tbuckley/cabot-search huggingface dataset:
Book: The Discovery of the Germ
Authors: Birte Twisselmann
Journal: BMJ (2003)

John Waller offers an in-depth history of what he calls the “extraordinary, albeit bloodless, scientific revolution” that took place between 1880 and 1900. This was a time when medicine underwent perhaps its biggest transformation and the way we think about disease was changed forever. The story he tells reads like a thriller on more than one occasion. He fills in the background from 500 bc and explains the prevailing theories of disease over time—from poisonous miasmas to the humours of the renaissance—in an instructive and amusing manner. He charts through the millenniums the process of discovery that led to the knowledge that disease is not just related to individual qualities of each patient, that there is such a thing as a specific disease, and that one disease would not develop into another through bad luck or improper treatment.​treatment.




Figure 1



John Waller

Icon Books, £9.99, pp 198 ISBN 1 84046 373 2

Rating: ★★★★




While emphasising the merits of Robert Koch and Louis Pasteur and their teams, Waller makes it clear that the fantastic discoveries of the “big four” pathogens (those causing tuberculosis, cholera, typhoid, and rabies) did not come from nowhere but had been preceded by 2000 years of observation and investigation and by the insights and discoveries of other 19th century scientists.

These precursors included the Dutchman Anthony van Leeuwenhoek, who discovered “little animals” in white matter scraped from his teeth, the English epidemiologist John Snow, who proved that cholera is waterborne, the Austro-Hungarian doctor Ignaz Semmelweis, with his work on puerperal fever, and the surgeon Joseph Lister, who discovered the importance of handwashing procedures. The fact that the Koch and Pasteur teams were in constant competition with each other only served to push forward the march of science, and Waller's description of this competition makes the book into a real page turner.

As Waller himself says: “Only the term `revolutionary' can convey a proper sense of the magnitude of the change that medical practice has undergone.” The previous cynicism with which doctors greeted medical remedies was replaced by sound scientific knowledge. Discoveries about germs paralleled advances in public health, and their combined insights led to fundamental changes in general health and standards of living—and did so in a mere 100 years.

A useful bibliography of source material rounds off this remarkable little book. My only criticism: an index would have been useful.
Incidence, characteristics and treatment of fatigue in oncological cancer patients (PTS) in Italy: A cross-sectional study.
Authors: Fausto Roila, Francesco Spina, Carla Ripamonti, Guglielmo Fumi, Andrea Antonuzzo, Luigi Cavanna, Stefania Gori, Aurora Mirabile, Alessandra Fabi, Nicola Marzano, Claudio Graiff, Vitaliana De Sanctis, Samantha Serpentini, Chiara Bocci, Maria SIMONA Pino, Giuseppina Cilenti, Claudio Verusio, Stefania Eufemia Lutrino, Sonia Fatigoni, Enzo Ballatori
Journal: Journal of Clinical Oncology (2016)

e21623 Background: Fatigue is one of the most distressing symptoms of cancer pts. Incidence, characteristics, impact on quality of life and treatment of cancer-related fatigue in Italian oncological centers is not known. Methods: A cross-sectional study was carried out on all patients attending for any reason the 25 participating centers in two different days. Patients with fatigue filled out the Brief Fatigue Inventory (BFI) questionnaire and reported any pharmacological or non-pharmacological treatment for fatigue. Results: From October 2014 to May 2015, 1394 cancer pts, 581 males and 813 females, mean age 62.2 years, accepted entrance to the study. Pts with locally or locally advanced (302), metastatic (674) or with no evidence of disease (417) who were in the center to receive chemotherapy (683), targeted therapies (148), radiotherapy (95), supportive care (154) or for a follow-up visit (314) were evaluated. Fatigue was referred by 866 (62.1%) of the pts; its duration was > 4 months in 441 pts (50.9%). In the investigators opinion, the most important (probable or almost sure) determinants of fatigue were: reduced physical activity (271 pts), anxiety (149), pain (131), insomnia (125), anemia (123) and depression (123). Fatigue intensity when filling out the BFI was moderate (score 4-6) / severe (score 7-10) in 43% / 29.2% of pts, while the usual fatigue in the last 24 hours was 45% / 33.1%, and the worst fatigue in the last 24 hours was 33% / 54.8%, respectively. Concerning the impact on quality of life, fatigue interfered moderately / severely with general activity in 30.8% / 38.6%, with mood in 26.1% / 32.8%, with the ability to work in 27.9% / 35.6%, with normal work in 26.7% / 38.9%, with the relationships with others in 21% / 23.4% and with the ability to amuse themselves in 22.2% / 33.1%. Only 117/866 pts (13.5%) received a pharmacological treatment represented by a corticosteroid in 101 pts (86.3%) while 188 pts (21.7%) received a non-pharmacologial treatment such as physical exercise (120 pts, 63.8%) and various alimentary supplements (52 pts, 27.6%). Conclusions: Cancer-related fatigue is frequently reported by oncological pts; its intensity and impact on quality of life is relevant.
Preclinical study on the anti-tumor effect of H1 and H2 peptide.
Authors: Wanru Hou, Yiling Hou, Xiang Ding, Xia Liu, Xue Feng, Yu Yan, Jiangnan Feng
Journal: Journal of Clinical Oncology (2018)

e14565 Background: H1 is a peptide with 15 AA which can bind to a cell membrane protein. H2 is a peptide with 12 AA which can bind to EGFR. The sequence of these two peptides are completely consistent with human proteins. It is used conduct experiment to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity. Methods: H1 and H2 peptide are synthesized with Peptide Synthesizer. Some of H1 and H2 peptide are processed by using PEG. The experiment of Pharmacodynamics, pharmacokinetics, pharmacology, drug toxicity test and drug safety test are adopting conventional standards. An improved tomographic method was used for target protein combined with H1 peptide detection. H1 and H2 peptides are conjugated with FITC for Pharmacokinetics respectively. Results: H1 peptide can bind to a cell membrane protein of 47KD. H1 peptide can cause some tumor cell of cell line dead but not impact normal cell in vitro. The tumor growth inhibition rate of H1 peptide with the dose of 2 ug/kg was 69%, and rate of the Cyclophosphamide as positive contrast was 67% in vivo. The rate of H2 at the same dose was 53%. No pathological lesion of tissue and organs of experimental animal were observed by acute toxicity test and subchronic toxicity test at the dose of 400000 ug/kg of H1 or H2 peptide. The half-life period of H1 peptide in blood was 3.6 minutes, while the half-life period of H1 peptide with PEG processing was 156 minutes. Conclusions: H1 and H2 peptide have anti-tumor effect in vivo and in vitro. It is worth pointing out that the anti-tumor effect of H1 and H2 peptide is as strong as Cyclophosphamide but has no toxic side-effects.
Hepatitis c virus infection risk tool for patients with cancer.
Authors: Jessica Hwang, Harrys A. Torres, Anna Lok, Maria E. Suarez-Almazor, Carla L. Warneke, Ethan Miller, Ahmed Omar Kaseb, Erich M. Sturgis, Georgios Angelidakis, Sairah Ahmed, Alessandra Ferrajoli, Lorna H McNeill, Felipe Samaniego, Ernest Hawk
Journal: Journal of Clinical Oncology (2018)

e18694 Background: Hepatitis C virus (HCV) infection can cause adverse hepatic and oncologic outcomes in cancer patients. In the general population, HCV screening is recommended using risk-factor-based and 1945-1965 birth-cohort-based strategies; however, in cancer patients the optimal screening strategies have yet to be established. Methods: We prospectively enrolled 2122 patients at MD Anderson Cancer Center prior to first anticancer therapy during 7/2013-12/2014 and surveyed HCV risk factors, including birth year, injection drug use, blood transfusion or organ transplant before 1992, clotting factor concentrate before 1987, chronic liver disease, and HIV. We estimated HCV prevalence by positive HCV antibody (anti-HCV) and examined associations of demographic, clinical, and behavioral factors with HCV status using Fisher’s exact test or Student’s t-test. False negative rates (FNR) are given for 3 screening strategies: risk-based cohort (positive for ≥1 risk factor), birth-year risk cohort, or both cohorts combined. Results: Prevalence of anti-HCV was 1.93% (41 patients; 95% CI 1.39-2.61%) and highest among blacks (5.0%; 95% CI 2.2-9.6%), followed by whites (1.9%; 95% CI 1.3-2.6%). Participant race/ethnicity was white (76%), Hispanic (11%), black (8%), or Asian (4%). Median age was 59 years (range 18-91), and 54% were female. Primary cancer diagnosis was non-hepatocellular carcinoma (HCC) solid cancers (79%), hematologic cancers (20%), or HCC (1%). Education less than a bachelor’s degree, birth-year cohort, injection drug use, blood transfusion or organ transplant, and chronic liver disease were each significantly associated with detectable anti-HCV. Sixty-two percent (n = 1,315) of participants, including 39 of 41 with anti-HCV, reported ≥1 risk factor. FNR for the 3 screening strategies was 32% (95% CI 18−48%) for the risk-based cohort, 20% (95% CI 9−35%) for birth-year cohort, and 5% (95% CI 1−17%) for the combined strategy. Conclusions: Combined birth-year and risk-based screening was superior to either screening strategy alone; however, this approach increases the burden placed upon the medical teams and yet still miss 5% of infected patients. Thus, universal HCV testing may be more efficient in patients with cancer.
Secondary solid tumors in patients younger than 55 with chronic lymphocytic leukemia (CLL).
Authors: Jordan Spencer Carter, William May Lee, Rachel Nathan, Doris Maria Rivas, Ya Yu Liang, Maneesh Rajiv Jain, Kristine Marie Ward, Michael Styler
Journal: Journal of Clinical Oncology (2017)

10083 Background: Patients with CLL are at an increased risk of secondary solid tumors. Few studies have looked at this risk in patients &lt; 55, despite research suggesting that this is a distinct cohort with a longer overall survival. What data does exist has yielded variable results in limited populations. In light of this, our study utilized the SEER registry to look at secondary solid tumors in patients &lt; 55 with CLL. Methods: 4559 patients 15-54 years old with CLL were identified in the SEER registry between 1973 and 2013. Cancer risk was assessed using standardized incidence ratios (SIR) of observed (O) and expected (E) cancers. 95% confidence intervals (CI) were calculated assuming a Poisson distribution. Results where the CI = 1 were excluded. Results: 498 patients (O/E = 1.4) developed a secondary solid tumor after CLL with a mean age at diagnosis of 48.8 and 59.9 years for CLL and a second tumor, respectively. Higher than expected risk was seen in lip (O/E = 7.5), non-epithelial skin (O/E = 5.4), salivary (O/E = 4.8), mesothelioma (O/E = 4.4), melanoma (O/E = 3.1), lung (O/E = 2.4), and kidney (O/E = 1.7) cancers. Uterine cancer had a lower risk (O/E = 0.4). Stratifying the cohort by gender and race found that lip cancer in whites (O/E = 7.6) and men (O/E = 7.3), descending colon cancer (O/E = 13.3) in blacks and ureter cancer (O/E = 19.8) in women posed the highest risks. Lung cancer was the most prevalent among all groups. Secondary tumor risk was elevated in the &lt; 1, 1-5, 5-10, and 10-15 years after diagnosis with CLL (O/E = 2.3, 1.4, 1.5, and 1.4, respectively). The cancers with the highest SIR in each period were thyroid ( &lt; 1 year, O/E = 9.2), lung (1-5 years, O/E = 3.1), nose/ear (5-10 years, O/E = 11.8), and lip (10-15 years, O/E = 15.6). In 4459 patients &gt; 55 (O/E = 1.1), Kaposi sarcoma (O/E = 4.9), non-epithelial skin (O/E = 3.6), salivary (O/E = 2.8), melanoma (O/E = 2.1), nose/ear (O/E = 2.0), lip (O/E = 1.7), soft tissue (O/E = 1.6), lung (O/E = 1.4), kidney (O/E = 1.3), and colon cancers (O/E = 1.2) were significant. Conclusions: Patients &lt; 55 have a unique tumor profile and greater risk of secondary solid tumors compared to patients &gt; 55. This risk differs on the basis of gender, race, and survival time. Further research may help influence screening guidelines.
Maintenance therapy with pemetrexed and bevacizumab versus pemetrexed monotherapy in non-squamous non-small-cell lung cancer.
Authors: Masato Karayama, Naoki Inui, Tomoyuki Fujisawa, Noriyuki Enomoto, Yutaro Nakamura, Shigeki Kuroishi, Koshi Yokomura, Naoki Koshimizu, Masaki Sato, Mikio Toyoshima, Toshihiro Shirai, Masafumi Masuda, Takashi Yamada, Shiro Imokawa, Takafumi Suda
Journal: Journal of Clinical Oncology (2016)

e20504 Background: Maintenance therapy with pemetrexed is accepted as a standard therapy for advanced non-squamous non-small-cell lung cancer (NSCLC). Bevacizumab improves the efficacy of chemotherapy in combination with cytotoxic agents; however, clinical benefit of adding bevacizumab to the maintenance therapy remains unclear. We previously reported a randomized phase II study comparing maintenance therapy with pemetrexed plus bevacizumab and pemetrexed monotherapy in patients with non-squamous NSCLC. Here we reported the upgraded analysis regarding survival profiles measured from the start of maintenance therapy. Methods: Chemotherapy-naïve patients with non-squamous NSCLC were assigned to receive four cycles of carboplatin (AUC 6), pemetrexed (500 mg/m2), plus bevacizumab (15 mg/kg) on day 1 of a 21-day cycle, followed by the maintenance therapy with pemetrexed plus bevacizumab (PB group) or pemetrexed alone (P group). Results: One hundred ten patients (55 patients in each group) were enrolled in the study. The median PFS from the start of maintenance therapy was 8.3 months (95% CI: 4.0–11.4) in PB group and 6.3 months (95% CI: 2.9–9.1) in P group (HR: 0.74, 95% CI: 0.42–1.30, p = 0.29). The median OS was 21.8 months (95% CI: 15.9–not estimable) in PB group and 23.3 months (95% CI: 16.8–not estimable) in P group (HR: 1.14, 95% CI: 0.53–2.54, p = 0.73). Nasal hemorrhage, hypertension, and proteinuria at all grades were significantly more frequent in PB group (29.1%, 30.9%, and 52.7%, respectively) than P group (12.7%, 21.8%, and 21.8%), but they were mild and tolerable. Conclusions: Compared with pemetrexed monotherapy, maintenance therapy with pemetrexed plus bevacizumab demonstrated a non-significant longer PFS measured from the start of maintenance therapy, with an increased risk of non-severe bevacizumab-associated adverse events. Clinical trial information: 000010002.
Evaluation of online search (OS) by patients with cancer in a private (Pr) and a public (Pu) institution.
Authors: Diego Espinoza, Victor Pastrana, Florencia Menocal, Gustavo Correa Zeballos, Elisa Arroyo, Rodrigo Segovia, Jorge Raul Arcuri, Juan Jose Zarba
Journal: Journal of Clinical Oncology (2017)

e18059 Background: Information technologies, such as Internet, have an impact on the field of medicine. Cancer diagnosis leads patients (pts) to inform about their illness. Objectives: To determine the percentage and motivation of pts who browse online about their illness. The most frequent cause to avoid OS according to the institution. Whether OS had an influence on the therapeutic decision. Whether the educational level (EL) and Age Cohort (AC) are related to the frequency of OS. Methods: Descriptive, cross-sectional study. The data was collected from anonymous surveys to pts who made a consult from March to April, 2015 in Pu; and from February to April, 2016 in Pr Results: 360 surveys were made. 180 in Pr, and 180 in Pu. Gender: 55% female. AC: 4% 18-31 y; 13% 32-45 y; 38% 46-59 y; and 45% of 60 y or older. EL: Elementary 43%; High school 42%; College/University 15%. OS: Pu: 17%. Pr: 32%. Reasons to avoid OS: The info provided by the doctor is enough Pr: 24% Pu: 16%; Pr 18.69%, Pu 1.35% avoid further info; Pr 40%, PuI 35% ignore how to use the Internet; Pr 17%, Pu 47% lack Internet access. Reasons for OS: the doctor does not provide enough info Pr 39% Pu 14%; to add further info: Pr 61% Pu 86%. Considers trustworthy info: Always Pr 13% PuI 31%; Sometimes Pr 81% PuI 66% Never Pr 6% PuI 6%.Useful information to make decisions about their treatment: Pr 83% Pu 81% EL/OS:p = 0.001. AT/OS: p = 0.001. Institution/OS:p = 0.001. Conclusions: More than 75% of pts did not consult online mainly due to lack of internet access. 20% considers that the information is always trustworthy, in 80% was useful for the decision making of their treatment. A significant relation among EL, AC and the institution was found, thus showing that the younger the age –and the higher the academic training-, the more OS is made by oncology pts. That is the reason why we consider that raising awareness about these factors in order to properly guide pts into an adequate and trustworthy OS could improve the process of decision making.
Circulating tumor DNA in advanced lung cancers: A prospective evaluation of matched therapy and shedding detection.
Authors: Michael David Offin, Dennis Stephens, Joshua K. Sabari, Alex Makhnin, Mackenzie Myers, Ai Ni, Nick Pavlakis, Stephen John Clarke, Nidhi Tandon, Sutirtha Datta, Lee Lim, Mark Li, Maria E. Arcila, Valerie W. Rusch, David Randolph Jones, Alexander E. Drilon, Charles M. Rudin, Andreas Rimner, James M. Isbell, Bob T. Li
Journal: Journal of Clinical Oncology (2018)

e21234 Background: Liquid biopsy of circulating tumor DNA (ctDNA) by next generation sequencing (NGS) is widely adopted in clinical practice. ctDNA shedding across different lung cancer histologies, metastatic sites, and survival benefit in patients (pts) matched to therapy is not known. Methods: Pts with advanced lung cancers with driver unknown or progression on targeted therapy were eligible. 200 pts from 10/2016 – 11/2017 with confirmed lung cancer were enrolled. Plasma ctDNA NGS was performed using a bias corrected hybrid capture 21 gene assay. Clinical endpoints included mutation and oncogenic driver detection, rate matched to therapy, shedding detection measured by site of metastases and site of maximum PET avidity, and OS. Results: 200 pts were evaluated; 58% female, median age 66 (range 28 - 91). 57% former smokers. 93% were metastatic and 62% were treatment naïve. Histologies included 86% adenocarcinoma, 5% squamous, 5% poorly differentiated, and 4% neuroendocrine. Median turnaround time for plasma result was 7 days [95% CI 6 – 8] and 21 days [95% CI 20-21] for tissue (p < 0.001). Plasma ctDNA was detected in 66% of pts (128/194; 6 test failures) 57% (73/128) of those were smokers (p = 0.9). ctDNA was detected in 62% (103/164) of adenocarcinoma pts versus 83% (30/36) with other histologies (p = 0.03). ctDNA detection based on metastatic site at the time of draw was: lung 94% (p = 0.95); nodal 72% (p = 0.8); pleura 38% (p = 0.21); bone 44% (p = 0.7); liver 20% (p = 1.0); visceral/adrenal 20% (p = 0.8); soft tissue 12% (p = 0.7); brain 26% (p = 0.13). 65% had PET scans within 3 months of draw, medium maximum SUV was 11.45, 69% (88/127) of which had ctDNA detected. 47% (42/88) of pts with maximum SUV ≥ median had ctDNA detected, p = 0.37. 21% of evaluable pts were matched to therapy, of whom 72% (28/39) had clinical response; median time from draw to treatment of 18 days. OS was 12 months versus 11 for those not matched (HR 0.81 [95% CI 0.37 – 1.8]; p = 0.61). Conclusions: Liquid biopsy detected actionable drivers with shorter turnaround and matched pts to therapy resulting in clinical response. Detection of ctDNA was higher in non-adenocarcinoma histologies and was not significantly associated with smoking, site of metastasis or PET SUV.
Patterns of utilization of imaging and tumor markers (TM) among metastatic breast cancer (MBC) patients (pts).
Authors: Antonio Di Meglio, Nancy U. Lin, Rachel A. Freedman, William Thomas Barry, Eric P. Winer, Ines Vaz Luis
Journal: Journal of Clinical Oncology (2016)

e18224 Background: The optimal strategies for utilization of imaging and TM, and how to integrate both among MBC pts are unclear. Methods: In aretrospective cohort study of pts with de novo MBC treated at Dana-Farber Cancer Institute from 2000-12, we described the type of imaging requested at baseline and used multivariate cox models to assess features associated with timing of subsequent disease re-evaluations, including use of TM. Results: Among 302 pts, median age at diagnosis was 54 (range 23-92); 67% had hormone receptor (HR)+, 23% had human epidermal growth factor receptor-2 (HER2)+, and 10% had HR-HER2- tumors. All pts had baseline scans, mostly computed tomography + bone scan (52%). Use of 18F-Fluoride positron-emission tomography increased over time (18% in 2000-02 vs. 40% in 2009-12). 30% of pts had central nervous system (CNS) evaluation, but only 7% presented with CNS-related symptoms, with no time trend for use of baseline CNS scans. 78% of pts had baseline TM testing. Subsequently, 87% of pts had at least 1 TM test, including 90% of the 17% of pts with normal baseline TM. Over a 6 month period, 43% of pts had >6 TM tests. Table 1 shows the analysis of re-evaluation times. Site of disease and year of diagnosis, but not use of TM (regardless of normal/abnormal values) were associated with time to first re-imaging. Conclusions: Patterns of imaging utilization appear to be appropriately influenced by factors including site of disease, while TM testing, although frequently ordered, did not impact on the timing of imaging. We encourage further studies to validate the true utility of TM and to avoid overuse. Timing of re-evaluations. Median time, days (range) Time from baseline to firs Re-imaging 91 (13-581) TM test 31 (5-480) Time between subsequent 107 (25-365) Imaging 41 (12-366) TM tests Hazard ratios* of time to first re-imaging (95% Confidence Interval) Metastatic Site . Bone 1 Brain 4.6 (1.6-13.2) Liver 2.3 (1.5-3.6) Lung 2.9 (1.7-4.8) Other 2.5 (1.5-4.3) Year of diagnosis 1 2000-02 1.8 (1.1-2.1) 2006-08 1.4 (1.0-2.3) 2009-12 1 TM tested 1.1 (0.8-1.5) No Yes *Adjusted for age, marital status, education, race, employment, comorbidities, histology, subtype, grade, n. of sites, symptoms, and therapy.
Bioactive Silk‐Based Nerve Guidance Conduits for Augmenting Peripheral Nerve Repair
Authors: Adrián Magaz, Alessandro Faroni, Julie E. Gough, Adam J. Reid, Xu Li, Jonny J. Blaker
Journal: Advanced Healthcare Materials (2018)

Abstract Repair of peripheral nerve injuries depends upon complex biology stemming from the manifold and challenging injury‐healing processes of the peripheral nervous system. While surgical treatment options are available, they tend to be characterized by poor clinical outcomes for the injured patients. This is particularly apparent in the clinical management of a nerve gap whereby nerve autograft remains the best clinical option despite numerous limitations; in addition, effective repair becomes progressively more difficult with larger gaps. Nerve conduit strategies based on tissue engineering approaches and the use of silk as scaffolding material have attracted much attention in recent years to overcome these limitations and meet the clinical demand of large gap nerve repair. This review examines the scientific advances made with silk‐based conduits for peripheral nerve repair. The focus is on enhancing bioactivity of the conduits in terms of physical guidance cues, inner wall and lumen modification, and imbuing novel conductive functionalities.