tbuckley/cabot-search huggingface dataset:
Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: an international collaborative study
Authors: J M Boer, A van der Veer, D Rizopoulos, M Fiocco, E Sonneveld, H A de Groot-Kruseman, R P Kuiper, P Hoogerbrugge, M Horstmann, M Zaliova, C Palmi, J Trka, E Fronkova, M Emerenciano, M do Socorro Pombo-de-Oliveira, W Mlynarski, T Szczepanski, K Nebral, A Attarbaschi, N Venn, R Sutton, C J Schwab, A Enshaei, A Vora, M Stanulla, M Schrappe, G Cazzaniga, V Conter, M Zimmermann, A V Moorman, R Pieters, M L den Boer
Journal: Leukemia (2015)
Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience.
Authors: K S Albain, J J Crowley, M LeBlanc, R B Livingston
Journal: Journal of Clinical Oncology (1991)

We analyzed the 2,531-patient Southwest Oncology Group extensive-stage non-small-cell lung cancer (ENSCLC) data base from 1974 to 1988 to (1) assess the interactions of host- or tumor-related prognostic factors and therapy using Cox modeling and recursive partitioning and amalgamation (RPA) to determine whether each independently predicts outcome, and (2) use RPA to define prognostic subsets with different survival potentials. Good performance status (PS), female sex, and age greater than or equal to 70 years were significant independent predictors in a Cox model applied to the entire population. In a second Cox model for patients with good PS enrolled on recent studies, hemoglobin level greater than or equal to 11.0 g/dL, normal lactate dehydrogenase (LDH), normal calcium, and a single metastatic site were significant favorable factors. The use of cisplatin was an additional independent predictor of improved outcome in both Cox models after adjustments for year of accrual and all prognostic variables. The favorable effect of cisplatin was observed in each of six RPA-derived subgroups from the entire population. A second RPA of 904 patients from recent trials (nearly all received cisplatin-based therapy) resulted in three distinct prognostic subsets based on PS, age, hemoglobin, and LDH; greater than or equal to 1-year survivals were 27%, 16%, and 6% (P less than .0001). The best survival occurred for patients with a good PS who had a hemoglobin level greater than or equal to 11 g/dL and who were older than 47 years. This analysis suggests that although several factors were independent variables in the Cox models, three important prognostic subgroups were easily defined through RPA. Together with other analyses, our results suggest the need to modify the stage IV category in NSCLC.
Exercise right heart catheterisation in the diagnosis of pulmonary hypertension
Authors: Stephan Keusch, Séverine Mueller-Mottet, Anina Bucher, Lars C. Huber, Rudolf Speich, Silvia Ulrich
Journal: European Respiratory Journal (2013)

Background:  Exertional dyspnea is the hallmark of pulmonary hypertension (PH). We explored exercise RHC for suspected PH.   Methods:  RHC including supine maximal cycling exercise tests between April 2005 and November 2012 were reviewed. Hemodynamic at rest and exercise was compared with demographics, oxygenation, function, diagnosis, adverse events and survival.   Results:  RHC from 101 patients (70 women, age 61±14y) were analysed. At rest, 27 were diagnosed with precapillary PH (9 idiopathic, 7 scleroderma, 1 HIV, 6 chronic lung disease, 3 thromboembolic, 1 sarcoidosis) and 7 with post-capillary PH. Form the 67 patients (50 females) without resting PH, exercise precapillary PH was found in 13 patients (6 scleroderma, 1 HIV, 2 chronic lung disease, 4 thromboembolic and 1 sarcoidosis) and exercise postcapillary PH in 27 (17 scleroderma, 1 chronic lung disease, 1 sarcoidosis, 8 other diastolic dysfunction). Patients with resting precapillary PH had a significantly higher NT-pro-BNP, lower blood oxygenation and increase in mPAP with exercise compared to exercise precapillary PH. These differences were not found in postcapillary PH. The mean follow-up time was 934±682 days without any event –free survival difference between groups. Exercise RHCs were well tolerated without any adverse events during the examination.   Conclusion:  Different pulmonary hemodynamic profiles defined as normal, pre- or postcapillary PH with rest and exercise might be all found in diseases like scleroderma, sarcoidosis, chronic lung and thromboembolic diseases. Supine exercise RHC in the diagnostic algorithm of PH is save, however; the diagnostic contribution of exercise RHCs must be studied in prospective trials.
Radiation Therapy for Intracranial Germinoma: Results of the German Cooperative Prospective Trials MAKEI 83/86/89
Authors: Michael Bamberg, Rolf-D. Kortmann, Gabriele Calaminus, Gerd Becker, Christoph Meisner, Dieter Harms, Ulrich Göbel
Journal: Journal of Clinical Oncology (1999)

A multicenter prospective trial was conducted (Maligue Keimzelltümoren [MAKEI] 83/86/89) to assess outcome in intracranial germinoma after treatment with radiotherapy alone at reduced doses.Between 1983 and 1993, 60 patients with histologically (n = 58) or cytologically (n = 2) confirmed germinoma were enrolled onto the study. Patients received radiotherapy alone (craniospinal axis/local boost). In the MAKEI 83/86 study (involving 11 patients), the dose to the craniospinal axis was 36 Gy and the dose to the tumor region was 14 Gy. In the MAKEI 89 study (involving 49 patients), doses were 30 and 15 Gy, respectively.Median patient age was 13 years (range, 6 to 31 years). Complete remission was achieved in all patients. The estimated (Kaplan-Meier) 5-year relapse-free survival rate was 91.0% +/- 3.9% at a mean follow-up of 59.5 months (range, 3 to 180 months); the estimated overall survival rate was 93.7% +/- 3.6%. Relapse occurred in five patients 10 to 33 months (mean, 18.4 months) after diagnosis (one patient developed a spinal canal metastasis and underwent salvage radiotherapy and chemotherapy; four patients had metastases outside the CNS and underwent salvage chemotherapy alone). Four patients died: one died from disease, two died from therapy-related complications, and one committed suicide. Acute complications with long-lasting sequelae were tumor or surgery related (three cases of blindness, six of reduced vision, two of hemiparesis). Psychosocial development was normal in the majority of patients.Radiotherapy directed toward the craniospinal axis or tumor site alone at decreased dose levels is effective. To reduce the risk of late side effects, further attempts to decrease total doses are justified. In cases of recurrent disease, chemotherapy administered outside the CNS is the treatment of choice.
Eosinophilic myocarditis: a paraneoplastic event
Authors: Enrico Ammirati, Miriam Stucchi, Michela Brambatti, Francesca Spanò, Edgardo Bonacina, Fabio Recalcati, Giulio Cerea, Angelo Vanzulli, Maria Frigerio, Fabrizio Oliva
Journal: The Lancet (2015)
Zonisamide reduces obstructive sleep apnea: A randomized placebo-controlled study
Authors: Davoud Eskandari, Ding Zou, Mahssa Karimi, Kaj Stenlöf, Ludger Grote, Jan Hedner
Journal: European Respiratory Journal (2013)

Background: Carbonic anhydrase inhibition is associated with reduction of apneic events in sleep disordered breathing. Zonisamide has carbonic anhydrase inhibitory properties, and induces weight loss in obese patients. Our aim was to determine the therapeutic effects of zonisamide in obstructive sleep apnea (OSA).

Methods: Forty-seven patients with moderate to severe OSA and a body mass index 27 to 35 kg/m2 were randomized to zonisamide, placebo or continuous positive airway pressure (CPAP) treatment for 4 weeks. In the open extension phase, all participants except those on CPAP received zonisamide for 20 weeks. Polysomnography, biochemistry and symptoms were evaluated.

Results: The placebo controlled effect of zonisamide at 4 weeks was a reduction of apnea hypopnea index (AHI) 33±39% and oxygen desaturation index 28±31% (p=0.02 and 0.014, respectively). At 24 weeks the mean reduction of AHI after zonisamide and CPAP (adjusted for compliance) was 14 and 61% (p=0.001 between groups). CPAP but not zonisamide reduced sleepiness. Body weight was marginally changed at 4 weeks but reduced after zonisamide and increased after CPAP at 24 weeks (-2.7±3.0 vs. 2.3±2.0 kg, p<0.001). Zonisamide treatment induc a reduction of bicarbonate at 4 and 24 weeks. Drop-out rate was similar in the zonisamide and CPAP groups.

Conclusions: Zonisamide reduced OSA independent of body weight potentially by mechanisms related to carbonic anhydrase inhibition. Added weight loss after long term zonisamide treatment may generate a further therapeutic potential for this class of drugs in OSA.

Clinical trials registration: EudraCT; No.: 2009-015859-24; URL: https://eudract.ema.europa.eu/.
Full and partial posttraumatic stress disorder: findings from a community survey
Authors: M B Stein, J R Walker, A L Hazen, D R Forde
Journal: American Journal of Psychiatry (1997)

Full and partial posttraumatic stress disorder (PTSD) following trauma exposure were examined in a community sample in order to determine their prevalence and their relative importance and functional significance.A standardized telephone interview with a series of trauma probes and a DSM-IV PTSD checklist was administered to a random sample of 1,002 persons in a midsized Midwestern Canadian city. The authors determined current (i.e., 1-months) prevalence rates of full PTSD, i.e., all DSM-IV criteria, and partial PTSD, i.e., fewer than the required number of DSM-IV criterion C symptoms (avoidance/numbing) or criterion D symptoms (increased arousal). Additional questions about interference with functioning were also posed.The estimated prevalence of full PTSD was 2.7% for women and 1.2% for men. The prevalence of partial PTSD was 3.4% for women and 0.3% for men. Interference with work or school was significantly more pronounced in persons with full PTSD than in those with only partial symptoms, although the latter were significantly more occupationally impaired than traumatized persons without PTSD.These findings in an epidemiologic sample underscore observations from patient and military groups that many traumatized persons suffer from a subsyndromal form of PTSD. These persons with partial PTSD, although somewhat less impaired than persons with the full syndrome, nonetheless exhibit clinically meaningful levels of functional impairment in association with their symptoms. This subthreshold form of PTSD may be especially prevalent in women. Additional study of partial PTSD is warranted.
Glutathione Synthetase Deficiency: A Family Report
Authors: R Kumar Pejaver, A H Watson
Journal: Journal of the Royal Society of Medicine (1994)

Glutathione synthetase deficiency is a rare inborn error of metabolism. Low levels of and at times unstable molecules of glutathione synthetase leads to glutathione deficiency affecting various systems of the body. The inheritance is thought to be of autosomal recessive variety. We diagnosed the condition in a neonate and proceeded to investigate the family. The results are discussed below.
Chrysotile asbestos exposures can produce an alveolitis with limited fibrosing activity in a subset of high fibre retainer sheep
Authors: R Begin, A Cantin, P Sebastien
Journal: European Respiratory Journal (1990)

Inhalation of fibrogenic mineral dust may enhance fibronectin (Fn) production by alveolar macrophages and increase fibroblast growth activity (FGA) in lung lavage fluid. To investigate the relationship of these changes to fibre retention and the development of asbestosis, we exposed 15 sheep to 100 mg Canadian chrysotile fibres in 100 ml saline, and ten sheep to 100 ml saline only, at ten day intervals. The animals were studied at 3 month intervals. At month 18, ten sheep had abnormal chest radiograph (category greater than or equal to 1) (group B) and five had normal radiograph (category 0) (group A). Pulmonary function data indicated restrictive patterns of abnormalities in both groups, more severe in group B. Sheep in group A had bronchoalveolar lavage (BAL) cellularity and biochemistry comparable to controls; sheep in group B had significant increases in total BAL cells (x2), macrophages (x2), neutrophils (x4) and eosinophils (x3), increased BAL lactate dehydrogenase and Fn, but FGA and procollagen 3 comparable to controls. Fibre retention was significantly increased in all exposed sheep and 2.5 x higher in group B vs group A despite similar exposures (70 intratracheal, 100 mg chrysotile infusions). Enhanced fibre retention in group B preceded the appearance of disease. This study confirms our earlier observation linking individual susceptibility to development of alveolitis to individual dust burden and provides evidence that the excess of fibre retention can be observed before detectable disease. In addition, we report a chrysotile-induced early alveolitis with incompletely expressed fibrosing activity at the time of initial radiographic detection. The intensity of the alveolitis is related to the degree of fibre retention.
Evaluation of the Combination of Nelarabine and Fludarabine in Leukemias: Clinical Response, Pharmacokinetics, and Pharmacodynamics in Leukemia Cells
Authors: Varsha Gandhi, William Plunkett, Steve Weller, Min Du, Mary Ayres, Carlos O. Rodriguez, Prameen Ramakrishna, Gary L. Rosner, Jeff P. Hodge, Susan O’Brien, Michael J. Keating
Journal: Journal of Clinical Oncology (2001)

A pilot protocol was designed to evaluate the efficacy of fludarabine with nelarabine (the prodrug of arabinosylguanine [ara-G]) in patients with hematologic malignancies. The cellular pharmacokinetics was investigated to seek a relationship between response and accumulation of ara-G triphosphate (ara-GTP) in circulating leukemia cells and to evaluate biochemical modulation of cellular ara-GTP metabolism by fludarabine triphosphate.Nine of the 13 total patients had indolent leukemias, including six whose disease failed prior fludarabine therapy. Two patients had T-acute lymphoblastic leukemia, one had chronic myelogenous leukemia, and one had mycosis fungoides. Nelarabine (1.2 g/m(2)) was infused on days 1, 3, and 5. On days 3 and 5, fludarabine (30 mg/m(2)) was administered 4 hours before the nelarabine infusion. Plasma and cellular pharmacokinetic measurements were conducted during the first 5 days.Seven patients had a partial or complete response, six of whom had indolent leukemias. The disease in four responders had failed prior fludarabine therapy. The median peak intracellular concentrations of ara-GTP were significantly different (P =.001) in responders (890 micromol/L, n = 6) and nonresponders (30 micromol/L, n = 6). Also, there was a direct relationship between the peak fludarabine triphosphate and ara-GTP in each patient (r = 0.85). The cellular elimination of ara-GTP was slow (median, 35 hours; range, 18 to > 48 hours). The ratio of ara-GTP to its normal counterpart, deoxyguanosine triphosphate, was higher in each patient (median, 42; range, 14 to 1,092) than that of fludarabine triphosphate to its normal counterpart, deoxyadenosine triphosphate (median, 2.2; range, 0.2 to 27).Fludarabine plus nelarabine is an effective, well-tolerated regimen against leukemias. Clinical responses suggest the need for further exploration of nelarabine against fludarabine-refractory diseases. Determination of ara-GTP levels in the target tumor population may provide a prognostic test for the activity of nelarabine.
Anesthesia for tracheal stenting
Authors: Milena Encheva, Alexandra Saltirova, Kosta Kostov, Hristo Yordanov
Journal: European Respiratory Journal (2013)

Anesthesia for tracheal stenting (TS) requires collaboration between anesthesiologist and bronchologist.Before the intervention is necessary to discuss diagnostic-therapeutic algorithm and possible complications.The forms of anesthesia depend on the difficulty and length of the procedure and spans from mild sedation to general anesthesia.Aims:To demonstrate our experience in preoperative evaluation, premedication, induction and anesthesia for patients, undergoing TS and to assess the early recovery period.Materials and methods:A prospective study in 22 patients with clinically significant tracheal stenosis (benign-17; malignant-5); average age 45.A total number of placed stents-28: Dumon– 21, Montgomery-7.An ASA assessment of risk is made.Premedication depends on degree of respiratory failure.In all patients induction with propofol and an opioid is administered, followed by muscle relaxant and rigid bronchoscopic intubation.JET-ventilation is used as alternative to conventional ventilation.Post-operative monitoring until full recovery is carried out in order to avoid respiratory complications and rapidly emerging lifethreatening complications.Results: In all patients, induction and anesthesia have taken place according to pre-established algorithm.In one patient postoperative monitoring in ICU is made for 24 hours due to bronchospasme and respiratory failure. In the others postoperative monitoring and recovery were uncomplicated. Conclusions:The jet ventilation is an ideal method for guaranteeing oxygenation during TS, whether the patient is breathing spontaneously or is under general anaesthesia.The provision of anaesthesia for TS requires anaesthetist to be familiar with different airway management, ventilation and anaesthesia techniques.
Endocinch treatment for gastro-oesophageal reflux (GORD): retention of plications are essential to control GORD * Author's response
Authors: Z Mahmood, A Zaheer, Y S Ang, N Mahmud, M. P Schwartz
Journal: Gut (2007)

Endocinch treatment for gastrooesophageal reflux (GORD): retention of plications are essential to control GORD We congratulate Schwartz et al for their first reported Endocinch sham control trial (Gut 2007;56:20-8).The results of this trial confirm those of earlier open-label studies [1][2][3] showing that in the short and intermediate term, endoscopic gastroplication improves gastro-oesophageal reflux disease symptoms and quality of life (QOL), and reduces the requirements of acidinhibitory drugs.In their current study design, they only performed endoscopy/gastroplications in patients who have treatment failure in the active treatment group, and hence the actual proportion of patients who have retention of stitches (or judged to be functional) is unknown in the active treatment group.However, the retention of stitches seems to be a major problem reported with this technique. 4 5In our group, we used only two plications 1 and 2 cm below the Z line along the lesser curve, and used the previous knot technique in comparison with a recent clip devise for anchoring sutures. 1 However, better outcomes with three plications have been shown by Thompson et al. 6 We have now completed a 5- year postprocedural study on our group of patients.Although the number is small (n = 22; 17 completed their 5-year follow-up for symptom scoring and usage of proton pump inhibitors (PPIs) and only 13 agreed for repeat endoscopy), it clearly showed potential to maintain significant control in gastro-oesophageal reflux disease symptoms and QOL, and reduction in the requirements of PPIs up to 5 years after the procedure. 7To further deter- mine whether retention of stitches is of significance, we further analysed our data.In our cohort, plications were intact in 70% of cases at 5 years after the procedure (confirmed by repeat endoscopy, which was performed by an independent blinded experienced endoscopist).It showed that the group of patients who retained plications showed significant improvement in symptom scoring (p = 0.01), regurgitation score (p = 0.007), QOL (p = 0.02) and 67% reduction in the requirement of PPIs at 5 years after the procedure as compared with the group of patients who lost plications. 8Hence, long-term failure seems to be related with loss of plications.At this stage of development, it is also important that those who are performing or have performed these procedures should follow-up their cases to further assess the retention of plications and their durability.We believe that better sedation and increasing depth of sutures with increasing size of suction chamber may help in retention of sutures. 9However, further modifi- cations are needed to improve this technique, in particular to improve the retention of sutures for achieving maximum clinical benefit.
The effects of increasing inflation pressures in the resuscitation of prematurely born infants
Authors: Prashanth Bhat, Vadivelam Murthy, Grenville Fox, Morag Campbell, Anthony Milner, Anne Greenough
Journal: European Respiratory Journal (2013)

Background: 

We have previously shown, using the UK recommended inflation pressures, expiratory tidal volumes (TV) rarely exceed the anatomical dead space during the first five inflations of face mask resuscitation in prematurely born infants, unless the inflations stimulated the infant to inspire.

Aim 

To measure the effects of increasing the peak inflation pressure from 20 to 25 cmH2O on TV and end tidal carbon dioxide (CO2) levels.

Method 

Eighteen infants (gestational age <34 weeks) resuscitated using peak inflation pressures of 25/5 cmH2O were matched by gestational age to 18 infants resuscitated with inflation pressures of 20/5 cmH2O. A respiratory on line monitor was used to record the inflation pressures, flow, volume and CO2 levels during the first five inflations during face mask resuscitation. Inflations during which the infant inspired were excluded from the analysis.

Results 

The median gestational age of the infants was 30 weeks. The median inflation pressures

(peak inflating pressure - PEEP) were 22 cmH2O (range 20-25.6) and 16.3 cmH2O (range 20 -25.6) respectively (p<0.001). The median TVs were 2.32 (range 0.4-0.94) and 0.95 (range 0.11-3.9) ml\kg respectively (p<0.001). The median CO2 levels were 2.32 (range 0.4-39) and 0.5 (range 0.2- 15.0) mmHg respectively (p<0.001). The facemask leaks in the two groups were similar (51 and 56% respectively)

Conclusion 

Commencing face mask resuscitation using peak inflation pressures of 25 cmH2O rather than 20 cmH2O was more effective as evidenced by producing a median TV exceeding the anatomical dead space and more effective ventilation as indicated by higher expiratory CO2 levels.