tbuckley/cabot-search huggingface dataset:
MRSA colonization and the nasal microbiome in adults at high risk of colonization and infection
Authors: Mary T. Bessesen, Cassandra Vogel Kotter, Brandie D. Wagner, Jill C. Adams, Shannon Kingery, Jeanne B. Benoit, Charles E. Robertson, Edward N. Janoff, Daniel N. Frank
Journal: Journal of Infection (2015)

The objective of this study was to define the nasal microbiome of hospital inpatients who are persistently colonized with methicillin-resistant Staphylococcus aureus (MRSA) compared with matched, non-colonized controls.Twenty-six persistently MRSA-colonized subjects and 26 matched non-colonized controls were selected from the screening records of the infection control program at the Department of the Veteran Affairs Eastern Colorado Health Care System (VA-ECHCS). The nasal microbiotas were analyzed with PCR amplification and sequencing of the 16S ribosomal RNA (rRNA) gene. Comparison of all variables across the groups was performed using stratified logistic regression to account for the one-to-one matching. Canonical discriminant analysis was performed to assess differences in bacterial community across the two groups. Competing organisms were cocultured with MRSA in vitro.There was a negative association between MRSA colonization and colonization with Streptococcus spp. At the species level, multivariate analysis demonstrated a statistically significant negative association between colonization with Streptococcus mitis or Lactobacillus gasseri and MRSA. Coculture experiments revealed in vitro competition between S. mitis and all of the 22 MRSA strains isolated from subjects. Competition was blocked by addition of catalase to the media. Persistently colonized subjects had lesser microbial diversity than the non-colonized controls.In a high-risk inpatient setting, bacterial competition in the nasal niche protects some patients from MRSA colonization.
RIP3 Regulates Autophagy and Promotes Coxsackievirus B3 Infection of Intestinal Epithelial Cells
Authors: Katharine G. Harris, Stefanie A. Morosky, Coyne G. Drummond, Maulik Patel, Chonsaeng Kim, Donna B. Stolz, Jeffrey M. Bergelson, Sara Cherry, Carolyn B. Coyne
Journal: Cell Host & Microbe (2015)
Shorter halving time of BCR‐ABL1 transcripts is a novel predictor for achievement of molecular responses in newly diagnosed chronic‐phase chronic myeloid leukemia treated with dasatinib: Results of the D‐first study of <scp>K</scp>anto CML study group
Authors: Noriyoshi Iriyama, Shin Fujisawa, Chikashi Yoshida, Hisashi Wakita, Shigeru Chiba, Shinichiro Okamoto, Kimihiro Kawakami, Naoki Takezako, Takashi Kumagai, Koiti Inokuchi, Kazuma Ohyashiki, Jun Taguchi, Shingo Yano, Tadahiko Igarashi, Yasuji Kouzai, Satoshi Morita, Junichi Sakamoto, Hisashi Sakamaki
Journal: American Journal of Hematology (2014)

To investigate the factors that affect molecular responses on dasatinib treatment in patients with chronic-phase chronic myeloid leukemia (CML-CP), we performed a clinical trial named the "D-First study." Fifty-two patients with newly diagnosed CML-CP were enrolled in this study and received 100 mg dasatinib once daily. A deep molecular response (DMR) was defined as <50 copies/μg RNA of BCR-ABL1 transcript value corrected by GAPDH, which ensures <0.01% of BCR-ABL1 transcript value according to International Scale (BCR-ABL1(IS)). The halving time for BCR-ABL1 transcripts was calculated using transcript levels before dasatinib treatment, transcript levels after 3 months of treatment, and the treatment time between these two points. In terms of molecular response, 38 of 51 (75%) patients reached major molecular response (MMR) by 12 months, and the rate of DMR by 18 months was 59% (30/51). While both BCR-ABL1 transcript levels before treatment and a shorter halving time of BCR-ABL1 transcripts (≤14 days) were significant factors affecting achievement of MMR by 12 months, the Sokal score at diagnosis was not associated with MMR. Importantly, the halving time was the only factor that predicted achievement of DMR by 18 months. We showed that patients with CML-CP treated with dasatinib can be stratified according to the early treatment response as determined by the halving time of BCR-ABL1 transcripts. These data emphasize the significance of the early response from dasatinib treatment in achieving a DMR. (ClinicalTrials.gov; NCT01464411).
Abstract P213: Regular Exercise Improves the Lipoprotein Subclass Profile: Meta-Analysis of 10 Exercise Training Intervention Groups
Authors: Mark A Sarzynski, Tuomo Rankinen, Jeffrey Burton, Timothy S Church, Jean-Pierre Després, James M Hagberg, Arthur S Leon, Catherine R Mikus, Dabeeru C Rao, Richard L Seip, James S Skinner, Cris A Slentz, Paul D Thompson, Kenneth R Wilund, William E Kraus, Claude Bouchard
Journal: Circulation (2015)

OBJECTIVE: The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. We hypothesized that regular exercise has beneficial effects on the overall lipoprotein subclass profile in previously sedentary adults. METHODS: NMR spectroscopy (LipoScience Inc., Raleigh, NC) was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P respectively) before and after an exercise intervention in 1,430 adults from six studies, encompassing 10 exercise training groups: APOE (N=106), DREW (N=298), GERS (N=79), HERITAGE (N=715), STRRIDE I (N=130) and II (N=102). Random-effects meta-analysis was performed to quantify the overall mean change across the unadjusted and adjusted mean change estimates from each exercise group of each study. A Bonferroni-adjusted p-value ≤ 0.003 was considered statistically significant. RESULTS: Meta-analysis of unadjusted data found that regular exercise induced significant decreases in the concentration of large VLDL-P (P=1.2x10 -6 ) and mean VLDL-P size (P=9.0x10 -5 ), with significant increases in the concentration of large LDL-P (P=4.9x10 -13 ). The changes in large VLDL-P and large LDL-P concentration and VLDL-P size remained significant after adjustment for age, sex, race, baseline body mass index, and baseline trait value ( Figure 1 ); while the increase in LDL-P size (P=0.003) became significant after adjustment. Nominally significant decreases in the concentration of small LDL-P (P=0.004) and medium HDL-P (P=0.007) and increases in large HDL-P (P=0.008) were observed in the adjusted meta-analysis. CONCLUSIONS: Despite differences in exercise programs and study populations, regular exercise led to significant improvements in the lipoprotein subclass profile across 10 exercise interventions, as highlighted by changes in VLDL and LDL subfractions.
Response to omalizumab therapy in a difficult to treat asthma cohort in Rio de Janeiro, Brazil
Authors: Fabio Aguiar, Lilian Rodrigues, Márcia Luduvice, Ana Maria Araújo, Alexandre Cardoso
Journal: European Respiratory Journal (2013)

Asthma is a leading cause of respiratory morbidity and mortality worldwide, and its prevalence is increasing. A significant proportion of patients have poorly controlled asthma, despite treatment with high doses of inhaled and oral drugs. Difficult to treat asthma is defined as asthma uncontrolled with a reliever medication plus two or more controllers medications. Omalizumab is an option for patients with elevated serum levels of IgE with severe allergic asthma. Unfortunatelly, due to its high cost, it is still scarcely used in Brazil. We describe the response to omalizumab in a cohort of difficult to treat asthma patients in Rio de Janeiro, Brazil. Fifty patients are currently under omalizumab treatment. All of them, also with high doses of inhaled corticosteroids and long acting bronchodilators. The mean age of the cohort is 55 yrs, 78% are women, and 58% have moderate to severe obstruction in spirometry. Astma control improved and hospitalization rates was significantly reduced after the beggining of omalizumab. No severe adverse reactions were found. In conclusion, we were able to achieve an increased control of the disease and reduce the number of hospitalizations after the beggining of omalizumab therapy.
Intensified and high-dose chemotherapy with granulocyte colony-stimulating factor and autologous stem-cell transplantation support as first-line therapy in high-risk diffuse large-cell lymphoma.
Authors: U Vitolo, S Cortellazzo, A M Liberati, R Freilone, M Falda, M Bertini, B Botto, S Cinieri, A Levis, F Locatelli, E Lovisone, F Marmont, M Pizzuti, A Rossi, P Viero, T Barbui, F Grignani, L Resegotti
Journal: Journal of Clinical Oncology (1997)

PURPOSE In our previous study with MACOPB, we identified a high-risk group of patients with a poor 3-year survival rate of 29%. These patients were defined as having at diagnosis advanced-stage disease with high tumor burden (TB) and elevated lactate dehydrogenase (LDH) level or bone marrow (BM) involvement. A novel therapeutic scheme was investigated to improve the outcome of these patients. PATIENTS AND METHODS Fifty patients with high-risk diffuse large-cell lymphoma (DLCL) were enrolled. The therapeutic scheme includes three phases: induction with 8 weeks of MACOPB; intensification with a 3-day course of mitoxantrone 8 mg/m2 plus high-dose cytarabine (HDARA-C) 2 g/m2 every 12 hours plus dexamethasone 4 mg/m2 every 12 hours (MAD protocol) and granulocyte colony-stimulating factor (G-CSF) 5 microg/kg on days 4 to 17 to harvest peripheral-blood progenitor cells (PBPC); consolidation with carmustine (BCNU), etoposide, ARA-C, and melphalan (BEAM) regimen; plus autologous stem-cell transplantation (ASCT) with PBPC, marrow, or both. RESULTS Thirty-six patients (72%) achieved a complete response (CR), 11 (22%) showed no response (NR), and three (6%) died of toxicity. Among the 22 PRs or NRs after the induction phase, 56% of patients achieved a CR with subsequent intensified therapy. With a median follow-up duration of 32 months, the overall survival and failure-free survival rates were 56% and 50%, respectively. The disease-free survival rate is 69% at 32 months. Leukapheresis after MAD and G-CSF yielded a median of 32 x 10(6)/kg CD34+ cells and 80 x 10(4)/kg granulocyte-macrophage colony-forming units (CFU-GM). Thirty-nine patients were autografted and 11 did not undergo ASCT: six because of disease progression, four due to toxicity, and one because of patient refusal. The median times to achieve engrafment were 11 days (range, 7 to 19) to a neutrophil count greater than 0.5 x 10(9)/L and 12 days (range, 8 to 60) to a platelet count greater than 50 x 10(9)/L. CONCLUSION This sequential scheme with intensified and high-dose chemotherapy with ASCT is feasible with moderate toxicity and may improve the outcome in high-risk DLCL.
Abstract 11082: Strategic Placement of Automated External Defibrillators at Twenty-Four-Hour Grocery Chain Stores
Authors: Patrick Chow-In Ko, Tzai-Hung Wen, Wen-Chu Chiang, Matthew Heui-Ming Ma
Journal: Circulation (2011)

Background:  Mortality of out-of-hospital cardiac arrest (OHCA) is high and public access early defibrillation (PAD) improves survival.   Objectives:  To evaluate the feasibility of strategic placement of automated external defibrillators (AED) at 24-hour grocery chain stores in metropolitan city.   Material and Methods:  A prospective five-year observational database of non-traumatic OHCA was assessed. Using geospatial information technology, we analyzed the locations of the largest chain of 24-hour grocery store, of prehospital ambulance stations, of total OHCA events, and of OHCA only at ground level. We presume to equip one AED in each designated store. Bystanders may get an AED from the nearest store to OHCA location. The buffer coverage of OHCA locations within a 100, 200, and 300-meter buffer radius (R) to the stores designated at that buffer set were compared.   Results:  There were a total of 8,094 OHCA locations, with 3,192 subjects at ground level. Among totally 677 stores in chain, the efficient number of stores designated for placing AED at 100-m buffer R would be 576; it would be 542 stores at 200-m R and 396 at 300-m R individually. The buffer coverage of total OHCA locations was 29.6% (n=2,396) at 100-m R by placing 576 AEDs, 69.2% (n=5,598) at 200-m R by 542 AEDs, and 86.5% (n=7,000) at 300-m R by 396 AEDs. The buffer coverage of OHCA at ground level was 26.8% (n=856) at 100-m R, 62.1% (n=1,981) at 200-m R, and 80.5% (n=2,570) at 300-m R. The averaged OHCA locations per AED covering were 1.5 to 17.7 in 5 years. For 17.7% (n=1,380) of OHCA locations not covered within 1.5-kilometer distance to ambulance stations (5-minute for ambulance response time), 45% (n=621) of them were covered within 100-m to 24-hour stores.   Conclusions:  Placing AEDs at 24-hour grocery stores in metropolitan city is highly efficient for OHCA location coverage, and complementary to area not covered by paramedics. It may provide bystanders easy and prompt access to an AED to improve usage, and is pivotal for PAD.
Rationing Cancer Care: A Survey Among the Members of the German Society of Hematology and Oncology
Authors: Stefan W. Krause, Jan Schildmann, Christian Lotze, Eva C. Winkler
Journal: Journal of the National Comprehensive Cancer Network (2013)

Rising costs of cancer care and the growing burden of cancer in a world of finite resources seem to make rationing in oncology inevitable. Information is currently lacking about oncologists' strategies in responding to resource constraints and the prevalence of withholding costly treatments. An online survey was offered via e-mail to physician members of the German Society of Hematology and Oncology. Those actively practicing were asked to complete an online questionnaire asking how limited resources were currently affecting their clinical practice. Two-thirds of 345 participating oncologists reported withholding costly treatments in at least some instances. Regarding their rationale, 70% stated that evidence for costly intervention was not convincing enough, and 59% said that they rationed approved treatments because of an unfavorable cost/benefit calculation. Only 29% reported being explicit about their rationing decision if the patient did not know or inquire about the respective intervention. Withholding expensive procedures from individual patients was widespread among the respondents. Oncologists withheld treatments not only if they perceived the scientific evidence to be questionable but also if they perceived reimbursement prospects or the cost/benefit ratio to be unfavorable, a behavior that could be called rationing. Currently this mostly refers to costly procedures with limited additional benefits. Although this result may be interpreted as indicating that oncologists assume responsibility for spending the resources in a justified way, more transparency and an open discussion on cost-effectiveness and the just allocation of costly treatments is needed.
Evolving Concepts in the Management of Lobular Neoplasia
Authors: Benjamin O. Anderson, Kristine E. Calhoun, Eric L. Rosen
Journal: Journal of the National Comprehensive Cancer Network (2006)

Lobular neoplasia broadly defines the spectrum of changes within the lobule, ranging from atypical lobular hyperplasia (ALH) to lobular carcinoma in situ (LCIS). This continuum of lesions is associated with an increased risk for developing subsequent invasive breast cancer, with the magnitude of that risk corresponding to the degree of proliferative change. The associated risk for developing invasive breast cancer after a diagnosis of lobular neoplasia is multicentric, bilateral, and equal in both breasts. Lobular neoplasia itself may transform into invasive carcinoma, although the frequency of this occurrence is unknown. Thus, lobular neoplasia is a risk factor for invasive breast cancer and may be a precursor lesion in unusual circumstances. The management of ALH and LCIS depends on the setting in which they are encountered. When ALH and LCIS are diagnosed after core needle breast biopsy, wire localization for surgical excision is required for definitive diagnosis because rates of histologic underestimation approach those of atypical ductal hyperplasia (ADH). When diagnosed on surgical biopsy, ALH and LCIS generally do not require further intervention, even when present at a surgical margin. However, bilateral breast cancer risk must be considered, especially when patients have a family history of breast cancer. In selected situations, bilateral prophylactic mastectomy with or without reconstruction may be considered when atypical hyperplasia or LCIS is diagnosed. Although this reduces risk for developing subsequent breast carcinoma by 90%, patients selected for prophylactic mastectomy represent a small subgroup of lobular neoplasia patients and generally have other risk factors, such as strong family history or evidence of genetic predisposition.
One-year mortality associated with COPD treatment: A comparison of tiotropium and long-acting beta-2-agonists
Authors: Silvia Cascini, Ursula Kirchmayer, Nera Agabiti, Mirko Di Martino, Giulio Formoso, Claudio Voci, Riccardo Pistelli, Elisabetta Patorno, Marina Davoli
Journal: European Respiratory Journal (2014)

Background. Long-acting bronchodilators, i.e. beta-2-agonists (LABA) and tiotropium (Tio) are used in COPD treatment. Choice of a specific agent is based on aspects regarding effectiveness and safety. Scientific evidence yields controversial results with respect to mortality.  Objectives. The present study compared 1-year mortality associated to treatment Tio versus LABA.  Methods. A population based cohort study using data from health information systems in 3 Italian regions was performed. Patients aged 45+ years, discharged from hospital with diagnosis of COPD in 2006-2009 were identified. Through record linkage with the drug claims register, patients who received a first prescription of LABA or Tio within 6 months after discharge were enrolled. The main analysis was restricted to naive users (no prior use of either LABA or Tio). We used intention to treat (ITT) and as treated (AT) approaches. We followed patients for a maximum of 12 months. Hazard ratios (HR) were calculated by Cox regression including quintiles of propensity score. In sensitivity analyses patients receiving Tio+LABA combination were included in the Tio group.  Results. Among the 33891 enrollees, 28% were exposed to Tio, 56% to LABA, 16% to both. The overall mean age was 74 years and the mortality rate was 108/1000 person-years (py) at the ITT analysis and 115/1000 py at the AT analysis.. The adjusted HR for Tio only compared to LABA only was 1.08 (95% CI: 0.95-1.23) at the ITT analysis and 1.00 (95% CI: 0.93-1.09) at the AT analysis. Results were robust in sensitivity analyses.  Conclusions. In this real-world study use of Tio was not associated with an increased risk of 1-year mortality compared to LABA.
Abstract 15473: Mitochondrial Transgenic Expression of Connexin 43 Confers Cytoprotection to he Stem Cells and Cardiomyocytes in Ischemic Myocardium
Authors: Gang Lu, Shujia Jiang, Linlin Wang, Ning Li, Motoi Okada, Muhammad Ashraf, Khawaja H Haider
Journal: Circulation (2011)

Background. Mitochondrial translocation of connexin 43 (Cx43) is an integral part of prosurvival signaling during preconditioning of stem cells. We hypothesized that transgenic expression of mitoch...
Some diseases must declare themselves
Authors: George Dunea
Journal: BMJ (2001)

When I was a house officer I would regularly see a dishevelled street woman who had numerous bizarre complaints. These she attributed to the dirt she had picked up at a flea market, and she would bring along crumpled bits of paper to prove her point. My chief eventually lost all patience and wrote to the general practitioner asking him not to send “this cantankerous woman” again. Two months later she returned jaundiced, her liver massively …
It’s time to apologise
Authors: Fiona Godlee
Journal: BMJ (2015)

Jeremy Corbyn says he’ll apologise for the Iraq war if he is the next leader of the Labour Party. Along with the wearily awaited Chilcot report to explain and apportion blame, this could offer some degree of closure and some lessons to be learnt.

Apologising when things go wrong for patients should be a simple matter. For UK doctors, the need to be open and honest with patients is enshrined in guidance from the General Medical Council. But it’s not always clear when to apologise or how to do so without necessarily admitting or apportioning blame. Sadly, as Nigel Hawkes explains, the UK’s new …
Survival benefit from high-dose therapy with autologous blood progenitor-cell transplantation in poor-prognosis non-Hodgkin's lymphoma.
Authors: R Pettengell, J A Radford, G R Morgenstern, J H Scarffe, M Harris, P J Woll, D P Deakin, D Ryder, P M Wilkinson, D Crowther
Journal: Journal of Clinical Oncology (1996)

PURPOSE To compare standard and intensive treatment strategies for patients with high-grade non-Hodgkin's lymphoma (NHL) of poor prognosis, defined by the international prognostic index. PATIENTS AND METHODS Thirty-four patients received standard chemotherapy with 11 weeks of doxorubicin, cyclophosphamide, vincristine, bleomycin, etoposide, prednisolone, and methotrexate (VAPEC-B), and 33 received intensive treatment with 7 weeks of VAPEC-B, three cycles of ifosfamide/cytarabine, then high-dose busulfan/cyclophosphamide followed by autologous blood progenitor-cell (BPC) transplantation. RESULTS Twelve of 33 patients in the intensive group and 26 of 34 patients in the standard group have died. The median follow-up time for the surviving patients is 31 months and 68 months, respectively. At 2 years, the actuarial estimates of event-free survival (EFS) were 61% versus 35% (P = .01) and of overall survival, 64% versus 35% (P = .01). A significant reduction in the event rate (progression or death) was maintained after adjustment for age and the number of risk factors. The estimated risk of experiencing an event was 0.37 (95% confidence interval [CI], 0.16 to 0.84) in the intensive group compared with the standard group. CONCLUSION Patients with poor prognostic features who received high-dose therapy and BPC rescue had a superior EFS. The survival differences observed in this study justify a formal comparison in a randomized study.
To Helen--A Footnote to Medical History
Authors: R. N. G.
Journal: CA A Cancer Journal for Clinicians (1968)

In the background of major scientific discoveries there is often a little known dramatic human interest story.One of these came to light recently with the appearance of an article in the Pro ceedings of the National Academy of Science of August 1967, entitled â€oe¿ In ducers of Interferon and Host Resist ance.Double-Stranded RNA from Ex tracts of Penicillium Funiculosum.â€• 1Although one could not tell from the title, the article reported research find ings which may hold the key to the eventual control of all or most virus caused diseases.It described a method for stimulating the production of inter feronâ€"a potent antiviral substance.