaths. 37% (20/54) of low volume units had lower mortality than the average of the high volume group, 2.61; 24% (13/54) of high volume units had higher mortality than the average of the low volume group. <h3>Conclusion</h3> Unlike previous smaller studies our analysis fails to demonstrate a significance in correlation between low, medium or high volume units and DMR (r = –0.097). The majority of surgeons had good outcomes delivering major resectional elective cancer care. The argument for centralisation develops the idea that there is an unacceptable risk adjusted mortality rate; here expressed as 3.4%. The argument fails to recognise the relatively large proportion of low volume centres with better outcomes than high volume centres. 22% more perioperative deaths occur in 13 large volume units with ‘unacceptable’ mortality rates than in 24 small units with these same rates. These observations add insight to the reasons many surgeons fail to engage with centralisation agenda. <h3>Disclosure of interest</h3> None Declared.
Prevention of Bone Loss with Alendronate in Postmenopausal Women under 60 Years of Age
Authors: David Hosking, Clair E.D. Chilvers, Claus Christiansen, Pernille Ravn, Richard Wasnich, Philip Ross, Michael McClung, Ana Balske, Desmond Thompson, Marianne Daley, A. John Yates
Journal: New England Journal of Medicine (1998)

Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear.
Osteopenia in Men with a History of Delayed Puberty
Authors: Joel S. Finkelstein, Robert M. Neer, Beverly M.K. Biller, John D. Crawford, Anne Klibanski
Journal: New England Journal of Medicine (1992)

The effect of delayed puberty on peak bone mineral density in men is unknown. To determine whether such a delay reduces normal peak bone density and leads to osteopenia during adulthood, we measured radial bone mineral density by single-photon absorptiometry and spinal bone mineral density by dual-energy x-ray absorptiometry in 23 men who had a history of constitutionally delayed puberty and 21 men who underwent normal puberty. Their mean ages were 26 and 24 years, respectively. The groups were matched for other factors known to affect bone mass.
Concomitant hyperfractionated accelerated radiotherapy (HART) with cisplatin and concurrent cetuximab for locoregionally advanced squamous cell head and neck cancer: a phase I dose escalation trial
Authors: T. Kuhnt, A. Sandner, T. G. Wendt, R. Engenhardt-Cabillic, G. Lammering, M. Flentje, G. G. Grabenbauer, A. Pirnasch, M. Baumann, J. Dunst
Journal: Journal of Clinical Oncology (2008)

6029 Background: Cetuximab is a potent inhibitor of the epidermal growth factor receptor and has shown activity in squamous cell carcinoma of the head and neck (SCCHN) enhancing both radiotherapy and chemotherapy. This phase I dose-escalation clinical trial was designed to investigate the safety and tolerability of the combination of cisplatinum, cetuximab, and hyperfractionated accelerated radiotherapy. Methods: Patients (pts) with stage III or IV, M0 SCCHN were enrolled and treated with an initial dose of cetuximab (400mg/m2), followed by weekly doses of 250mg/m² during the hyperfractionated accelerated radiotherapy (HART), which started with a prescribed dose of 2.0 Gy per day for three weeks followed by 1.4 Gy twice daily to a total dose of 70.6 Gy to the gross tumor volume. Cisplatinum was administered weekly from the first day of radiotherapy until week 6 at escalating doses ranging from 20- 40 mg/m². Three patients were accrued in each cohort using a 3+3dose escalation trial design. Results: 14 patients were enrolled (median age: 53 years, range 44 to 62 years; median Karnofsky status: 90%, range 90% to 100%; cavum oris and oropharynx primary tumor: 50% of patients; T4: 71%; N2/3: 79%; stage IV disease: 93%). Three patients discontinued the study treatment. One was due to a hypersensitivity reaction after the initial dose of cetuximab, another was diagnosed with a secondary carcinoma and the third developed a stomach perforation in week 3. No dose-limiting toxicities were observed. The most common grade 3 adverse events were mucositis (46%), dysphagia (32%) and neutropenia (16%). Grade 3 cetuximab related toxicities included acne-like rash within the radiotherapy portals (38%) and hypersensitivity (7%). The objective remission rate was 91% (CR 33% and PR 58%, one patient unknown). No patients have died to date (Dec 2007). Conclusions: The trimodal regimen of cisplatinum with cetuximab and HART is active and well tolerated. The 40-mg dose of cisplatinum was chosen as the recommended phase II dose in combination with cetuximab plus HART based on acceptable toxicity when administered. No significant financial relationships to disclose.
Subclavian-Vein Thrombosis Associated with Fractures of the Clavicle
Authors: Israel Steinberg
Journal: New England Journal of Medicine (1961)

THE possibility that immediate neurovascular injury will follow fracture of the clavicle has become generally known. Delayed involvement of the subclavian vessel or brachial plexus after ununited or excessively callused fractures of the clavicle, however, has rarely been reported.1 2 3 4 For this reason the cases of 2 patients with malunion of fractured clavicles associated with thrombosis of the subclavian vein are recorded below. In 1, an ununited clavicle with a pseudoarthrosis narrowed the costoclavicular space. In the other, excessive callus formation followed an operation for a nonunited fracture; undue hyperabduction of the arm (the patient was a house painter) played a . . .
Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance
Authors: Bruno Paiva, Luis A. Corchete, Maria-Belen Vidriales, Noemi Puig, Patricia Maiso, Idoia Rodriguez, Diego Alignani, Leire Burgos, Maria-Luz Sanchez, Paloma Barcena, Maria-Asuncion Echeveste, Miguel T. Hernandez, Ramón García-Sanz, Enrique M. Ocio, Albert Oriol, Mercedes Gironella, Luis Palomera, Felipe De Arriba, Yolanda Gonzalez, Sarah K. Johnson, Joshua Epstein, Bart Barlogie, Juan José Lahuerta, Joan Blade, Alberto Orfao, María-Victoria Mateos, Jesús F. San Miguel
Journal: Blood (2016)
Serum Beta-Carotene, Vitamins a and E, Selenium, and the Risk of Lung Cancer
Authors: Marilyn S. Menkes, George W. Comstock, Jean P. Vuilleumier, Knud J. Helsing, Agatha A. Rider, Ronald Brookmeyer
Journal: New England Journal of Medicine (1986)

We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974. Levels of the nutrients in serum samples from 99 persons who were subsequently found to have lung cancer (in 1975 to 1983) were compared with levels in 196 controls who were matched for age, sex, race, month of blood donation, and smoking history. A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung was observed (relative odds, 4.30; 95 percent confidence limits, 1.38 and 13.41). Mean (+/- SD) levels of vitamin E were lower among the cases than the controls (10.5 +/- 3.2 vs. 11.9 +/- 4.90 mg per liter), when all histologic types of cancer were considered together. In addition, a linear trend in risk was found (P = 0.04), so that persons with serum levels of vitamin E in the lowest quintile had a 2.5 times higher risk of lung cancer than persons with levels in the highest quintile. These data support an association between low levels of serum vitamin E and the risk of any type of lung cancer and between low levels of serum beta-carotene and the risk of squamous-cell carcinoma of the lung.
Periodic Breathing in an Infant with Hydrocephalus
Authors: C L Marcus
Journal: New England Journal of Medicine (1996)

Figure 1. A portion of a polysomnogram recorded in a neonate with congenital hydrocephalus and resultant periodic breathing shows frequent, short periods of central apnea, as demonstrated by the cessation of oronasal air flow and the absence of a wave form on the tracing for end-tidal partial pressure of carbon dioxide (PCO2), in association with the absence of chest- and abdominal-wall motion (arrows). Inspiration is represented by an upward deflection in the air-flow and chest- and abdominal-wall signals. There is a six-second delay in the recording of end-tidal PCO2. Oronasal air flow was measured with a . . .
Case 39-2006
Authors: Jang-Ho J. Cha, Karen Furie, Jonathan Kay, Rochelle P. Walensky, Mark E. Mullins, E. Tessa Hedley-Whyte
Journal: New England Journal of Medicine (2006)

A woman was transferred to this hospital because of seizures and a lesion in the brain. The patient had a history of systemic lupus erythematosus, for which she had received corticosteroids and other immunosuppressive medications. Despite negative biopsy specimens and cultures, broad-spectrum antimicrobial therapy, and escalating doses of corticosteroids, fever persisted, neurologic function worsened, and the patient died on the 54th hospital day. An autopsy was performed.
P166 The frequency of chest radiographs prior to the onset of lung cancer symptoms
Authors: MPT Kennedy, O Walkowiak, MEJ Callister
Journal: Thorax (2015)

<h3>Introduction</h3> Previous data has shown wide variation in the frequency of CXRs requested by GPs that is not explained by case mix factors. The relationship between threshold for CXR request and lung cancer characteristics at diagnosis is unknown. <h3>Aim</h3> To analyse the frequency of CXRs prior to the development of lung cancer symptoms according to stage at presentation. <h3>Method</h3> Retrospective review of an electronic database of lung cancer patients, excluding small cell, from 2010–2013. The dates of all CXRs in the three years before the first appointment with the lung cancer team were recorded. The frequency of CXRs was compared using Mann-Whitney U test with normal approximation. <h3>Results</h3> 1750 patients were included. 589 had early stage disease (I/II) and 1161 had late stage disease (III/IV). The frequency of CXRs from 36 to 6 months prior to diagnosis is shown in Figure 1 according to stage at diagnosis. Patients subsequently diagnosed with early stage cancer had significantly more CXRs performed during this period compared to late stage patients (1.70 vs 0.92, p &lt; 0.001). The number of CXRs performed during the 6 months leading up to diagnosis was much higher for both groups, but remained significantly higher for early vs late stage disease (1.32 vs 1.15, p = 0.009). This will include many CXRs which triggered referral to the lung cancer team. The number of patients with no CXR in the three years before diagnosis (excluding the six months immediately before diagnosis) was higher in late stage (64.6%) than in early stage (45.0%). <h3>Conclusion</h3> Differences are apparent in the frequency of CXRs many months prior to lung cancer diagnosis. We speculate that these changes are seen at a time when symptoms attributable to the lung cancer are unlikely to have been present. Instead, this may reflect differences in patient behaviour (threshold for seeking review for respiratory symptoms) and GP behaviour (threshold for requesting CXR). There may be a degree of incidental detection of more indolent early stage cancers (i.e. length-time bias). A patient-GP relationship that results in increased frequency of CXR seems to be associated with increased detection of early stage disease.
Case 48-1966
Authors: John M. Moses, Martin H. Flax
Journal: New England Journal of Medicine (1966)

Presentation of CaseA twenty-four-year-old man was admitted to the hospital because of fever.He had been well until five weeks previously, when coryza, cough, inflammation of the throat and enlargement of cervical lymph nodes developed, with a rise in the temperature to 103°F. Penicillin and a cough medication were prescribed. During the next week he lost his taste for cigarettes and food, noticed that his urine was unusually dark, experienced fatigue and stiffness in the muscles and joints and vomited on several occasions. The eyes became markedly inflamed, and cutaneous icterus appeared. One month before admission he entered another . . .
Brief Communication: Delayed Lethal Response to Candida albicans Infection in Mice Bearing the Lewis Lung Carcinoma2
Authors: E. H. Robinette, D. N. Mardon
Journal: JNCI Journal of the National Cancer Institute (1975)

Lethality of Candida albicans was monitored in (C57BL × DBA/2)F1 mice bearing the transplanted Lewis lung carcinoma and in sham-operated controls inoculated with Hanks' balanced salt solution. The lethal response to C. albicans infection was significantly delayed in animals inoculated with the microorganism 6–16 days after transplantation of the Lewis lung carcinoma. Maximal increases in survival times were observed when C. albicans was inoculated 8–12 days following tumor transplantation. Therefore, a delay in the lethal response to C. albicans in this untreated model murine tumor system could be elicited through implantation of the Lewis lung carcinoma; preliminary studies with some other model murine tumors and with cell-free filtrates indicated that this phenomenon is not restricted to the Lewis lung carcinoma.
P172 Training nurses in sampling and acquisition of specimen during EBUS guided transbronchial needle aspiration
Authors: V Johnson, W Stables, S Binu, C Smyth, M Walshaw, K Mohan
Journal: Thorax (2015)

<h3>Introduction</h3> EBUS has now become the standard of choice for mediastinal staging and in the diagnosis of paratracheal and peribronchial lesions. EBUS is usually performed as a 2 person procedure, one to locate and align the bronchoscope and a second to carry out node sampling. Whilst these have traditionally both been medical personnel, with the increase in use of this procedure and alterations in the training and availability of medical staff, we wished to look at the feasibility of empowering nurses to perform needle aspiration during EBUS. <h3>Methods</h3> We provide a regional service for EBUS, carrying out over 420 procedures per year, often in technically difficult cases where local hospital EBUS has been unhelpful. From January 2015 we trained a band 5 registered nurse in needle aspiration, who randomly assisted in the procedure in 93 of 172 cases up to June 2015. We report our experience in these 93 cases. <h3>Results</h3> These 93 patients were referred from 12 hospitals and 20 had undergone previous undiagnostic procedures (6 EBUS, 14 bronchoscopy). The mean age was 67 years (range 27 – 87) and 50 were male. 82 were performed under local anaesthesia using lignocaine spray and intravenous midazolam (1 – 10 mg; mean 4 mgs) and the remaining 11 under general anaesthesia. 200 lymph nodes (2R, 4R, 4L, 7, 10R, 10L, 11R) and 13 lung lesions were biopsied. Results were as follows: Adequate samples were obtained in 99% (91/93) and the NSCLC - NOS rate was 2%. 31 adenocarcinoma, 10 squamous cell carcinoma, 10 small cell carcinoma, 1 NSCLC - NOS, 1 large cell neuroendocrine carcinoma, 1 soft tissue lesion (repeat EBUS showed myxoid spindle cell mesenchymal lesion), 1 breast carcinoma, 19 nonspecific benign nodes, 15 sarcoid and 2 TB. There were no complications. <h3>Conclusion</h3> Our findings suggest that with motivated staff and adequate training, it is possible for nurses to perform needle aspiration during EBUS procedure with excellent results. This could be adopted as the method of choice by other centres as EBUS services continue to expand.
SAT0108 Misdiagnosis of Rheumatoid Arthritis – The Photography
Authors: D. Gomez, G. Saavedra-Martinez, L. Villarreal, P. Santos-Moreno, J. Bello-Gualtero, V. Giraldo, P. Martinez, A. Sanchez, M. Sanchez, E. Uribe, M. Boon
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> There is a lack of expertise in rheumatoid arthritis (RA) diagnosis in primary level of Colombian medical centers, leading to misdiagnosis; many times osteoarthritis (OA) and another rheumatic diseases are misdiagnosed as RA which derives in wrong treatment for patients with clinical and health economics implications. <h3>Objectives</h3> The objective of this study was to describe demographic and clinical characteristics of a cohort of patients derived to a specialized RA center with presumptive RA diagnosis and finally diagnosed as osteoarthritis. <h3>Methods</h3> A descriptive, cross sectional study. Were included patients who were referred from primary care centers to a RA specialized center in a 36 month period with presumptive diagnosis of this disease. Each patient was evaluated to confirm or rule-out diagnosis of RA as follows: a rheumatologist fulfilled a complete medical record, including joint counts; it was assessed rheumatoid factor and anti-citrullinated antibodies, and other laboratories depending on each case. Also were made x-rays of hands and feet, and in some cases of persistent doubt about the diagnosis was requested comparative MRI of hands or/and feet. Frequencies and percentages were calculated for the demographic and clinical characteristics of the cohort of patients in which the diagnosis of RA was ruled-out. <h3>Results</h3> Of the 4780 patients evaluated, in 2905 patients (60.7%) diagnosis of RA was confirmed, the remaining 1875 patients (39.3%) had a wrong diagnosis of RA. Of these misdiagnosed patients, 1377 (73.5%) were women, and 498 (26.5%) men, with an average age of 57.6 (±12 years). Between differential diagnosis which were found in this cohort of misdiagnosed patients: osteoarthritis in 1108 patients (50.1%), systemic lupus erythematosus (SLE) in 84 patients (4.5%), Sjögren syndrome in 62 patients (3.3%), spondyloarthropathies in 21 patients (1.1%), gout in 31 patients (1.7%), and (39,3%) other diagnoses in of the remaining population. <h3>Conclusions</h3> Almost half patients with presumptive RA diagnosis in primary care centers in Colombia are misdiagnosed as shown in this large cohort. The most important cofounding diagnosis was osteoarthritis and many patients were receiving DMARDs for treatment. For this reason there is an urgent need of education strategies for primary care physicians and the implementation of centers of excellence in RA, in order to conduct a proper diagnose and avoid clinical and health economics consequences of misdiagnosis. <h3>Disclosure of Interest</h3> None declared
Dose-dependent inhibition of the EGFR and signalling pathways with the anti-EGFR monoclonal antibody (MAb) EMD 72000 administered every three weeks (q3w). A phase I pharmacokinetic/pharmacodynamic (PK/PD) study to define the optimal biological dose (OBD)
Authors: R. Salazar, J. Tabernero, F. Rojo, E. Jimenez, I. Montaner, E. Casado, G. Sala, J. Tillner, R. Malik, J. Baselga
Journal: Journal of Clinical Oncology (2004)

2002 Background: EMD 72000, an IgG1 humanized anti-EGFR MAb, has a prolonged half life and we showed that 1200q3w has favorable PK profile when compared to more frequent schedules (Tabernero et al, Proc ASCO 2003, abst 770). To define the OBD of q3w EMD 72000, we have now studied additional dose levels: 400, 800 and 1600 mg. Methods: Skin and tumor biopsies were performed at - 24 hrs and + 43 days of treatment. pEGFR, pMAPK, Ki67 and p27 were done by immunohistochemistry. Results: 51 patients (p) with EGFR+ tumors were treated, including the 1200 mg cohorts (also q1w and q2w). Patient characteristics, median (range): Karnofsky 90% (80%–100%), age 59 (43–79), and prior chemotherapy 3 (1–11). To date, 22 paired skin samples have been analyzed. Data on 1600 mg are not yet available. EMD 72000 induced decreases in Ki67, pMAPK, pEGFR and an increase in p27. The two best discriminating markers were pEGFR and pMAPK with a dose-dependent incremental inhibition and near complete signaling suppression at the 1200 mg dose level (Table). Data is reported as mean inhibition from baseline and as number of p with complete inhibition (<5% residual positivity). Grade 1 and 2 skin toxicity was observed in 43% and 35% of p, respectively. Skin toxicity was lower in the 400 mg. Drug troughs at 800-1200 mg q3w were 4–10 times higher than preclinical active levels. Activity: 3 PRs, 4 prolonged SD out of 39 evaluable p with colon cancer. Conclusions: This PD skin study with EMD 72000 shows a dose response effect on EGFR pathway inhibition. The dose level with suboptimal receptor inhibition also resulted in lower skin rash. Our findings suggest that the OBD will be close to 1200 mg q3w and supports a surrogate marker approach to OBD identification with anti-EGFR agents. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Merck KGaA