tbuckley/cabot-search huggingface dataset:
Evaluation of symptom burden in patients receiving concurrent biochemotherapy for metastatic malignant melanoma (MMM)
Authors: M. T. Harle, C. S. Cleeland, K. B. Kim, M. R. Domine, I. Gning, G. Mobley, C. A. Parker, L. H. Camacho
Journal: Journal of Clinical Oncology (2004)

6143 Background: Combination of cytotoxic chemotherapy and immunoregulators (biochemotherapy) is commonly used to treat patients with MMM. Response rates reported with this regimen vary between 18% and 60%. This treatment course is limited by acute toxicity and the resulting substantial symptom burden. Methods: Using the M. D. Anderson Symptom Inventory (MDASI) and ECOG performance status (PS), we evaluated the symptom burden in 12 patients receiving 1–5 cycles of concurrent biochemotherapy for MMM. Patients received Dacarbazine 800mg/m2 D1, Cisplatin 20 mg/m2 D1–4, Vinblastine 1.5 mg/m2 D1–4, Interleukin-2 9 MU/m2 IVCI D1–4, and Interferon-alpha-2b 5 MU/m2 SC D1–4. The MDASI was administered at baseline and daily for 21days. ECOG PS was evaluated at baseline and day 5. Data was collected by personal interview during hospitalization and by daily mail after discharge. Results: Most significant symptoms included fatigue, nausea, sleep disturbance, depressed appetite, drowsiness, dry mouth, and itching. Symptom intensity was graphed over time to develop a symptom curve. Consistently, the symptoms peaked at day 4 to 5 and returned almost to baseline levels at day 21. ECOG PS decreased from day 0 to day 5 and returned to baseline prior to the next treatment cycle. The table below shows the 7 highest reported symptoms rated on a 0–10 scale. Conclusions: Concurrent biochemotherapy induces substantial toxicity during the first 5–7 days of therapy. Acute toxicity seems tightly related to drug administration. Short-term symptom burden is more severe than seen with most treatment modalities. If substantial tumor response is not evident after 2 courses of therapy, the treatment-related symptom burden further limits its overall clinical benefit. Future studies will assess correlations with serum release of various cytokines and compare with high-dose Interleukin-2. No significant financial relationships to disclose.
The Operative and Postoperative Management of Hypertensive Patients Undergoing Thoracolumbar Sympathectomy
Authors: Jere W. Lord, J. William Hinton
Journal: New England Journal of Medicine (1947)

THE surgical treatment of hypertension had its origin in the pioneer work of Crile,1 Adson et al.,2 , 3 Page and Heuer,4 Peet5 and others, but it was not until the brilliant clinical studies of Smithwick,6 first published in 1940, that a truly effective operative procedure was available. The extent of the operation described by Smithwick and employed by him for the past eight years included removal of the thoracolumbar chain from the eighth or ninth thoracic ganglion through the first or second lumbar ganglion, along with portions of the greater, lesser and least splanchnic nerves.Hinton and Lord7 reported 152 hypertensive . . .
Twelve Years' Experience in Roentgenotherapy for Chronic Arthritis
Authors: John G. Kuhns, Sidney L. Morrison
Journal: New England Journal of Medicine (1946)

ROENTGENOTHERAPY as a local treatment to the joints in chronic arthritis was begun by us over twelve years ago. We were prompted to institute this form of treatment after reading the early optimistic reports of Kahlmeter1 in Sweden and of Scott2 in London. At first the treatments were given with great caution. After a number of unexpected successes and an equal number of failures, a general plan of treatment for certain articular lesions in chronic arthritis was developed. During this time we learned to expect certain effects in the joints, and by trial and error we found some of the . . .
Lack of necessity of granuloctye-colony stimulating factor (GF) in Hodgkin’s disease (HD) treated with ABVD
Authors: A. M. Evens, J. Cilley, M. Gounder, T. Ortiz, S. Miyata, K. Catsaros, A. Rademaker, M. S. Tallman, J. N. Winter, L. I. Gordon
Journal: Journal of Clinical Oncology (2006)

7515 Background: DI is important in the therapy of HD, and GF has been used to maintain DI. Recent data suggest that toxicity (bleomycin pulmonary toxicity [BPT]) is higher in patients (pts) who receive GF (JCO 2005;23:7614). We reviewed all HD pts treated since Jan 1996 with attention to GF use, DI, blood counts, BPT and survival. Methods: We analyzed biopsy-confirmed HD pts who received all of their therapy at NU from Jan 1996 to Oct 2005. BPT was defined as: pulmonary symptoms, bilateral infiltrates on scans and no infection. Results: We identified 95 pts, of whom 77 (81%) received ABVD, 7 (7.4%) Stanford V, and 11 (11.6%) other. Of the 77 ABVD pts, 51 completed all cycles with no GF, 23 received GF and 3 are unknown. In the “no GF” group, median age was 31 yrs, 31% had stage III/IV disease (33% Hasenclever Index &gt; 3); 18% had bulky disease, 37% B symptoms and 53% received radiation (RT). In the GF group (n = 23), median age was 33, 42% had stage III/IV disease (21% Hasenclever index &gt; 3); 17% had bulky disease, 42% B symptoms and 50% had RT. Among the 51 “no GF” ABVD pts (287 cycles), median treatment-day ANC were 0.9, while % monocytes were consistently elevated (see Table). There were no dose adjustments or treatment delays for ANC on day of treatment. Normalized DI was &gt; 99% for all treatment days and median cycle duration was 28.6 days (planned = 28 days). 1/51 of these pts had BPT and 2 episodes of uncomplicated neutropenic fever were seen (2/287 cycles = 0.6% incidence). If Stanford V pts are included (n = 7, 2 without and 5 with GF), BPT occurred in 1/53 with “no GF” and 2/28 with GF (see Table). CR rate (100%), PFS and OS were similar in all groups (see Table). Conclusion: 1) GF is not necessary in order to administer ABVD at &gt; 99% DI, and its absence is associated with low toxicity. 2) ABVD should be given at 100% dose with no delay despite ANC on day of treatment. 3) GF should not be used routinely in HD pts treated with ABVD. [Table: see text] No significant financial relationships to disclose.
The Chromosomes in a Child with Mongolism and Acute Leukemia
Authors: Alan W. Johnston
Journal: New England Journal of Medicine (1961)

THE association of mongolism with leukemia was firmly established by Stewart and her colleagues1 in 1958 from their survey of neoplastic disease in childhood. They found mongolism in 17 of 677 cases of leukemia and in only 1 among 739 cases of cancer. This association had been suggested before, particularly by Ingalls2 in 1947 and then by Krivit and Good,3 by Merritt and Harris4 and by Carter,5 all in 1956, as well as in a number of other case reports.6 7 8 9 10 Several authors had speculated on the nature of the association, but the theories of the etiology of mongolism then current . . .
Patients face five hour delays after private firm takes over transport service
Authors: Adrian O’Dowd
Journal: BMJ (2016)

GPs have ordered an independent investigation into severe delays experienced by patients waiting for a privately run NHS non-emergency patient transport service.

Patients in Sussex have been waiting in some cases more than five hours for the patient transport service to take them to hospital since the firm Coperforma took over the service on 1 April. MPs, unions, and NHS organisations have all received complaints from patients who experienced delays and difficulties contacting the service.

Seven clinical commissioning groups in Sussex jointly ran a procurement process last year after the South East Coast Ambulance Service served notice on its contract to …
A Study of Magnesium Metabolism in Acute Renal Failure Employing a Multichannel Flame Spectrometer
Authors: Warren E. C. Wacker, Bert L. Vallee
Journal: New England Journal of Medicine (1957)

THE advances in the knowledge of the pathologic physiology of potassium and sodium during the past decade can be attributed directly to the development of precise and accurate flame photometric methods for their measurement. By contrast, the metabolism of magnesium, its normal variations and its changes in pathologic processes have received but little attention. Magnesium is second only to potassium in terms of intracellular abundance. It is estimated that there is a total of 20 gm. of magnesium in the human body. The present state of knowledge concerning this element, however, is not dissimilar to that prevailing for the alkali . . .
Chronic Conditions and Utility-Based Health-Related Quality of Life in Adult Childhood Cancer Survivors
Authors: Jennifer M. Yeh, Janel Hanmer, Zachary J. Ward, Wendy M. Leisenring, Gregory T. Armstrong, Melissa M. Hudson, Marilyn Stovall, Leslie L. Robison, Kevin C. Oeffinger, Lisa Diller
Journal: JNCI Journal of the National Cancer Institute (2016)

Health utility, a summary measure of quality of life, has not been previously used to compare outcomes among childhood cancer survivors and individuals without a cancer history. We estimated health utility (0, death; 1, perfect health) using the Short Form-6D (SF-6D) in survivors (n = 7105) and siblings of survivors (n = 372) (using the Childhood Cancer Survivor Study cohort) and the general population (n = 12 803) (using the Medical Expenditures Panel Survey). Survivors had statistically significantly lower SF-6D scores than the general population (mean = 0.769, 95% confidence interval [CI] = 0.766 to 0.771, vs mean = 0.809, 95% CI = 0.806 to 0.813, respectively, P < .001, two-sided). Young adult survivors (age 18-29 years) reported scores comparable with general population estimates for people age 40 to 49 years. Among survivors, SF-6D scores were largely determined by number and severity of chronic conditions. No clinically meaningful differences were identified between siblings and the general population (mean = 0.793, 95% CI = 0.782 to 0.805, vs mean = 0.809, 95% CI = 0.806 to 0.813, respectively). This analysis illustrates the importance of chronic conditions on long-term survivor quality of life and provides encouraging results on sibling well-being. Preference-based utilities are informative tools for outcomes research in cancer survivors.
Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2)
Authors: Arthur Kavanaugh, Lluis Puig, Alice B Gottlieb, Christopher Ritchlin, Yin You, Shu Li, Michael Song, Bruce Randazzo, Proton Rahman, Iain B McInnes
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objective</h3> To evaluate ustekinumab efficacy and safety in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (termed the 'spondylitis subset'). <h3>Methods</h3> Adults with active PsA (PSUMMIT-1/PSUMMIT-2, n=615/312) were randomised to ustekinumab 45 mg, 90 mg or placebo at week 0/week 4/q12 week. At week 16, patients with &lt;5% improvement in tender and swollen joints entered blinded early escape. A subset of patients with physician-identified spondylitis was evaluated with spondylitis-specific assessments, including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score employing C reactive protein (ASDAS-CRP), through week 24. <h3>Results</h3> 256/927 (27.6%) PSUMMIT-1/PSUMMIT-2 patients (placebo/ustekinumab, n=92/164) comprised the evaluable spondylitis subset. At week 24, in this analysis subset, significantly more patients achieved BASDAI20/50/70 responses (54.8%/29.3%/15.3% vs 32.9%/11.4%/0%; p≤0.002), improvement in BASDAI question 2 concerning axial pain (1.85 vs 0.24; p&lt;0.001) and mean per cent ASDAS-CRP improvements (27.8% vs 3.9%; p&lt;0.001) for ustekinumab versus placebo recipients, respectively. Comparable to the overall study population, significant improvements were also achieved in psoriasis, peripheral arthritis, enthesitis, dactylitis, physical function and peripheral joint radiographs in the spondylitis subset. <h3>Conclusions</h3> In this post-hoc analysis of PsA patients with baseline peripheral arthritis and physician-reported spondylitis, ustekinumab-treated patients demonstrated significant improvements in axial signs and symptoms through week 24. <h3>Trial registration number</h3> PSUMMIT-1 (NCT01009086, EudraCT 2009-012264-14) and PSUMMIT-2 (NCT01077362, EudraCT 2009-012265-60); post-study results.
Interpretation of Genetic Testing for Lynch Syndrome in Patients With Putative Familial Colorectal Cancer
Authors: Christina Rybak, Michael J. Hall
Journal: Journal of the National Comprehensive Cancer Network (2011)

Colorectal cancer (CRC) risk assessment involves the evaluation of an individual's personal and family history for characteristics of an inherited susceptibility to develop CRC. Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is the most common cause of hereditary CRC, underlying 2% to 3% of patients with newly diagnosed (incident) CRC. Risk assessment for LS is complex, and the interpretation of the many available tests can be challenging even for the genetics specialist. A move toward universal (reflex) LS screening for mismatch repair in all patients with incident CRC supports the importance of improving the awareness and understanding of LS testing, teaching rational testing approaches, and honing interpretive skills among cancer care providers. This article reviews important clinical features of LS genetic evaluation using 3 pedigree-based case examples from the Fox Chase Cancer Center Gastrointestinal Risk Assessment Clinic.
Determination of Extracellular pH and Tissue Temperature in Transplantable Rat Tumors by Use of Inductive Loop Telemetry
Authors: S. M. Hinsull, R. H. Colson, A. Franklin, B. W. Watson, D. Bellamy
Journal: JNCI Journal of the National Cancer Institute (1984)

Radiotelemetry was used to determine changes in extracellular pH and tissue temperature during tumor development in rats of an inbred WAB substrain. A progressive decrease in the pH of the tumor tissue compared with the pH level in control tissue was observed, so that by 4 days after tumor implantation the tumor tissue was about 0.4 pH units lower than control values. Thereafter, tumor pH rose progressively to reach a value comparable with control levels at 8 days, when the experiment was terminated. No significant difference was detected between the temperature in the tumor tissue and the temperature in the control tissue. Therefore, the observed changes in pH appeared to be independent of temperature. Studies on the rate of tumor cell proliferation during the experiments demonstrated a significant inverse relationship between tumor cell mitotic rate and pH, with the highest rates of cell proliferation occurring at the time of lowest pH values.
DEVA: Randomized trial of sequential epirubicin and docetaxel versus epirubicin alone in node-positive postmenopausal early breast cancer (EBC) patients.
Authors: R. C. Coombes, J. M. Bliss, M. Espie, F. Erdkamp, J. J. Wals, A. Tres, R. E. Coleman, J. Reise, D. Cooper, P. Hupperets
Journal: Journal of Clinical Oncology (2010)

536 Background: This group previously showed that fractionated epirubicin (EPI) alone is an active, well tolerated adjuvant regimen in postmenopausal women (Wils, JCO, 1999). DEVA evaluated the efficacy and toxicity of incorporating docetaxel (DOC) to create a sequential anthracycline-taxane regimen. Methods: Following complete tumour excision, postmenopausal women with node-positive EBC were randomised to either EPI 50 mg/m2 d1 and 8 every 4 weeks for 6 cycles, or EPI-DOC 3 cycles EPI (as above) then 3 cycles of docetaxel 100 mg/m2 d1 every 3 weeks. Patients with ER positive EBC also received endocrine therapy for 5 years. Disease-free survival (DFS) (local and distant relapse, 2nd primary breast cancer, intercurrent death) and overall survival (OS) were evaluated. Results: From 1997 to 2005, 803 patients at 36 centres entered DEVA (EPI n = 397, EPI-DOC n = 406). 198 DFS events have been reported (EPI-DOC n = 84 EPI n = 114); median follow-up 64.7 months (IQR 45.2-84.4 months). 5-year DFS rates were EPI-DOC 79.5% (CI 75.2-83.8) and EPI 72.7% (CI 68.0-77.3) with evidence of improvement in DFS with EPI-DOC (HR = 0.68; 95% CI 0.52-0.91; p = 0.008). Adjustment for factors known to affect prognosis (ER status, grade, tumour size, extent of node involvement) slightly increased size of DFS effect (HR = 0.58; 95% CI 0.43-0.79) with no evidence of a differential effect within the subgroups. 127 patients have died (EPI-DOC 52, EPI 75) with a reduction in deaths with EPI-DOC (HR = 0.66; CI 0.46-0.94; p = 0.02). 5-year OS rates were EPI-DOC 88.9 (CI 85.5-92.2) and EPI 81.8 (CI 77.7-85.9). 20 patients (EPI-DOC n = 7 EPI n = 13) died with no evidence of breast cancer relapse; 6 were due to cardiac disease (EPI-DOC n = 1 EPI n = 5). From cycles 4-6 onwards, with exception of nausea/vomiting (p = 0.003), EPI-DOC was more toxic than EPI including infection (p = 0.001), febrile neutropenia, myalgia, peripheral neuropathy, oedema, skin and nail abnormalities, and stomatitis (all p < 0.001). Conclusions: These mature results suggest, within a relatively small trial, that substitution of docetaxel for epirubicin for the last three cycles of chemotherapy results in improved outcome in postmenopausal, node-positive EBC patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis Pfizer, sanofi-aventis Pfizer
Efficacy of a novel schedule of decitabine in previously untreated AML, age 60 or older
Authors: W. G. Blum, R. Klisovic, S. Liu, C. Kefauver, M. R. Grever, L. Schaaf, K. Chan, J. C. Byrd, M. Villalona-Calero, G. Marcucci
Journal: Journal of Clinical Oncology (2009)

7010 Background: We established an optimal daily dose of decitabine in AML at 20mg/m 2 /day based on re-expression of epigenetically silenced genes, with promising clinical activity seen in poor risk older patients (pts) (Blum, J Clin Oncol. 2007). Methods: We designed a phase II study of decitabine for untreated AML pts of age≥60 who were not candidates for intensive chemotherapy (or who refused it). PS was ECOG &lt;3. All pts received induction with decitabine at 20mg/m 2 IV on days 1–10 of 4 week cycles. Pts with persistent AML at the end of a cycle received a repeat of the 10 day course, but responding pts received maintenance with abbreviated courses of 3–5 days depending on degree and duration of neutropenia. Results: 33 pts had median age of 74 years (range, 60–83). 15 pts had either secondary or t-AML. Median WBC count was 2400/μL (range, 400–58,800/μL) with marrow blasts of 44% (range, 21–92%). 13 pts had complex karyotype (≥3 abnormalities); 13 had normal karyotype; one pt had t(8;21). 31/33 pts had at least 2 poor-risk factors of age ≥70, antecedent hematologic disorder, unfavorable karyotype, or ECOG 2, and 28/33 had HCT-CI scores of ≥2. 42% of pts achieved CR (14/33). 58% achieved either CR or CRi (19/33). CR occurred in all subsets of disease and cytogenetic risk groups. CR durations to date are 2–14+ months. Median time from initial response to relapse for 6 pts who relapsed after CR was 6.5 months. Median OS has not been reached; median f/u of 19 surviving pts is 8 months. The median number of cycles received to date is 5 (range, 1–10). 9 of 14 pts who achieved CR required only a single 10 day course before initial response was achieved (CR, N = 2; CRi, N = 7). For pts who had CRi as initial response, the median number of additional cycles to achievement of full CR was 1 (range, 1–3). Death within 8 weeks of any cause occurred in 15% of pts (due to infection in each case). Though non-hematologic toxicities were infrequent, infection and/or febrile neutropenia were common (in 24/33 pts). Correlative studies are ongoing. Conclusions: Decitabine in this novel schedule of induction with outcome-adapted modification of maintenance therapy was highly active in this poor risk cohort. Survival results warrant comparison with intensive therapy for pts eligible to receive it. (supported by NO1-CM62207, K23 CA120708–01, RO1CA102031) [Table: see text]
A Mathematical Model of the Mitotic Cycle and Its Application to the Interpretation of Percentage Labeled Mitoses Data&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J. C. Barrett
Journal: JNCI Journal of the National Cancer Institute (1966)

A model of the mitotic cycle, with independent probability density functions for the durations of the phases G1, S, and G2, is examined. A Monte Carlo program for the computation of percentage labeled mitoses in accordance with the model is described and results are shown for log-normal distributions of the phase durations. This work is applied to the results of an experiment performed with transplanted Marshall rat mammary tumors. From the cell cycle times and age distributions thus obtained, the doubling time and labeling index are calculated and related to observed values.
MIX (mitomycin C, irinotecan, capecitabine) regimen in the treatment of advanced gastric cancer (AGC). A phase I study of the Gruppo Oncologico dell’Italia Meridionale (GOIM)
Authors: F. Giuliani, R. Romano, S. Romito, M. Di Bisceglie, D. Galetta, E. Maiello, G. Vinciarelli, R. Mallamaci, L. Manzione, G. Colucci
Journal: Journal of Clinical Oncology (2005)

4195 Background: In our previous experience the combination of MMC (M) and Irinotecan (I) demonstrated to be active in pretreated advanced gastric cancer pts. Capecitabine (X) more active than fluorouracil plus folinic acid and is synergic when combined with CPT-11 in patients with colorectal cancer. Taking into account these data the GOIM started a phase I study to determine the dose-limiting toxicities (DTLs) and the maximum tolerated dose (MTD) of the MIX triple drugs combination in AGC pts. Methods: M and I were administered at fixed doses, according to our previous experience, and as follow: M 8 mg/mq on day 8, I 150 mg/mq on day 1 and 15; X was administered at escalated doses starting from 1250 mg/mq p.o. in two divided doses, from 2 to 15 day, and increasing of 250 mg/mq at each dose level. The cycles were administered every 4 weeks. DLTs were evaluated in the first cycle and defined as: NCI grade 3–4 febrile neutropenia, grade 4 thrombocytopenia, and any ≥ grade 3 non haematologic toxicity. The MTD was defined as the dose level immediately below that at which the DLTs were observed in 2/3 patients. Results: Nine patients (male/female: 5/4) with median ECOG PS 1, were treated on 3 dose-levels. Dose escalation and DLTs are listed in the following table. A median of 3 cycles for patient was administered. On first and second dose level no grade 3–4 haematological toxicity was observed. At the third dose level, one pt had grade 3 febrile neutropenia that required hospitalizaton and one pt had grade 4 neutropenia without fever. Conclusions: In our study the DLT of the MIX combination therapy was neutropenia reached at the third dose level. The recommended dose for phase II-III studies is 8, 150, and 1500 mg/mq for the three drugs, respectively. A phase II study with this combination in previously untreated pts is started. No significant financial relationships to disclose.
Case 49-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Arlan F. Fuller, Joanne L. Rutgers
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 48-year-old woman was admitted to the hospital because of a question of renal colic.She was well until six weeks earlier, when she began to experience vague pains in the right lower quadrant of the abdomen as well as in the right flank that were ascribed to "muscle strain" and were treated with methocarbamol, without improvement. The pains waxed and waned until two days before admission, when they worsened greatly, became colicky, and were centered in the right lower abdominal quadrant, right groin, right anterior thigh, and right buttock. Because of persistent pain the patient came . . .