tbuckley/cabot-search huggingface dataset:
Cancer Patterns of Four Ethnic Groups in Hawaii&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Laurence N. Kolonel
Journal: JNCI Journal of the National Cancer Institute (1980)

Cancer risks were compared in the Japanese, Chinese, Hawaiian, and Filipino populations of Hawaii with those in the U.S. white population. The analysis used standardized incidence ratio(s) (SIR), based on the U.S. white incidence rates for 1970. In general, the risks for many major cancers in the Japanese, Chinese, and Filipinos were low in relation to U.S. whites, whereas those for Hawaiians were high. However, the SIR values for the various cancer sites and types varied considerably within each ethnic group. Ethnic-specific data on smoking, drinking, and dietary habits and on sociologic and demographic factors were examined in relation to the SIR findings. Some of the results were consistent with current etiologic hypotheses, whereas others suggested areas for further epidemiologic study.
Diagnostic and Therapeutic Phlebotomy in Hemochromatosis with Anemia
Authors: Stuart C. Finch, Roy N. Barnett
Journal: New England Journal of Medicine (1957)

THIS report is concerned principally with the correction, by means of repeated phlebotomies, of moderate anemia and neutropenia, probably caused by hypersplenism, in a patient with idiopathic hemochromatosis. It also emphasizes that anemia per se is not a contraindication to embarking on a therapeutic phlebotomy program. Finally, it illustrates how the diagnosis of iron-storage disease may be established in a patient in whom a liver biopsy could not be performed.Numerous cases in the literature have emphasized the clinical and histologic improvement that follows the removal of excess iron stores.1 Similarly, a striking clinical improvement was observed in this patient. . . .
P185 Evaluation of the LENT Prognostic Score in a Large Tertiary Pleural Service
Authors: H Balata, N Anwar, P Foden, M Al-Aloul, J Holme, M Evison
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Reliable predictors of survival in malignant pleural effusions (MPE) have far reaching applications in clinical practice, not least tailoring individual treatment strategies. The ‘LENT’ score (pleural fluid <b>L</b>actate dehydrogenase; <b>E</b>astern Cooperative Oncology Group performance score; <b>N</b>eutrophil-to-lymphocyte ratio; <b>T</b>umour type) was developed and validated as a clinical prognostic scoring system from three international prospective patient databases.<sup>1</sup> The aim of this study was to evaluate the LENT score in a further UK population of patients with MPE, geographically separate from those in the original study. <h3>Methods</h3> Our hospital is a large tertiary centre for a physician-led pleural service (including medical thoracoscopy), a regional mesothelioma centre and a regional thoracic surgical centre. A retrospective study of all patients with positive (i.e. diagnostic for malignancy) pleural cytology or histology from 2010 to 2014 was undertaken. This timeframe allowed a minimum of 12 months follow-up for all patients. Survival data was obtained from national death registries. All patients in whom all LENT criteria were available were included in the analysis. A Kaplan-Meier curve and a Cox regression model were used to assess the LENT risk category. Harrell’s C statistic was used to assess the accuracy of the regression model and mortality rates at time points of interest were calculated. <h3>Results</h3> The LENT score was calculated for 101 patients diagnosed with MPE. The median survival (days, IQR) for the low (n = 18), medium (n = 54) and high risk (n = 29) groups were: 254 (152–602), 102 (40–301) and 16 (7–42). In the high risk group, only 31% of patients survived 1 month and 7% survived 6 months. There is a statistically significant difference in the survival times in the different risk groups according to the log-rank test (p &lt; 0.001). Harrell’s C statistic in this cohort is 0.69 (see Figure 1). <h3>Conclusions</h3> The LENT scoring system has again been shown to be a good tool for predicting survival in patients with MPE when applied to a geographically distinct cohort of patients to the original study. The LENT score continues to be a clinically valuable tool in the assessment of patients with MPE. <h3>Reference</h3> 1 Clive AO, <i>et al</i>.<i> Thorax</i> 2014;<b>69</b>(12):1098–104
Soundings: Postmenopausal doctors
Authors: James Owen Drife
Journal: BMJ (2002)

The medical menopause affects doctors of both sexes. It normally occurs in the mid 50s but its basis is controversial. Those who believe in a hormonal cause say it is the end result of decades of disturbed circadian rhythm combined with bursts of excessive adrenalin secretion. Others argue that it is psychological, triggered by reaching the horizontal phase of medicine's 30 year learning curve.

In many cultures it is welcomed and the postmenopausal doctor (PMD) is valued for his or her wisdom. In Britain and the United States, however, attitudes are ambivalent. PMDs are appreciated by patients but not by healthcare systems. One of the features of the medical menopause is disinhibition, and the NHS has difficulty in relating to professionals who speak their minds.

Self medication for the condition has been used for centuries but modern sufferers are particularly hard hit. In the early part of their careers they worked long hours to maintain the service while their seniors had a pleasant lifestyle. Now they work long hours to maintain the service while their juniors enjoy a pleasant lifestyle.

In Britain, today's PMDs have worked throughout their careers in a severely underfunded service. When they pointed this out they were ignored. Indeed, the public was told that if only the doctors would work harder, the NHS would be fine. The recently announced cash boost will produce improvements shortly after these PMDs retire.

Pharmacological treatments remain inadequately researched. Clinical opinion is divided between Highland and Islay malts on the one hand and claret and burgundy on the other. The most effective remedy, however, is surgical. Cutting oneself off from the NHS produces immediate and lasting relief of symptoms. Sleep and temper improve, the will to live returns, and the doctor alarms his or her friends by becoming cheerful again.

The NHS, having previously encouraged such surgery, is now beginning to question the high rates. Britain needs more doctors and its major suppliers—developing countries—may not be able to cope. Stopping the haemorrhage of PMDs would help but cannot be achieved unless the system recognises and manages this treatable condition.
Plasma PD-L1 concentration in patients with brain metastases from solid tumors.
Authors: Anna Sophie Berghoff, Sahra Pajenda, Ayseguel Ilhan-Mutlu, Georg Widhalm, Karin Dieckmann, Johannes A. Hainfellner, Ludwig Wagner, Christoph Zielinski, Peter Birner, Rupert Bartsch, Matthias Preusser
Journal: Journal of Clinical Oncology (2015)

e13026 Background: Immune Checkpoint inhibitors of the programmed cell death (PD1) / programmed cell death ligand 1 (PD-L1) axis have shown remarkable clinical activity in various malignancies. We aimed to investigate soluble PD-L1 in the plasma of brain metastases (BM) patients, as the identification of new predictive factors is urgently warranted. Methods: We collected EDTA plasma samples from 43 patients with BM (29/43 (67.4%) lung cancer; 4/43 (9.3%) breast cancer; 4/43 (9.3%) melanoma; 6/43 (14.0%) renal cell carcinoma (RCC). Plasma PD-L1 concentration was analyzed using a sandwich ELISA. A rabbit polyclonal anti-PDL1/CD274 antibody (Millipore ABF 133) was used as capture reagent and a non-commercial PD-L1 monoclonal antibody (clone 5H1) as detection antibody. The lower limit of detectable plasma PD-L1 concentration was 50 pg/ml. Results: Overall, 6/43 (14.0%) patients presented with detectable PD-L1 concentration in the plasma (median 225 pg/ml; range 128-3648). PD-L1 was most frequently detected in melanoma BM patients (2/4; 50.0%; median 1888 pg/ml), followed by breast cancer (1/4; 25.0%; median 200 pg/ml), lung cancer (3/29; 10.3%; median 250 pg/ml) and RCC BM patients (0/6; 0.0%; p = 0.111; Chi Square test). No correlation between presence of plasma PD-L1 and extent of extracranaial disease, as defined by involved metastatic sites (p = 0.956; Chi Square), white blood cell count (p = 0.630; Chi Square test) or overall survival time (p = 0.514, log-rank test) was evident. BM tissue was available in 6/45 (13.3%) patients. Five/6 (83.3%) presented with PD-L1 expression on BM tumor cells, however none of the patients with tissue PD-L1 expression presented with detectable plasma PD-L1 (no statistical analysis due to small sample size). Conclusions: Soluble PD-L1 is evident in the plasma of some BM patients with melanoma, breast and lung cancer. Our results support the further investigation of plasma PD-L1 concentration as clinical biomarker in cancer patients.
Primary Epstein–Barr-Virus Infections in Acute Neurologic Diseases
Authors: Charles Grose, Werner Henle, Gertrude Henle, Paul M. Feorino
Journal: New England Journal of Medicine (1975)

Infectious mononucleosis has been associated with Guillain--Barré syndrome, Bell's palsy, meningoencephalitis and transverse myelitis. Since it is not known that many children with infectious mononucleosis do not develop heterophil antibodies, we looked for evidence of current or recent Epstein-Barr virus infection in young patients with these neurologic diseases by using serodiagnostic procedures for detection and titration of antibodies to various antigens related to Epstein-Barr virus. Seven of 24 cases with Guillain-Barre syndrome and three of 16 with facial palsy were definitely associated with primary infection with Epstein-Barr virus as were two cases each of the other two neurologic diseases. Only one of these patients had obvious clinical infectious mononucleosis, and only a few demonstrated heterophil agglutinins. It is evident that the virus must be considered in the diagnosis of various acute neurologic diseases affecting children and young adults, even in the absence of heterophil-antibody response or other signs of infectious mononucleosis.
Posterior Urethrovaginal Communication in Apparent Males with Congenital Adrenocortical Hyperplasia
Authors: B. Rosenberg, W. H. Hendren, J. D. Crawford
Journal: New England Journal of Medicine (1969)

In each of four female infants in whom an extreme degree of virilization during fetal development resulted from the adrenocortical-hyperplasia syndrome the urethra extended to the tip of the phallus. At urethroscopy it resembled that of the normal male, with a verumontanum situated between the bladder neck and the external urethral sphincter. The vagina opened into the urethra at the verumontanum. Urethroscopy should be included in the evaluation of all virilized females in whom the vaginal outlet is not otherwise easily demonstrated because the vagina may communicate with the urethra proximal to the external sphincter. Recognition of this anatomic variant is important since it predisposes to urinary-tract infection, and, to avoid incontinence, special consideration is required in its surgical correction. This anomaly can be corrected surgically without injury to the external urethral sphincter.
Utilizing metformin to enhance the efficacy of androgen-deprivation therapy in the treatment of prostate cancer.
Authors: L. Klotz, N. Venier, A. Vandersluis, R. Besla, N. Fleshner, M. N. Pollak, V. Venkateswaran, A. J. Colquhoun
Journal: Journal of Clinical Oncology (2011)

22 Background: Prostate cancer (PCa) incidence varies by geographic location, with developed countries exhibiting higher levels of disease. Some attribute this to the “Westernized lifestyle” of high energy diets and limited physical activity with consequent obesity. Obesity and related diseases like diabetes, cause hyperinsulinemia, which upregulates pro-survival insulin/insulin-like growth factor signalling. Previous work shows diet-induced hyperinsulinemia enhances PCa tumor growth in vivo. Metformin, a diabetic treatment, reduces hyperinsulinemia, and also exhibits anti-neoplastic properties. We assessed the potential benefit of combining a standard PCa treatment (bicalutamide) with metformin in vitro and in vivo. Methods: The effect of bicalutamide and/or metformin on colony formation rates was assessed in LNCaP, PC3, DU145 and PC3AR2 PCa cell lines using clonogenic assay. Western blot and cell cycle analyses were used to elucidate mechanisms of interaction between the drugs. The combination treatment regimen was assessed in vivo using a murine xenograft model. Results: Micromolar bicalutamide or millimolar metformin caused significant dose-dependent reduction in colony formation rates (p&lt;0.001). Combination treatment further significantly reduced colony formation rates (p&lt;0.005). Differing mechanisms of interaction occurred in AR positive and negative cell lines. Following combination treatment LNCaP cells exhibited altered cell proliferation (decreased PCNA) and perturbed cell cycle kinetics (G1/S arrest). PC3 cells showed evidence of enhanced apoptosis (increased BAX, decreased caspase 3, phospho-Akt). Preliminary in vivo results show significantly diminished tumor growth following combination treatment (p&lt;0.0001). Conclusions: Combining bicalutamide and metformin significantly reduces PCa cell colony formation rates further than either monotherapy. In AR positive cells this effect is mediated by reducing cell proliferation rates, whereas in AR negative cells combination treatment promotes apoptosis. This combination drug regimen may potentially improve prostate-cancer specific survival via the direct anti-neoplastic properties outlined. [Table: see text]
Effect of Host Age, Virus Dose, and Route of Inoculation on Tumor Incidence, Latency, and Morphology in Syrian Hamsters Inoculated Intravenously With Oncogenic DNA Simian Virus 40&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: G T Diamandopoulos, M F McLane
Journal: JNCI Journal of the National Cancer Institute (1975)

Three-week-old to 12-month-old male Syrian hamsters were inoculated iv with 10(8.5) median tissue culture infective dose of simian virus 40 (SV40). Three-week-old hamsters were similarly inoculated with aliquots of SV40 of progressively decreasing titers. The tumor incidence and, to a lesser extent, the tumor latency were directly dependent on the age of the animals at the time of virus exposure and on the dose of the virus. However, this age-dose dependence was not of the magnitude usually observed in hamsters inoculated with SV40 sc or im. Moreover, the wide morphologic spectrum of neoplasms induced, i.e., lymphosarcoma, reticulum cell sarcoma, and osteogenic sarcoma, by iv route of inoculation, contrasted sharply with the anaplastic and spindle-cell sarcomas which were the only types of malignant tumors resulting when other routes were used.
The definition of a psychiatrist: eight years later
Authors: D G Langsley, J Yager
Journal: American Journal of Psychiatry (1988)

In 1980, psychiatric practitioners and educators were surveyed to determine their concepts of the knowledge and skills that define a specialist in psychiatry. The authors repeated this survey, expanding the list of skill and knowledge items and asking respondents to comment on whether particular skills or knowledge were important to a psychiatric subspecialty. Less importance was ascribed in the current survey than in the earlier survey to certain long-term and social psychotherapies, and more importance was ascribed to descriptive or biological psychiatry; brief or supportive therapies; psychopharmacological agents; consultation-liaison psychiatry; evaluation of children, the aged, and alcoholics; and certain desirable personal characteristics of the psychiatrist.
Efficacy of Patritumab (U3-1287), a Fully Human Anti–Human Epidermal Growth Factor Receptor 3 (Her3) Monoclonal Antibody (Mab), in Head and Neck (H&N) Cancer Models
Authors: C. Wenzl, M. Schneider, H. Kallus, K. Selle, M. Redondo-Mueller, T. Inoue, J. Bange, J. Ruhe
Journal: Annals of Oncology (2014)
Disease activity-guided dose optimisation of adalimumab and etanercept is a cost-effective strategy compared with non-tapering tight control rheumatoid arthritis care: analyses of the DRESS study
Authors: Wietske Kievit, Noortje van Herwaarden, Frank HJ van den Hoogen, Ronald F van Vollenhoven, Johannes WJ Bijlsma, Bart JF van den Bemt, Aatke van der Maas, Alfons A den Broeder
Journal: Annals of the Rheumatic Diseases (2016)

Background A disease activity-guided dose optimisation strategy of adalimumab or etanercept (TNFi (tumour necrosis factor inhibitors)) has shown to be non-inferior in maintaining disease control in patients with rheumatoid arthritis (RA) compared with usual care. However, the cost-effectiveness of this strategy is still unknown. Method This is a preplanned cost-effectiveness analysis of the Dose REduction Strategy of Subcutaneous TNF inhibitors (DRESS) study, a randomised controlled, open-label, non-inferiority trial performed in two Dutch rheumatology outpatient clinics. Patients with low disease activity using TNF inhibitors were included. Total healthcare costs were measured and quality adjusted life years (QALY) were based on EQ5D utility scores. Decremental cost-effectiveness analyses were performed using bootstrap analyses; incremental net monetary benefit (iNMB) was used to express cost-effectiveness. Results 180 patients were included, and 121 were allocated to the dose optimisation strategy and 59 to control. The dose optimisation strategy resulted in a mean cost saving of −€12 280 (95 percentile −€10 502; −€14 104) per patient per 18 months. There is an 84% chance that the dose optimisation strategy results in a QALY loss with a mean QALY loss of −0.02 (−0.07 to 0.02). The decremental cost-effectiveness ratio (DCER) was €390 493 (€5 085 184; dominant) of savings per QALY lost. The mean iNMB was €10 467 (€6553–€14 037). Sensitivity analyses using 30% and 50% lower prices for TNFi remained cost-effective. Conclusions Disease activity-guided dose optimisation of TNFi results in considerable cost savings while no relevant loss of quality of life was observed. When the minimal QALY loss is compensated with the upper limit of what society is willing to pay or accept in the Netherlands, the net savings are still high. Trial registration number NTR3216; Post-results.
Detection of frequent MET Exon 14 skipping events in pulmonary sarcomatoid carcinoma and response to targeted inhibition.
Authors: Xuewen Liu, Yuxia Jia, Yufeng Shen, Jinli Chen, Mahesh Mansukhani, Haiying Cheng, Sanjay Koul, Alain C. Borczuk, Balazs Halmos
Journal: Journal of Clinical Oncology (2015)

8020 Background: Pulmonary sarcomatoid carcinoma (PSC) represents a category of highly aggressive carcinomas associated with a poor prognosis. New therapeutic strategies based on better knowledge of the molecular pathogenesis of PSC are needed. We recently identified a high frequency of a unique type of MET alterations leading to exon 14 skipping (exon 14Δ) in PSC. Methods: Whole-exome sequencing in a discovery set and targeted MET mutation screening in an independent validation set of PSC were performed. RT-PCR and Western blotting were performed to validate MET exon 14Δ. A lung adenosquamous cell line H596 (MET exon 14Δ and PIK3CA mutated) and a gastric adenocarcinoma cell line Hs746T (MET exon 14 Δ) were used for functional studies. Ablation of MET signaling by siRNA or pharmacological inhibitor (Crizotinib) was conducted, and subsequent MTS assays and Western blotting were then performed. Simultaneous MET signaling blockade and PIK3CA signaling inhibition using PIK3CA inhibitor (GDC0941) were performed to assess synergistic effects in H596 cells. Results: Alterations affecting MET exon 14 splice sites, including deletions at the 5’ splice site (n = 3) and point mutations at the 3’ splice site (n = 5) were found in 22% (8/36) of PSC. One PSC harbored MET exon 14Δ and a concurrent PIK3CA mutation. RT-PCR and Western blotting confirmed the presence of MET exon 14Δ in tumor and in H596 and Hs746T cells. Both MET siRNA silencing and crizotinib decreased cell proliferation and inhibited downstream AKT and MAPK activation in Hs746T cells, whereas effects were modest in H596 cells and negligible in control Calu-3 and HCC827 cells. Concomitant MET and PI3K blockade had synergistic effects in H596 cells. Migration/invasion assays in H596 and Hs746T cells, as well as further functional studies utilizing specific MET exon 14 expression constructs are ongoing. Conclusions: Our study finds that MET exon 14Δ alterations are a frequent and potentially targetable event in PSC. Our studies also suggest that concurrent PIK3CA mutations require combined treatment. Clinical studies assessing biomarker-driven MET/PI3K inhibition should be explored in PSC as well as other malignancies harboring MET exon 14Δ events.
Brain Tumors in Children
Authors: Ian F. Pollack
Journal: New England Journal of Medicine (1994)

Tumors of the central nervous system constitute the largest group of solid neoplasms in children and are second only to leukemia in their overall frequency during childhood. Each year, brain tumors develop in approximately 1500 to 2000 children in the United States; the number of tumors appears to have increased slightly from 1974 to 198813. Although the mortality rate for these neoplasms exceeds the rates for many other childhood tumors, recent therapeutic advances coupled with refinements in neuroimaging techniques, which have facilitated earlier diagnosis and improved treatment planning, have increased the percentage of affected children who survive to . . .
P78 Study of mortality in severe and difficult to treat asthma
Authors: J Sullivan, K O’Shea, A Mansur
Journal: Thorax (2015)

<h3>Introduction</h3> The National Report on Asthma Death (NRAD 2014) highlighted important shortcomings related to asthma management and an important number of patients still die from asthma. However, the mortality rate and causes of mortality in the severe asthma services has not been previously reported. <h3>Aim</h3> To study what patients with severe asthma die from and what is their risk of mortality <h3>Methods</h3> All patients attending our severe asthma service who had died between March 2009 and December 2014 were identified. We retrieved data from case notes, GPs, local hospitals and local database using a pre designed proforma which included cause of death, place of death, age at time of death, clinical details on asthma duration, lung function, biomarkers, medication, exacerbations including hospitalisation and co-morbidities. Causes of death was obtained from death certificates and when available coroner’s post-mortem reports. <h3>Results</h3> Of the 520 patients attended our service between January 2009 and December 2014, there were 24 deaths (4.6% over 72 months, 0.7% annually). The mean age of death was 51 yrs (range 21–69), 17/24 (71%) were females. 50% had poorly controlled asthma with a mean predicted FEV1 of 54%. 13/24 (61%) were on a maintenance dose of oral corticosteroids (mean dose 19 mg/day). The mean inhaled corticosteroids was 1006 µg. The cause of death was not known in 6 cases, with majority of cases died from non-asthma causes (78%) with cardiovascular disease being the most common. Asthma was the cause of death in 4/18 (22%) cases. Co-morbid diseases were prevalent particularly those that form the metabolic syndrome. Non-concordance with asthma medications and smoking history (current and ex-smokers) were also common (50% and 60% respectively). <h3>Conclusion</h3> Although death is a rare event in our severe asthma service (0.7%), patients did die prematurely (mean age 51 yrs) usually from non-asthma causes, but asthma still accounted for death in the fifth of this group. Larger multicentre study with control data will be needed to confirm these finding and look for drivers and predictors of mortality in severe asthma.