tbuckley/cabot-search huggingface dataset:
Primary Care Screening for Dementia and Mild Cognitive Impairment
Authors: Michael S. Rafii
Journal: JAMA (2008)

Primary Care Screening for Dementia and Mild Cognitive Impairment To the Editor: In their Commentary, Dr Brayne and colleagues raise many critical issues regarding the need to identify effective methods to screen for dementia. We suggest that this include detection of the mild cognitive impairment (MCI) syndrome, where there is objective decline in cognitive functioning. Longitudinal clinical studies indicate that participants with amnestic MCI have a substantially increased rate of progression to clinically probable Alzheimer disease. As the authors point out, it is extremely unusual to find reversible causes of dementia. However, many potentially reversible factors can contribute to MCI with cognitive performance that is worse than expected as a result of aging alone, such as medical illness, depression, medication adverse effects, or cardiovascular factors. Many of these may be amenable to intervention if a patient screens positive on routine testing. Moreover, nonpharmacological therapies such as psychosocial interventions have been reported as effective in improving cognitive performance in aging persons. A negative screen for MCI can be used to reassure individuals who are concerned about their self-perceived decline in cognitive performance and confirm that they are most likely experiencing age-related changes, rather than the beginnings of Alzheimer disease or another dementia. Two of the larger studies of normal aging vs MCI have demonstrated benefits derived from screening asymptomatic individuals in a primary care setting. In both studies, more than 90% of patients identified with MCI had a progressive disorder as the underlying cause of the cognitive impairment. The potential for intervention and delaying disease progression in most of these patients argues for detection as early as possible, in the MCI stage, so that the underlying cause of the cognitive impairment can be treated when possible. If one applied to diabetes mellitus the approach of not screening at-risk asymptomatic individuals and instead waited until symptoms developed, many of these symptoms (including neuropathy, retinopathy, nephropathy, and cerebrovascular disease) would not reverse with treatment. This would be considered unacceptable clinical practice for diabetes. We do not think that Alzheimer disease should be viewed differently, given that there is at least some substantive evidence that at-risk individuals can be diagnosed in the earliest stages and that potentially reversible factors contributing to cognitive performance declines can be further investigated and treated.
Case 15-1964
Authors: Hibbard E. Williams, Robert E. Scully
Journal: New England Journal of Medicine (1964)

Presentation of Case First admission. A seventy-four-year-old man entered the hospital because of fever.He had been well until two weeks previously, when he became weak and lethargic and had a lowgrade fever. During the six weeks before admission he had restricted his caloric intake and had lost 20 pounds in weight. Ten days before admission a friend noticed asymmetry of the patient's face, which subsequently improved gradually; the ankles became swollen at that time. There had been no chills, sweating, skin rash, headache, pain in the ear, weakness of the extremities, chest pain, dyspnea, orthopnea or jaundice.Four . . .
Multiple allogeneic progenitors in combination function as a unit to support early transient hematopoiesis in transplantation
Authors: Takashi Ishida, Satoshi Takahashi, Chen-Yi Lai, Masanori Nojima, Ryo Yamamoto, Emiko Takeuchi, Yasuo Takeuchi, Masaaki Higashihara, Hiromitsu Nakauchi, Makoto Otsu
Journal: The Journal of Experimental Medicine (2016)

Cord blood (CB) is a valuable donor source in hematopoietic cell transplantation. However, the initial time to engraftment in CB transplantation (CBT) is often delayed because of low graft cell numbers. This limits the use of CB. To overcome this cell dose barrier, we modeled an insufficient dose CBT setting in lethally irradiated mice and then added hematopoietic stem/progenitor cells (HSCs/HPCs; HSPCs) derived from four mouse allogeneic strains. The mixture of HSPCs rescued recipients and significantly accelerated hematopoietic recovery. Including T cells from one strain favored single-donor chimerism through graft versus graft reactions, with early hematopoietic recovery unaffected. Furthermore, using clinically relevant procedures, we successfully isolated a mixture of CD34+ cells from multiple frozen CB units at one time regardless of HLA-type disparities. These CD34+ cells in combination proved transplantable into immunodeficient mice. This work provides proof of concept that when circumstances require support of hematopoiesis, combined multiple units of allogeneic HSPCs are capable of early hematopoietic reconstitution while allowing single-donor hematopoiesis by a principal graft.
SMYD3-Mediated H2A.Z.1 Methylation Promotes Cell Cycle and Cancer Proliferation
Authors: Cheng-Hui Tsai, Yun-Ju Chen, Chia-Jung Yu, Shiou-Ru Tzeng, I-Chen Wu, Wen-Hung Kuo, Ming-Chieh Lin, Nei-Li Chan, Kou-Juey Wu, Shu-Chun Teng
Journal: Cancer Research (2016)

Abstract SMYD3 methyltransferase is nearly undetectable in normal human tissues but highly expressed in several cancers, including breast cancer, although its contributions to pathogenesis in this setting are unclear. Here we report that histone H2A.Z.1 is a substrate of SMYD3 that supports malignancy. SMYD3-mediated dimethylation of H2A.Z.1 at lysine 101 (H2A.Z.1K101me2) increased stability by preventing binding to the removal chaperone ANP32E and facilitating its interaction with histone H3. Moreover, a microarray analysis identified cyclin A1 as a target coregulated by SMYD3 and H2A.Z.1K101me2. The colocalization of SMYD3 and H2A.Z.1K101me2 at the promoter of cyclin A1 activated its expression and G1–S progression. Enforced expression of cyclin A1 in cells containing mutant H2A.Z.1 rescued tumor formation in a mouse model. Our findings suggest that SMYD3-mediated H2A.Z.1K101 dimethylation activates cyclin A1 expression and contributes to driving the proliferation of breast cancer cells. Cancer Res; 76(20); 6043–53. ©2016 AACR.
Salvage Radiotherapy for Biochemically Recurrent Prostate Cancer After Prostatectomy
Authors: Zachary S. Zumsteg, Timothy J. Daskivich, Howard M. Sandler
Journal: Journal of Clinical Oncology (2016)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 67-year-old man had presented to his primary physician for routine health maintenance. A digital rectal examination was performed and revealed a suspicious nodule in the right lobe of the prostate without any extraprostatic extension. A serum prostate-specific antigen (PSA) test was 12.4 ng/mL. He had no previous PSA tests. Transrectal ultrasound-guided prostate biopsy showed Gleason 3 + 4 prostate adenocarcinoma in seven of 12 cores. Bone scan and computed tomography scan of the pelvis showed no evidence of metastatic disease, and the patient underwent a robotic-assisted radical prostatectomy with bilateral pelvic lymphadenectomy. Pathology revealed Gleason 3 + 4 adenocarcinoma bilaterally, with extracapsular extension, no seminal vesicle invasion, a 2-mm positive margin at the right mid gland, and 0 of 15 lymph nodes containing adenocarcinoma. Two months after surgery, he had mild stress urinary incontinence and PSA of &lt; 0.1 ng/mL. Adjuvant radiotherapy was discussed, but he elected to have careful follow-up. His PSA was monitored every 6 months and gradually increased from &lt; 0.1 ng/mL to 0.4 ng/mL over the next 3 years. He was asymptomatic. He was referred to discuss the role of salvage radiotherapy.
Bevacizumab + folfiri as first-line treatment in advanced colorectal cancer (ACC): A multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale (prot. GOIM 2601)
Authors: G. Colucci, F. Giuliani, V. Lorusso, F. De Vita, S. Cinieri, E. Maiello, I. Nugnes, S. Del Prete, M. Orditura, S. Leo, R. Addeo
Journal: Journal of Clinical Oncology (2008)

15048 Background: The addition of Bevacizumab (BEV) to Irinotecan (CPT-11) plus bolus Fluorouracil (FU) and folinic acid (FA) (IFL) demonstrated to be more active and more effective than chemotherapy alone in a phase III trial. However IFL is more toxic than FOLFIRI. So we started a phase II trial to evaluate the activity and the safety of the combination of BEV plus FOLFIRI as first-line therapy in ACC pts. Methods: Untreated pts with histologically diagnosis of ACC entered into the trial if they satisfied the following inclusion criteria: presence of measurable disease, age > 18 yrs, PS ≤ 2 (ECOG), adequate bone marrow reserve and renal and hepatic function, informed written consent. An history of cardiovascular disease, thromboembolic events and/or coagulative desorders were exclusion criteria. The enrolled pts were treated with CPT-11 at 180 mg/m2 on day 1, FA at 100 mg/m2 as 2h infusion on days 1–2, FU at 400 mg/m2 as bolus on days 1–2 and FU at 600 mg/m2 as 22h infusion on days 1–2 (FOLFIRI) plus BEV at the dosage of 5 mg/Kg on day 1, every 2 weeks. A maximum of 12 cycles of chemotherapy was planned and a mainteinance with BEV for 6 months was permitted. The evaluation of the activity (Recist) was performed every 4 cycles. Results: Up to now 72 pts have been enrolled and 61 are evaluable for activity and safety (11 pts are too early). The main characteristics of the evaluable pts were M/F: 32/29; median PS: 0 (range 0–2); median age 61 (range 33–73); primary site (colon/rectum): 40/21; main sites of disease: liver 45, lung 16, lymphnodes 15, others 6. 3 CR (5%) and 25 PR (41%) were observed for an ORR of 46%; 26 pts had SD (43%) for an overall TGCR of 89%. Only 7 PRO (11%) were observed. The RR according to site were: liver 21/45 (46.6%), lung 8/16 (50%). The median TTP was 13.0 months. The only grade 3–4 toxicity (NCI criteria) were neutropenia 10% and thrombocytopenia 2%. 10 pts (16%) had hypertension but only one was uncontrolled by medical therapy and interrupted the study. One pts had epistaxis. Conclusions: Our results indicate that the addition of BEV to FOLFIRI regimen is an active and well tolerated first-line treatment for ACC pts; the observed median TTP is very interesting. Survival data are pending. No significant financial relationships to disclose.
Current Cigarette Smoking, Access, and Purchases from Retail Outlets Among Students Aged 13–15 Years — Global Youth Tobacco Survey, 45 Countries, 2013 and 2014
Authors: Denise D’Angelo, Indu B. Ahluwalia, Eugene Pun, Shaoman Yin, Krishna Palipudi, Lazarous Mbulo
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Tobacco use is a leading preventable cause of morbidity and mortality, with nearly 6 million deaths caused by tobacco use worldwide every year (1). Cigarette smoking is the most common form of tobacco use in most countries, and the majority of adult smokers initiate smoking before age 18 years (2,3). Limiting access to cigarettes among youths is an effective strategy to curb the tobacco epidemic by preventing smoking initiation and reducing the number of new smokers (3,4). CDC used the Global Youth Tobacco Survey (GYTS) data from 45 countries to examine the prevalence of current cigarette smoking, purchase of cigarettes from retail outlets, and type of cigarette purchases made among school students aged 13-15 years. The results are presented by the six World Health Organization (WHO) regions: African Region (AFR); Eastern Mediterranean Region (EMR); European Region (EUR); Region of the Americas (AMR); South-East Asian Region (SEAR); and Western Pacific Region (WPR). Across all 45 countries, the median overall current cigarette smoking prevalence among students aged 13-15 years was 6.8% (range = 1.7% [Kazakhstan]-28.9% [Timor-Leste]); the median prevalence among boys was 9.7% (2.0% [Kazakhstan]-53.5% [Timor-Leste]), and among girls was 3.5% (0.0% [Bangladesh]-26.3% [Italy]). The proportion of current cigarette smokers aged 13-15 years who reported purchasing cigarettes from a retail outlet such as a store, street vendor, or kiosk during the past 30 days ranged from 14.9% [Latvia] to 95.1% [Montenegro], and in approximately half the countries, exceeded 50%. In the majority of countries assessed in AFR and SEAR, approximately 40% of cigarette smokers aged 13-15 years reported purchasing individual cigarettes. Approximately half of smokers in all but one country assessed in EUR reported purchasing cigarettes in packs. These findings could be used by countries to inform tobacco control strategies in the retail environment to reduce and prevent marketing and sales of tobacco products to youths (5).
Antiviral Reduces Mother-to-Child Transmission of Hepatitis B
Authors: Anita Slomski
Journal: JAMA (2016)

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Sea-Blue Histiocytosis
Authors: M. N. Silverstein
Journal: JAMA (1973)

<h3>To the Editor.—</h3> In the recent paper "Familial Sea-Blue Histiocytosis" by Blankenship et al (225:54, 1973), the authors observed that the syndrome of the sea-blue histiocyte has been reported with increasing frequency, both as a primary disorder and in association with a variety of diseases; but they do not mention the article that brought the attention of this cell to the medical public.<sup>1</sup>In their discussion the authors quote a letter to the editor by Kattlove et al<sup>2</sup>but nowhere do they give our reply to Dr. Kattlove's letter. Dr. Reynolds wrote to me on May 4, 1972, requesting my thoughts regarding the patients that they subsequently described. I told them that in a subsequent paper<sup>3</sup>we would (and did) suggest succinct criteria for the diagnosis of the primary syndrome of the sea-blue histiocyte and ways in which the primary syndrome might be distinguished from the numerous
A Phase 1/2, Open-Label, Dose-Escalation, Multi-Center Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered NS-018 in Patients with Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (postPV MF), or Post-Essential Thrombocythemia Myelofibrosis (postET MF)
Authors: Srdan Verstovsek, Moshe Talpaz, Ellen K. Ritchie, Martha Wadleigh, Olatoyosi Odenike, Catriona Jamieson, Brady L Stein, Uno Tomonori, Ruben Mesa
Journal: Blood (2014)
Swedish government sacks entire Karolinska Institute board over Macchiarini
Authors: Nigel Hawkes
Journal: BMJ (2016)

Swedish authorities have sacked the entire board of the Karolinska Institute in an attempt to limit any further damage to the country’s premier medical research centres in the wake of a series of highly critical reports regarding surgeon Paolo Macchiarini.

An investigation published on Monday said that the institute had shown “a stunning indifference” towards highly negative references when it hired Macchiarini,1 an Italian …
A Comprehensive Analysis of Cytogenetic Abnormalities in Myeloma: Results of the FISH Analysis of 1000 Patients Enrolled in the IFM99 Trials.
Authors: Herve Avet Loiseau, Michel Attal, Philippe Moreau, Catherine Charbonnel, Frederic Garban, Jean-Luc Harousseau, Thierry Facon, Claire Mathiot
Journal: Blood (2005)
Purinergic receptors in the carotid body as a new drug target for controlling hypertension
Authors: Wioletta Pijacka, Davi J A Moraes, Laura E K Ratcliffe, Angus K Nightingale, Emma C Hart, Melina P da Silva, Benedito H Machado, Fiona D McBryde, Ana P Abdala, Anthony P Ford, Julian F R Paton
Journal: Nature Medicine (2016)
(Q)-TWiST analysis of trastuzumab plus fluoropyrimidine/cisplatin (T-XP/FP) versus XP/FP alone as first-line therapy for advanced HER2-positive gastric cancer.
Authors: H. C. Chung, Y. Bang, E. Van Cutsem, Y. Kang, Y. Hamamoto, V. Moiseyenko, E. Gotovkin, A. Urspruch, P. Ducournau
Journal: Journal of Clinical Oncology (2010)

4048 Background: The international, randomized phase III Trastuzumab for Gastric Cancer (ToGA) study has shown that trastuzumab (T) in combination with capecitabine/5-FU and cisplatin (XP/FP) improves overall survival vs. XP/FP alone (median: 13.8 vs. 11.1 mo, HR=0.74, p=0.0046) in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) cancer, without impacting on safety. Here we assess the OS gain in the trastuzumab arm, by applying the quality-adjusted time without disease symptoms or treatment toxicity (Q-TWiST) methodology. Methods: The area under the OS curve was partitioned into 3 health states: duration of toxicity (TOX: time spent experiencing grade 3/4 adverse events while in PFS and on study medication), TWiST (PFS minus TOX), and time from progression until end of follow-up or death (REL: OS minus PFS). To exclude treatment bias, clinical follow-up for this analysis was truncated to longest follow-up of the shortest curve (31.3 mo). In a scenario analysis, each health state was utility adjusted per the Q-TWiST methodology. Sensitivity analyses were conducted. Results: No significant difference in time spent in either TOX or REL was observed between arms. Time spent in TWiST was significantly longer for T-XP/FP vs. XP/FP (Table). Overall Q-TWiST results (utility adjusted for treatment toxicities and disease relapse) showed a mean difference of 2.42 mo (95% CI: 1.53–3.25) between treatment arms. Results were confirmed in sensitivity analyses. Conclusions: Per Q-TWiST analysis, the OS gain in HER2-positive advanced gastric or GEJ cancer patients seen with T-XP/FP vs. XP/FP translates into longer PFS without disease symptoms or treatment toxicity. These results confirm earlier findings that the improved OS comes without a negative impact on safety or QoL, which are considered main treatment objectives for advanced gastric cancer. Mean time in each health state by treatment arm, mo (95% CI) Health state XP/FP (n=290) T-XP/FP (n=294) Mean difference PFS 7.07 (6.24–7.89) 9.36 (8.27–10.45) 2.29 OS 13.01 (11.79–14.24) 15.54 (14.24–16.84) 2.52 TOX 2.52 (2.13–2.9) 2.54 (2.10–2.98) 0.02 TWiST 4.55 6.82 2.27 REL 5.95 6.18 0.23 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche Roche
Use of Low Molecular Weight Heparin (LMWH) in Thrombocytopenic Patients with Hematologic Malignancy-Associated Venous Thromboembolism (VTE)
Authors: Nabin Khanal, R. Gregory Bociek, Baojiang Chen, Julie M. Vose, James O. Armitage, Philip J Bierman, Lori J. Maness, Matthew A. Lunning, Krishna Gundabolu, Vijaya R. Bhatt
Journal: Blood (2015)
Information and drugs at our fingertips
Authors: Sophie Cook
Journal: BMJ (2016)

International groups of patients are linking up 24/7 through social media to disseminate knowledge, provide peer support, and offer clinical advice. And all of this is delivered quickly, at the touch of a button.

Evolution of patient groups from infrequent local meetings in person to virtual international networks is surely a good thing? Stephen Armstrong explores the role of social media in patient support (doi:10.1136/bmj.i4201) and considers the benefits, ethical dilemmas, and confidentiality issues that arise. Maureen Baker, chair of the Royal College of …
Predictors of atrial fibrillation and inpatient mortality in post lobectomy lung cancer patients.
Authors: Supreet Kaur, Abhishek Kumar, Rahul Vasudev, Robert Conner Dixon, Raman Dhillon, Shoaib Azam, Mahendar Kumar, Michael Maroules
Journal: Journal of Clinical Oncology (2016)

e20060 Background: Atrial Fibrillation (AF) after lobectomy for lung cancer (LC) is major cause of morbidity and mortality. The incidence is as high as 10-20% post lobectomy and 40% post pneumonectomy have been reported. The aim of our study was to assess the predictors of AF and inpatient mortality post lobectomy for LC. Methods: We retrospectively analyzed data for all patients who underwent lobectomy for LC at our 850 bed tertiary care teaching hospital between January 2001 and September 2015. Patients with post-operative AF were identified and studied regarding predictors of postoperative AF and inpatient mortality. Results: A total of 38 patients underwent lobectomy. The mean age of the patients was 73.6 ± 7.1 years with 52.6 % females. Squamous cell carcinoma (65.6%) was the most common type identified in this group. Open chest lobectomy (71%) was performed in majority of these patients. Post-operative AF was seen in 12 patients (31.6%). Females were seen to have higher odds for post lobectomy AF (OR 8(1.44 – 44.29, p = 0.018). Nine cases (23.7%) of inpatient mortality were recorded. Inpatient mortality was lower in adenocarcinoma than squamous cell carcinoma (OR 0.139 (0.025-0.763, p = 0.03). Advanced age was also a predictor of inpatient mortality. The mean age of people who survived the surgery was 71.9 ± 7.2 years and the patients who died during surgery was 79.1 ± 3.5 (p = 0.0004). Whereas factors like hypertension, CAD, COPD, thyroid dysfunction, history of previous chemotherapy or radiation, tumor size, lymph node status, side of surgery, surgical technique (open v/s VATS) were not predictive of inpatient mortality in our study. Conclusions: Our study shows that AF is a common arrhythmia in patients undergoing lobectomy after lung cancer and females have higher odds of developing it post operatively. Factors like squamous cell cancer and advanced age were associated with increased inpatient mortality. More studies with bigger sample size are needed to better predict risk factors and outcomes in patients who develop AF after lobectomy.