tbuckley/cabot-search huggingface dataset:
Utility of interim and end-of-treatment PET/CT in peripheral T-cell lymphomas: A review of 124 patients
Authors: Tarec Christoffer El‐Galaly, Martin Bjerregård Pedersen, Martin Hutchings, Karen Juul Mylam, Jakob Madsen, Anne Ortved Gang, Martin Bøgsted, Peter de Nully Brown, Annika Loft, Anne Lerberg Nielsen, Helle Westergreen Hendel, Victor Iyer, Lars Christian Gormsen
Journal: American Journal of Hematology (2015)

According to the updated guidelines for imaging in lymphoma, 18F-FDG positron emission tomography/computed tomography (PET/CT) is recommended for staging and evaluation of treatment response in FDG-avid lymphomas. The purpose of the study was to evaluate the utility of PET/CT in nodal peripheral T-cell lymphomas (PTCL). Patients with newly diagnosed nodal PTCL (peripheral T-cell lymphoma NOS, anaplastic large-cell lymphoma, or angioimmunoblastic T-cell lymphoma) seen at five Danish hematology centers during the period 2006 to 2012 were included, if they had been pretherapeutically staged with PET/CT. Medical records were reviewed for baseline clinical and follow-up information. Staging, interim (I-PET), and end-of-treatment PET/CT (E-PET) studies were centrally reviewed, and reported using the Deauville 5-point score (DS). A total of 124 patients fulfilled the inclusion criteria. The median age was 58 years, and 88% received CHOP/CHOP-like therapy. Five years PFS and OS of the study population was 36.8% (95% CI 27.3-46.4) and 49.7% (95% CI 38.9-59.6), respectively. The presence of PET/CT-ascertained lung and/or liver involvement was associated with a worse outcome. The sensitivity of PET/CT for detecting biopsy-defined bone marrow involvement was only 18% (95% CI 4-43). An interim DS >3 was not prognostic for worse OS and PFS among CHOP/CHOP-like treated patients in uni- or multivariate analyses. A DS >3 after treatment predicted a worse prognosis. In conclusion, I-PET was not predictive of outcome in CHOP/CHOP-like treated PTCL patients when using the DS. Prospective studies are needed to determine the optimal use of PET/CT in PTCL including the role of quantitative PET/CT analysis.
Outcome of acute drug-induced pneumonias in ICU
Authors: Amandine Vial-Dupuy, Olivier Sanchez, Karine Juvin, Dominique Israël-Biet
Journal: European Respiratory Journal (2013)

Background: Limited data are available on the outcome of patients with acute respiratory failure due to drug-induced pneumonia (DIP). We aimed at assessing the clinical and BAL characteristics and the outcome of patients with DIP admitted in ICU.  Methods: Retrospective analysis of medical records of all patients with an acute DIP admitted in our ICU between 2002 and 2012.  Results: Sixteen subjects were included. The majority (56%) were males; medium age : 63 [56-75] years. The responsible drugs were mainly amiodarone (n=5) and cytotoxic ones (n=4). At admission in ICU, APACHE II and SAPS II median scores were 33 [23-41] and 17 [14-20], respectively. The PaO2/FiO2 ratio was 128 [92-151]. The predominant CT scan pattern was ground glass opacities in all cases with an additional honeycombing in 2, occasional reticulations and/or condensations in others. BAL showed 20 [6-50] % lymphocytes, 19 [3-38] % PMN and 2 [0-7] % PE. All infectious searches remained negative. Ten subjects (62%) required mechanical ventilation, whether invasive (n=8) or not (n=2). The overall mortality rate in ICU was 25% reaching 50% in intubated patients. Eleven subjects (69%) had a dramatic response to corticosteroids while 1 recovered after drug withdrawal only.  Conclusion: The prognosis of DIP-associated acute respiratory failure is severe particularly in subjects requiring ventilation. It is nevertheless largely better than that of pulmonary fibrosis acute exacerbation for which DIP is sometimes mistaken due to a comparable CT scan pattern. This highlights the importance of distinguishing these entities.Type of alveolitis and history of drug intake are crucial for a proper diagnosis and management of acute DIP based upon drug withdrawal and steroids.
High-dose cisplatin in hypertonic saline: reduced toxicity of a modified dose schedule and correlation with plasma pharmacokinetics. A Northern California Oncology Group Pilot Study in non-small-cell lung cancer.
Authors: D R Gandara, M W DeGregorio, H Wold, B J Wilbur, M Kohler, H J Lawrence, A B Deisseroth, C B George
Journal: Journal of Clinical Oncology (1986)

Although increased efficacy has been described with a five-day schedule of high-dose cisplatin (CDDP) in hypertonic saline, severe myelosuppression and cumulative neurotoxicity have limited the usefulness of this therapy. In order to evaluate a possible dose-response relationship in non-small-cell lung cancer (NSCLC), 17 patients with metastatic disease were treated with a modified dose schedule delivering the same total dose (200 mg/m2) in a divided day 1 and 8 schedule. During a pilot study, a total of 47 cycles of therapy were administered, with a median of three cycles per patient and a median total cumulative dose of 600 mg/m2. Nine of 17 patients received at least 600 mg/m2. While nephrotoxicity was similar to previous reports of the five-day schedule, the incidence and severity of myelosuppression and peripheral neuropathy were markedly reduced. Using this modified schedule, severe myelosuppression did not occur. Clinically severe peripheral neuropathy developed in only one patient (6%). The overall response rate was 47% (eight of 17 patients). Plasma platinum pharmacokinetics during five cycles of the modified day 1 and 8 schedule were compared with pharmacokinetics of the five-day schedule. Accumulation of plasma ultrafiltrate platinum occurred in the five-day schedule, but not in the day 1 and 8 schedule. This difference in pharmacokinetics is one possible explanation for the reduced toxicity of this modified schedule. Although the degree of activity seen in this pilot study is encouraging, the efficacy of high-dose CDDP in NSCLC remains to be defined. In view of reduced myelosuppression and neurotoxicity, further trials with this modified schedule are indicated.
Neutropenic Enterocolitis in Patients With Acute Leukemia: Prognostic Significance of Bowel Wall Thickening Detected by Ultrasonography
Authors: Claudio Cartoni, Francesco Dragoni, Alessandra Micozzi, Edoardo Pescarmona, Sergio Mecarocci, Piero Chirletti, Maria Concetta Petti, Giovanna Meloni, Franco Mandelli
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Neutropenic enterocolitis (NE) is a severe complication of intensive chemotherapy and is barely identifiable by clinical signs alone. Ultrasonography (US) supports the diagnosis of NE by showing pathologic thickening of the bowel wall. The aim of this study was to evaluate the prognostic value of the degree of mural thickening evaluated by US in patients with clinically suspected NE. PATIENTS AND METHODS: Neutropenic patients with fever, diarrhea, and abdominal pain after intensive chemotherapy for hematologic malignancies were studied with abdominal US. We evaluated the degree of bowel wall thickening detected by US and its correlation with the duration of the clinical syndrome as well as NE-related mortality. RESULTS: Eighty-eight (6%) of 1,450 consecutive patients treated for leukemia had clinical signs of NE. In 44 (50%) of 88 patients, US revealed pathologic wall thickening (mean ± SD, 10.2 ± 2.9 mm; range, 6 to 18). The mean duration of symptoms was significantly longer in this group (7.9 days) than among patients without mural thickening (3.8 days, P &lt; .0001), and the NE-related mortality rate was higher (29.5% v 0%, P &lt; .001). Patients with bowel wall thickness of more than 10 mm had a significantly higher mortality rate (60%) than did those with bowel wall thickness ≤ 10 mm (4.2%, P &lt; .001). CONCLUSION: Symptomatic patients with sonographically detected bowel wall thickening have a poor prognosis compared with patients without this finding. In addition, mural thickness of more than 10 mm is associated with poorer outcome among patients with NE.
Lidocaine use in bronchoscopy: A UK national survey
Authors: Raghu Raju, Ian Sutcliffe, Dipansu Ghosh
Journal: European Respiratory Journal (2013)

Introduction: The current guideline on flexible bronchoscopy stipulates a maximum total dose of lidocaine to be 8.2 mg/kg in adults with extra care in elderly, hepatic and cardiac dysfunction. Higher dose can be associated with complications. Anecdotally, practice in the UK varies widely. We attempt to ascertain the current practice among respiratory physicians.  Methods: An online questionnaire was sent via the Regional Deaneries to try to reach a large proportion of Respiratory Consultants & Trainees in the UK. It included knowledge of safe dose of lidocaine, mode of maximum dose calculation, documenting recent lidocaine usage and strength and formulations of lidocaine used.  Results: 105 physicians responded (63% trainees & 37% Consultants).  60% do not calculate safe dose. Lidocaine usage in previous 24 hours was not checked by 88%. 61% used 2% Lidocaine, 21% used 1% & 23% used combination. For nasal passage 72% use gel and 10% use spray. For oropharynx, 90% used sprays. For vocal cords and beyond, most respondents use fixed number of doses.  Conclusion & Discussion: Majority of bronchoscopists do not calculate safe dose of lidocaine. There is wide variation of practice across the UK. Calculating safe dose of lidocaine before hand, and using 1% solution can potentially reduce total lidocaine use & hence be safer for patients. Guideline in this respect is needed for a more standardized & safer practice.
Recurrent <i>Pseudomonas aeruginosa</i> Pneumonia in Ventilated Patients
Authors: JORDI RELLO, DOLORS MARISCAL, FRANCESCA MARCH, PAOLA JUBERT, FERRAN SANCHEZ, JORDI VALLES, PERE COLL
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

A prospective observational study was performed to determine whether recurrent episodes of pneumonia caused by Pseudomonas aeruginosa in ventilated patients were due to a relapse of the previous clone or to reinfection with a new one. Diagnosis was based on quantitative cultures of secretions obtained by bronchoscopy. Comparison of strains was made by chromosomal fingerprinting based on pulsed field gel electrophoresis (PFGE). Thirty-three (89.1%) of 37 patients survived the initial week after pneumonia diagnosis; six survivors (18.1%) had multiple episodes caused by the same species. Presence of adult respiratory distress syndrome (83.3% versus 22.2%, p = 0.02) was the only factor significantly associated with clinical recurrences. The 16 isolates from five patients (nine recurrences) were analyzed by PFGE. All new isolates from recurrent episodes, excepting one, were considered as relapses. These data suggest that most recurrent episodes of P. aeruginosa pneumonia in ventilated patients occur due to persistence of strains present in a prior infection.
DNA methylation analysis of the temporal artery microenvironment in giant cell arteritis
Authors: Patrick Coit, Lindsey B De Lott, Bin Nan, Victor M Elner, Amr H Sawalha
Journal: Annals of the Rheumatic Diseases (2015)

To investigate the inflammatory response in giant cell arteritis (GCA) by characterising the DNA methylation pattern within the temporal artery microenvironment.Twelve patients with non-equivocal histological evidence for GCA and 12 age-matched, sex-matched and ethnicity-matched controls with normal biopsies were studied. DNA was extracted from the affected portions of temporal artery tissue in patients with GCA and from histologically confirmed normal arteries in controls. Genome-wide DNA methylation status was evaluated using the Illumina Infinium HumanMethylation450 BeadChip Array. Differentially methylated loci between affected and unaffected arterial tissues were identified, and subsequent bioinformatic analysis performed. Immunohistochemistry was used to examine tissue expression patterns in temporal artery biopsies.We identified 1555 hypomethylated CG sites (853 genes) in affected temporal artery tissue from patients with GCA compared with normal controls. Gene ontology enrichment analysis of hypomethylated genes revealed significant representation in T cell activation and differentiation pathways, including both TH1 and TH17 signatures. Our DNA methylation data suggest a role for increased activity of the calcineurin/nuclear factor of activated T cells (NFAT) signalling pathway in GCA, confirmed by immunohistochemistry showing increased expression and nuclear localisation of NFAT1. NFAT signalling downstream targets such as interleukin (IL)-21/IL-21R and CD40L were overexpressed in GCA-affected arteries. Further, proinflammatory genes including TNF, LTA, LTB, CCR7, RUNX3, CD6, CD40LG, IL2, IL6, NLRP1, IL1B, IL18, IL21, IL23R and IFNG were hypomethylated in the cellular milieu of GCA arteries.We characterised the inflammatory response in GCA-affected arteries using 'epigenetic immunophenotyping' and identified molecules and pathways relevant to disease pathogenesis in GCA.
The relationship of IL-4 cytokine gene polymorphisms, HRCT and histopathological score in patients with idiopathic pulmonary fibrosis
Authors: Martina Vasakova, Martina Sterclova, Radoslav Matej, Libor Kolesar, Jelena Skibova, Ilja Striz
Journal: European Respiratory Journal (2011)

Introduction:  Idiopathic pulmonary fibrosis (IPF) is a serious disease with unknown etiology, where an influence of cytokine gene polymorphisms is presumed. We compared HRCT alveolar (AS) and interstitial score (IS) and histoptahologic score with IL-4, and IL-4RA gene polymorphisms in IPF patients.   Subjects and methods:  IPF was diagnosed in 46 patients according to ATS/ERS consensus statement. 43 patients had evaluable HRCT investigations, 14 patients had surgical lung biopsy. HRCT scans were evaluated using IS and AS scales by Gay et al. The histopathological evaluation of lung biopsies comprised: myofibroblast foci (MF), inflammation, eosinophils, granulomas and Ashcroft criteria for fibrosis grading. The IL-4 (-1098) (-590) (-33) and IL-4 RA +1902 gene polymorphisms were characterized utilizing a PCR- SSP method.   Results:  AS was higher in IL-4 haplotypes 1 TTC and TTT carrierrs (p=0.0423). Ashcroft score was more advanced in IL-4 haplotype 2 GCC (p= 0,013) and MF counts were higher in TCC carriers (p=0,0736). IL-4 RA +1902 A1 G and IL-4 -590 A1 T correlated with higher AS (p=0,0335; p=0,0123). Ashcroft score was higher in IL-4 -1098 A2 G and IL-4 -33 A1 T carriers (p= 0,0443, p=0,0915).   Conclusions:  We assume that IL-4 and IL-4RA polymorphisms might influence HRCT and histopathological phenotype of IPF. The correlation of functionally relevant IL-4 genes polymorphisms (especially IL-4 -33 T) with AS could mean, that new alveolar lesions with continuing fibrosis are more pronounced in these polymorphisms carriers. The positive correlation of IL-4 -33 A1 T with Ashcroft score might support a hypothesis of fibrogenetic role of IL-4 in IPF.
Characterization and immunotherapeutic potential of γδ T-cells in patients with glioblastoma
Authors: Nichole L. Bryant, Catalina Suarez-Cuervo, G. Yancey Gillespie, James M. Markert, L. Burt Nabors, Sreelatha Meleth, Richard D. Lopez, Lawrence S. Lamb
Journal: Neuro-Oncology (2009)

Classical immunotherapeutic approaches to glioblastoma multiforme (GBM) have shown mixed results, and therapies focused on innate lymphocyte activity against GBM have not been rigorously evaluated. We examined peripheral blood lymphocyte phenotype, γδ T-cell number, mitogenic response, and cytotoxicity against GBM cell lines and primary tumor explants from GBM patients at selected time points prior to and during GBM therapy. Healthy volunteers served as controls and were grouped by age. T-cell infiltration of tumors from these patients was assessed by staining for CD3 and T-cell receptor γδ. Our findings revealed no differences in counts of mean absolute T-cells, T-cell subsets CD3+CD4+ and CD3+CD8+, and natural killer cells from healthy volunteers and patients prior to and immediately after GBM resection. In contrast, γδ T-cell counts and mitogen-stimulated proliferative response of γδ T-cells were markedly decreased prior to GBM resection and throughout therapy. Expanded/activated γδ T-cells from both patients and healthy volunteers kill GBM cell lines D54, U373, and U251, as well as primary GBM, without cytotoxicity to primary astrocyte cultures. Perivascular T-cell accumulation was noted in paraffin sections, but no organized T-cell invasion of the tumor parenchyma was seen. Taken together, these data suggest that γδ T-cell depletion and impaired function occur prior to or concurrent with the growth of the tumor. The significant cytotoxicity of expanded/activated γδ T-cells from both healthy controls and selected patients against primary GBM explants may open a previously unexplored approach to cellular immunotherapy of GBM.
Effects of breath-stacking maneuver and incentive spirometry on chest Wall compartmental volumes distribution in patients With Parkinson's disease
Authors: Rhayssa Ribeiro, Taciano Rocha, Jasiel Nascimento Junior, Catarina Rattes, Daniella Brandao, Shirley Campos, Guilherme Fregonezi, Vanessa Resqueti, Andrea Aliverti, Armele Dornelas de Andrade
Journal: European Respiratory Journal (2013)

Introduction: Pulmonary dysfunctions contribute significantly to morbidity and mortality of Parkinson9s disease patients (PD). Therapeutic strategies are needed to optimize lung function in these patients. Aim: To evaluate the effects of Breath Stacking(BS) maneuver and Incentive Spirometry (IS) on the pattern of rib cage volumes distribution immediately after and within thirty minutes of their execution in patients with PD. Methods: A cross-over study with 14 patients with mild to moderate PD. Subjects were randomized in three groups: BS, volume-oriented IS and control. All volunteers were assessed before, immediately after and 30min after techniques execution by optoelectronic plethysmography. ANOVA repeated measures with post hoc Tukey test and the Friedman test with post-hoc Dunns it was used. Results: BS and EI increased tidal volume and minute volume(p  Supported by: CNPq, FACEPE and CAPES/PROCAD-NF.
Comedogenesis: some new aetiological, clinical and therapeutic strategies
Authors: W.J. Cunliffe, D.B. Holland, S.M. Clark, G.I. Stables
Journal: British Journal of Dermatology (2000)

Abstract Hypercornification is an early feature of acne and precedes inflammation. It is associated with ductal hyperproliferation and there are many controlling factors such as androgens, retinoids and cytokines. Cycling of normal follicles and of comedones may explain the natural resolution of comedones and, in the longer term, resolution of the disease itself. There is a need to tailor treatment according to comedonal type. Suboptimal therapy can often result from inappropriate assessments of comedones, especially microcomedones, missed comedones, sandpaper comedones, submarine comedones and macrocomedones. Macrocomedones can produce devastating acne flares, particularly if patients are inappropriately prescribed oral isotretinoin. Gentle cautery under topical local anaesthesia is a useful therapy in the treatment of such lesions. The newer retinoids and new formulations of all-trans-retinoic acid show a better benefit/risk ratio. Evidence-based studies are required to allow adequate comparisons.
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, Fifth Editionedited by Marc Galanter, M.D., Herbert D. Kleber, M.D., and Kathleen T. Brady, M.D., Ph.D. Washington, D.C., American Psychiatric Association Publishing, 2015, 980 pp., $199.00 (hardcover).
Authors: Christian Thurstone
Journal: American Journal of Psychiatry (2015)
Antioxidative and Clinical Effects of High-dose<i>N</i>-Acetylcysteine in Fibrosing Alveolitis
Authors: JÜRGEN BEHR, KONRAD MAIER, BARBARA DEGENKOLB, FRITZ KROMBACH, CLAUS VOGELMEIER
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

In fibrosing alveolitis (FA), activated phagocytes cause excessive oxidative stress in the lower respiratory tract. Additionally, levels of glutathione, a major antioxidant of the human lung, are markedly reduced. Since N-acetylcysteine (NAC) is a known precursor for glutathione synthesis, we investigated the effect of NAC on redox balance and lung function in FA. Eighteen patients with an established diagnosis of FA were treated with 600 mg NAC three times daily for 12 wk in addition to their latest immunosuppressive therapy. Before and after NAC therapy, pulmonary function tests (PFTs) and bronchoalveolar lavage (BAL) were performed. BAL fluid was analyzed with regard to cell differential, glutathione status, and methionine sulfoxide content of BAL proteins (Met(O)), as an indicator of oxidative stress at the alveolar surface. There was an increase of total glutathione (GSHt = GSH + 2 × GSSG: 3.43 ± 0.30 μ M versus 4.20 ± 0.66 μ M, p < 0.05) and of reduced glutathione (GSH: 2.58 ± 0.24 μ M versus 3.42 ± 0.54 μ M, p < 0.005) in native BAL fluid and in the epithelial lining fluid (GSHt: 267.3 ± 26.0 μ M versus 367.1 ± 36.0 μ M, p < 0.005; GSH: 204.5 ± 20.7 μ M versus 302.9 ± 32.2 μ M, p < 0.005). The increase of GSH was accompanied by a decrease of Met(O) (6.83 ± 0.71% versus 4.60 ± 0.40%, p < 0.005). PFTs significantly improved during NAC treatment. We conclude that high-dose NAC significantly improved the antioxidant screen of the lungs by elevating GSH levels. Moreover, the decrease of Met(O) levels indicated an antioxidant effect at the alveolar surface. These biochemical changes were accompanied by an improvement of PFTs in patients under maintenance immunosuppression. NAC supplementation should, therefore, be considered as an adjunct therapy for FA.
Pneumothorax in treatment of severe emphysema with endobronchial valves
Authors: Wolfgang Gesierich, Michael Kraft, Frank Reichenberger, Norbert Weber, Juergen Behr
Journal: European Respiratory Journal (2014)

Background:   Pneumothorax is a well known complication of endoscopic lung volume reduction with endobronchial valves (EBV).   Aims and objectives:   To investigate the frequency and impact of pneumothorax in EBV therapy for severe emphysema.   Methods:   103 patients treated with EBV from 2011 -13 were retrospectively analysed for events of pneumothorax. Fissure analysis and bronchoscopic assessment (Chartis) had been used in patient- and target lobe selection to confirm absence of collateral ventilation (CV negative status). Complete occlusion of the target lobe with EBV had been achieved.   Results:   Table 1: Events of pneumothorax in 103 pts treated with EBV  22/23 events needed insertion of a chest drain, 4/23 needed removal of EBV, 5/23 needed thoracoscopy for adhesiolysis and closure of bronchopleural fistula.   Conclusion:   In a CV negative cohort treated with EBV for severe emphysema pneumothorax is considerably more frequent compared to historical data (e.g. US- and EURO-VENT trials; pneumothorax rate 4,2% and 4,5%, respectively; Sciurba et al. NEJM 2010:363:1233-44; Herth et al. ERJ 2012:39:1334-42), and is associated with relevant morbidity. Frequency, however, still remains in an acceptable range. Patients and carers should be aware of the possibility of late events.