tbuckley/cabot-search huggingface dataset:
Community-acquired pneumonia
Authors: Elena Prina, Otavio T Ranzani, Antoni Torres
Journal: The Lancet (2015)

Community-acquired pneumonia causes great mortality and morbidity and high costs worldwide. Empirical selection of antibiotic treatment is the cornerstone of management of patients with pneumonia. To reduce the misuse of antibiotics, antibiotic resistance, and side-effects, an empirical, effective, and individualised antibiotic treatment is needed. Follow-up after the start of antibiotic treatment is also important, and management should include early shifts to oral antibiotics, stewardship according to the microbiological results, and short-duration antibiotic treatment that accounts for the clinical stability criteria. New approaches for fast clinical (lung ultrasound) and microbiological (molecular biology) diagnoses are promising. Community-acquired pneumonia is associated with early and late mortality and increased rates of cardiovascular events. Studies are needed that focus on the long-term management of pneumonia.
Influence of dose and duration of infusion of interleukin-2 on toxicity and immunomodulation.
Authors: J A Thompson, D J Lee, C G Lindgren, L A Benz, C Collins, D Levitt, A Fefer
Journal: Journal of Clinical Oncology (1988)

The purpose of this study was to investigate the effect of dose and duration of infusion of recombinant interleukin-2 (IL-2) on toxicity and immunomodulation. In a phase I/II study, IL-2 was administered intravenously (IV) daily for five consecutive days every other week for 4 weeks of treatment to 23 patients with progressive melanoma, renal, colon, or ovarian cancer by one of four regimens: groups I and II received 3 X 10(5) U/m2/d by two-hour or 24-hour infusion, respectively; groups III and IV received 3 X 10(6) U/m2/d by two-hour or 24-hour infusion, respectively. In a subsequent study, six patients (group V) received a single priming cycle of daily IL-2 for five days at 3 X 10(6) U/m2/d in divided 15-minute infusions every eight hours, before undergoing leukapheresis for lymphokine-activated killer (LAK) cell generation. Toxicity was mild with 3 X 10(5) U/m2/d, but severe chills and fever, moderate hypotension (not requiring IV pressors), and weight gain were observed with 3 X 10(6) U/m2/d. Toxicity was also related to the duration of infusion. In group IV (continuous infusion), fluid retention, weight gain, and azotemia were more frequent and severe than in groups III or V, in which the same total dose was administered by two-hour infusion or in three divided 15-minute infusions. IL-2 induced rebound lymphocytosis, which was directly dose-related and significantly higher in group IV (continuous infusion) than in groups III or V. Dramatic increases in the percentage and absolute number of cells expressing the IL-2 receptor were also most pronounced in group IV. With the higher dose of IL-2, LAK cells appeared in the circulation, and natural killer (NK) cytotoxicity was augmented. The results showed that the toxicity and immunomodulation by IL-2 are dose-dependent and are maximal by continuous infusion compared with two-hour or divided every eight hours infusions.
Abstract #5443: Pharmacokinetics (PK) of PF-04929113 (SNX5422), an orally bioavailable heat shock protein 90 (Hsp90) inhibitor after single and multiple dose administration in patients with refractory solid tumor malignancies
Authors: Brett Houk, Judy Bryson, Merrill Egorin, Ramesh Ramanathan, Jamey Skillings, Howard Burris
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Introduction: Hsp90 inhibitors have the potential for broad anti-cancer effects based on the spectrum of known client proteins and increased effect on mutations that drive malignant transformation and cancer growth. PF-04929113 (SNX5422; 113) is a novel, oral, non-antibiotic, selective Hsp90 inhibitor prodrug, with preclinical anti-tumor activity in multiple tumor models and is a potentially important cancer therapy. The objective of this analysis was to describe the PK of 113 and its active moiety (PF- 04928473 /SNX2112; 473) after oral administration in patients with refractory solid tumor malignancies. Methods: Twenty-two subjects were enrolled in a multi-center, Phase 1, open-label, dose-escalation study. Subjects were treated with113 QOD for 21 days at doses ranging from 4 to 56 mg/m2. Subjects at the 4 mg/m2 dose level received an additional single dose of 113, 7 days before beginning the 21-day cycle (PK from Day -7 in this cohort summarized with Day 1 data from other cohorts). Serial plasma concentrations of 113 and 473 were measured by LC-MS/MS after the first dose (Day 1) and after 11 doses (Day 21). PK parameters (mean ± standard deviation) were calculated using non-compartmental methods in WinNonLin (v.5.2, Pharsight, Mountain View, CA). Results: Concentrations of the prodrug (113) were <1 ng/ml at all timepoints. Concentrations of 473 were detectable immediately after administration (0.33 hr) and remained detectable through 48 h after administration. 473 reached maximal concentrations at a median of 2 h (range:0.33-6 h) after administration. . 473 terminal elimination half-life was 9.8 h on both Day 1 and Day 21 (±2.1 h and 1.5 h on Days 1 and 21, respectively). Area under the 473 plasma concentration versus time curve increased dose proportionally, with clearance estimated at 20 (±12) and 28 (±13) L/hr on Days 1 and 21, respectively. Maximal 473 concentrations did not display accumulation between Days 1 and 21, when normalized for dose, at 7.4 (±3.7) and 7.1 (±4.8) ng/mL/mg, respectively. Conclusions: The Hsp90 inhibitor prodrug 113 is orally bioavailable, rapidly converted to the active moiety (473), and displays linear PK. Maximal concentrations were observed 2 h after oral administration. The terminal elimination half-life was estimated at 9.8 h, consistent with the lack of significant drug accumulation after 21 days of QOD dosing.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5443.
When Knowing More About a Patient Enables Us to Do Less
Authors: Jennifer DeVoe
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
One-step ultrasound-based high dose rate (HDR) prostate brachytherapy with dose escalation to the dominant intra-prostatic lesion.
Authors: Juanita M. Crook, Ana Ots, Brent Parker, Matt Schmid, Deidre Batchelar, Cynthia Araujo, Michelle Hilts, Francois Bachand
Journal: Journal of Clinical Oncology (2014)

106 Background: To demonstrate feasibility of using high dose rate (HDR) brachytherapy to deliver 25% higher than prescription dose to the dominant intra-prostatic lesion (DIL) as defined on multi-parametric MRI for intermediate and high risk prostate cancer. Methods: Twenty six patients with predominantly unilateral disease consented to a University Ethics-approved phase II study of selective dose escalation. HDR brachytherapy was performed in weeks 1 and 3 of treatment, each delivering one fraction of 10 Gy to the whole prostate. External beam consisted of 46Gy/23 fractions starting 3 days after the first HDR fraction.T2 FSE images were obtained using 1.5T endorectal MRI in transverse, sagittal and coronal planes followed by Dynamic Contrast Enhancement after injection of gadolinium. Apparent Diffusion Coefficient maps were calculated. The DIL was contoured on the MRI and, following image registration, transposed to the preoperative TRUS performed in the treatment position. Intra-operative TRUS with source-delivery catheters in place was fused to the pre-op TRUS with the transposed DIL. The DIL was included in dose optimization criteria. Results: Twenty five of 26 patients had a visible DIL. Mean prostate percentage receiving the prescription dose (V100) was 98.2% (SD:1.1). Mean dose to 90% of the DIL (D90) was 13.2 Gy (SD: 1.7). DIL mean volume was 2.9 cc (SD:1.8) representing 9.5% (SD: 7.6) of the prostate volume. Coverage of the DIL was excellent with a median of 97% receiving the planned escalation of 25%. Established dose constraints to rectum and urethra were respected in all cases. The factor that limited DIL coverage was proximity to organs at risk. Peri-urethral location of the DIL limited coverage in five cases and two had a posterior DIL such that dose to the rectum limited escalation. However, these seven cases still achieved a mean DIL D90 of 12.2 Gy. Conclusions: Dose manipulation using US-planned HDR brachytherapy is readily achievable within the practice setting of a community cancer center. Dose escalation to the DIL to a mean of 132% of the prescribed dose for selected intermediate and high risk prostate cancer patients is feasible while respecting critical organ constraints. Further escalation is planned. Clinical trial information: NCT01605097.
Allogeneic stem cell transplantation (allo-SCT) in T-cell lymphomas: A French national survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Authors: S. le Gouill, N. Milpied, A. Buzyn, G. Socié, M. Mothy, J. Vernant, N. Ifrah, C. Haioun, M. Michallet, C. Volteau, D. Blaise
Journal: Journal of Clinical Oncology (2007)

8095 Background: T- and NK-cell lymphomas represent 10–15% of non-Hodgkin's lymphoma in adults.Despite intensive chemotherapy including or not autologous stem cell transplantation upfront, a majority of patients experience relapse. Methods: We retrospectively analyzed T-cell lymphomas patients transplanted from a related or unrelated HLA identical sibling donor with myeloablative or non-myeloablative conditioning regimen. Patients younger than 15 years at the time of transplantation, HIV positive patients or lymphoblastic lymphomas were excluded. We present the results of this study based on the SFGM-TC data-base. At the present time, we analyzed 57 cases from 10 french centers. Results: Diagnosis was PTCL (n=19) , AITL (n=8), anaplastic large cell lymphoma (ALCL) (n=20), hepatosplenic γ/d lymphoma (n=2), T-cell granular lymphocytic leukemia (n=1) and localized nasal NK/T cell lymphoma (n=3), NK/T cell lymphoma (n=1), HTLV1 cell lymphoma (n=2) and enteropathy-associated T-cell lymphoma (n=1). There were 38 males and 19 females. Median age at diagnosis was 38 years (13 - 61 y). At diagnosis, 51 patients had IPI score &gt; or = 3. Median time from diagnosis to transplantation was 12 months (4.6–17). All patients but 15 underwent myeloablative conditioning regimen. Source of stem cells was BMSC (n=38), peripheral stem cells (n=18) or cord blood (n=1). Transplantation was performed from a related HLA-matched sibling donor in 53 cases. Disease status at the time of transplantation was CR in 25 cases, PR in 19 cases and SD/PD/refractory in 13 cases. Eleven patients presented acute GVH grade 3/4. After transplantation, 91% of patients were in CR compared to 43 % before. Six patients experienced relapse and eighteen patients died because toxicity related mortality. Conclusions: Preliminary results show that allo-SCT is an attractive option in aggressive T-cell lymphomas and confirm the role of a graft versus T-cell lymphoma effect. Ongoing analysis will identify prognostic factors and be presented at the time of the meeting. The present study will provide usefull tools for clinicians to evaluate the role of allo-SCT in the specific field of adult T- cell lymphomas. No significant financial relationships to disclose.
Critical care surveillance: insights into the impact of the 2010/11 influenza season relative to the 2009/10 pandemic season in England
Authors: H K Green, J Ellis, M Galiano, J  M Watson, R  G Pebody
Journal: Eurosurveillance (2013)

In 2010/11, the influenza season in England was marked by a relative increase in impact on the population compared to that seen during the 2009/10 pandemic, with the same influenza subtype, A(H1N1)pdm09, circulating. The peaks in critical care bed occupancy in both seasons coincided with peaks in influenza A(H1N1)pdm09 activity, but onset of influenza in 2010/11 additionally coincided with notably cold weather, a comparatively smaller peak in influenza B activity and increased reports of bacterial co-infection. A bigger impact on critical care services was seen across all regions in England in 2010/11, with, compared to 2009/10, a notable age shift in critical care admissions from children to young adults. The peak of respiratory syncytial virus (RSV) activity did not coincide with critical care admissions, and regression analysis suggested only a small proportion of critical care bed days might be attributed to the virus in either season. Differences in antiviral policy and improved overall vaccine uptake in 2010/11 with an influenza A(H1N1)pdm09 strain containing vaccine between seasons are unlikely to explain the change in impact observed between the two seasons. The reasons behind the relative high level of severe disease in the 2010/11 winter are likely to have resulted from a combination of factors, including an age shift in infection, accumulation of susceptible individuals through waning immunity, new susceptible individuals from new births and cold weather. The importance of further development of severe influenza disease surveillance schemes for future seasons is reinforced.
Conservative treatment of rectal adenocarcinoma with endocavitary irradiation or wide local excision and postoperative irradiation.
Authors: W M Mendenhall, W R Rout, J N Vauthey, L S Haigh, R A Zlotecki, E M Copeland
Journal: Journal of Clinical Oncology (1997)

To evaluate the role of endocavitary irradiation and wide local excision followed by irradiation in the treatment of early-stage rectal adenocarcinoma.Sixty-five patients with early-stage adenocarcinoma of the rectum were treated with endocavitary irradiation (n = 20) or wide local excision followed by external-beam irradiation (n = 45) between 1974 and 1994 at the University of Florida. All patients were monitored for a minimum of 2 years or until death.The rates of local-regional control at 5 years were 80% after endocavitary irradiation and 86% after wide local excision and radiotherapy. The ultimate 5-year local-regional control rates were 85% and 92%, respectively. Multivariate analysis of local-regional control with sphincter preservation showed that tumor configuration (exophytic v ulcerative) significantly influenced this end point; local-regional control was decreased in patients with ulcerated cancers. Five-year cause-specific survival rates were 84% after endocavitary irradiation and 88% after wide local excision and radiotherapy. Multivariate analysis revealed that tumor configuration significantly influenced cause-specific survival; patients with ulcerated tumors had a worse prognosis.Endocavitary irradiation is a highly effective treatment for properly selected patients with early-stage rectal adenocarcinoma. Patients with less favorable lesions that appear to be limited to the muscularis propria have a high chance of cure with sphincter preservation after wide local excision and external-beam irradiation.
Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis
Authors: Marianna Fontana, Silvia Pica, Patricia Reant, Amna Abdel-Gadir, Thomas A. Treibel, Sanjay M. Banypersad, Viviana Maestrini, William Barcella, Stefania Rosmini, Heerajnarain Bulluck, Rabya H. Sayed, Ketna Patel, Shameem Mamhood, Chiara Bucciarelli-Ducci, Carol J. Whelan, Anna S. Herrey, Helen J. Lachmann, Ashutosh D. Wechalekar, Charlotte H. Manisty, Eric B. Schelbert, Peter Kellman, Julian D. Gillmore, Philip N. Hawkins, James C. Moon
Journal: Circulation (2015)

Background— The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. Methods and Results— Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume ( P &lt;0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1–13.7; P &lt;0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E′, and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3–13.1; P &lt;0.05). Conclusions— There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors.
When Accommodation Gets Complicated
Authors: Nicole M. Glenn, Marianne Clark
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Regression of human metastatic renal cell carcinoma after vaccination with tumor cell–dendritic cell hybrids
Authors: Alexander Kugler, Gernot Stuhler, Peter Walden, Gerhard Zöller, Anke Zobywalski, Peter Brossart, Uwe Trefzer, Silke Ullrich, Claudia A. Müller, Volker Becker, Andreas J. Gross, Bernhard Hemmerlein, Lothar Kanz, Gerhard A. Müller, Rolf-Hermann Ringert
Journal: Nature Medicine (2000)
Carotid endarterectomy for asymptomatic carotid stenosis
Authors: C. Warlow
Journal: BMJ (1998)

Papers p 1477 

Eleven years ago, before any randomised trials were published, a BMJ editorial came down against endarterectomy for asymptomatic carotid stenosis.1 In 1995, based on what now would be regarded as a less than rigorous review of the trials then available, I thought surgery was still not worthwhile. Too many operations would have to be done to prevent one patient having a stroke.2 Today the BMJ publishes the first systematic review of the evidence (p 1477).3 Should the earlier conclusions be modified, and what should we do now?

The present review is far more rigorous: there was an extensive search strategy (which didn't reveal any previously unknown trials); only randomised controlled trials were included; publication bias was considered; sensible outcomes were defined, although some might want to see the outcome of stroke combined with all rather than just with surgical deaths; trial quality was taken into account; the relevant data were extracted independently by two people; appropriate sensitivity analyses were done; …
Does the 6-minute walk test elicit maximal exercise responses in people following lobectomy for non-small cell lung cancer?
Authors: Vinicius Cavalheri, Sue Jenkins, Nola Cecins, Kevin Gain, Kylie Hill
Journal: European Respiratory Journal (2014)

Aim:  To compare symptoms, peak heart rate (HR) and nadir arterial oxygen saturation (SpO 2 ) during a 6-minute walk test (6MWT) in people following lobectomy for non-small cell lung cancer (NSCLC) with those elicited during a maximal symptom-limited cardiopulmonary exercise test (CPET).   Methods:  People 6 to 10 weeks following lobectomy for primary NSCLC completed two 6MWTs (data were taken from the best) and one symptom-limited ramp CPET, over two days. Peak HR, nadir SpO 2  and symptoms of dyspnoea (BORGd) and leg fatigue (BORGf) at the end of the tests were compared.   Results:  Data were available on 19 participants (13 females, age 68±9yr [mean±SD]; BMI 26±6kg·m -2 ). Peak rate of oxygen uptake [VO 2peak ] was 15±3ml·kg -1 ·min -1  (64±15%predicted) and 6-minute walk distance [6MWD] was 501±72m [82±10%predicted]). Three participants reached a VO 2peak  >80%predicted during the CPET, whereas 10 participants had a 6MWD >80%predicted. Peak HR and symptoms were higher during the CPET than the 6MWT (HR 127±18  vs  118±15bpm; BORGd 7±3  vs  3±2; BORGf 7±3  vs  2±2, respectively; p  2  was lower during the 6MWT (93±3%  vs  95±3%; p = 0.01). VO 2peak  and 6MWD were moderately correlated (r = 0.6; p = 0.007).   Conclusions:  Although eliciting a lower SpO 2 , the 6MWT elicited less symptoms and a submaximal HR in people following lobectomy for NSCLC compared with the CPET. Studies investigating ventilatory and metabolic responses during the 6MWT are needed. More detailed analysis is required to determine responsiveness as well as usefulness of the 6MWT in this population.
Social Causes of Low Birth Weight
Authors: Michael D Kogan
Journal: Journal of the Royal Society of Medicine (1995)

The manifest importance of reducing the incidence of low birth weight is most obvious for the first year of life: low birth weight is the single most important factor affecting infant morbidity and mortality 1 . However, there is growing evidence that the adverse consquences of low birth weight continue throughout the life cycle. This review deals primarily with social causes of low birth weight.