tbuckley/cabot-search huggingface dataset:
A sequential treatment approach to muscle-invasive urothelial cancer: A phase II Southwest Oncology Group Trial (S0219) of neoadjuvant paclitaxel, carboplatin, and gemcitabine (PCG)
Authors: P. N. Lara, B. Goldman, R. De Vere White, C. M. Tangen, D. C. Smith, D. Wood, M. H. Hussain, E. D. Crawford
Journal: Journal of Clinical Oncology (2008)

5022 Background: S8710 demonstrated a survival benefit for neoadjuvant MVAC prior to a radical cystectomy for patients (pts) with myoinvasive bladder cancer (Grossman, NEJM 2003). In S8710, 38% of pts achieved a pathologic complete response (pT0) to chemotherapy. A phase II trial of neoadjuvant PCG was conducted to evaluate the clinical T0 (cT0) rate with PCG & to pilot a sequential approach of either cystoscopic surveillance or immediate cystectomy for pts with cT0 status following chemotherapy. Tumor tissue was collected pre/post-PCG & at cystectomy for biomarker studies. Methods: Pts with T2-T4a chemo- & radiation-naive urothelial cancer with adequate end- organ function & Zubrod performance status 0–2 were eligible. T2+ tumor must be diagnosed by a transurethral resection of bladder tumor (TURBT) followed by another TURBT to confirm persistent disease (dz) w/in 16 weeks of the first TURBT and 2–8 weeks pre-study. Chemo: 3 cycles of P 80 mg/m2 + G 800 mg/m2 on days 1&8, and C (AUC=5) on day 1. Pts with cT0 status post-PCG opted for immediate cystectomy or cystoscopic surveillance; those with >cT0 post-PCG were to undergo immediate cystectomy. A cT0 rate (at the post-PCG TURBT) > 40% was pre-specified as a positive signal. Results: Of 77 pts, 74 were eligible. The most common Grade 3+ PCG toxicities were neutropenia (51%), leukopenia (30%), & thrombocytopenia (18%). There was one Gr 5 toxicity (neutropenic infection). 12 (16%) did not have a post-PCG TURBT. Post-PCG cT0 status was achieved in 34/74 pts, for a cT0 rate of 46%. 10/34 pts had an immediate cystectomy; 6/10 were found to have persistent dz. Tumor >T0 at the post-PCG TURBT was seen in 28 (38%), 21 of whom had a cystectomy. Thus 35/74 pts underwent cystectomy. With median follow-up of 20 months, 79% (27/34) of cT0 pts are alive vs. 53% (21/40) of non-responders. Conclusions: Although neoadjuvant PCG had a promising 46% cT0 rate, there was an unacceptably high rate (60%) of persistent dz at cystectomy in pts presumed to be pT0 after post-PCG TURBT. Pts completing neoadjuvant chemotherapy should strongly consider definitive local therapy rather than cystoscopic surveillance, irrespective of post-chemo cT0 status. Biomarker results will be presented. No significant financial relationships to disclose.
Coroner's Cases of Death Due to Errors in Prescribing or Giving Medicines or to Adverse Drug Reactions: Birmingham 1986–1991
Authors: R E Ferner, R M Whittington
Journal: Journal of the Royal Society of Medicine (1994)

The records for Coroner's Inquests in one district during a 6 year period were examined retrospectively to establish the number and nature of deaths which were due to errors in the prescription or administration of medicines, and those due to adverse drug reactions. The district has a population of 1.19 million (1991), and a total of 3277 inquests were opened during the period 1986–1991. Ten of the deaths were identified as due to errors of prescribing or giving drugs. During the same period, 36 deaths were caused by adverse drug reactions. These 46 deaths made up approximately one in 2000 of all deaths during the study period. About a fifth of deaths related to prescribing and administering drugs are due to errors and may be more easily preventable than deaths due to adverse reactions.
Lymphatic Pathways from the Tail in Rats and Mice
Authors: Arnfinn Engeset, Enok Tjötta
Journal: Cancer Research (1960)

Summary  It has been demonstrated that lymphatic drainage in the tail of mice, and usually also of rats, passes through the lymphonodus ischiadicus, which is situated just above the root of the tail dorsal to the pelvis. This lymph node is often absent in rats. In such animals the lymph from the tail sometimes drains to the knee node.
Prevalence of ATM gene mutations in young breast cancer patients with a known BRCA1 and BRCA2 status: A population-based study
Authors: J. Brunet, V. Berez, S. Sanjosé, A. Pelegrí, A. Izquierdo, E. Vilella, A. Torres, J. Galceran, J. L. Borràs
Journal: Journal of Clinical Oncology (2004)

9566 Background: The role of ATM gene mutations in sporadic young breast cancer (BC) is controversial due to the population selected for the studies or incomplete genetic testing that may overlook relevant missense mutations. One hundred thirty six incident BC patients diagnosed before the age of 46 years were prospectively identified from two Population-based Cancer Registries in Catalonia (Girona and Tarragona) between 1995–1997 and were included in a previous study of BRCA1/BRCA2 mutations prevalence (Int J Cancer 2003;106:588–93). Methods: The aim of present study was to find out the prevalence of ATM gene mutations in the 66 patients from one of the two cancer registries (Tarragona). Of these, 20 patients were not included because: 14 had died, 4 were lost in follow-up and 2 declined consent. Throughout 2002 the remaining 46 patients were newly interviewed for updating the personal and familial history. A specific informed consent was again obtained as required by the local ethics committee. Three patients (6.5%) were carriers of BRCA1/2 deleterious mutations and 8 (17%) were detected with rare BRCA1/2 variants of unknown significance (UV).The screening of variants in the entire coding sequence and intron-exon junctions of the ATM gene was performed by CSGE from peripheral blood leukocytes. Results: Two patients (4%) were found to carry ATM deleterious mutations (one was a frameshift deletion and the other was a missense mutation), 11 were detected with rare ATM UV, and further 15 ATM variants were classified as polymorphisms based on an allele frequency > 0.01. Only one patient was found to carry both BRCA and ATM variants (2 UV in ATM and 1 UV in BRCA1). Conclusions: Our results suggest that ATM gene mutations play a significant role in sporadic young BC patients in our population. The study of ATM UV in a control group of individuals from the same geographical area is under way. Supported by FIS (01/1597)and IRCIS grants. No significant financial relationships to disclose.
Connor Edward Morris
Authors: Derek Summerfield
Journal: BMJ (2015)

Like his father, Charles, who lectured for many years at the Royal College of Surgeons, Connor Edward Morris (“Ed”) was a Barts man. He went from house jobs on to the GP rotational scheme at the Royal Free Hospital and got his MRCGP. In 1984 he moved to Witney, Oxfordshire, to take up a post at the Nuffield Health Centre, where he remained for the rest of his career, latterly as senior partner. Ed’s reputation was as a committed and compassionate doctor. During his memorial service in St Mary’s Church, Witney, conducted by the Bishop of Reading, former patients or their family members stood up spontaneously across the church to testify to the quality of attention and care he had afforded them across three decades.

Trying to summarise Ed’s contribution over these 30 years puts me in mind of John Berger’s classic 1960s study of a west country GP, The Fortunate Man . Berger asked what was the social value of a pain eased, or of the witness that a GP offered families and individuals across time, across life events. He concluded that society did not …
Non-Convulsive Status Epilepticus Presenting as a Psychiatric Condition
Authors: M C Walker, O C Cockerell, J W A S Sander
Journal: Journal of the Royal Society of Medicine (1996)

Non-convulsive status epilepticus may present as confusion, behavioural disturbances and psychiatric conditions. We present the case of a 17-year-old man who had episodes of non-convulsive status epilepticus as his only manifestation of epilepsy which was mis-diagnosed as a psychiatric condition for over 10 years. He has had almost complete resolution of his symptoms with the introduction of carbamazepine. Non-convulsive status epilepticus is probably commoner than previously thought, and should be considered as a possible diagnosis in all patients presenting with prolonged episodes of altered consciousness even without other manifestations of epilepsy.
Adult Primary Central Nervous System Vasculitis Treatment and Course: Analysis of One Hundred Sixty‐Three Patients
Authors: Carlo Salvarani, Robert D. Brown, Teresa J. H. Christianson, John Huston, Caterina Giannini, Dylan V. Miller, Gene G. Hunder
Journal: Arthritis & Rheumatology (2015)

To describe the treatment and outcomes of patients with primary central nervous system (CNS) vasculitis.We retrospectively studied a cohort of 163 consecutive patients with primary CNS vasculitis who were seen at the Mayo Clinic over a 29-year period. We analyzed treatments, treatment responses, and factors predictive of outcomes.A favorable response was observed in 85% of patients treated with prednisone alone and in 80% of patients treated with prednisone and cyclophosphamide. Relapses were observed in 27% of patients, and 25% of patients had discontinued therapy by the time of the last followup visit. Treatment with prednisone alone was associated with more frequent relapses (odds ratio [OR] 2.90), while large vessel involvement (OR 6.14) and cerebral infarcts at the time of diagnosis (OR 3.32) were associated with a poor response to treatment. Prominent gadolinium-enhanced cerebral lesions or meninges were linked with continued treatment at the last followup encounter (OR 2.28). Higher disability scores at the last followup visit were associated with increasing age at the time of diagnosis (OR 1.44) and cerebral infarctions (OR 3.74), while lower disability scores were associated with gadolinium-enhanced cerebral lesions or meninges (OR 0.35) and cerebral amyloid angiopathy (OR 0.24). Increased mortality was associated with increasing age at diagnosis (hazard ratio [HR] 1.39), diagnosis by angiography (HR 3.28), cerebral infarction (HR 4.44), and large vessel involvement (HR 4.98), while reduced mortality was associated with gadolinium-enhanced cerebral lesions or meninges (HR 0.20).The majority of patients with primary CNS vasculitis responded to treatment. Recognition of findings at diagnosis that predict the course or outcome may aid in decision-making regarding therapy.
Effect of recurrent growth of aspergillus on lung function in paediatric population with cystic fibrosis (CF)
Authors: A. Adams, R. Thursfield, A. Bush
Journal: European Respiratory Journal (2011)

Background: Allergic bronchopulmonary aspergillosis (ABPA) is well described in CF. Many CF patients grow Aspergillus fumigatus (AF) on sputum and cough swabs but do not have ABPA. There is evidence that this is clinically important [Chest 2006;130:222, Ped Pulm 2007;42:785]

Hypothesis: Isolation of AF from sputum or cough swab is associated with a worse clinical state in CF children.

Methods: A retrospective cohort study of all children with CF who had sputum samples or cough swabs positive for AF on >1 occasion at least one month apart between 2008 and 2010. Lung function results and nutritional status were recorded.

Results: 35 children (15 male) were identified who fit the criteria, mean age 11.2 years (SD2.1) mean BMI 17.5. Data were collected on 21 controls (7 male) with CF who had not grown AF during the study period and had never had a diagnosis of ABPA, mean age 11.12 years (SD2.21) mean BMI 17.2. Children with AF had a lower mean FEV1(p<0.0001) over the follow-up period (69.8, SD13.8 vs 89.4, SD11.5), despite a greater number of days of intravenous antibiotics (45 days vs. 2.6 days in the 2 year period (p<0.0001))

![Figure][1] 



Conclusions: Recurrent growths of AF are associated with a worse clinical state, manifest by lower lung function, despite the use of significantly more intravenous antibiotics.

 [1]: pending:yes
Indicators of Lifetime Estrogen Exposure: Effect on Breast Cancer Incidence and Interaction With Raloxifene Therapy in the Multiple Outcomes of Raloxifene Evaluation Study Participants
Authors: Marc E. Lippman, Kathryn A. Krueger, Stephen Eckert, Andreas Sashegyi, Erin L. Walls, Sophie Jamal, Jane A. Cauley, Steven R. Cummings
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To test the hypothesis that risk factors related to lifetime estrogen exposure predict breast cancer incidence and to test if any subgroups experience enhanced benefit from raloxifene. PATIENTS AND METHODS: Postmenopausal women with osteoporosis (N = 7,705), enrolled onto the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, were randomly assigned to receive placebo, raloxifene 60 mg/d, or raloxifene 120 mg/d for 4 years. Breast cancer risk was analyzed by the following baseline characteristics indicative of estrogen exposure: previous hormone replacement therapy, prevalent vertebral fractures, family history of breast cancer, estradiol level, bone mineral density (BMD), body mass index, and age at menopause. Therapy-by-subgroup interactions were assessed using a logistic regression model. RESULTS: Overall, women with the highest one-third estradiol levels (≥ 12 pmol/L) had a 2.07-fold increased invasive breast cancer risk compared with women with lower levels. Raloxifene significantly reduced breast cancer risk in both the low- and high-estrogen subgroups for all risk factors examined (P &lt; .05 for each comparison). The women with the highest BMD and those with a family history of breast cancer experienced a significantly greater therapy benefit with raloxifene, compared with the two thirds of patients with lower BMD or those without a family history, respectively; the subgroup-by-therapy interactions were significant (P = .005 and P = .015, respectively). CONCLUSION: The MORE trial confirms that increased lifetime estrogen exposure increases breast cancer risk. Raloxifene therapy reduces breast cancer risk in postmenopausal osteoporotic women regardless of lifetime estrogen exposure, but the reduction is greater in those with higher lifetime exposure to estrogen.
Spirometry longitudinal data analysis software (SPIROLA) in a routine clinical laboratory
Authors: Catherine Billings, David Fishwick
Journal: European Respiratory Journal (2014)

Background: We aimed to assess long-term spirometry precision using Spirometry Longitudinal Data Analysis (SPIROLA), software {1].

Methods: Retrospective data from consenting patients were entered into SPIROLA.

Results: Table 1 shows the precision found for patients as a) a whole, b) with asthma patients excluded, and also c) asthma patients alone. Figure 1 show mean pair-wise within-person FEV1 relative standard deviation over time for these groups. Mean yearly FEV1varied between 19-22 mL with z scores ranging between -1.91 to -1.49. The COV for FEV1 was 7.6% in the group of patients excluding asthma

Discussion: Hnizdo et al. suggest that sr should be < 4%, however, our study found long-term patient testing in our laboratory is less precise. An increase in within-subject variability in FEV1 has previously been observed among patients compared with the general population. Our results were obtained on multiple machines and performed by multiple operators. Further work to establish the standard that can be expected for long-term precision of patients' spirometry and to evaluate decline in FEV1 needs to be done.

Reference 1. Hnizdo et al. Open Med Informat J , 2010; 4: 94-102..

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![Figure][1]  [1]: pending:yes
Induction of Vascular Endothelial Growth Factor by Hypoxia Is Modulated by a Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in Ha-ras-Transformed Cells Through a Hypoxia Inducible Factor-1 Transcriptional Element
Authors: Nathalie M. Mazure, Eunice Y. Chen, Keith R. Laderoute, Amato J. Giaccia
Journal: Blood (1997)
Drug-induced dystonia
Authors: Chester Swett
Journal: American Journal of Psychiatry (1975)

Among 1,152 psychiatric inpatients who received a phenothiazine, a butyrophenone, or a thioxanthene, 116 developed dystonia attributed to one or more of these drugs. The highest frequencies of dystonia occurred among recipients of haloperidol and the long-acting injectable fluphenazines. For all patients at risk, dystonia was more common in men and in younger patients. For chlorpromazine, high doses, male sex, and low age were each positively associated with dystonia.
Perioperative versus Preoperative Chemotherapy with Surgery in Patients with Resectable Squamous Cell Carcinoma of Esophagus
Authors: Yang Zhao, ZhiJun Dai, WeiLi Min, Xin Sui, HuaFeng Kang, YunFeng Zhang, Hong Ren, Xi Jing Wang
Journal: Journal of Thoracic Oncology (2015)
Degeneration and Regeneration of Subbasal Corneal Nerves after Infectious Keratitis
Authors: Rodrigo T. Müller, Farshad Abedi, Andrea Cruzat, Deborah Witkin, Neda Baniasadi, Bernardo M. Cavalcanti, Arsia Jamali, James Chodosh, Reza Dana, Deborah Pavan-Langston, Pedram Hamrah
Journal: Ophthalmology (2015)
Discontinuation of maintenance therapy against toxoplasma encephalitis in AIDS patients with sustained response to anti-retroviral therapy
Authors: S. Bertschy, M. Opravil, M. Cavassini, E. Bernasconi, V. Schiffer, P. Schmid, M. Flepp, J-P. Chave, A. Christen, H. Furrer
Journal: Clinical Microbiology and Infection (2006)
Asthma and obesity in children: The role of physical activity and airway inflammation
Authors: Maartje Willeboordse, Kim van de Kant, Charlotte van der Velden, Onno van Schayck, Edward Dompeling
Journal: European Respiratory Journal (2013)

Background : There is increasing evidence for an association between asthma and obesity in childhood. Characteristics of the asthma-obesity phenotype are high medication use, low asthma control and an altered inflammatory pattern. Obesity is associated with low Physical Activity (PA) levels; however, studies are inconsistent about an association between asthma and low PA levels. As obesity often antedates asthma, low PA levels might play a role in the development of the asthma-obesity phenotype. We aim to investigate the role of PA and airway inflammation in pediatric asthma and obesity.   Methods : In total, 122 children (aged 6-12 years) were recruited via an online questionnaire and divided into four groups; Asthma n=29, overweight n=30, asthma-overweight n=30, and healthy control n=33. PA was defined by the average step count of seven consecutive days, measured by an accelerometer. Eosinophilic airway inflammation was measured by Fractional exhaled Nitric Oxide (FeNO).   Results : Step count did not differ among the four groups (p>0.05). Significant predictors for a high step count included season of measurement, a younger age and the male sex (P   Conclusion : Although asthma was characterised by increased FeNO levels, the paediatric asthma obesity phenotype cannot be characterized by altered FeNO levels and decreased PA levels. In future studies, other factors such as systemic inflammatory markers, dietary factors and chest wall mechanisms would be of interest to study in order to characterize the paediatric asthma-obesity phenotype.
Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed Pulmonary Tuberculosis
Authors: Olalekan A. Uthman, Charles Okwundu, Kayode Gbenga, Jimmy Volmink, David Dowdy, Alimuddin Zumla, Jean B. Nachega
Journal: Annals of Internal Medicine (2015)

Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment remains challenging.To assess evidence from randomized, controlled trials of the timing of ART initiation in HIV-infected adults with newly diagnosed pulmonary TB.PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference abstracts, and ClinicalTrials.gov (from January 1980 to May 2015).Randomized, controlled trials evaluating early versus delayed ART initiation (1 to 4 weeks vs. 8 to 12 weeks after initiation of TB treatment) or deferred ART initiation (after the end of TB treatment).Three reviewers independently extracted data and assessed risk of bias. The main outcome measures were all-cause mortality and the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS).The 8 included trials (n = 4568) were conducted in Africa, Asia, and the United States and were generally at low risk of bias for the assessed domains. Overall, early ART reduced mortality compared with delayed ART (relative risk [RR], 0.81 [95% CI, 0.66 to 0.99]; I2 = 0%). In a prespecified subgroup analysis, early ART reduced mortality compared with delayed ART among patients with baseline CD4+ T-cell counts less than 0.050 × 109 cells/L (RR, 0.71 [CI, 0.54 to 0.93]; I2 = 0%). However, a mortality benefit from early ART was not found among those with CD4+ T-cell counts greater than 0.050 × 109 cells/L (RR, 1.05 [CI, 0.68 to 1.61]; I2 = 56%). Early ART was associated with a higher incidence of TB-IRIS than delayed ART (RR, 2.31 [CI, 1.87 to 2.86]; I2 = 19%).Few trials provided sufficient data for subgroup analysis.Early ART in HIV-infected adults with newly diagnosed TB improves survival in those with CD4+ T-cell counts less than 0.050 × 109 cells/L, although this is associated with a 2-fold higher frequency of TB-IRIS. In patients with CD4+ T-cell counts greater than 0.050 × 109 cells/L, evidence is insufficient to support or refute a survival benefit conferred by early versus delayed ART initiation.None. (PROSPERO registration: CRD42012001884).
An open-label, randomized phase II study comparing first-line treatment with dovitinib (TKI258) versus sorafenib in patients with advanced hepatocellular carcinoma.
Authors: Ann-Lii Cheng, Ho Yeong Lim, Ronnie Tung Ping Poon, Sumitra Throngprasert, Cathy Reddick, Yong Zhang, Michael Shi, Eugene Tan, Yongyu Wang
Journal: Journal of Clinical Oncology (2012)

TPS4147 Background: Hepatocellular carcinoma (HCC) is a highly vascularized tumor that may rely on tumor angiogenesis for growth, invasion, and metastasis. Inhibition of the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) pathways temporarily prevents HCC tumor progression. However, because the fibroblast growth factor receptor (FGFR) pathway can serve as an escape pathway for these tumors, simultaneous inhibition of FGFR may be required to provide a sustainable antitumor response. Dovitinib (TKI258) has been shown to be a potent oral tyrosine kinase inhibitor that inhibits multiple angiogenic factors, including FGFR, VEGFR, and PDGFR, with IC 50 values of &lt; 20 nM. Preclinical studies in HCC xenograft models have demonstrated that the antitumor effects of dovitinib are superior to those of the kinase inhibitor sorafenib, which is approved for use in advanced HCC. These data support additional testing of dovitinib in advanced HCC patients. Methods: This study (NCT01232296) is an open-label, randomized phase II trial being conducted at multiple centers in the Asia-Pacific region. Adult patients are eligible if they have advanced HCC (Barcelona Clinic Liver Cancer stage C) with Child-Pugh class A cirrhotic status. Patients must also have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and cannot be eligible for (or have had disease progression after) surgical or locoregional therapies. Patients are randomized 1:1 to receive dovitinib (500 mg/day on a 5-days-on/2-days-off dosing schedule) or sorafenib (400 mg twice daily). Patients will be treated until disease progression, unacceptable toxicity, death, or discontinuation for any other reason. No treatment crossover will be permitted. The primary end point of this trial is overall survival. Secondary end points include time to tumor progression, disease control rate, time to definitive deterioration in ECOG status, safety, and pharmacokinetics. The pharmacodynamic effects of dovitinib and sorafenib on plasma/serum biomarkers will also be explored. As of 30 January 2012, 93 of the planned 150 patients have been enrolled.