tbuckley/cabot-search huggingface dataset:
Infusion carboplatin treatment of relapsed and refractory acute leukemia: evidence of efficacy with minimal extramedullary toxicity at intermediate doses.
Authors: F J Meyers, J Welborn, J P Lewis, N Flynn
Journal: Journal of Clinical Oncology (1989)

Carboplatin (CBDCA) is a second-generation platinum analog with prominent myelotoxicity and modest extramedullary toxicity. We performed a phase I study of CBDCA in adult patients with relapsed acute leukemia. Therapy was administered as a five-day continuous infusion. The initial dose of 875 mg/m2 over five days was escalated in 15% increments to a final dose of 2,100 mg/m2 over five days. Twenty-eight patients received 35 induction courses of CBDCA, including two patients who achieved a complete remission (CR) following the first course, and received a second induction course at the time of relapse. Therapy was well tolerated. No grade 3 or 4 extramedullary toxicity was seen. Myelosuppression was regularly observed, with prolonged myelosuppression at 2,100 mg/m2 over five days being the indication to cease dose escalation. Eight of 28 patients (28.5%) responded to CBDCA therapy (six CR, two partial remission [PR]) or ten of 30 initial induction courses (33.3%). Continuous-infusion CBDCA has an advantage over other therapy for acute leukemia because of its highly selective myelotoxicity and minimal gastrointestinal and renal toxicity. A standard phase II study should be undertaken to establish a more accurate response rate.
Results of COMFORT-I, a randomized double-blind phase III trial of JAK 1/2 inhibitor INCB18424 (424) versus placebo (PB) for patients with myelofibrosis (MF).
Authors: S. Verstovsek, R. A. Mesa, J. R. Gotlib, R. S. Levy, V. Gupta, J. F. DiPersio, J. Catalano, M. Deininger, C. B. Miller, R. T. Silver, M. Talpaz, E. F. Winton, J. H. Harvey, K. Vaddi, S. K. Erickson-Viitanen, I. Koumenis, W. Sun, V. Sandor, H. Kantarjian
Journal: Journal of Clinical Oncology (2011)

6500 Background: Dysregulated JAK-STAT signaling is a key feature in MF, which is characterized by splenomegaly, debilitating symptoms, cytopenias and shortened survival. There are currently no effective drug therapies for MF. 424 is a selective JAK 1 and 2 inhibitor with clinical activity in MF. Methods: Patients (pts) with intermediate-2 or high-risk MF were randomized to start PB or 424 at a dose of 15 mg or 20 mg PO BID depending on baseline platelet count (100-200 X 109/L or >200 X 109/L, respectively). The dose was optimized for efficacy and safety during treatment. The primary endpoint was the proportion of pts with ≥ 35% reduction in spleen volume at week (wk) 24 of therapy, assessed by blinded review of spleen MRI or CT. Secondary endpoints were durability of spleen response, changes in symptom burden (symptom score [SS] measured daily with MFSAF v2.0), and survival. Exploratory endpoints included change in quality of life (QoL; EORTC-QLQ C30) and fatigue (PROMIS-FS), molecular and serum biomarkers, and transfusion dependence. Results: 309 pts were randomized; 155 to 424 and 154 to PB. Median follow-up is 32.2 weeks. The primary endpoint response rate was 41.9% vs 0.7% (424 vs PB p<0.0001). Median duration of response has not been reached. At wk 24 the proportion of pts with ≥ 50% improvement in SS was 45.9% vs 5.3% (424 vs PB p<0.0001) and change in total SS was an improvement of 46.1% vs a worsening of 41.8% (424 vs PB p<0.0001). There were 10 vs 14 deaths (424 vs PB, HR 0.67, p=0.33). Changes in both QoL and fatigue mirrored changes in SS over time and all showed improvement relative to PB regardless of changes in hemoglobin. The most common AEs of any grade seen in >20% of pts on either arm of the study were (424 vs PB) abdominal pain (10.3% vs 41.1%), thrombocytopenia (34.2% vs 9.3%), fatigue (25.2% vs 33.8%), anemia (31% vs 13.9%), diarrhea (23.2% vs 21.2%) and peripheral edema (18.7% vs 22.5%). Anemia and thrombocytopenia were manageable and rarely (0.6% 424 vs 0.7% PB, each) led to withdrawal from the study. Conclusions: In this study, 424 demonstrated marked and sustained clinical benefits in spleen size, debilitating symptoms and QoL and an acceptable safety profile relative to PB in MF.
Thrombopoietin receptor agonist (TPO-RA) usage and treatment patterns among patients with chronic immune thrombocytopenic purpura (cITP) in a large U.S.-managed care plan.
Authors: N. M. Engel-Nitz, P. F. Wang, G. Gomez Rey, A. Teitelbaum
Journal: Journal of Clinical Oncology (2011)

e16586 Background: Little is known about real-world usage of TPO-RAs and treatment patterns for patients with cITP. Methods: Using medical/pharmacy claims and enrollment data of a large US managed care plan, adults being treated for cITP (ICD-9 287.31) were identified from Aug 2008 to Dec 2009. Patients were stratified into cohorts based on the treatments for cITP prescribed. Patients treated with chemotherapy were excluded, as were those with hepatitis, HIV or heparin-induced thrombocytopenia. Patients were followed from start of treatment until death, plan disenrollment, or March 2010. Sequence and rates of ITP treatments and splenectomy were assessed. Results: A total of 927 patients met study criteria. Corticosteroids were the most frequent first-line therapy (86.8%) while the most common second-line options were rituximab, IVIG, anti-D, or splenectomy, recorded for 24.7%, 18.3%, 14.6%, and 8.9%. Treatment with TPO-RA increased in later lines of therapy: second line (6.9%), third line (13.1%), fourth line (26.2%). About 21.4% received > 3 therapies; 2.3% of patients received > 5 therapies. The proportion of patients aged > 65 years was similar (≈ 25% in each group) among TPO-RA-treated patients and patients initiating other treatments, although the anti-D and splenectomy cohorts were slightly younger (8.3% and 17.0% respectively). Splenectomy was recorded in 12.7% of the total study population. Among TPO-RA-treated patients, 3.7% of eltrombopag- and 6.2% of romiplostim-treated patients had splenectomy prior to TPO-RA treatment; 11.5% of eligible eltrombopag- and 23.3% of eligible romiplostim- treated patients had post-TPO-RA splenectomies. Among TPO-RA users, 10.5% received both eltrombopag and romiplostim during their course of treatment. Conclusions: Wide practice variations, likely influenced by personal experience with different treatment options, were observed for management of cITP after initial treatment with corticosteroids. TPO-RAs were used mainly in later lines of therapy. Evidence-based treatment algorithms and guidelines for management of cITP may optimize treatment strategies, especially with introduction of new agents.
Myeloma today: Disease definitions and treatment advances
Authors: S. Vincent Rajkumar
Journal: American Journal of Hematology (2015)

There have been major advances in the diagnosis, staging, risk‐stratification, and management of multiple myeloma (MM). In addition to established CRAB (hypercalcemia, renal failure, anemia, and lytic bone lesions) features, new diagnostic criteria include three new biomarkers to diagnose the disease: bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain ratio ≥100, and &gt;1 focal lesion on magnetic resonance imaging. MM can be classified into several subtypes based on baseline cytogenetics, and prognosis varies according to underlying cytogenetic abnormalities. A Revised International Staging System has been developed which combines markers of tumor burden (albumin, beta‐2 microglobulin) with markers of aggressive disease biology (high‐risk cytogenetics and elevated serum lactate dehydrogenase). Although the approach to therapy remains largely the same, the treatment options at every stage of the disease have changed. Carfilzomib, pomalidomide, panobinostat, daratumumab, elotuzumab, and ixazomib have been approved for the treatment of the disease. These drugs combined with older agents such as cyclophosphamide, dexamethasone, thalidomide, bortezomib, and lenalidomide dramatically increase the repertoire of regimens available for the treatment of MM. This review provides a concise overview of recent advances in MM, including updates to diagnostic criteria, staging, risk‐stratification, and management. Am. J. Hematol. 91:90–100, 2016. © 2015 Wiley Periodicals, Inc.
Quality of Medical Care
Authors: Millard C. Beyer
Journal: JAMA (1977)

To the Editor.—  The special communication by Dr W. E. Mitchell entitled How to Deal With Poor Medical Care (236:2875, 1976) describes two examples of poor medical care. Dr A performs too many unnecessary appendectomies. Dr B performs unrecognized or inappropriate procedures.  The diagnosis of acute appendicitis is sometimes difficult to make because many other conditions can mimic it. Frequently, a patient with all the signs and symptoms of appendicitis will have a normal appendix with perhaps a few enlarged mesenteric lymph nodes. Again, the appendix may be normal, but a foreign body (such as a toothpick) may have perforated the cecum. Patients are usually referred for surgery by a well-qualified physician. It takes a brave man to dispute the diagnosis. Dr A may have missed the diagnosis and not operated, only to see peritonitis develop, with its morbidity and sometimes mortality.  Dr B, who probably continues to use obsolete
Administration of a vasoactive intestinal peptide antagonist significantly enhances the autologous anti-leukemia T cell response in a murine model of AML
Authors: Christopher Petersen, Jian-Ming Li, Edmund Waller
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Products secreted from nerve terminals can have profound effects on the phenotype and functioning of T cells. One such product, vasoactive intestinal peptide (VIP) is a small neuroendocrine peptide hormone with potent anti-inflammatory activities. Binding to either of its type B G
Factors affecting mortality in a respiratory intensive care unit
Authors: Pelin Ozdemir, Burcu Basarik, Mehmet Sezai Tasbakan, Alev Gurgun, Ozen Kacmaz Basoglu, Feza Bacakoglu
Journal: European Respiratory Journal (2011)

Introduction and aim:  Underlying diseases, comorbidities and hospital acquired infections are the main factors that affect mortality in intensive care unit (ICU) patients. In this study, the factors affecting mortality in respiratory ICU were evaluated.   Methods:  The ICU patients followed-up between February 2008 and September 2010 were assessed retrospectively. The relationship between mortality and demographic features, underlying diseases, comorbidities, APACHE II and SAPS II scores on admission, invasive diagnostic and therapeutic procedures and, hospital acquired infections were investigated.   Results:  Out of 240 patients (165 men, mean age 58.2±16.6 yrs) included in the study, 118 patients (49.2%) died. The mortality rate was higher in immunosuppressive patients than immunocompetent ones (71.4% vs. 41.2%, p   Conclusion:  Immunosupression, severity of illness, IMV requirement and development of lower respiratory infections were the most important factors affecting ICU mortality.
Phase III, randomized, open-label study of durvalumab (MEDI4736) monotherapy, or durvalumab + tremelimumab, versus standard of care (SoC), in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): eagle
Authors: Robert L Ferris, Caroline Even, Robert Haddad, Makoto Tahara, Trishna Goswami, April Franks, Ugochi Emeribe, Anthony Jarkowski, Giovanni Melillo, Lisa Licitra
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Patients with R/M SCCHN have a poor prognosis, and current therapies used after failure of first-line platinum-based chemotherapy provide transient, limited benefit. SCCHN tumors are highly immunosuppressive and evade immune detection by exploiting inhibitory immune checkpoints
Varicella-Zoster Virus in Giant Cell Arteritis
Authors: Ibrahim Almaghlouth, Ismail Sari, Robert D. Inman
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
PET response following stereotactic body radiotherapy for non-small cell lung carcinoma correlates with local control
Authors: S. J. Feigenberg, J. Q. Yu, T. Eade, M. Buyyounouski, L. Wang, C. Langer, W. Scott, B. Movsas
Journal: Journal of Clinical Oncology (2007)

18013 Background: Given the success of Stereotactic Body Radiotherapy (SBRT) for Non-Small Cell Lung Carcinoma (NSCLC), early surrogates of local failure (LF) are necessary to allow timely surgical salvage. This study tries to determine the utility of PET response as an early surrogate for LF. Methods: Eligible patients(pts) had biopsy proven NSCLC &lt; 5 cm in size who underwent a pre- and post- SBRT PET scans. Pts treated at Fox Chase Cancer Center were either: 1. early stage (10 pts), 2. biopsy-proven local recurrences (4 patients) or 3. oligometastases (3 patients). Eleven of the 17 pts were treated on a prospective phase I dose escalation protocol and received either 40 Gy or 48 Gy in 4 fractions over 8 days. Non-protocol pts generally received 48 Gy in 4 fractions (5 of 6 pts). Treatment volumes were individualized for each pt using either 4 D or multi-phase CT simulation. As part of the prospective study design, PETs scan was obtained pre- and post-SBRT to correlate metabolic response with LF based on the work by MacManus. The post-SBRT PET scan was obtained at a median of 3 months following treatment (range, 2 to 6 months). LF was defined by my an increase in size on CT on serial imaging. Results: With a median follow up of 14 months (range 4 to 31 months), 3 LF have been documented. The median SUV max pre-SBRT was 4.7 (range 1.32 to 18.2) and 1.9 (range 0.9 to 7.0) post-SBRT. Only four pts had a post-SBRT SUV max &gt; 2.5 (2.8, 5.1, 5.3 and 7). Overall, twelve pts had a drop in their SUV max following SBRT, while 1 pt had stabilization and 4 had an increase . Of these last 5 pts, 3 developed LF. The other two have been followed without any intervention and remain free of recurrence for &gt; 2 years, respectively. No pt with an initial drop in post SBRT PET scan SUV has had LF. Conclusions: PET response (defined as a drop in the SUV max by 3 months) correlates with LF, and appears to be a good early surrogate of outcomes following SBRT. Larger studies are required to confirm this finding. No significant financial relationships to disclose.
PD-L1 biology in response to chemotherapy in vitro and in vivo in ovarian cancer
Authors: Shannon Grabosch, Feitianzhi Zeng, Lixin Zhang, Mary Strange, Joan Brozick, Robert P Edwards, Anda Vlad
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts PD-L1 is an immune checkpoint molecule expressed by a variety of tumors, including ovarian, which binds to circulating PD-1 expressing effector T cells allowing for tumor escape from the immune system. PD-L1 blockade prevents PD-L1/PD-1 interaction and is currently explored as
An analysis of replacement and synonymous changes in the rodent L1 repeat family.
Authors: S C Hardies, S L Martin, C F Voliva, C A Hutchison, M H Edgell
Journal: Molecular Biology and Evolution (1986)

L1 is a family of long interspersed repetitive sequences in mammals that includes the BamHI family in rodents and the KpnI family in primates. Previous studies have shown that L1 repeats contain a long open reading frame and that the family evolves in concert. Working with 32 rodent elements for which DNA sequence is available, we used the distribution of replacement and synonymous changes to determine which L1 lineages had been expressing their reading frame. The evidence obtained is consistent with there having been a small number of L1 genes that have been expressing a functional protein. Much of the concerted evolution in L1 is accounted for by the tendency of these functioning L1 genes to continually create nonfunctional pseudogenes by reinsertion into the genome of sequences derived from their transcripts. The gain of new pseudogenes is balanced by the loss of old pseudogenes with a half-life of 2 Myr. Therefore, most of the observed L1 repeats are at a dead end with respect to either the expression of the L1 protein or the potential to elaborate further copies of themselves. However, the turnover of L1 pseudogenes is sufficient to constitute a vast flux of sequences into and then out of the flanking regions of all cellular genes. If the presence of flanking L1 pseudogenes affects the expression of other genes in even a subtle fashion, this process should represent a major source of genetic variation. A second level of concerted evolution occurs within the functional L1 sequences in a pattern that did not meet our expectations for selfish DNA. Also, in spite of the marked suppression of replacement relative to synonymous changes in functioning L1 genes, they evolve at an overall rate accelerated to the level of their own pseudogenes.
Islet Transplantation as a Treatment for Diabetes
Authors: David M Harlan, Kristina I Rother
Journal: New England Journal of Medicine (2004)

To the Editor: We respectfully disagree with two points in Robertson's comprehensive review of islet transplantation (Feb.12 issue) 1 : the assertions that patients with diabetes and autonomic insufficiency have a "dramatically shortened life span" and that transplantation necessarily reduces the rate of death.In the cited articles and an additional article by Navarro et al., 2 most persons with diabetes had autonomic insufficiency.In fact, autonomic insufficiency lost its statistical significance after adjustment for renal dysfunction and cardiovascular disease in two population-based studies. 3,4When Navarro et al. compared pancreas-transplant recipients with medically treated patients, mortality rates were indistinguishable.
Prevalence of Vision Impairment in Older Adults in Rural China
Authors: Jialiang Zhao, Leon B. Ellwein, Hao Cui, Jian Ge, Huaijin Guan, Jianhua Lv, Xianzhi Ma, Jinglin Yin, Zheng Qin Yin, Yuansheng Yuan, Hu Liu
Journal: Ophthalmology (2010)
Diagnostic yield of EBUS-TBNA in mediastinal lymphadenopathy of extrapulmonary malignancies
Authors: Daniel López-Padilla, Ricardo García-Luján, Perla Valenzuela Reyes, Eduardo De Miguel Poch
Journal: European Respiratory Journal (2014)

Introduction 

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has not been widely described as an accurate diagnostic procedure in mediastinal lymphadenopathy of extrapulmonary malignancies. The aim of this study was to estimate the diagnostic yield of EBUS-TBNA in this scenario.

Methods 

Descriptive study of 47 consecutive patients with extrapulmonary malignancies for mediastinal lymphadenopathy study, from January 2010 to July 2013. Malignancy findings were not confirmed since a specificity of 100% was assumed. Negative results were confirmed with mediastinoscopy or at least 6 months of clinical and radiological follow up. Non representative tissue samples were excluded.

Results 

EBUS-TBNA found malignancy in 24 out of 47 (51%) patients. Malignancy was ruled out in 18 cases (38%) and mediastinoscopy confirmed these results in 5 patients. There were 5 false negative results (11%), confirmed through mediastinoscopy or clinical and radiological progression. Sensitivity, negative predictive value and accuracy of EBUS-TBNA were 83% (CI95% 64 – 94), 78% (CI95% 56 – 92) and 89%, respectively. Immunohistochemical staining was performed in 18 cases (38%). Histological findings are presented in Table 1.

View this table:

Table 1. Histological findings.





Conclusions 

EBUS-TBNA has a reliable diagnostic yield in extrathoracic malignancies with mediastinal lymphadenophaty. Head and neck, breast and kidney represented half of metastasis origin in this study.
Bridging Lung Development with Chronic Obstructive Pulmonary Disease. Relevance of Developmental Pathways in Chronic Obstructive Pulmonary Disease Pathogenesis
Authors: Olivier Boucherat, Mathieu C. Morissette, Steeve Provencher, Sébastien Bonnet, François Maltais
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation. This generic term encompasses emphysema and chronic bronchitis, two common conditions, each having distinct but also overlapping features. Recent epidemiological and experimental studies have challenged the traditional view that COPD is exclusively an adult disease occurring after years of inhalational insults to the lungs, pinpointing abnormalities or disruption of the pathways that control lung development as an important susceptibility factor for adult COPD. In addition, there is growing evidence that emphysema is not solely a destructive process because it is also characterized by a failure in cell and molecular maintenance programs necessary for proper lung development. This leads to the concept that tissue regeneration required stimulation of signaling pathways that normally operate during development. We undertook a review of the literature to outline the contribution of developmental insults and genes in the occurrence and pathogenesis of COPD, respectively.
Deconstructing the Psychosis Risk Syndrome
Authors: Barbara A. Cornblatt, Ricardo E. Carrión
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal