tbuckley/cabot-search huggingface dataset:
Cost Containment and the Tale of Care Coordination
Authors: J. Michael McWilliams
Journal: New England Journal of Medicine (2016)

Interview with Dr. J. Michael McWilliams on the merits of care coordination — and why it's unlikely to reduce health care spending. (07:14)Download The notion that care coordination not only improves outcomes but also lowers costs is not evidence-based, and it poses many potential dangers, beginning with the diminution of the importance of coordinated care itself as a worthy goal.
Purinergic Signaling Differentially Modulates Normal and Leukemic Hematopoiesis.
Authors: Valentina Salvestrini, Sara Gulinelli, Roberta Zini, Luisa Caione, Giorgia Migliardi, Wanda Piacibello, Davide Ferrari, Francesco Di Virgilio, Sergio Ferrari, Rossella Manfredini, Roberto M Lemoli
Journal: Blood (2009)
Clinical features and outcome of brain metastasis in breast cancer patients (Saudi Arabia).
Authors: O. A. M. Abulkhair, W. K. S. Elmelouk, A. Albabtain, S. Musaad, A. R. Jazieh
Journal: Journal of Clinical Oncology (2011)

e11516 Background: Brain metastasis may occur in 10-15% of patients with breast cancer (BC). Such a diagnosis is associated with poor survival. In Saudi Arabia, there is no data on brain metastasis in BC patients. Our aim is to analyze the clinical characteristics, survival of different subtypes of BC patients with brain metastasis and to identify possible prognostic factors. Methods: Patients with brain metastasis were identified from a data base of BC cases diagnosed from January 2002 to July 2009 at King Abdulaziz Medical City, Saudi Arabia. Their clinical characteristics, pathological features and prognostic factors were analyzed. Survival since diagnosis of brain metastasis was calculated using Kaplan-Meier estimate. A proportional hazards regression model was conducted to evaluate the effect of different subtypes. Results: Out of total 594 BC patients, 34 (5.72%) with brain metastasis were identified based on imaging and clinical findings. Median age at primary BC diagnosis was 39 years (range, 26 to 69) and median time to CNS metastasis was 16.01 months (range 0.03 to 47.7), 29 (85.29%) were ductal carcinoma, 3 (8.82%) lobular and 2 (5.88%) were unknown. HER2 overexpression was found in tumor from 16 patients, 6 (17.65%) of them were triple positive, 9 (26.47%) lacked expression of ER and PR and 1 (2.94%) had estrogen ER over expression with no progesterone PR overexpression. Of the 15 that lacked HER 2 overexpression, 7 (20.59%) overexpressed ER/PR, 2 (5.88%) overexpressed ER alone and 6 (17.65%) were triple negative (TNBC), while the remainder were unknown. Regarding CNS involvement, 25 (73.53%) were intraparenchymal while 3 (8.82%) had leptomeningeal involvement and 6 (17.65%) had both. Conclusions: Nearly half of the BC patients with brain metastasis express HER2 TNBC confers the worst outcome among all histological subtypes. Multiple Cox proportional hazards regression analysis for overall survival (n=34). Variable Hazard ratio 95% confidence interval P value Receptor status (vs. triple negative) ER-/PR-/HER2 + 0.151 0.042-0.541 0.0037 ER+ or PR+/HER2 - 0.132 0.023-0.753 0.0227 ER+/PR+/HER2 - 0.262 0.078-0.880 0.0302 Triple positive 0.128 0.030-0.543 0.0053
Impact of the gene expressions of thymidylate synthase and dihydropyrimidine dehydrogenase on survival in patients enrolled in the ACTS-GC study.
Authors: Mitsuru Sasako, Masanori Terashima, Wataru Ichikawa, Atsushi Ochiai, Koji Kitada, Issei Kurahashi, Shinichi Sakuramoto, Hitoshi Katai, Takeshi Sano, Hiroshi Imamura
Journal: Journal of Clinical Oncology (2012)

52 Background: The efficacy of 5-FU-based therapy is basically related to the expression of enzymes involved in pyrimidine metabolism, such as thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyltransferase (OPRT). Biomarker analysis was conducted to evaluate the influence of these expressions on the outcomes of patients enrolled in the ACTS-GC study, a randomized phase III trial, which demonstrated the efficacy of adjuvant treatment with S-1 after D2 dissection for stage II and III gastric cancer (Sakuramoto et al., NEJM 2007) Methods: Formalin-fixed paraffin-embedded specimens were available for 829 of a total of 1,059 (78.3%) patients. Expressions of TS, DPD, TP and OPRT were measured by RT-PCR in macrodissected tumor specimens and normalized to β-actin expression as the reference gene. The expression levels of each gene were categorized as low or high at the 33.3rd or 66.7th percentile. If the p-value of the interaction was less than 0.1, statistical significance was assumed. Results: Expressions of the 4 genes were quantifiable in 97% of the 829 specimens and the distributions were balanced across the arms. The hazard ratio (HR) for overall survival (OS) of S-1 to surgery alone was smaller in the high-TS (highest one-third) (HR, 0.370; 95%CI, 0.221-0.619) than in the low-TS group (lower two-thirds) (HR, 0.757; 95%CI, 0.563-1.018). This interaction between TS expression and OS was statistically significant (p=0.015). Similarly, the HR for OS of S-1 to surgery alone was smaller in the high-DPD (higher two-thirds) (HR, 0.520; 95%CI, 0.376-0.720) than in the low-DPD group (lowest one-third) (HR, 0.848; 95%CI, 0.563-1.276). This interaction (p=0.065) was also statistically significant. There was no interaction between the TP or OPRT expression and OS. Conclusions: This large biomarker study showed that intratumoral TS and DPD gene expressions may be predictive markers of the efficacy of S-1 in gastric cancer patients receiving postoperative adjuvant chemotherapy with S-1.
Reasons for choosing contralateral prophylactic mastectomies in women who test negative for the BRCA mutation: A retrospective questionnaire.
Authors: M. M. Howard-McNatt, G. Hurt, E. A. Levine
Journal: Journal of Clinical Oncology (2011)

192 Background: Determination of BRCA1and 2 mutation carrier’s status has become increasingly important. BRCA1/2 carriers are offered bilateral mastectomy (BLM) and prophylactic oophorectomy. Those who test negative typically do not undergo such extensive surgery. However, there is a cohort of women who still decide to have BLM at the time of their breast cancer diagnosis despite testing negative for the mutation. A questionnaire was sent to women who had prophylactic mastectomies to determine the reasons for their surgical choice. Methods: Women who received BRCA1 and 2 testing and tested negative but chose bilateral mastectomies between January 2005- May, 2010 were sent a questionnaire. For those who expressed an opinion, a two-sided Fisher exact test was used to compare responses. Patient demographics, family history, reasons for choosing mastectomy, and satisfaction were recorded. Results: A total of 35 surveys were mailed, and 28 were returned (80%). The mean patient age at diagnosis was 41.9 years. The majority of women were Caucasian, had some college to postgraduate education, and had children. 64% had a relative with breast cancer. Fear was the main reason why these women choose BLM. The majority had breast reconstruction and overall 71% were very satisfied with their surgical choice. Conclusions: Increased rates of contralateral prophylactic mastectomies have been observed in women with negative BRCA results. In our study Caucasian, educated, married women were more likely to choose BLM. The main reason women gave for choosing BLM was fear of recurrence. Prospective studies are needed to examine factors effecting patient decision-making.
Arsenic Trioxide (Trisenox® ATO), Ascorbic Acid (AA) and Dexamethasone (Dex) Pulses (TAD) for Relapsed Refractory Progressive Multiple Myeloma (MM) Patients (pts); a Final Report.
Authors: Rony M. Abou-Jawde, Janice Reed, Megan Kelly, Luba Platt, Mary Ann Karam, Mary Ruth Kovak, Gordan Srkalovic, Mohamad A. Hussein
Journal: Blood (2004)
Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning
Authors: Ivan Azarov, Ling Wang, Jason J. Rose, Qinzi Xu, Xueyin N. Huang, Andrea Belanger, Ying Wang, Lanping Guo, Chen Liu, Kamil B. Ucer, Charles F. McTiernan, Christopher P. O’Donnell, Sruti Shiva, Jesús Tejero, Daniel B. Kim-Shapiro, Mark T. Gladwin
Journal: Science Translational Medicine (2016)

A mutant five-coordinate neuroglobin with a very high carbon monoxide binding affinity acts as an antidote to bind and eliminate CO.
β Cells led astray by transcription factors and the company they keep
Authors: Peter Thompson, Anil Bhushan
Journal: Journal of Clinical Investigation (2016)

Pancreatic β cells have one of the highest protein secretion burdens in the body, as these cells must synthesize and secrete insulin in proportion to postprandial rises in blood glucose. Remarkably, it is now becoming clear that adult β cells retain plasticity and can dedifferentiate into embryonic fates or adopt alternate islet endocrine cell identities. This property is especially important, because changes in cell fate alter β cell function and could form the basis for defects in insulin secretion that occur early in the pathogenesis of the most prevalent form of β cell dysfunction, type 2 diabetes. In this issue, three different studies provide complementary perspectives on how the transcription factors NK2 homeobox 2 (NKX2.2), paired box 6 (PAX6), and LIM domain-binding protein 1 (LDB1) serve to maintain mature adult β cell identity, revealing clues as to how adult β cells can partially dedifferentiate or become reprogrammed into other islet endocrine cells.
Effect of axillary dissection for occult detected sentinel nodes metastases on survival: NSABP B-32.
Authors: T. B. Julian, S. J. Anderson, E. P. Mamounas, D. N. Krag, D. Weaver, T. Ashikaga, S. P. Harlow, N. Wolmark
Journal: Journal of Clinical Oncology (2011)

80 Background: In NSABP B-32 trial 5,611 women with invasive breast cancer were randomly assigned to sentinel lymph node biopsy (SLNB) plus axillary dissection (Group [Grp] 1) or SLNB alone (Grp 2). There was no significant difference in OS or DFS reported between the two groups. Initial permanent pathologic assessment of the SLNs at participating sites was designed to identify all macrometastases &gt;2 mm and consisted of slicing the SLNs at approximately 2.0 mm intervals, embedding all slices in paraffin tissue blocks, and examining one hematoxylin and eosin stained slide from each block. Routine use of IHC or sectioning of deeper levels was prohibited. SLN paraffin tissue blocks from cases with pathologically negative SLNs were later evaluated centrally for occult metastases deeper in the blocks. This study evaluates group outcomes related to occult metastases. Methods: Routine and cytokeratin IHC stains were used at two widely spaced additional levels. Using this technique, occult metastases were detected in 15.9% of the patients (pts) with initially negative SLNs (616 / 3884 cases). Of the 616 cases, 431 (69.8%) had isolated tumor-cell clusters, 171 (27.9%) had micrometastases, and 14 (2.3%) had macrometastases (Weaver D, et al: N Engl J Med, 2011). Results: 316 (16.4%) of 1924 pts had occult metastases in Grp 1 and 300 (15.3%) of 1960 in Grp 2. Non-sentinel node status was available in 312/316 pts in Grp 1; 23 (7.4%) had positive non-sentinel nodes. In pts with occult metastases, there were no significant differences in OS or DFS between groups (Grp 2 vs. Grp 1 OS HR: 0.89, p=0.62; DFS HR: 0.79, p=0.16). There were no significant differences in OS or DFS between the groups in pts who were negative for occult metastases (Grp 2 vs. 1 OS HR:1.25, p=0.07; DFS HR: 1.11, p=0.22). Conclusions: A more detailed assessment of the SLNs with deeper sectioning and IHC staining detected a significant level of occult metastases in clinically node negative pts. However, no benefit was seen by the addition of axillary dissection in pts with occult SLN metastases. Supported by NCI: U10-CA-12027, U10-CA-37377, U10-CA-69974, U10-CA-69651, and ARRA ROI CA 74137
Correlations Between Ratings on the Resident Annual Evaluation Summary and the Internal Medicine Milestones and Association With ABIM Certification Examination Scores Among US Internal Medicine Residents, 2013-2014
Authors: Karen E. Hauer, Jonathan Vandergrift, Brian Hess, Rebecca S. Lipner, Eric S. Holmboe, Sarah Hood, William Iobst, Stanley J. Hamstra, Furman S. McDonald
Journal: JAMA (2016)

US internal medicine residency programs are now required to rate residents using milestones. Evidence of validity of milestone ratings is needed.To compare ratings of internal medicine residents using the pre-2015 resident annual evaluation summary (RAES), a nondevelopmental rating scale, with developmental milestone ratings.Cross-sectional study of US internal medicine residency programs in the 2013-2014 academic year, including 21 284 internal medicine residents (7048 postgraduate-year 1 [PGY-1], 7233 PGY-2, and 7003 PGY-3).Program director ratings on the RAES and milestone ratings.Correlations of RAES and milestone ratings by training year; correlations of medical knowledge ratings with American Board of Internal Medicine (ABIM) certification examination scores; rating of unprofessional behavior using the 2 systems.Corresponding RAES ratings and milestone ratings showed progressively higher correlations across training years, ranging among competencies from 0.31 (95% CI, 0.29 to 0.33) to 0.35 (95% CI, 0.33 to 0.37) for PGY-1 residents to 0.43 (95% CI, 0.41 to 0.45) to 0.52 (95% CI, 0.50 to 0.54) for PGY-3 residents (all P values <.05). Linear regression showed ratings differed more between PGY-1 and PGY-3 years using milestone ratings than the RAES (all P values <.001). Of the 6260 residents who attempted the certification examination, the 618 who failed had lower ratings using both systems for medical knowledge than did those who passed (RAES difference, -0.9; 95% CI, -1.0 to -0.8; P < .001; milestone medical knowledge 1 difference, -0.3; 95% CI, -0.3 to -0.3; P < .001; and medical knowledge 2 difference, -0.2; 95% CI, -0.3 to -0.2; P < .001). Of the 26 PGY-3 residents with milestone ratings indicating deficiencies on either of the 2 medical knowledge subcompetencies, 12 failed the certification examination. Correlation of RAES ratings for professionalism with residents' lowest professionalism milestone ratings was 0.44 (95% CI, 0.43 to 0.45; P < .001).Among US internal medicine residents in the 2013-2014 academic year, milestone-based ratings correlated with RAES ratings but with a greater difference across training years. Both rating systems for medical knowledge correlated with ABIM certification examination scores. Milestone ratings may better detect problems with professionalism. These preliminary findings may inform establishment of the validity of milestone-based assessment.
Three-dimensional ultrasound-based spectroscopic imaging for detection of prostate cancer in men.
Authors: H. T. Chung, E. Sofroni, N. Papanicolau, L. Sugar, G. Morton, M. Yaffe, R. Nam, G. J. Czarnota
Journal: Journal of Clinical Oncology (2011)

57 Background: The objective of this translational research was to investigate the use of real-time novel three-dimension, quantitative ultrasound-based spectroscopic imaging of the prostate as a means of cancer detection. Methods: Ten patients with T2-3 prostate cancer underwent a 6-9 MHz trans-rectal ultrasound scan of the prostate prior to radical prostatectomy. Equally spaced axial ultrasound images (0.5 cm separation) corresponding elasticity and spectroscopy data were collected in each patient. Colour-coded spectroscopic parametric maps of 0-Mhz intercept (0-Mhz), mid-band fit (MBF) and slope of line of best fit (slope) were generated indicating where the disease in the prostate gland is hypothetically located. Quantitative data (% volume of cancer over the prostate gland) were compared to whole-mount radical prostatectomy histopathology maps to determine the sensitivity and accuracy in parametrically delineating prostate cancer. Results: Representative data indicate spectral changes were associated with the presence of co-incident disease as located on correlative histopathology whole mount sections. Of the 10 patients enrolled, 7 have been analyzed and presented here. The mean % difference between 0-MHz and MBF, with H&amp;E, was 14% (SD 38%) and 21% (SD 24%), respectively. Gross areas of disease were readily visualized in ultrasound parametric maps and corresponded to a maximum 10dB decrease in 0-MHz or MBF. Parametric maps generated from the spectral slope offered no discrimination of disease. Conclusions: Initial results suggest that there is good correlation between spectroscopic maps with disease on whole-mount specimens. This method may ultimately permit ultrasound-guided targeted biopsies to improve detection rates and non-invasive assessment of disease for radiotherapy planning. No significant financial relationships to disclose.
Differential Expression of microRNAs and Transcription Factors in Primary Human Erythroblast Culture of β-Thalassemia Intermedia Patients
Authors: Regiane Ferreira, Carolina Lanaro, Kleber Yotsumoto Fertrin, Marcos André Cavalcanti Bezerra, Aderson da Silva Araujo, Dulcinéia Martins Albuquerque, Fernando Ferreira Costa
Journal: Blood (2014)
MP and former GP challenges Uruguay’s compulsory breast screening programme
Authors: Sophie Arie
Journal: BMJ (2016)

Uruguay’s government is being challenged to end its compulsory breast screening programme, after a court ruled that one woman with concerns about possible harms caused by mammography should be exempt.

On 6 December Daniel Radio, a deputy in the opposition Independent party and a former GP, presented a bill to parliament for legislation to ensure that women are asked for their informed consent to undergo screening for breast cancer and are not penalised if they refuse to give it.

Uruguay’s compulsory policy, introduced in 2006 under …
Is there any utility to frozen section or immunohistochemistry examination of the sentinel lymph node (SLN) in patients with ductal carcinoma in situ (DCIS)?
Authors: U. K. Ballehaninna, A. R. Reeves, R. S. Chamberlain
Journal: Journal of Clinical Oncology (2011)

1091 Background: Whether SLN biopsy (SLNB) should be performed in patients with DCIS is controversial. Many centers perform SLNB in DCIS believing it obviates the need for re-operation for axillary staging when invasive cancer (IC) is discovered. Given the low incidence of occult IC detected, whether intra-operative pathologic evaluation during SLNB in DCIS patients provides value has not been addressed. Methods: Demographic and clinico-pathologic data was collected and analyzed for all patients undergoing surgical resection for DCIS between 2004-2010 in order to determine the sensitivity, specificity and accuracy of frozen section (FS) and immuno-histochemistry (IHC) examination of the SLN, and its’ impact on axillary management. Results: 267 DCIS patients (median age 57 years) underwent lumpectomy (N=72) or mastectomy (N=195) with SLNB, intra-operative FS and IHC evaluation. Pre-operative pathology was DCIS (N=231), DCIS with micro-invasion (< 2 mm, N= 24) and DCIS associated with other lesions (N=12). SLN metastasis (SLNM) was identified in 13 patients (4%), of which only 4 were FS positive (1%). SLN micrometastasis (≤ 2 mm) and individual tumor cells (ITCs) were detected by IHC in 10 of 13 patients, while 3 patients had macro-metastasis. Overall, 50 patients (19%) had IC on final pathology. The FS was falsely negative in 9 patients (7%), and had sensitivity, specificity and accuracy of 31%, 100% and 98% respectively in identifying SLNM. 8 of 13 patients with SLNM underwent axillary lymph node dissection (ALND) of which only 1 patient (with macro-metastasis) had further axillary metastasis. On a need to treat basis, 30 and 91 patients would have to undergo FS and IHC exam respectively to identify 1 patient with a metastasis. Conclusions: SLN metastasis in DCIS is uncommon and the prognostic significance of micro-metastasis or ITCs in DCIS is unknown. Given the infrequent higher axillary nodal involvement and low sensitivity and yield of FS and IHC evaluation in DCIS particularly for identifying candidates for ALND, these procedures can be safely omitted thereby reducing operative time and cost. Additional studies are needed to validate these results.
Unusual Presentation of Poppers Dermatitis
Authors: Alessandra Latini, Viviana Lora, Mauro Zaccarelli, Antonio Cristaudo, Carlo Cota
Journal: JAMA Dermatology (2016)

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Diabetes mellitus, race, and the odds of high-grade prostate cancer in men diagnosed with prostate cancer in the United States.
Authors: T. Mitin, M. Chen, B. J. Moran, D. E. Dosoretz, M. J. Katin, M. H. Braccioforte, S. Salenius, A. V. D'Amico
Journal: Journal of Clinical Oncology (2011)

180 Background: African American (AA) men present more frequently with high-grade prostate cancer (PCa) and are also more likely to have diabetes mellitus (DM). We evaluated whether there is an independent association between DM and the risk of high-grade PCa in men diagnosed with PCa, adjusting for the known predictors of high-grade PCa including AA race. Methods: Between 1991 and 2009 15,377 men newly diagnosed with PCa and treated at 1 of 26 centers, were analyzed in 2 cohorts. Multivariable logistic regression was performed to evaluate whether a diagnosis of DM was associated with the odds of Gleason 7 or 8 to 10 PCa, adjusting for AA race, advancing age, PSA level, and DRE findings. Results: AA men (AOR, 1.87; 95% CI, 1.04-3.37, P=0.04) and non-AA men (AOR, 1.61; 95% CI, 1.34-1.93; P&lt;0.001) with diabetes were more likely to have GS 8 to 10 versus GS 6 or less PCa, compared to non-diabetic men. AA as compared to non-AA race was not significantly associated with the odds of having GS 8 to 10 as compared to 6 or less PCa, both in men with a diagnosis of DM (AOR, 1.47; 95% CI, 0.87-2.50; P=0.15) and without DM (AOR, 1.27; 95% CI, 0.92-1.74, P=0.14). AA race, however (AOR, 1.37; 95% CI, 1.17-1.60, P&lt;0.001), but not DM (AOR 1.09; 95% CI, 0.97-1.22, P=0.16), was associated with GS 7 versus 6 or less PCa. Conclusions: A diagnosis of DM is a risk factor for presenting with Gleason 8 to 10 PCa independent of race. [Table: see text] No significant financial relationships to disclose.