tbuckley/cabot-search huggingface dataset:
A randomized phase II neoadjuvant study (GeparNuevo) to investigate the addition of durvalumab, a PD-L1 antibody, to a taxane-anthracycline containing chemotherapy in triple negative breast cancer (TNBC).
Authors: Sibylle Loibl, Michael Untch, Nicole Burchardi, Jens Bodo Huober, Jens Uwe Blohmer, Eva-Maria Grischke, Jenny Furlanetto, Hans Tesch, Claus Hanusch, Mahdi Rezai, Christian Jackisch, Wolfgang D Schmitt, Gunter Von Minckwitz, Jörg Thomalla, Sherko Kummel, Beate Rautenberg, Peter A. Fasching, Kerstin Rhiem, Carsten Denkert, Andreas Schneeweiss
Journal: Journal of Clinical Oncology (2017)

3062 Background: Adding an anti-PD-L1 checkpoint inhibitor durvalumab to standard chemotherapy (CT) may increase pathological complete response (pCR) in patients (pts) with TNBC. Methods: GeparNuevo randomizes pts to durvalumab (D) 1.5 g i.v. or placebo (pl) every 4 weeks (wks). D/pl monotherapy (0.75 g i.v.) is given for the first 2 wks (window phase), followed by a biopsy and D/pl plus nab-paclitaxel (nP) 125 mg/m² weekly for 12 wks, followed by D/pl plus epirubicin/cyclophosphamide (EC) q2 wks for 4 cycles. Randomization is stratified by stromal TILs (sTILs) (low (≤10%), intermediate (11-59%), high (≥60%)). Pts with primary cT1b-cT4a-d disease, centrally confirmed TNBC, and sTILs status can be included. Primary objective compares pCR (ypT0 ypN0) rates. Secondary objectives are pCR rates in stratified subpopulations and according to other pCR definitions; response rates; breast conservation rate; toxicity; compliance and survival. Change in sTILs, Ki67 and other immune biomarkers before CT, after the window phase and after CT will be correlated with outcome. The first 10, 20 and 30 pts will be included in safety interim analyses (SIA). Sample size was planned assuming a pCR rate of 48% for pl (nP treated TNBC cohort in GeparSepto) and of 66% for D (as clinically meaningful benefit), requiring 158 pts to show superiority of D (2-sided α = 0.2, 80% power). Assuming a 10% drop-out rate 174 pts will be randomized. Results: Since 6/2016, 50 pts were recruited within 16 sites; data are presented as available until 01/2017. Median age is 49 years; 86% NST and G3 tumors; sTILs categories 40% low, 40% intermediate and 20% high. Blinded SIA was performed. No pt interrupted D/pl, one nP and one EC. Treatment delay was observed in 9 pts (20.0%) in D/pl, 18 (41.9%) in nP and 2 (13.3%) in EC; dose was reduced in 10 pts (23.3%) in nP and in 4 (26.7%) in EC. 10 pts (20%) had at least one grade 3-4 AE: 4 haematological and 6 non-haematological AEs. 4 SAEs and 5 immune related AEs were reported. 2 pts discontinued study treatment prematurely in the EC phase. Conclusions: The addition of D to standard nP-EC is feasible and does not result in an increased toxicity. Clinical trial information: NCT02685059.
Programmed death-ligand 1 characterization of circulating tumor cells and white blood cells in muscle-invasive and metastatic bladder cancer patients.
Authors: Terence W. Friedlander, David Lu, Rachel Krupa, Gayatri Premasekharan, Christopher J. Welty, Rosa Paz, Adam Jendrisak, Mark Landers, Jessica Louw, Sarah Orr, Dena Marrinucci, Lawrence Fong, Ryan Vance Dittamore, Pamela Paris
Journal: Journal of Clinical Oncology (2015)

353 Background: Muscle invasive(MIBC) and metastatic (mBCa) bladder cancer patients have few options to extend survival. Recent studies have shown that PD-1 and programmed death-ligand 1 (PD-L1) checkpoint inhibitors have activity even in chemotherapy refractory patients and it has been proposed that PD-L1 expression on tumors or lymphocytes may correlate with response to therapy. To identify potential patients who may benefit from PD-1/PD-L1 targeted immunotherapeutics, we utilized a non-invasive, real-time blood test for PD-L1 protein expression in circulating tumor cells (CTCs) and white blood cells (WBCs) of bladder cancer patients. Methods: Twelve blood samples from unique patients with MIBC or mBCa were collected and shipped to Epic Sciences. All nucleated cells were plated onto glass slides and subjected to IF staining and CTC identification by fluorescent scanners and algorithmic analysis. CTCs, defined as traditional (CK+ CD45- w/ intact DAPI nuclei and morphologically distinct) or CK- (CK-, CD45-, intact and distinct) were identified. PD-L1 biomarker characterization was assessed by IF staining, and UroVysion FISH testing was used to assess genomic abnormalities in a subset of patient samples. Additionally, WBCs (CD45+ cells) were assessed for PD-L1 expression. Results: Traditional CTCs were detected in 6/12 (50%) patients. 3/12 (25%) patients had PD-L1+ cells, 2 of these patients were exclusively CK-/PD-L1+ CTCs, which were confirmed as cancer via FISH. CK- CTCs were detected in 83% (10/12) patients. 5 patients had greater than 4 fold PD-L1 positivity in WBCs as compared to healthy donor controls. Conclusions: MIBC and mBCa patients have detectable CTCs with a high frequency of CK-/PD-L1+ CTCs. Utilization of a liquid biopsy to identify patients with PD-L1+ CTCs and PD-L1+ WBCs may enable both patient selection or short term therapeutic monitoring for measuring pharmacodynamics to ensure therapy effectiveness. Further studies are planned to investigate association of PD-L1+ CTCs and WBCs with response to PD-1 and PD-L1 checkpoint immunotherapy.
Light and electron microscopic studies of physical injury to the skin I. Suction
Authors: J. A. A. HUNTER, EVA McVITTIE, J. S. COMAISH
Journal: British Journal of Dermatology (1974)

Suction applied to the skin causes almost immediate paranuclear vacuolization in keratinocytes but does not affect the dendritic cells. If suction is prolonged dermo‐epidermal separation occurs at a level between the basal cell membrane and basal lamina.
Declining Semen Quality and Increasing Incidence of Testicular Cancer: Is There a Common Cause?
Authors: Elisabeth Carlsen, Aleksander Giwercman, Niels Keiding, Niels E. Skakkebaek
Journal: Environmental Health Perspectives (1995)

Male reproduction has been given little attention in science and in medical practice.However, a recent metaanalysis on semen quality, which clearly pointed to a decrease over the past 50 years, has been repeatedly quoted.Three recent reports have found that semen quality has declined among candidate semen donors during the past 20 years.The evidence of decline in the quality of semen is not the only indicator that the human testis is at risk.During the past 50 years, cancer of the testis has also become more common.This is a disorder of young men, and it is associated with a high rate of other abnormalities of the testis including undescended testis and poor semen quality.Furthermore, the incidence of both hypospadias and undescended testis has been reported to be rising in the general population.We believe that the evidence of declining semen quality should be seen in the light of these trends in other reproductive disorders of men.However, the etiology is unknown.A recent hypothesis that links the trends in the health of the male reproductive system to xenoestrogens in the environment is discussed.
Effect of HMG-Co-Reductase Inhibitor Use on 1-Year Mortality and Hospitalization Rates in Elderly Cardiovascular Disease Patients in Nursing Homes
Authors: Charles B Eaton, Kate L Lapane, John B Murphy, Anne L Hume
Journal: Circulation (2001)

P43 Background:The risks and benefits of HMG-Co-Reductase Inhibitor therapy in elderly cardiovascular disease patients is not known. Aims: To compare the effects of statins on the 1-year mortality, and hospitalization rate in a cohort of elderly CVD patients. Methods: We conducted a historical cohort study using the SAGE database (1992-1997), a long-term care database linking patient clinical information with data on drug utilization, hospital discharges, and death. Among 51,599 newly admitted nursing home patients with CVD, we compared 1313 statin users to non-users matched by facility. The effects of statins on outcomes was estimated using a Cox proportional hazards model. Results: Prevalence of statin use in this CVD cohort was 2.5%. Statin use varied by age, gender, co-morbid condition,CHD risk factors, medication use, cognitive and physical function(p&lt;.05). The number of deaths at one year was 265 in the statin users and 410 in the non-users. The 1-year all-cause mortality adjusted hazards ratio comparing statin users to non-users was HR=0.73, 95%CI (0.61-0.87). Number needed to treat(NNT)was 9. Results were similar for men and women, and for ages 65-74, 75-84, and 85 and older. Similar results were found for 1-year rates of hospitalization. Conclusion: HMG-Co-reductase inhibitor therapy appears to signficantly reduce 1-year all-cause mortality and hospitalization rates in a frail elderly population after adjusting for potential confounding.
MEDICAL SOCIETY OF NEW JERSEYOne Hundred and Forty-fourth Annual Meeting, held at Atlantic city, June 28-30, 1910
Journal: JAMA (1910)

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 Journals 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 2024 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
Course in Hospital Epidemiology
Journal: JAMA (1996)

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
Plasma Tumor Necrosis Factor Levels in Patients With Presumed Sepsis
Authors: Mary Ann de Groote
Journal: JAMA (1989)

Using an enzyme-linked immunosorbent assay, we measured plasma levels of tumor necrosis factor (TNF) in 38 patients who were treated with either antilipid A antibody or a placebo for presumed gram-negative bacteremia. Sixteen of the 38 patients had positive blood cultures: 14 with gram-negative rods and 2 with<i>Streptococcus pneumoniae</i>. Initial serum samples for TNF determinations were obtained within 2 to 72 hours (mean, 18.8 hours) after the onset of clinical signs of sepsis. Six (16%) of 38 patients had detectable TNF levels: 4 of 14 with positive blood cultures for gram-negative rods but only 2 of 22 with negative blood cultures (odds ratio, 4; 95% confidence limits, 0.5 and 24.3). Of the 6 patients, 4 had received the placebo and 2 had received the antibody. Tumor necrosis factor levels did not predict adult respiratory distress syndrome, shock, disseminated intravascular coagulation, renal failure, or mortality. The highest TNF levels (500 and 250 pg/mL) were observed in 2 patients with<i>Enterobacter cloacae</i>bacteremia who had received the placebo and antilipid A antibody, respectively. The other 2 patients with bacteremia and detectable TNF levels had positive blood cultures for<i>Haemophilus influenzae</i>(50 pg/mL) and<i>Bacteroides fragilis</i>(120 pg/mL), respectively. Despite negative blood cultures, the remaining 2 patients repeatedly had detectable TNF levels and a clinical picture consistent with gram-negative sepsis. (<i>JAMA</i>. 1989;262:249-251)
Table of Diseases Treated Between the 24th of February, 1843, and the 31st of January, 1846
Authors: G. Fife
Journal: BMJ (1846)

hsemorrhage before, during, and after, labour in the latter months of pregnancy; and it must always be reiuem.bered that its application need not, in any way, lead us to naglect the ordinary methods of treating these cases, if there is any reason for giving them a previous trial.Of course from this statement must be excepted the old plan of delivering the child where great exhaustion of the inother is present, to supersede which practice galvanism was specially broughL forward.
Amyotrophic Lateral Sclerosis
Authors: Lewis P. Rowland, Neil A. Shneider
Journal: New England Journal of Medicine (2001)

Charcot described amyotrophic lateral sclerosis (ALS) in 1874. Despite progress, this creeping paralysis, known colloquially as Lou Gehrig's disease, is still not visibly affected by available therapies. However, advances in genetics have accelerated the pace of ALS research in the past decade, promising more effective treatment.Definition of the DiseaseALS has two meanings. In one sense, it refers to several adult-onset conditions characterized by progressive degeneration of motor neurons (Figure 1). In the United Kingdom, the term motor neuron disease is used for these disorders. In the second sense, ALS refers to one specific form of motor neuron disease . . .
Is Vitamin B12 of Value in Psoriasis?
Journal: JAMA (1963)

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
Legislation, Regulation, Drug Lag, and New Drugs
Journal: JAMA (1979)

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
Hepatology Highlights
Authors: Neil Kaplowitz
Journal: Hepatology (2004)

Serum alanine aminotransferase (ALT) is an universally employed marker of liver injury. ALT is present in most tissues. Two forms of human ALT have been described, encoded by two genes on separate chromosomes. Since there are two ALTs, Jadaho et al. initiated studies that could permit the testing of the hypothesis that isoenzyme-specific assay of ALT might improve diagnostic value in liver disease. They cloned the murine homologs of human ALT1 and ALT2. Mouse ALT2 messenger RNA was highly expressed in muscle, liver, and white adipose tissue, whereas mouse ALT1 was expressed in liver, white adipose tissue, intestine, and colon. Compared to lean mice, ob/ob mice expressed increased (double) mouse ALT 2 messenger RNA (but not ALT1) and about a 30% increase in liver ALT, but not aspartate aminotransferase, enzyme activity. Unfortunately, serum ALT and its isoenzyme pattern was not reported. However, this is a very interesting study, as it paves the way for examining the source of ALT in normal and diseased mouse models and ultimately humans using isoenzyme specific immunoassays, yet to be developed. It remains to be demonstrated that such an approach will yield improved diagnostics. Furthermore, since the expression of ALT2 is not static, as seen in fatty liver, this study raises the question of interpretation of mild ALT abnormalities. Does a mild increase in serum ALT reflect injury or the “physiological” release of ALT from a liver with more ALT? Serum ALT can be increased in rhabdomyolysis, causing confusion regarding liver injury. Since ALT1 is not expressed in muscle, in theory a raised serum ALT activity without an increase in the serum ALT1 isoenzyme might be useful in excluding liver injury. However, since both ALT1 and ALT2 are expressed in liver, the interpretation of the relative increases in serum may be difficult without knowledge of expression in the liver. (See HEPATOLOGY 2004;1297–1302.)
Freshwater wound infection due to Aeromonas hydrophila
Authors: P. G. Hanson
Journal: JAMA (1977)

<i>AEROMONAS hydrophila</i>is a Gramnegative bacillus, member of the family Vibrionaceae, which is a common inhabitant of freshwater lakes and streams.<sup>1-4</sup>It is not commonly identified as an agent of human infection. Most reports have described gastroenteritis, septicemia, meningitis, pneumonia, or surgical wound infections, primarily in immunocompromised patients.<sup>1,4-8</sup> Infections of immunologically competent persons have been rare. We report a well-documented case of severe cellulitis in a previously healthy young man that derived from a laceration acquired during swimming.<i>Aeromonas hydrophila</i>was recovered in large numbers from the wound and was subsequently shown to be the major bacterial contaminant of the freshwater lake where the injury occurred. The clinical features of<i>Aeromonas</i>infections of freshwater traumatic wounds suggest a characteristic syndrome, indistinguishable from cellulitis caused by group A<i>Streptococcus</i>. <h3>Report of a Case</h3> A 22-year-old man sustained a full-thickness scalp laceration while diving in shallow water in Lake Mendota,
Late phase II study of amrubicin in previously untreated patients with non-Hodgkin’s lymphoma (NHL)
Authors: K. Suzuki, N. Uike, J. Suzumiya, F. Kawano, T. Takeo, S. Okamura, C. Sakai, M. Mori, K. Tamura
Journal: Journal of Clinical Oncology (2005)

6644 Background: Amrubicin (AMR), a totally synthetic 9-amino-anthracycline, demonstrated excellent combination activity with cyclophosphamide (C), vincristine (O), and predonisolone (P) for NHL. The aim of this trial was to confirm the reproducibility of strong efficacy and safety of AMR in combination with COP for 8 cycles of the therapy. Methods: Eligibility criteria were defined as 20 to 74 year-old previously-untreated patients who were diagnosed as having histologically-proven intermediate- to high-grade NHL according to Working Formulation classification, a stage II, III, or IV disease, an ECOG PS of 0–2, and adequate organ function. AMR (100mg/m2), C (750mg/m2) and O (1.4mg/m2, up to a maximal dose of 2 mg) were administered intravenously on day 1, and P (60mg/m2) was orally administered on day 1 to 5 of each cycle. Treatment was repeated every 3 weeks for 8 cycles. Assuming 50 eligible patients (pts) and a true CR rate of 70% (based on previous clinical results of AMR), the study had 80% power to demonstrate that a lower limit of 95% confidence interval (C.I.) of CR rate is more than 50%. Results: A total of 63 pts were enrolled and 57 of them were eligible. Median age was 59 years and 75.4% of pts had diffuse large B-cell lymphoma histology. Eight cycles of treatment were completed in 80.7% of the pts. The CR rate (including 14.3% of CRu) and response rate (CR+PR) were 69.6% and 92.9%, respectively. Thus the lower limit of 95% C.I. of CR rate was calculated to be 55.9%. Grade 3/4 neutropenia and leukopenia were experienced in 100% and 82.5% of patients, respectively. Grade 3/4 non-hematological adverse events more than 5% in frequency were constipation (15.8%), anorexia (10.5%), infection (5.3%). Severe or irreversible cardiac toxicity of AMR, and treatment related death were not observed. Conclusions: The excellent activity of AMR in combination with COP against untreated intermediate-grade or high-grade non-Hodgkin’s lymphoma has been demonstrated. The most common adverse events observed were grade 3/4 neutropenia and leukopenia. Irreversible cardiac toxicity of AMR did not occur. No significant financial relationships to disclose.
Therapeutics.
Journal: JAMA (1904)

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 Journals 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 2024 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