tbuckley/cabot-search huggingface dataset:
PSA doubling time (PSADT) and serum testosterone (T) during intermittent androgen deprivation (IAD) in patients with biochemically relapsed prostate cancer (BRCP; M0): Potential predictive implications.
Authors: V. J. Sinibaldi, P. Huang, E. S. Antonarakis, M. A. Carducci, S. R. Denmeade, J. J. Kim, M. A. Eisenberger, D. Keizman
Journal: Journal of Clinical Oncology (2011)

e15006 Background: The systemic management of patients with BRPC remains controversial. IAD is commonly employed. Aims: To evaluate the PSA dynamics and serum T in pts with BRPC treated with IAD until the development of PSA refractoriness or clinical evidence of metastatic disease. Methods: Data were retrospectively analyzed in all pts with BRCP treated with GnRH at PSA thresholds according to pre-treatment PSADT (10-15ng/ml, 15-20, and 20-30 for PSADT ≤3 mos, 3-9 mos, and ≥ 9 ms, respectively) and continued until PSA nadir. Antiandrogen,(AA) was added for PSA > 1.0 ng/ml after 3 mos). Follow-up (FU) consisted of PSA and T q3 mos. Cycles were repeated at the above preselected PSA thresholds and continued until lack of PSA response. Scans were obtained prior to cycles and at the time of CRPC state. Mixed effects model was used to study PSADT change over cycles. Multivariate cox regression model was used to identify prognostic variables. Results: From 1995-2010, with a mean FU of 71 mos (range 22-183 months),96 pts received a mean of 2.8 cycles (range 1-9) of IAD; 58 (60%) remain on treatment and 38 (40%) were switched to continuous ADT due to PSA refractoriness (n=11) or positive scans (n=27). PSADT at the first off treatment (tx) interval (mean 3.1, 0.59-30.5 range, median 2.3) was significantly shorter than the baseline (p<0.0001) (mean 9.7, range 0.27-53.9, median 7.34) but remained relatively stable (p=0.29) in subsequent cycles. PSADT adjusted for T recovery (≥3 ms after T recovery to ≥ 150 ng/dl) was significantly longer (p=0.006) than that based only on all PSA determinations (mean 5.4, range 1.31-30.5, median 3.7 versus mean 3.1, range 0.59-30.5, median 2.3). Significant factors associated with probability of PSA refractoriness were pre-IAD PSADT (≥ 6 vs <6 ms), first off tx interval PSADT (≥3 ms vs <3m), and PSA nadir during the first tx interval (<0.1 vs ≥0.1 ng/ml). Conclusions: Our data suggest that PSADT becomes shorter after the initial cycle of IAD and correlate with T recovery. PSA dynamics are associated with PSA refractoriness in pts with BRPC treated with IAD.
Aneurysm of the Abdominal Aorta with Rupture into the Inferior Vena Cava
Authors: R. Clement Darling, Robert R. Linton
Journal: New England Journal of Medicine (1962)

RUPTURE of an arteriosclerotic abdominal aneurysm into the inferior vena cava is unusual. The production of an aortocaval fistula by this means has rarely been emphasized and less frequently corrected. There are individual reports1 2 3 4 5 6 but on only 6 such patients in whom successful surgical treatment has been carried out. This paper is prompted by the diagnostic, as well as the technical implications raised in the successful management of 2 additional patients.Case ReportsCase 1. L.L. (M.G.H. 860748), a 52-year-old man, was admitted to the private service of the Massachusetts General Hospital on July 7, 1961, because of shortness of . . .
A progression-risk score to predict treatment-free survival for early stage chronic lymphocytic leukemia patients
Authors: M Gentile, T D Shanafelt, G Cutrona, S Molica, G Tripepi, I Alvarez, F R Mauro, N Di Renzo, F Di Raimondo, I Vincelli, K Todoerti, S Matis, C Musolino, S Fabris, E Vigna, L Levato, S Zupo, F Angrilli, U Consoli, G Festini, G Longo, A Cortelezzi, A Arcari, M Federico, D Mannina, A G Recchia, A Neri, N E Kay, M Ferrarini, F Morabito
Journal: Leukemia (2015)
Chemotherapy for advanced aggressive lymphoma: more is better ...isn't it?
Authors: D L Longo
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.6.952 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2189956 Chemotherapy for advanced aggressive lymphoma: more is better ...isn't it? D L LongoxD L LongoSearch for articles by this author Show More National Cancer Institute, Frederick Cancer Research Facility, MD. https://doi.org/10.1200/JCO.1990.8.6.952 First Page PDF © 1990 by American Society of Clinical Oncology
Differentiation of Hemophilia into Two Groups
Authors: J. P. Soulier, M. J. Larrieu, O. Wartelle
Journal: New England Journal of Medicine (1953)

PREVIOUS articles1,2 have described a new test for the specific determination of antihemophilic factor that measures its effect on the recalcification time of a standard reagent plasma, prepared from the plasma of a typical patient with hemophilia and supplemented with heated platelet extracts. To evaluate the specificity of the new test we reexamined the bleeders previously considered to be hemophiliac by our laboratory. In each case the diagnosis had been based on the following data: the patient's past hemorrhagic history, with or without typical familial transmission and such laboratory findings as prolonged clotting time, poor prothrombin consumption and correction . . .
Case 12-2004
Authors: Patrick T. O'Gara, Alan J. Greenfield, Nadeem A. Afridi, Stuart L. Houser
Journal: New England Journal of Medicine (2004)

A 38-year-old woman who had given birth to a healthy infant by cesarean section two weeks earlier experienced a sudden onset of pain in her throat, anterior chest, and back, maximal at onset, accompanied by shortness of breath, sweating, and nausea. Physical examination revealed symmetric pulses, normal blood pressure, and a diastolic heart murmur. Initial imaging studies showed widening of the aortic root, with inflammatory changes in the mediastinum, mild aortic regurgitation, and a pericardial effusion. The differential diagnosis of acute chest pain in a young woman is discussed.
Quality control of point of care INR devices is essential
Authors: D P Kitchen, S Kitchen, I Jennings, T A L Woods, M Makris, I D Walker
Journal: BMJ (2016)

In response to Cohen’s article questioning the ROCKET AF data,1 we report on the need for point of care international normalised ratio (POC INR) testing devices to be quality controlled. Such testing should be subjected to the same quality control and quality management systems as laboratory INR testing. Appropriate and effective external quality assessment (EQA) for these …
Hereditary Defect of Cobalamin Metabolism (<i>CblG</i>Mutation) Presenting as a Neurologic Disorder in Adulthood
Authors: Ralph Carmel, David Watkins, Stephen I. Goodman, David S. Rosenblatt
Journal: New England Journal of Medicine (1988)

AN increasing variety of hereditary disorders of intracellular cobalamin metabolism, usually first detected because of the presence of methylmalonic aciduria (cblA, cblB, and cblF mutations), homocystinuria (cblE and cblG mutations), or both (cbIC and cblD mutations), have been defined on the basis of complementation studies.1 , 2 Methylmalonic aciduria results when the conversion of methylmalonyl-CoA (coenzyme A) to succinyl-CoA by methylmalonyl-CoA mutase, mediated by 5′-deoxyadenosylcobalamin, becomes impaired. Homocystinuria occurs when methylcobalamin and its cofactor, 5-methyltetrahydrofolate, cannot be used in the methylation of homocysteine to methionine, mediated by methionine synthase.Neurologic dysfunction and often megaloblastic anemia are prominent signs . . .
Circulating Immune Complexes in Steroid-Responsive Nephrotic Syndrome
Authors: Roland J. Levinsky, Peter N. Malleson, T. Martin Barratt, John F. Soothill
Journal: New England Journal of Medicine (1978)

We analyzed serums from 39 children with steroid-responsive nephrotic syndrome for the presence of circulating soluble immune complexes. Seventeen of 18 children in relapse had raised levels of IgG complexes: median titers were significantly higher in these patients than in control children (P less than 0.001) or in nephrotic children in sustained remission (P less than 0.001). Seven of nine children followed sequentially had raised complex levels in early remission but became normal after six weeks in remission. In contrast to patients with systemic lupus erythematosus these IgG complexes were not able to bind C1q. Serums from five patients in relapse contained complexes intermediate in size (2 to 2.5 X 10(6) daltons) as compared to those seen in systemic lupus erythematosus, and four of the five had small complexes as well (3 to 5 X 10(5) daltons). These findings suggest that immune complexes may have a pathologic role in steroid-responsive nephrotic syndrome, but the mechanism by which proteinuria is effected remains unclear.
Antitumor activity of CTO given orally in combination with temozolomide in the SC251 human glioblastoma model.
Authors: R. A. Karmali, G. Gorman, Y. Maxuitenko
Journal: Journal of Clinical Oncology (2010)

e13643 Background: 5-amino-1-(4-[4-chlorobenzoyl])-3,5-dicholobenzyl)-1,2,3-triazole-carboxamide orotate (CTO, M.W 580.8), a PI3 inhibitor, was tested against s.c. implanted SC U251 human glioblastoma xenografts in male, athymic NCr-nu/nu mice when given as monotherapy or in combination with temozolomide (Temodar). CTO and temozolomide were given orally (PO). To test whether CTO crossed the blood brain barrier, brains from mice treated orally with CTO were analyzed to measure concentrations of CTO. Methods: This study compares temozolomide alone, CTO alone against temozolomide + CTO. 6 week old mice were implanted with SC U251 fragments and 13 days later were sorted in 6 groups of ten (groups 1-6) and 2 groups of six (groups 7-8). The treatment regiments for groups 1 through 6 were drug(s) given PO daily for 5 days (Q1D × 5) for two rounds starting on day 13 to 17 and again on day 27 to 31. The treatments included: group 1- vehicle for temozolomide + CTO; group 2- 513 mg/kg/day; group 3- 342 mg/kg/day; group 4- temozolomide 17mg/kg/day; group 5- temozolomide 17mg/kg/day + 513 mg/kg/day CTO; group 6- temozolomide 17mg/kg/day + 342 mg/kg/day CTO. Groups 7 and 8 received 513 mg/kg/day or 342 mg/kg/day CTO for only one round PO daily for 5 days (Q1D x 5) starting on day 13 to 17, respectively. Groups 7 and 8 were euthanized on day 17 for brain tissue collection and analysis of CTO. Groups 1 to 6 were terminated at day 76 after tumor implantation. Results: Compared to the control group, CTO at the dose of 513mg/kg/day resulted in statistically significant inhibition of tumor growth (p=0.034). Temozolomide 17mg/kg/day significantly inhibited tumor growth (p=0.004). Growth of tumors in the combination therapy groups 5 and 6 was significantly inhibited compared to CTO alone at respective dose (p<0.001 and p<0.001, respectively). Conclusions: These results show that the antitumor activity of the combination treatment of CTO and temozolomide was greater than additive compared to the antitumor activity of each drug alone. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tactical Therapeutics, Inc. Tactical Therapeutics, Inc. Tactical Therapeutics, Inc. Tactical Therapeutics, Inc.
The Use of Trientine in Preventing the Effects of Interrupting Penicillamine Therapy in Wilson's Disease
Authors: I. Herbert Scheinberg, Marvin E. Jaffe, Irmin Sternlieb
Journal: New England Journal of Medicine (1987)

Penicillamine is known to be effective therapy for Wilson's disease. However, the clinical consequences of the abrupt and permanent withdrawal of penicillamine have not been investigated. We studied 11 patients who stopped their own treatment after having been treated successfully with penicillamine (1 to 2 g per day) for periods of 3 to 19 years. Eight died of hepatic decompensation or fulminant hepatitis after an average survival of only 2.6 years. In another 13 patients, penicillamine was discontinued by the physician because of serious adverse reactions. In these patients, penicillamine was replaced with trientine (1 to 1.5 g per day), a newer chelating agent. All but one of these patients (who was killed accidentally) are alive at this writing, from 2 to 15 years later. Our observations suggest that discontinuation of penicillamine in patients with Wilson's disease results in rapid clinical deterioration, which is often fatal. The replacement of penicillamine with trientine appears to prevent this adverse clinical course.
Recovery of Pituitary Thyrotropic Function after Withdrawal of Prolonged Thyroid-Suppression Therapy
Authors: Apostolos G. Vagenakis, Lewis E. Braverman, Fereidoun Azizi, Gary I. Portnay, Sidney H. Ingbar
Journal: New England Journal of Medicine (1975)

The pattern of thyrotropin secretion was analyzed in seven euthyroid women, before and after withdrawal of long-term thyroid hormone, by serial measurements of thyroid 131l uptake, serum thyroxine, tri-iodothyronine, and thyrotropin concentrations, and the response to thyrotropin-releasing hormone. During exogenous hormone administration, 131l uptake was suppressed, and serum thyrotropin concentrations before and after administration of thyrotropin-releasing hormone were undetectable. After withdrawal of exogenous hormone, thyrotropin secretory function was transiently impaired, as indicated by undetectable basal thyrotropin concentrations together with absence of response to thyrotropin-releasing hormone, and subsequently by normal values of basal thyrotropin concentration and normal responses to releasing hormone while serum thyroxine and tri-iodothyronine concentrations were subnormal. Decreased thyrotropin reserve persisted for two to five weeks. Detectable values of serum thyrotropin (less than 1.2 muU per milliliter) and a normal 131l uptake usually occurred concurrently in two to three weeks. Serum thyroxine concentration returned to normal at least four weeks after hormone withdrawal.
Oxaliplatin (OXP) plus protracted infusion 5-fluorouracil (PIFU) and external beam radiation (EBRT) prior to surgery (S) for potentially curable esophageal adenocarcinoma (EA): A Southwest Oncology Group (SWOG) phase II trial with molecular correlates (S0356)
Authors: L. Leichman, B. H. Goldman, J. K. Benedetti, K. G. Billingsley, C. R. Thomas, S. Iqbal, H. Lenz, C. Blanke, P. J. Gold, C. L. Corless
Journal: Journal of Clinical Oncology (2009)

4513 Background: Although neoadjuvant combined modality therapy (NACMTX) has become a standard of care in the United States, median overall survival (OS) for patients (PTS) with EA has changed little over the past 25 years. Progression free survival (PFS) and OS after NACMTX depend on extent of primary tumor response. New regimens to increase pathologic complete response (pCR) are needed. Based on phase I data, SWOG designed a phase II trial (S0356) to test OXP with PI5FU and EBRT for PTS with EA. Objectives included pCR rate ≥ 25%, acceptable toxicity (TOX), PFS, OS and exploration of molecular parameters relevant to pCR. Methods: Eligibility: clinical stage II/III EA, ≥ 18 years, Zubrod PS ≤ 2, standard hematologic/non-hematologic values, and tumor &lt; 2 cm into the gastric cardia. OXP 85 mg/m 2 was given day (d) 1, 15 and 29; PI5FU 180 mg/m 2 /d was given d 8-d43. EBRT 180 cGy/d started d 8 x 25 fractions, 5 d/week to total dose 4500 cGy. S was planned 2–4 weeks after NACMTX, with a second cycle of OXP/ PI5FU after S. Central pathology review of surgical specimens was mandated. The trial used a 2-stage design; the trial was halted at 45 PTS to review pCR rate; it reopened to full accrual. Results: 98 PTS enrolled between 9/15/04 and 8/18/08. 6 PTS were ineligible; 2 PTS did not receive therapy (TX). 90 PTS, 84 men (93%), median age 61.7 years, were analyzed. 4 deaths (4.5%) were due to protocol TX; 2 due to NACMTX, 2 to S. 43% and 18% of PTS had grade 3/4 toxicity, respectively: 39% GI, 22% flu-like/fatigue, 17% pulmonary, 16% hematologic, 14% mucositis and 3% neurologic. 77 PTS (86%) underwent S. 30 PTS (33%) had pCR. 9 PTS (10%) had in-situ cancer or T1N0M0. &lt;50% received postoperative CTX. Conclusions: OXP, PI5FU and EBRT for PTS with EA has produced the highest pCR rate reported to date for a cooperative group trial. Significant but manageable non-hematologic TOX was observed. S mortality is acceptable. Future trials built on this platform should plan to complete all TX before S. Tumor molecular profiles (analyses in progress) may predict benefit from this treatment. Data on PFS and OS will follow. [Table: see text]
EORTC 24051: Unexpected side effects of a phase I study of TPF induction chemotherapy (IC) followed by chemoradiation (CRT) with lapatinib (LAP), a dual EGFR/ErbB2 inhibitor, in patients with locally advanced larynx and hypopharynx squamous cell carcinoma (LA-LxHxSCC)
Authors: P. M. Specenier, Y. Lalami, J. Vermorken, D. Lacombe, I. El-Hariry, J. Bogaerts, A. Awada
Journal: Journal of Clinical Oncology (2009)

6017 Background: CRT is considered a standard approach for LA-LxHxSCC. TPF IC regimen seems to improve outcome in locally advanced head and neck SCC. The addition of LAP was investigated in combination with a sequential therapeutic approach (IC→ CRT). Methods: Eligible tumors were SCCHN: T3-T4 larynx (Lx), T2-T4 hypopharynx (Hx) N0–3 M0. The objective of this trial is to determine MTD, DLT and recommended dose of LAP when administered with TPF IC (docetaxel (T) 75mg/m2 (60 mg/m2 for the first cycle) d1, CDDP 75mg/m2 d1, 5FU 750mg/m2/d continuous infusion d1-d5 q3weeks) followed by CRT (weekly carboplatin AUC 1.5 and RT 70Gy in 7 weeks; 2Gy/fx). LAP is administered concomitantly with IC (escalating dose 500–1500mg po daily) and during CRT (1,500 mg daily). Results: Seven male patients were included; tumor sites: LX (n = 3) / Hx: (n = 4), median age 59 years (range: 47–79), WHO PS 0–1, no severe or uncontrolled comorbidity. Three pts were included in the first cohort, at dose level 1 (LAP 500 mg daily plus TPF IC). Renal toxicity was observed among these 3 pts (grade 4 [n = 1], grade 2 [n=1] and grade 1 [n=1]), with 1 DLT, leading to treatment interruption in this group. This nephrotoxicity was reversible after stopping lapatinib and hydration of the patients. As LAP plus cisplatinum plus RT was feasible in another study, a second cohort was conducted in 4 pts, receiving LAP at the same dosage, and docetaxel (T) was only introduced from cycle 2 of IC to see what is the role of T in the observed side effect. Two DLTs were observed among this second cohort of subjects: one pt presented a grade 2 renal toxicity, grade 3 diarrhea and dehydration and a second pt presented a grade 3 anorexia and grade 3 stomatitis. Based on the occurrence of 3 DLTs at the first dose level of LAP, patient recruitment was closed. Despite these safety issues, all patients recovered and were treated off-study. They will receive follow-up as foreseen by the protocol. Conclusions: These data suggest that LAP should not be combined with TPF IC regimen for LA-LxHxSCC due to prohibited toxicity. [Table: see text]
M1 An audit of electronic oxygen prescribing and oxygen saturation readings showing a high prevalence of risk factors for hypercapnia and a high incidence of iatrogenic hyperoxaemia: Abstract M1 Table 1
Authors: P Whittemore, BR O’Driscoll
Journal: Thorax (2015)

<h3>Background</h3> BTS audits have shown that about 14% of UK hospital patients are on oxygen therapy at any given time but only half of these patients have a prescription or written order for oxygen use. Our 600 bed teaching hospital has electronic prescribing linked to an electronic bedside observations system (modified NEWS score). Hospital policy is to set a target oxygen saturation range for all in-patients. Patients score points if their oxygen saturation (SpO<sub>2</sub>) falls below their target range or if SpO<sub>2</sub> rises above their target range on oxygen therapy. <h3>Methods</h3> We audited oxygen prescribing and SpO<sub>2</sub> for all patients treated on medical and surgical wards during the month of December 2014. All data was contained within the electronic patient record. <h3>Results</h3> We audited 80,391 sets of observations for 6,800 patients (2239 medical, 4561 surgical). 99.8% of all patients had an oxygen target range prescribed electronically 12.7% of all patients (18.9% of medical patients and 9.6% of surgical patients) had risk factors for hypercapnia with a prescribed target range of 88–92% or less Overall 90.6% of oxygen saturation measurements were within target range (or above the target range breathing air). 59.9% of measurements on oxygen and 97.2% of observations on air were within the target range 3.7% of oximetry measurements were below the target range (7.9% of those on oxygen) 5.8% of all oximetry measurements were above the target range due to use of oxygen (32.2% of measurements on oxygen were above target range) For patients using oxygen therapy with target range 94–98% or 88–92%, the percent of measurements within range, below range or above range is shown in the Table 1 53.2% of observations on patients using oxygen with target range 88–92% showed SpO<sub>2</sub> above target range <h3>Conclusions</h3> An oxygen target range is prescribed for almost all inpatients at this hospital but hyperoxaemia (with associated risk of hypercapnia) remains prevalent amongst patients on oxygen therapy, especially those who have been identified as at increased risk of hypercapnia. This has led to a revised educational programme for nursing staff with an emphasis on keeping patients within their target range.
Teaching Clinical Medicine in the Ambulatory Setting
Authors: Gerald T. Perkoff
Journal: New England Journal of Medicine (1986)

Abstract A resurgence of general interest in teaching clinical medicine in ambulatory-care settings has occurred for several reasons, including changes in the case mix in teaching hospitals, the new responsibilities of house officers and attending physicians brought about by the current payment systems for health care, the increased expectations of patients that medical care will be "personal," the progressive limitations imposed on the education of medical students by the shorter lengths of stay sought by hospitals under the diagnosis-related-groups system of payment, and the growing need for well-trained primary care physicians that has resulted from the increase in medical care organizations. In this paper, I review earlier attempts to emphasize ambulatory care, to identify the pitfalls that new efforts in this direction should avoid. I also compare inpatient and ambulatory-care teaching to provide a basis for understanding the educational goals that can be achieved more easily in each setting. In addition, I suggest major changes in the flow and use of clinical-practice funds and hospital payments so that they can become possible sources of the financing and organization of an expanded effort to teach clinical medicine in ambulatory-care settings. (N Engl J Med 1986; 314:27–31.)