tbuckley/cabot-search huggingface dataset:
High-dose combination alkylating agent chemotherapy with autologous bone marrow support for metastatic breast cancer.
Authors: J P Eder, K Antman, W Peters, W D Henner, A Elias, T Shea, S Schryber, J Andersen, S Come, L Schnipper
Journal: Journal of Clinical Oncology (1986)

Seventeen patients with metastatic breast cancer were treated with a high-dose combination chemotherapy regimen and autologous bone marrow support. Thirteen patients had prior combination chemotherapy. Fifteen patients were treated with a phase II regimen of cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (600 mg/m2). Bone marrow harvest and reconstitution were uncomplicated. All patients became profoundly myelosuppressed. Fourteen of 16 evaluable patients (88%) responded, including six complete responses (CRs) (38%). The median time to tumor progression was 5 months. The median survival was 8 months. CRs occurred more frequently in patients with no prior chemotherapy for metastatic disease, inflammatory breast cancer; and patients treated within 3 months of first recurrence. The rate of tumor regression was rapid, with a median of 11 days to partial response (PR) and 12 days to CR. Those patients achieving a PR by day 7 had a greater likelihood (P = .03) of attaining a CR than those patients whose PR occurred later. Three deaths (18%) occurred, all in women with inflammatory breast cancer treated with prior chemotherapy. High-dose combined alkylating agent therapy produced high PR and CR rates in metastatic breast cancer patients, most of whom had failed prior chemotherapy. The rate of tumor regression was rapid. Current efforts are directed at developing a regimen using drugs specifically active in breast cancer, with an intent of combining an effective high-dose regimen with additional modalities of therapy in the treatment of breast cancer.
Inappropriate Sympathetic Activation at Onset of Septic Shock
Authors: DJILLALI ANNANE, FABIEN TRABOLD, TAREK SHARSHAR, IRÈNE JARRIN, ANNE SOPHIE BLANC, JEAN CLAUDE RAPHAEL, PHILIPPE GAJDOS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The autonomic cardiovascular control was investigated in 10 patients with septic shock, 10 patients with sepsis syndrome, and six tilted healthy subjects. Overall variability, high- and low-frequency components (AUC, HF, and LF, beats/min(2)/Hz or mm Hg(2)/Hz) from heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures spectra were obtained from 5-min recordings. LF(HR)/HF(HR) and the square root of LF(SBP)/LF(HR) (alpha) were used as indices of sympathovagal interaction and baroreflex control of the heart, respectively. Compared with tilted control subjects and patients with sepsis syndrome, septic shock is characterized by reduction in: (1) HR variability, i.e., decreased AUC(HR) (p = 0.007), LF(HR) (p = 0.002), and LF(HR)/HF(HR) (p = 0.0002); (2) DBP variability, i.e., decreased AUC(DBP) (p = 0.003) and LF(DBP) (p = 0.001), (3) alpha (p = 0.003). In septic shock, LF(HR)/HF(HR), alpha, and LF(DBP) correlated with mean blood pressure (r = 0.67, p = 0.04, r = 0.64, p = 0.03, and r = 0.88, p = 0.0008, respectively), and with plasma norepinephrine levels (r = -0.65, p = 0.03, r = -0.79, p = 0.006, and r = -0.69, p = 0.03, respectively). In conclusion, onset of septic shock is characterized by high concentrations of circulating catecholamines but impaired sympathetic modulation on heart and vessels, suggesting that central autonomic regulatory impairment contributes to circulatory failure.
Late-breaking abstract: Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnea
Authors: M.I. Queipo-Ortuño, I. Moreno-Indias, M. Torres, J.M. Montserrat, L. Sanchez-Alcoholado, F. Cardona, R. Farre
Journal: European Respiratory Journal (2014)

BACKGROUND: Current research is revealing important interactions between human metabolism and gut microbiota. We hypothesize that intermittent hypoxemia characterizing sleep apnea may modify the intestinal barrier and alter gut microbioma. METHODS: 10 male mice (C57BL/6; 6 wk-old) were chronically subjected to a pattern of intermittent hypoxia mimicking severe sleep apnea (20 s at 5% O2 followed by 40 s at 21% O2; 6h/day for 6 weeks) and 10 control mice breathed room air. Fecal samples were obtained and immediately frozen at -80°C. V2-V3 regions of the 16s rRNA genes of bacteria in the fecal samples were amplified and examined by Pyrosequencing (454 GS Junior System). Data analysis was performed with QIIME. RESULTS: 16s rRNA pyrosequencing showed a significant effect of hypoxia on overall microbial community structure. Intermittent hypoxia increased the α-diversity (Shannon and observed-species indexes, P<0.05); and induced a change in the gut microbiota (ANOSIM analysis of beta-diversity, P<0.05). Intermittent hypoxia group showed a higher abundance of Firmicutes and a smaller abundance of Bacteroidetes phyla than the control group (P<0.05). At the level of genus, hypoxia resulted in significant greater values of Paraprevotella and Prevotella, and smaller ones of Odoribacter and Bacteroides (according to the Bacteroidetes Genera), and in the case of the Firmicutes genera, smaller abundances of Turicibacter, rc4-4, Oscillospira and Allobaculum, than the control group (P<0.05). CONCLUSION: Intermittent hypoxia has a significant impact on overall microbial community structure, suggesting that the homeostatic relationship between host and gut microbiota could be compromised in sleep apnea patients.
Low ADAMTS13 activity is associated with an increased risk of ischemic stroke
Authors: Michelle A. H. Sonneveld, Moniek P. M. de Maat, Marileen L. P. Portegies, Maryam Kavousi, Albert Hofman, Peter L. Turecek, Hanspeter Rottensteiner, Fritz Scheiflinger, Peter J. Koudstaal, M. Arfan Ikram, Frank W. G. Leebeek
Journal: Blood (2015)
A highly sensitive novel PCR assay for detection of Pneumocystis jirovecii DNA in bronchoalveloar lavage specimens from immunocompromised patients
Authors: T. Tia, C. Putaporntip, R. Kosuwin, N. Kongpolprom, K. Kawkitinarong, S. Jongwutiwes
Journal: Clinical Microbiology and Infection (2011)
Factors Modifying Stem Cell Proliferation of Myelomonocytic Leukemic Cells &lt;italic&gt;In Vitro&lt;/italic&gt; and &lt;italic&gt;In Vivo&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Donald Metcalf, Malcolm A. S. Moore
Journal: JNCI Journal of the National Cancer Institute (1970)
Abstract 172: Adipocytes decrease daunorubicin concentration in acute lymphoblastic leukemia cells
Authors: Xia Sheng, Jonathan Tucci, James Behan, Steven D. Mittelman
Journal: Cancer Research (2014)

Abstract Obesity is associated with increased cancer incidence and mortality. Adipose tissue has been shown to play a role in several types of cancer, including acute lymphoblastic leukemia (ALL). We have demonstrated that murine ALL cells actively migrate into adipose tissue in mice, and that adipocytes protect ALL cells from daunorubicin (DNR) in vitro. We have further shown that media cultured by both adipocytes and ALL cells together (ALCM) can protect ALL cells from DNR. We hypothesize that adipocytes protect ALL cells from DNR by decreasing ALL cell intracellular drug accumulation. Human pre B ALL cells (BV173) were co-cultured with 3T3-L1 adipocytes using a transwell system. Intracellular DNR was visualized using con-focal fluorescence microscopy at various time points in leukemia cells during DNR treatment. Drug uptake in leukemia cells treated with DNR and co-cultured with adipocytes was measured by flow cytometry. By preloading cells with DNR, drug efflux assays were also performed with ALL cells. Gene expression of ABCB1a and cell surface expression of MDR1 were quantified using qPCR and flow cytometry, respectively, in ALL cells co-cultured with adipocytes. After 72 hours of DNR treatment, there were significantly more viable BV173 cells in the transwells placed over adipocytes than those over fibroblasts (290,000± 60,500 vs. 108,000± 13,000, p=0.008, n=4). Co-culture with adipocytes was associated with a lower intracellular DNR in BV173 cells. After 4 hours, DNR was 30% lower, and by 24 hours intracellular DNR was 80% less (n=1). However, co-culturing ALL cells with adipocytes was not associated with a significant increase in efflux rate of DNR from preloaded BV173 (half-life = 36±13 vs. 31±9 min., p=0.23, n=3). The mRNA expression of ABCB1a, the gene encoding MDR1, was increased in BV173 cells (130% increase, n=1) co-cultured with adipocytes for 24 hours. However, we did not detect an increase in surface MDR1 expression in BV713 co-cultured with adipocytes. We then tested whether adipocyte-secreted factors would cause efflux of DNR from ALL cells. There was a tendency for DNR efflux rate to be higher in BV173 cells cultured in ALCM (half-life = 36±13 vs. 27±10 min., p=0.08, n=3). Further investigation is needed to confirm this effect. These findings demonstrate that adipocytes may protect ALL cells from daunorubicin treatment in part by decreasing intracellular drug accumulation. However, it is not clear whether this effect is due to altered uptake, efflux, or intracellular drug action. Citation Format: Xia Sheng, Jonathan Tucci, James Behan, Steven D. Mittelman. Adipocytes decrease daunorubicin concentration in acute lymphoblastic leukemia cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 172. doi:10.1158/1538-7445.AM2014-172
But where does it take us?
Authors: David S Sanders, Andrew D Hopper, John S Leeds, Marios Hadjivassiliou
Journal: BMJ (2008)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which usually arrive
Possible Origin of Synovial Lining Cell Hyperplasia in Rheumatoid Arthritis
Authors: D W Howat
Journal: Journal of the Royal Society of Medicine (1987)

A perplexing feature of rheumatoid arthritis is the increase in the number of synovial lining cells with no mitotic activity. This feature has been investigated in the rabbit model. Rabbits with the established condition were injected into the affected joint with tritiated thymidine and killed either up to 24 hours later, or at 3 or 7 days. The location of labelled cells, detected by autoradiography, showed the label predominantly in the stroma in the former, and mainly in the lining cells in the latter, indicating that the lining cells were derived by recruitment from active cells deep in the stroma.
Alternating pressure systems are useful
Authors: E. Bethell
Journal: BMJ (1994)

Pressure soresNot considered a priority by medical staff EDrrOR,-R K Vohra and C N McCollum's review of pressure sores is a timely reminder of the continuing silent epidemic of pressure sores both in hospital and in the community.'Pressure sores impose two main penalties, financial and human.The financial costs are high and result from additional treatment, a prolonged stay in hospital, and a further demand on clinic (nursing) time.Prevention of pressure sores is based on constant vigilance and early action, with awareness being the keynote of success.A colleague and I conducted a detailed survey with a semistructured questionnaire in a university teaching hospital; medical staff responded poorly to the questionnaire because pressure sores were not considered to be a priority.2Only about a quarter of medical staff routinely assessed patients with regard to their risk of pressure sores, though most nursing and therapy staff performed routine assessments.Hospital staff other than nursing staff were unaware of any protocols for assessing pres- sure sores.Most of the respondents thought that the cost of treating an inpatient with a pressure sore was less than £;1000; this indicates their unaware- ness of the true cost.It is prudent to apply low technology early rather than high technology at a later stage.If equipment is required it should be compatible with existing equipment, and unless costs are realistic the strategy is doomed to failure.
Performance of segmentation software on large longitudinal database of pulmonary nodules in the Danish Lung Cancer Screening Trial (DLCST)
Authors: Zaigham Saghir, Colin Jacobs, Bram van Ginneken, Marleen de Bruijne, Asger Dirksen, Jesper Holst Pedersen
Journal: European Respiratory Journal (2012)

Introduction and aim   Growth measurements of pulmonary nodules are subject to great interest due to the risk of malignancy. We examined the reproducibility of lung nodule volumetric software that offers two different volumetric algorithms.   Materials and methods   In the Danish Lung Cancer Screening trial, 2,052 participant with high risk of lung cancer where randomized to five annual multislice low-dose scans. All scans were double-read by two experienced chest radiologists and the location and size of nodules were registered. Subsequently the nodules were linked chronologically (same nodule in different scans) and independently reviewed by two readers using volumetric software. The software offers readers two different analysing algorithms, “solid nodule algorithm” and “partsolid/nonsolid algorithm”. We compared the inter-observer variability regarding use of algorithm and rate of success.   Results   1442 nodules were measured 5988 times. The readers reviewed the segmentations visually and were able to correctly segment and measure 94% and 97% of the nodules, respectively. In 90% of these cases, the readers chose the same algorithm.   Conclusion   Using this volumetric software on a large database with longitudinal data shows a high success rate and large agreement in choosing algorithm.
Breathing muscle activity during expiration in patients with chronic airflow obstruction
Authors: MJ Morris, RG Madgwick, AJ Frew, DJ Lane
Journal: European Respiratory Journal (1990)

During quiet ventilation in 10 patients with severe chronic airflow obstruction (AFO) there were large tidal swings of pleural pressure, 15.8 +/- 5.1 cmH2O, with high negative pressures achieved, 15.2 +/- 5.2 cmH2O. The pattern of pleural pressure mirrored that of tidal expiratory flow with a rapid rise to maximum of pleural pressure and flow at the beginning of expiration, a slow decline of both throughout most of expiration, and just before the onset of inspiration at flow reversal, a sharp fall in pleural pressure and expiratory flow. The shape of expiratory flow and pleural pressure tracings and the pattern of EMG recordings are compatible with loss of post-inspiratory muscle braking of flow. The generally negative pleural pressure and the EMG silence during expiration indicated relaxation of expiratory muscles throughout expiration. Extrapolation of the tidal expiratory flow curve to zero, and calculation of the area under the extrapolated curve showed the volume of dynamic hyperinflation to be a small proportion of the total increase in functional residual capacity above the predicted value in these patients.
The use of transbronchial biopsies in pediatric lung diseases in a tertiary care hospital in Bogota, Colombia
Authors: Patricia Panqueva, Fernando Polo, Jorge Carrillo, Alvaro Morales
Journal: European Respiratory Journal (2012)

A total of 12 Transbronchial Biopsies (TBB) were performed in pediatric patients during the last year at the Hospital Universitario San Ignacio, using an adult small bronchoscope (5.3 mm outer diameter Olympus).  Results:  In 9 patients adequate lung tissue for histological diagnosis was obtained.  In two patients with HIV infection, respiratory symptoms and chest x-ray abnormalities, pathogens were identified and successfully treated: positive ZN (13 y.o. female) and P. Jiroveci (12 y.o. female). Several patients presented with dyspnea and mosaic patterns in the chest x-ray: in three cases the information was useful, and all of them improved after treatment. 12 y.o.male in whom lung metastasis were found (successful chemotherapy initiated), 14 y.o. male in whom capillaritis was found (improvement after treatment). In an 8 y.o. male insufficient sample was reported. In patients with malignancies, useful information was provided: in patients with lymphomas and lung infiltrates CMV was identified and treated (10 y.o. male) and P. Jiroveci was found in two patients with leukemia. The only complications were a small pneumothorax that did not require intervention and hypotension in a septic HIV patient that was sent to Intensive Care for management.  Conclusion: The Transbronchial biopsie is an effective and safe procedure to obtain lung tissue for histologic diagnosis in a variety of conditions such a tumors, infections or pulmonary infiltrates and that can be considered as first –line diagnostic procedure in pediatric patients.  References.  1. Visner GA, Faro A, Zander DS. Role of transbronchial biopsies in pediatric lung disease.Chest 2004; 126:273-280.
Seeking Rational Approaches to Fixing Hospital Readmissions
Authors: Ashish K. Jha
Journal: JAMA (2015)

Spurred by federal policy makers, US hospitals have made substantial efforts to address the problem of high rates of patients being readmitted to the hospital within 30 days of discharge. Underlying this policy focus is a straightforward idea: when patients are discharged from the hospital, with some exceptions, they shouldn’t have to return within 30 days. The Hospital Readmissions Reduction Program (HRRP), part of the Affordable Care Act (ACA), codified this notion by penalizing hospitals with higher-thanexpected readmission rates up to 3% of their totalMedicarepayments (http://go.cms .gov/1L93Lh4). The early evidence on HRRP’s effects was largely positive. Readmission rates declined nationally and the Centers for Medicare & Medicaid Services (CMS) touted these results (http://1.usa.gov /1k0tw2B) as evidence that the ACA had begun to bend the cost curve. From 2008 through 2013, the likelihood of a Medicare beneficiary being readmitted within 30 days decreased from 19.0% to 17.8%, translating to hundreds of millions of dollars in savings to Medicare.
Can blood investigations be utilised to predict treatment response to omalizumab
Authors: Caroline Gouder, Lorna West, Stephen Montefort
Journal: European Respiratory Journal (2013)

Background  Physician9s overall assessment after 16 weeks of omalizumab for severe persistent allergic asthma has been identified as the most meaningful measure of response to therapy (Bousquet et al, 2007).  Aim  The aim of this study was to identify whether blood investigations could identify responders at 16 weeks of treatment, in addition to proposed methods.  Method  All patients who were recruited for an on-going prospective study and received 16 weeks of omalizumab for severe IgE-mediated asthma in Malta were included. CBC, ESR and CRP were taken prior to and 16 weeks after treatment initiation. Treatment effectiveness was evaluated using the Asthma Control Test and physician’s assessment.  Results  Our cohort included 22 patients (64% males, mean age ± SD 53±11). Response rate at 16 weeks was 82%. When comparing baseline versus 16 week results, a significant decline was noted in the mean (±SD) peripheral eosinophil count (x10ˆ9/L) 0.74±0.88 vs 0.38±0.38 (p=0.04) in responders as opposed to 0.34±0.36 vs 0.25±0.16 (p=0.23) in non-responders. Mean CRP (mg/L) decreased significantly in responders 10±9.9 vs 6.3±1.41 (p=0.04) when compared to non-responders 15.5±13.7 vs 8.2±3.9 (p=0.1). WCC (x10ˆ9/L) diminished significantly, 9±1.75 vs 7.7±1.34 (p=0.003) in responders contrary to 8.9±1.03 vs 9.37±1.7 (p=0.31) in non-responders. Platelet counts (x10ˆ9/L) diminished significantly in responders, 245±36 vs 231±30 (p=0.02) as opposed to 200±84 vs 247±17 (p=0.2) in non-responders. Changes in ESR did not reach statistical significance.  Conclusion  The potential of utilizing eosinophil and platelet counts, CRP and WCC as markers of treatment effectiveness should be further evaluated in larger studies.
Negative consequences of immunosuppressive therapy on bronchial healing following lung transplantation (LTx)
Authors: Anne Olland, Sandrine Hirschi, Jérémie Reeb, Stéphane Renaud, Nicola Santelmo, Anne Roche, Pierre-Emmanuel Falcoz, Romain Kessler, Gilbert Massard
Journal: European Respiratory Journal (2013)

Introduction

Immunosuppressive therapy presents with well-known anti-proliferative properties. We studied the impact of different immunosuppressive combinations on bronchial healing in LTx.

Method

We conducted a retrospective historical study on all LTx performed in a single center between January 2004 and May 2012. We recorded the demographic characteristics of the recipients and the donors. We focused on lung disease in the recipient, denutrition, surgical technique for transplantation, graft ischemia, primary graft dysfunction, mechanical ventilation support, lung infection, and the post-operative combination of immunosuppressive therapy. These characteristics were compared to bronchial complications defined as: (i) symptomatic dehiscence (extended chest tube drainage, need for surgery, recipient death) or (ii) symptomatic stenosis (bronchoscopic dilation or stenting).

Results

Among 169 LTx, we found 35 bronchial complications leading to death in 7 patients. Meanwhile 134 patients remained unharmed. Both groups received overall the same amount of steroids. Patients with the combination basiliximab/steroid/tacrolimus/mycophenolate had significantly more bronchial complications (p=0.03) in comparison to patients with the combination steroid/ ciclosporin/azathioprine . There was no significant difference for the other studied factors.

Conclusion

The combination basiliximab/steroid/tacrolimus/mycophenolate has a negative effect on bronchial healing. The anti-proliferative effects of immunosuppressive drugs should be studied when given in a combination and not as a single drug.
Measurement properties of patient-reported outcome measures (PROMs) in adults with obstructive sleep apnea (OSA): A systematic review
Authors: Inger L. Abma, Philip J. van der Wees, Vik Veer, Gert P. Westert, Maroeska Rovers
Journal: Sleep Medicine Reviews (2015)

This systematic review summarizes the evidence regarding the quality of patient-reported outcome measures (PROMs) validated in patients with obstructive sleep apnea (OSA). We performed a systematic literature search of all PROMs validated in patients with OSA, and found 22 measures meeting our inclusion criteria. The quality of the studies was assessed using the consensus-based standards for the selection of health status measurement instruments (COSMIN) checklist. The results showed that most of the measurement properties of the PROMs were not, or not adequately, assessed. For many identified PROMs there was no involvement of patients with OSA during their development or before the PROM was tested in patients with OSA. Positive exceptions and the best current candidates for assessing health status in patients with OSA are the sleep apnea quality of life index (SAQLI), Maugeri obstructive sleep apnea syndrome (MOSAS) questionnaire, Quebec sleep questionnaire (QSQ) and the obstructive sleep apnea patient-oriented severity index (OSAPOSI). Even though there is not enough evidence to fully judge the quality of these PROMs as outcome measure, when interpreted with caution, they have the potential to add value to clinical research and clinical practice in evaluating aspects of health status that are important to patients.