tbuckley/cabot-search huggingface dataset:
Lymelight: forecasting Lyme disease risk using web search data
Authors: Adam Sadilek, Yulin Hswen, Shailesh Bavadekar, Tomer Shekel, John S. Brownstein, Evgeniy Gabrilovich
Journal: npj Digital Medicine (2020)

Abstract Lyme disease is the most common tick-borne disease in the Northern Hemisphere. Existing estimates of Lyme disease spread are delayed a year or more. We introduce Lymelight—a new method for monitoring the incidence of Lyme disease in real-time. We use a machine-learned classifier of web search sessions to estimate the number of individuals who search for possible Lyme disease symptoms in a given geographical area for two years, 2014 and 2015. We evaluate Lymelight using the official case count data from CDC and find a 92% correlation ( p &lt; 0.001) at county level. Importantly, using web search data allows us not only to assess the incidence of the disease, but also to examine the appropriateness of treatments subsequently searched for by the users. Public health implications of our work include monitoring the spread of vector-borne diseases in a timely and scalable manner, complementing existing approaches through real-time detection, which can enable more timely interventions. Our analysis of treatment searches may also help reduce misdiagnosis of the disease.
The road to real‐time, bedside, optical imaging pathology: basal cell carcinoma and beyond
Authors: C. Navarrete‐Dechent, A.A. Marghoob, C.‐S.J. Chen
Journal: British Journal of Dermatology (2020)

Linked Article:Pérez‐Anker et al. Br J Dermatol 2020; 182:468–476.
Association of SMAD4 loss with response to neoadjuvant chemotherapy with the autophagy inhibitor hydroxychloroquine in patients with pancreatic adenocarcinoma.
Authors: Naomi Fei, Sijin Wen, Pavan Rao, Rajesh Ramanathan, Melissa E. Hogg, Amer H. Zureikat, Michael T. Lotze, Nathan Bahary, Aatur D. Singhi, Herbert Zeh, Brian A. Boone
Journal: Journal of Clinical Oncology (2020)

761 Background: SMAD4, a tumor suppressor gene, is inactivated or deleted in 60-90% of pancreatic adenocarcinomas (PDA). Loss of SMAD4 allows tumor progression by limiting cell cycle arrest and apoptosis and increasing metastases. SMAD4 deficient PDA cells are resistant to radiotherapy by upregulation of autophagy, a cell survival mechanism that allows intracellular recycling of macromolecules and organelles. Hydroxychloroquine (HCQ) is a known autophagy inhibitor, suggesting that HCQ treatment in SMAD4 deficient PDA may prevent therapeutic resistance induced by autophagy upregulation. Methods: We retrospectively analyzed the SMAD4 status of PDA patients enrolled in two prospective clinical trials evaluating preoperative HCQ. The first dose escalation trial demonstrated the safety of preoperative gemcitabine with HCQ ( NCT01128296 ). More recently, a randomized trial of gemcitabine/nab-paclitaxel +/- HCQ evaluated Evans Grade histopathologic response ( NCT01978184 ). Immunohistochemistry of resected specimens for SMAD4 was previously performed. Patients not treated at the max HCQ dose (n = 5), not resected (n = 2) or with SMAD4 staining unavailable were excluded (n = 10). The effect of SMAD4 loss on response to HCQ and chemotherapy was studied for association with clinical outcome. Fisher’s exact test and log-rank test were used to assess response and survival. Results: 52 patients receiving HCQ with neoadjuvant chemotherapy and 24 patients receiving neoadjuvant chemotherapy alone were studied. Of the HCQ group, 25 patients had SMAD4 loss (48%), compared with 15 control patients (63%, p = 0.32). 76% of HCQ treated patients with SMAD4 loss obtained a histopathologic response ≥2A, compared to only 37% with SMAD4 intact (p = 0.006). In the control group, loss of SMAD4 was associated with a nonsignificant detriment in 3 year OS (25% vs. 78%, p = 0.3) that was less apparent in patients treated with HCQ (46% vs. 47%, p = 0.18). Conclusions: The addition of HCQ to neoadjuvant chemotherapy in PDA may improve treatment response in patients with SMAD4 loss. Further study of the relationship between SMAD4, autophagy and treatment outcomes in PDA is warranted.
Laparoscopic versus open total gastrectomy for clinical stage I gastric cancer: Morbidity and mortality results from a prospective randomized multicenter controlled trial (CLASS02).
Authors: Fenglin Liu, Changming Huang, Zekuan Xu, Xiangqian Su, Gang Zhao, Jianxin Ye, Xiaohui Du, Hua Huang, Jiankun Hu, Guoxin Li, Peiwu Yu, Yong Li, Jian Suo, Naiqing Zhao, Wei Zhang, Haojie Li, Hongyong He, Yihong Sun
Journal: Journal of Clinical Oncology (2020)

378 Background: The safety of laparoscopic total gastrectomy (LTG) for the treatment of gastric cancer remains lack of clinical evidence. The aim of this study was to compare the safety of LTG for clinical stage I gastric cancer with the conventional open total gastrectomy (OTG). Methods: From January 2017 to September 2018, a total of 227 patients with clinical stage T1N0-1M0/T2N0M0 gastric cancer were enrolled in this clinical trial and randomly assigned to Laparoscopic Gastrectomy group (LG, n=113) or Open Gastrectomy group (OG, n=114). The morbidity and mortality within 30 days following surgery, the recovery course, and the postoperative hospital stay between LG group (n=105) and OG group (n=109) were compared. Clavien-Dindo classification system was used to stratify surgical complications. Results: The overall morbidity rate was not significantly different in each group (LG group: 19.05%; OG group: 20.18%; Rate difference [RD]: -1.14%, 95%CI, -11.75%-9.58%). Intraoperative complications occurred in 3 (2.86%) patients in LG group and 4 (3.67%) patients in OG group (RD: -0.81%, 95%CI, -6.52%-4.85%). In addition, there was no significant difference in the overall postoperative complication rate of 18.10% in LG group and 17.43% in OG group (RD: 0.66%, 95%CI, -9.61%-11.01%). Each subtypes of postoperative complication were not significantly different between groups. One patient in LG group died of intra-abdominal bleeding from splenic artery, and there was no significant difference in mortality between LG group and OG group (RD: 0.95%, 95%CI, -2.54%-5.20%). The distribution of severity was similar between the two groups. Conclusions: Experienced surgeons can safely perform LTG with lymphadenectomy for clinical stage I gastric cancer. Clinical trial information: NCT03007550.
<i>NTRK</i> gene fusions in biliary tract cancers.
Authors: Anne Demols, Laureen Rocq, Manon Charry, Nancy De Nève, Audrey Verrellen, Ali Ramadhan, Claude Van Campenhout, Sarah De Clercq, Isabelle Salmon, Nicky D'Haene
Journal: Journal of Clinical Oncology (2020)

574 Background: Gene fusions involving one of the 3 neurotrophic tyrosine receptor kinases ( NTRK) have been identified in approximately 1% of solid tumors and inhibitors of TRK (e.g. larotrectinib) have been shown to have anti-tumor activity regardless of tumor type. NTRK gene fusions have been previously reported in bilio-pancreatic cancers. It is of interest therefore to determine the incidence and molecular characteristics of NTRK gene fusions in patients with bilio-pancreatic cancers. Methods: Formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies or cytological samples of biliary tract tumors including intra-hepatic cholangiocarcinoma (IH), extra-hepatic cholangiocarcinoma (EH), perihilar cholangiocarcinoma (PH) and gallbladder tumors (G) were selected/retrieved from the tumor bank of the CUB Hôpital Erasme between January 2010 and July 2019. A two-step diagnostic method incorporating immunohistochemistry (IHC) screening followed by NGS analysis was used. Pan–TRK IHC (monoclonal antibody clone EPR17341 [AbCam, Cambridge, MA]) was used for the screening method. Staining intensity (negative, weak, moderate or strong) and localization (cytoplasmic or nuclear) were evaluated. The presence of at least weak staining tumor cells led to testing by a RNA-based NGS panel (Oncomine Focus Assay, ThermoFisher scientific). Results: 145 archival tumors samples (81 surgical resections, 48 biopsies and 16 cytology) have been selected, including 61 IH, 32 PH, 26 EH and 26 G (67 female and 78 male). 134 samples were suitable to perform IHC. 17 samples were IHC positive. Intensity of staining was weak in 16 samples and moderate in one. Staining location was cytoplasmic (14/17), nuclear (2/17), and nuclear+cytoplasmic (1/17). NGS testing of the 17 IHC positive samples revealed a single NTRK3 gene fusion ( ETV6(4)- NTRK3(14)). In this case (female patient with a poorly differentiated PH, deceased), IHC had a weak focal cytoplasmic and nuclear staining. Overall in the patients screened by IHC and confirmed by NGS, the percentage of NTRK fusions was 0.75%. Conclusions: NTRK gene fusions are rare in biliary cancers but testing is of high interest due to the emergence of possible treatment with specific TRK inhibitors.
Letter in response to: ‘Which specific modes of exercise training are most effective for treating low back pain? Network meta-analysis’ by Owen<i>et al</i>
Authors: Chris G Maher, Jill A Hayden, Bruno T Saragiotto, Tie P Yamato, Matthew K Bagg
Journal: British Journal of Sports Medicine (2020)

The recent network meta-analysis by Owen and colleagues1 included 89 trials of exercise for chronic low back pain (LBP) and reported low quality evidence that Pilates, stabilisation, resistance and aerobic exercises are the most effective treatments for these patients. We were surprised by how few trials were included and even more surprised by how large the estimates of treatment effect were. For example, with Pilates the effect is reported to be 1.86 standardised mean difference (SMD) in the abstract and 2.32 SMD in online supplementary table 5. These estimates are about 3–4 times effect sizes normally reported for exercise interventions in LBP and so we took a closer look at the review to try to understand what had happened. That investigation revealed some important issues that we would like to share with readers.

First, the review has missed a lot of relevant trials. The Cochrane review of exercise for chronic LBP that is currently underway has identified over 350 trials, whereas the Owen review included only 89. Even applying the restrictive selection criteria of the Owen …
Abstract 13391: Exaggerated Blood Pressure Response and Outcomes in Asymptomatic Executives Undergoing Exercise Treadmill Testing
Authors: Haris Riaz, Alaa Alashi, Richard Lang, Raul Seballos, Steven Feinleib, Roxanne Sukol, Leslie Cho, Paul Cremer, Wael Jaber, Brian Griffin, Milind Desai
Journal: Circulation (2018)

Introduction: Exaggerated systolic blood pressure response (ESBPR,> 220 mm Hg) during exercise treadmill testing (TMT) is associated with incident hypertension. Hypothesis: EBPR may add incremental...
Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of gastrointestinal (GI) tract: A single institution experience.
Authors: Manik A. Amin, Nikolaos Trikalinos
Journal: Journal of Clinical Oncology (2020)

633 Background: MiNENs are heterogeneous group of rare tumors and represent less than 1% of all GI malignancies. These are pathologically classifiable according to neuroendocrine component into low grade, intermediate grade and high grade MiNENs but and managed based upon non-neuroendocrine component rather than true NENs. They have poor prognosis and less is known about treatment options. Methods: We identified 34 cases of MiNENs from 1/1/2000 to 1/1/2018 from Siteman Cancer Registry Database at Siteman Cancer Center, Washington University, St. Louis. Treatment and follow up information was obtained from medical charts of patients. Results: Of 34 identified cases of MiNENs, our database showed equal distribution of MiNENs in male and female patients (N = 17 each). Site of origin included appendix (N = 14), colon (N = 10), esophageal (N = 2), stomach (N = 3), rectum (N = 3), small intestine (N = 1) and ampulla of Vater (N = 1) locations. Histology was high grade (N = 22), intermediate grade (N = 8), low grade (N = 3) and unknown (1). Twenty nine (85%) underwent surgical resection with curative intent and 13 (40%) patients were disease free at five years of follow up. Disease was localized in 15 patients (44%) and distant metastasis were reported in 13 patients (40%). Ten out of 15 patient with localized disease were disease free with combined modality therapy of surgery and chemotherapy. Most common chemotherapy regimen used in the metastatic setting was FOLFOX (11), 5FU/capecitabine (3), and carboplatin plus etoposide (5). Next generation sequencing analysis was available on limited patients which showed MMR proficient (3), MMR deficiency (1), BRAF V600E mutation (1) and KRAS wild type (1). Conclusions: MiNENs of GI tract are rare and aggressive tumors and represent a distinct entity. Surgical resection whenever possible offers curative option. Our database of GI MiNENs showed efficacy with commonly used GI chemotherapy regimens. Patients with low grade tumor histology had better survival as compared to moderately and poorly differentiated tumors. Genomic testing through NGS would be recommended for personalized treatment decisions given poor prognosis in these patients.
A Text-Book of Diseases of Women.
Journal: JAMA (1900)

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
Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: a randomized, open-label, multicenter, phase 2 study (CENTAURUS)
Authors: C. Ola Landgren, Ajai Chari, Yael C. Cohen, Andrew Spencer, Peter Voorhees, Jane A. Estell, Irwindeep Sandhu, Matthew W. Jenner, Catherine Williams, Michele Cavo, Niels W. C. J. van de Donk, Meral Beksac, Philippe Moreau, Hartmut Goldschmidt, Steven Kuppens, Rajesh Bandekar, Pamela L. Clemens, Tobias Neff, Christoph Heuck, Ming Qi, Craig C. Hofmeister
Journal: Leukemia (2020)

Abstract Current guidelines for smoldering multiple myeloma (SMM) recommend active monitoring until the onset of multiple myeloma (MM) before initiating treatment or enrollment in a clinical trial. Earlier intervention may delay progression to MM. In CENTAURUS, 123 patients with intermediate-risk or high-risk SMM were randomly assigned to daratumumab 16 mg/kg intravenously on extended intense (intense), extended intermediate (intermediate), or short dosing schedules. At the prespecified primary analysis (15.8-month median follow-up), the complete response (CR) rates (co-primary endpoint) were 2.4%, 4.9%, and 0% for intense, intermediate, and short dosing, respectively; the co-primary endpoint of CR rate &gt;15% was not met. Progressive disease (PD)/death rates (number of patients who progressed or died divided by total duration of progression-free survival [PFS] in patient-years; co-primary endpoint) for intense, intermediate, and short dosing were 0.055 (80% confidence interval [CI], 0.014–0.096), 0.102 (80% CI, 0.044–0.160), and 0.206 (80% CI, 0.118–0.295), respectively, translating to a median PFS ≥24 months in all arms ( P &lt; 0.0001, &lt;0.0001, and =0.0213, respectively). With longer follow-up (median follow-up, 25.9 months), CR rates were 4.9%, 9.8%, and 0% for intense, intermediate, and short dosing, respectively. PD/death rates for intense, intermediate, and short dosing were 0.059 (80% CI, 0.025–0.092), 0.107 (80% CI, 0.058–0.155), and 0.150 (80% CI, 0.089–0.211), respectively, again translating to a median PFS ≥ 24 months in all arms ( P &lt; 0.0001 for all arms). Twenty-four–month PFS rates were 89.9% (90% CI, 78.5–95.4%), 82.0% (90% CI, 69.0–89.9%), and 75.3% (90% CI, 61.1–85.0%) for intense, intermediate, and short dosing, respectively. Pharmacokinetic analyses indicated that intense dosing maintained target-saturating trough concentrations in most patients throughout weekly, every-2-week, and every-4-week dosing periods. No new safety signals were observed. These data provide the basis for an ongoing phase 3 study of daratumumab in SMM.
Effect of phenotype on outcome in synchronously resected primary colorectal cancer and matched liver metastases.
Authors: Kathryn AF Pennel, Colin William Steele, Jean A. Quinn, Antonia K. Roseweir, Rene Jackstadt, Colin Nixon, Xabier Cortes-Lavaud, Campbell SD Roxburgh, Hester Catharina Van Wyk, Donald C. McMillan, Paul G. Horgan, Owen Sansom, Joanne Edwards
Journal: Journal of Clinical Oncology (2020)

221 Background: 5-year survival of patients with resectable colorectal liver metastases is 25-40%. Mechanisms of disease progression are heterogenous and do not follow a clearly defined pathway from genotype to phenotype. In stage I-III colorectal cancer (CRC), patients with high tumor stroma exhibit poor prognosis, while those with high immune cell infiltrate do well following resection. We hypothesise that stromally-dense phenotypes lead to T cell exclusion, myeloid cell accumulation and aggressive metastatic progression. Here, we examine relationships between histological tumor phenotype, cellular infiltrate and outcomes in metastatic CRC. Methods: A unique cohort of synchronously resected primary CRC and matched liver metastases (n = 46) were assessed for immune cell infiltration (CD3, CD4, CD8, CD68, CD66b), inflammatory signalling (CXCR2, PDL-1, MMP9) and hypoxia (CAIX) using immunohistochemistry. Tumors were phenotypically subtyped using immune infiltrate (Klintrup-Makinen Grade (KM)), stromal invasion (tumor-stroma percentage (TSP)) and proliferation (Ki67). Results: Phenotypic subtype of primary tumors was predictive of metastatic subtype (rho = 0.522, p = 0.003). Immune phenotypes were associated with good prognosis and stromal phenotypes with poor prognosis (p = 0.004). Infiltration of macrophages and granulocytes associated with poor outcomes (p = 0.018) and increased CXCR2 expression (p = 0.03) at both sites. Increased CXCR2+ cells and macrophages at both sites associated with stromal phenotype (p = 0.02), tumour budding (p = 0.002), low KM grade (p = 0.05) and poor prognosis (p = 0.002). Macrophage and MMP9 levels increased in metastases compared to primary tumour, but no changes were seen in lymphocyte infiltration, CXCR2 and CD66b. Conclusions: Density of immune cell infiltrate, in the primary and metastatic niche, conferred good prognosis. In contrast, stromal, myeloid rich tumors convey poor prognosis. This clinically relevant and histologically efficient process permits segregation of disease and supports further study of relationships in the tumour microenvironment of CRC in the context of chemotherapy to better target therapeutics to individual patients.
Validation of Patient‐Reported Outcomes Information System Sleep Disturbance and Sleep‐Related Impairment in adults with atopic dermatitis*
Authors: D.K. Lei, M. Yousaf, S.R. Janmohamed, P.P. Vakharia, R. Chopra, R. Sacotte, K.R. Patel, V. Singam, S. Immaneni, R. Kantor, D.Y. Hsu, J.I. Silverberg
Journal: British Journal of Dermatology (2020)

Sleep disturbances are common in adults with atopic dermatitis (AD). Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) are validated questionnaires to assess sleep in adults. Little is known about their measurement properties in adults with AD.To assess the measurement properties of the PROMIS SD and SRI eight-item short forms in AD.We performed a prospective dermatology-practice-based study using questionnaires and evaluation by a dermatologist (n = 420).PROMIS SD and SRI showed moderate correlations to each other (ρ = 0·67), and weak correlations with Patient-Oriented Eczema Measure (ρ = 0·43 and 0·39, respectively); average (ρ = 0·31/0·30) and worst numerical rating scale for itch (ρ = 0·32/0·30); Eczema Area and Severity Index (ρ = 0·41/0·31); and Scoring Atopic Dermatitis (SCORAD) (ρ = 0·44/0·30) (Spearman correlations, P < 0·001). PROMIS SD and SRI increased significantly and stepwise with more frequent sleep disturbance, severe itch and self-reported global AD severity (ancova, P < 0·001). PROMIS SD and SRI showed good internal consistency (Cronbach alpha 0·84 and 0·91). Changes from baseline in PROMIS SD and SRI were weakly to moderately correlated with each other and with changes of multiple patient-reported and clinician-reported AD outcomes. There were no floor or ceiling effects for PROMIS SD or SRI. The median completion time for PROMIS SD and SRI was 2 min.PROMIS SD and SRI showed good construct validity, internal consistency, responsiveness and feasibility to assess sleep in adult patients with AD. What is already known about this topic? The Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) scales were found to be valid in adults with chronic disease. However, the validity and feasibility of PROMIS SD and SRI in atopic dermatitis remain unknown. What does this study add? This study demonstrated that PROMIS SD and SRI had good content, concurrent, convergent and discriminant validity; feasibility; and responsiveness, with no floor or ceiling effects observed. What are the clinical implications of this work? The PROMIS SD and SRI eight-item bank short forms appear to have sufficient validity and feasibility to be used as assessments for burden of sleep in adults with atopic dermatitis in clinical practice.