tbuckley/cabot-search huggingface dataset:
PTH-006 Should we perform colonic polypectomy in patients over 80?
Authors: Jabed Ahmed, Jonathan Landy
Journal: Endoscopy (2018)

<h3>Introduction</h3> Previous studies highlight the increased risks attendant with colonoscopy in the elderly population1. Case reports and reviews also suggest avoidance of polypectomy for &lt;2 cm polyps in patients≥85 years 2. We aimed to assess the outcomes of polypectomy in patients≥80 at our trust with five years of follow up. <h3>Methods</h3> Colonoscopic data was analysed from the endoscopy reporting system for patients aged ≥80 who had colonoscopy and polypectomy performed in 2011 and 2012. Endoscopy reports, histology reports and patient notes were reviewed. Mortality and cause of death within 5 years of the procedure date were also recorded from the patient mortality coding database. Patients with a synchronous cancer at index procedure were excluded from 5 year colorectal cancer (CRC) mortality analysis. <h3>Results</h3> 180 patients (median age 83; range 80–92) were identified with 313 polyps removed. The median ASA grade was 2 (range 1–4) with hypertension, COPD, Cardiac disease and Diabetes the most frequent co-morbidities. 224 (72%) polyps removed were &lt;10 mm in size, 58 (19%) 10–19 mm, 20 (6%)&gt;20 mm (range 20–50 mm) and size was not documented in 9 (3%). In polyps&lt;10 mm in size, 99% had histology showing low grade or no dysplasia. 1% had high grade dysplasia (HGD) and there were no polyp cancers. For polyps 10–19 mm, histology showed low grade or no dysplasia in 81%, HGD in 14% and cancer in 5%. For polyps&gt;20 mm; 30% (6) showed HGD and 5% (1) cancer on histology. There were 3 (1.6%) peri-procedure complications identified (desaturation and bleeding post polypectomy) none requiring admission. 42 (23%) of the patients died within 5 years of the procedure date. The commonest causes of patient mortality were pneumonia, heart failure and stroke. CRC was the cause of death in 1 patient (0.6%) and in this case the index polypectomy was a polyp cancer. <h3>Conclusions</h3> The rate of significant complications in patients≥80 undergoing colonic polypectomy is low. However, mortality at 5 years is high in patients≥80 undergoing colonic polypectomy due to co-morbid diseases other than CRC and no significant pathology is seen in diminutive (&lt;10 mm) polyps in this age group. The number of polyps&gt;10 mm in our cohort was small. We would recommend that polypectomy should be avoided for polyps&lt;10 mm in patients≥80 rather than ≥85 as previously suggested and that polypectomy of polyps&gt;10 mm should only be considered after careful deliberation with the patient. <h3>References</h3> . Lin OS, et al. Screening Colonoscopy in very elderly patients.<i>The Journal of the American Medical Association</i>2006;295(20):2357–2365. . Baker G, et al. Learning from adverse outcomes: guidelines on colonoscopic polypectomy in patients aged 85 years and older. Frontline Gastroenterology2016;(7):199–201.
Fracture Prevention with Zoledronate in Older Women with Osteopenia
Authors: Shotaro Suzuki, Noboru Hagino, Eishu Nango
Journal: New England Journal of Medicine (2019)

Fracture Prevention with Zoledronate in Older Women with OsteopeniaTo the Editor: In the trial reported by Reid et al.(Dec.20 issue), 1 zoledronic acid led to a lower risk of fragility fractures than placebo among postmenopausal women with osteopenia.We have concerns about the conclusion.First, nonvertebral fractures were seen in 24% of the participants at screening.A clinical diagnosis of osteoporosis includes the presence of fragility fractures. 2,3Thus, more than 24% of the participants actually had osteoporosis rather than osteopenia.Second, if the 10-year risk of major osteoporotic fractures among women with osteopenia is estimated to be 3.9% by the Fracture Risk Assessment Tool (FRAX), a hazard ratio of 0.65 with zoledronate provides a number needed to treat of 74 to prevent the occurrence of a single fragility fracture.We do not think that the absolute effect is similar in higher-risk patients (i.e., those with osteoporosis).Would the authors provide data regarding the incidence of fragility fractures among patients who completely fulfilled the diagnosis of osteopenia?Third, additional baseline characteristics are important considerations in evaluating the probability of falls.These characteristics include cataracts, glaucoma, dysuria, neurologic disorders (e.g., stroke, Parkinson's disease, and epilepsy), anemia, arrhythmia, frequency of previous falls, and measures of activities of daily living (e.g., with the Barthel scale), all of which might be confounders.
Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy
Authors: Christopher N. Toepfer, Amanda C. Garfinkel, Gabriela Venturini, Hiroko Wakimoto, Giuliana Repetti, Lorenzo Alamo, Arun Sharma, Radhika Agarwal, Jourdan K. Ewoldt, Paige Cloonan, Justin Letendre, Mingyue Lun, Iacopo Olivotto, Steve Colan, Euan Ashley, Daniel Jacoby, Michelle Michels, Charles S. Redwood, Hugh C. Watkins, Sharlene M. Day, James F. Staples, Raúl Padrón, Anant Chopra, Carolyn Y. Ho, Christopher S. Chen, Alexandre C. Pereira, Jonathan G. Seidman, Christine E. Seidman
Journal: Circulation (2020)

Hypertrophic cardiomyopathy (HCM) is caused by pathogenic variants in sarcomere protein genes that evoke hypercontractility, poor relaxation, and increased energy consumption by the heart and increased patient risks for arrhythmias and heart failure. Recent studies show that pathogenic missense variants in myosin, the molecular motor of the sarcomere, are clustered in residues that participate in dynamic conformational states of sarcomere proteins. We hypothesized that these conformations are essential to adapt contractile output for energy conservation and that pathophysiology of HCM results from destabilization of these conformations.
Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline
Authors: Panagiotis A. Konstantinopoulos, Barbara Norquist, Christina Lacchetti, Deborah Armstrong, Rachel N. Grisham, Paul J. Goodfellow, Elise C. Kohn, Douglas A. Levine, Joyce F. Liu, Karen H. Lu, Dorinda Sparacio, Christina M. Annunziata
Journal: Journal of Clinical Oncology (2020)

To provide recommendations on genetic and tumor testing for women diagnosed with epithelial ovarian cancer based on available evidence and expert consensus.
China coronavirus: what do we know so far?
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Since reports of a mysterious pneumonia-like condition began circulating in December, the public health world has been keeping its eye on the events unfolding in China.1 As the numbers of confirmed cases and deaths have risen, details of the novel coronavirus now known as 2019-nCoV have dripped through. Here’s what we know so far about this evolving situation.

The initial source of 2019-nCoV is still unknown, but the first cases were linked to a seafood market in the city of Wuhan, capital of the central Hubei province. The market was closed on 1 January 2020 as part of efforts to contain the outbreak.2

As at 24 January 830 cases and 26 deaths had been confirmed worldwide.3 Of the confirmed cases, around 25% are thought to be severe. Outside mainland China cases have been confirmed in Thailand, Japan, Hong Kong, Taiwan, South Korea, and the US. Cases had been reported in the UK but not yet confirmed.

The MRC Centre for Global Infectious Disease Analysis at Imperial College London has estimated that by 18 January 4000 people in Wuhan should have shown symptoms caused by the novel disease (uncertainty range 1000 to 9700).4 Their estimate …
Navigating Through Time: A Spatial Navigation Perspective on How the Brain May Encode Time
Authors: John B. Issa, Gilad Tocker, Michael E. Hasselmo, James G. Heys, Daniel A. Dombeck
Journal: Annual Review of Neuroscience (2020)

Interval timing, which operates on timescales of seconds to minutes, is distributed across multiple brain regions and may use distinct circuit mechanisms as compared to millisecond timing and circadian rhythms. However, its study has proven difficult, as timing on this scale is deeply entangled with other behaviors. Several circuit and cellular mechanisms could generate sequential or ramping activity patterns that carry timing information. Here we propose that a productive approach is to draw parallels between interval timing and spatial navigation, where direct analogies can be made between the variables of interest and the mathematical operations necessitated. Along with designing experiments that isolate or disambiguate timing behavior from other variables, new techniques will facilitate studies that directly address the neural mechanisms that are responsible for interval timing.
Abstract 17592: Novel Score for Prediction of Late Recurrence in the Patients Without Recurrence > 12 Months After Catheter Ablation of Atrial Fibrillation
Authors: Yasuyuki Egami
Journal: Circulation (2017)

Background: Many studies have reported a gradual increase in the arrhythmia recurrence in patients who underwent atrial fibrillation catheter ablation (AFCA). Although some observational studies ha...
The large single-copy (LSC) region functions as a highly effective and efficient molecular marker for accurate authentication of medicinal Dendrobium species
Authors: Ludan Li, Yu Jiang, Yuanyuan Liu, Zhitao Niu, Qingyun Xue, Wei Liu, Xiaoyu Ding
Journal: Acta Pharmaceutica Sinica B (2020)

Having great medicinal values, Dendrobium species of "Fengdou" (DSFs) are a taxonomically complex group in Dendrobium genus including many closely related and recently diverged species. Traditionally used DNA markers have been proved to be insufficient in authenticating many species of this group. Here, we investigated 101 complete plastomes from 23 DSFs, comprising 72 newly sequenced and 29 documented, which all exhibited well-conserved genomic organization and gene order. Plastome-wide comparison showed the co-occurrence of single nucleotide polymorphisms (SNPs) and insertions/deletions (indels), which can be explained by both the repeat-associated and indel-associated mutation hypotheses. Moreover, guanine-cytosine (GC) content was found to be negatively correlated with the three divergence variables (SNPs, indels and repeats), indicating that GC content may reflect the level of the local sequence divergence. Our species authentication analyses revealed that the relaxed filtering strategies of sequence alignment had no negative impact on species identification. By assessing the maximum likelihood (ML) trees inferred from different datasets, we found that the complete plastome and large single-copy (LSC) datasets both successfully identified all 23 DSFs with the maximum bootstrap values. However, owing to the high efficiency of LSC in species identification, we recommend using LSC for accurate authentication of DSFs.
Contribution of GABAergic interneurons to amyloid-β plaque pathology in an APP knock-in mouse model
Authors: Heather C. Rice, Gabriele Marcassa, Iordana Chrysidou, Katrien Horré, Tracy L. Young-Pearse, Ulrike C. Müller, Takashi Saito, Takaomi C. Saido, Robert Vassar, Joris de Wit, Bart De Strooper
Journal: Molecular Neurodegeneration (2020)

Abstract The amyloid-β (Aβ) peptide, the primary constituent of amyloid plaques found in Alzheimer’s disease (AD) brains, is derived from sequential proteolytic processing of the Amyloid Precursor Protein (APP). However, the contribution of different cell types to Aβ deposition has not yet been examined in an in vivo, non-overexpression system. Here, we show that endogenous APP is highly expressed in a heterogeneous subset of GABAergic interneurons throughout various laminae of the hippocampus, suggesting that these cells may have a profound contribution to AD plaque pathology. We then characterized the laminar distribution of amyloid burden in the hippocampus of an APP knock-in mouse model of AD. To examine the contribution of GABAergic interneurons to plaque pathology, we blocked Aβ production specifically in these cells using a cell type-specific knock-out of BACE1. We found that during early stages of plaque deposition, interneurons contribute to approximately 30% of the total plaque load in the hippocampus. The greatest contribution to plaque load (75%) occurs in the stratum pyramidale of CA1, where plaques in human AD cases are most prevalent and where pyramidal cell bodies and synaptic boutons from perisomatic-targeting interneurons are located. These findings reveal a crucial role of GABAergic interneurons in the pathology of AD. Our study also highlights the necessity of using APP knock-in models to correctly evaluate the cellular contribution to amyloid burden since APP overexpressing transgenic models drive expression in cell types according to the promoter and integration site and not according to physiologically relevant expression mechanisms.
Wildervanck症候群(頸-眼-聴覚症候群),眼瞼下垂小人症を有するバルサルバ洞の破裂した動脈瘤 症例報告
Authors: OE Kotaro, Mori Kiyoo, Konno Tetsuo, Yoneda Takashi, Ueyama Katsushi, Yamagishi Masakazu
Journal: Circulation (2007)
Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors
Authors: Matthew H. Taylor, Chung-Han Lee, Vicky Makker, Drew Rasco, Corina E. Dutcus, Jane Wu, Daniel E. Stepan, Robert C. Shumaker, Robert J. Motzer
Journal: Journal of Clinical Oncology (2020)

Modulation of vascular endothelial growth factor-mediated immune suppression via angiogenesis inhibition may augment the activity of immune checkpoint inhibitors. We report results from the dose-finding and initial phase II expansion of a phase Ib/II study of lenvatinib plus pembrolizumab in patients with selected advanced solid tumors.Eligible patients had metastatic renal cell carcinoma (RCC), endometrial cancer, squamous cell carcinoma of the head and neck (SCCHN), melanoma, non-small-cell lung cancer (NSCLC), or urothelial cancer. The primary objective of phase Ib was to determine the maximum tolerated dose (MTD) for lenvatinib plus pembrolizumab (200 mg intravenously every 3 weeks). In the preplanned phase II cohort expansion, the primary objective was objective response rate at week 24 (ORRweek 24) at the recommended phase II dose.Overall, 137 patients were enrolled during phase Ib (n = 13) and the initial phase II expansion (n = 124). Two dose-limiting toxicities (DLTs; grade 3 arthralgia and grade 3 fatigue) were reported in the initial dose level (lenvatinib 24 mg/d plus pembrolizumab). No DLTs were observed in the subsequent dose-de-escalation cohort, establishing the MTD and recommended phase II dose at lenvatinib 20 mg/d plus pembrolizumab. ORRweek24 was as follows: RCC, 63% (19/30; 95% CI, 43.9% to 80.1%); endometrial cancer, 52% (12/23; 95% CI, 30.6% to 73.2%); melanoma, 48% (10/21; 95% CI, 25.7% to 70.2%); SCCHN, 36% (8/22; 95% CI, 17.2% to 59.3%); NSCLC, 33% (7/21; 95% CI, 14.6% to 57.0%); and urothelial cancer 25% (5/20; 95% CI, 8.7% to 49.1%). The most common treatment-related adverse events were fatigue (58%), diarrhea (52%), hypertension (47%), and hypothyroidism (42%).Lenvatinib plus pembrolizumab demonstrated a manageable safety profile and promising antitumor activity in patients with selected solid tumor types.
Trial of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) in patients with EGFR-expressing recurrent/metastatic non-small cell lung cancer (NSCLC) and solid tumors.
Authors: Bharti Rathore, Pam Davol, Ritesh Rathore, Francis Cummings, Ariel E. Birnbaum, Abby Maizel, Lawrence G Lum
Journal: Journal of Clinical Oncology (2012)

e13124 Background: Patients (pts) with advanced NSCLC and solid tumors have a poor prognosis and novel approaches to improve targeting and cytotoxicity directed at these cancers are needed. Anti-CD3 activated T cells (ATC) can be expanded and armed with anti-CD3 x anti-EGFR bispecific antibody (EGFRBi). Methods: In a phase I trial using ATC armed with EGFRBi, 6 pts (NSCLC = 5 pts, pancreatic cancer =1 pt) were treated with 8 infusions (twice/week) for 4 weeks with 5, 10 billion armed ATC/dose to determine the maximum tolerated dose (3 pts each). T cells from leukopheresis were activated and expanded with anti-CD3/IL-2 for 14 days, harvested, armed with EGFRBi and cryopreserved. IL-2 (3 x 10 5 IU/m 2 /daily) and GM-CSF (250 µg/m 2 twice/week) was given beginning 3 days prior to the 1st infusion and ending++ 3, performance status (PS 0= 2 pts, PS 1= 4 pts). Results: Restaging scans revealed stable disease in 2 pts and progression in 4 pts. One pt with NSCLC at each dose level had stable disease (23 mths, 11 mths). ATC infusions were well tolerated and noticeable toxicities included chills (grade 2= 1 pt, grade 3= 1 pt); headache (grade 1= 2 pts, grade 2= 2 pts), dizziness (grade 2= 1 pt), nausea (grade 1= 2 pts). Accrual continues for dose levels at 20, 40 billion armed ATC per dose. No major toxicities with IL-2 were observed; bone pain resulted in dose reductions for GM-CSF in 2 pts. Conclusions: Infusions of EGFRBi armed ATC can be safely accomplished in patients with advanced NSCLC and solid tumors; accrual continues.
The significance of genetic mutations and their prognostic impact on patients with incidental finding of isolated del(20q) in bone marrow without morphologic evidence of a myeloid neoplasm
Authors: Aishwarya Ravindran, Rong He, Rhett P. Ketterling, Majd D. Jawad, Dong Chen, Jennifer L. Oliveira, Phuong L. Nguyen, David S. Viswanatha, Kaaren K. Reichard, James D. Hoyer, Ronald S. Go, Min Shi
Journal: Blood Cancer Journal (2020)

Abstract Patients with a sole del(20q) chromosomal abnormality and without morphologic features of a myeloid neoplasm (MN) have shown variable clinical outcomes. To explore the potential risk stratification markers in this group of patients, we evaluated their genetic mutational landscape by a 35-gene MN-focused next-generation sequencing (NGS) panel and examined the association of mutations to progression of MNs. Our study included 56 patients over a 10-year period with isolated del(20q), of whom 23 (41.1%) harbored at least one mutation. With a median follow-up of 32.6 months (range: 0.1−159.1), 9 of 23 patients with mutation(s) progressed to MNs, while all 33 patients without mutations did not progress to MN. Kaplan−Meier survival analysis demonstrated the presence of mutation(s) as a significant risk factor for progression to MN ( P &lt; 0.0001). MN progression was strongly associated with the presence of non- DNMT3A/TET2/ASXL1 epigenetic modifiers and nonspliceosome mutations ( P = 0.003). There was no significant difference among patients with and without MN progression with respect to the number of mutations, variant allele frequency, percentage of del(20q), and other clinical/laboratory variables. This study illustrates the underlying genetic heterogeneity and complexity of isolated del(20q), and underscores the prognostic value of NGS mutational analysis in these cases.
Antibiotic resistance: more companies are withdrawing sales reps or incentives in order to limit use, finds report
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Pharmaceutical companies are tackling the overselling of antimicrobials by withdrawing their sales agents or removing the incentives for sale representatives to oversell antibiotics or antifungals, according to 2020 Antimicrobial Resistance Benchmark report.1

The report, which looked at the progress that companies have made since 2018, found that while there has been some improvement, change is not happening at the scale needed to radically impact the threat from drug resistance.

The Access to Medicine Foundation—an independent non-profit organisation—launched the report at the World Economic Forum 2020, and called on governments and the pharmaceutical industry to take the situation seriously and work together to solve it.

“We’re not asking for a scientific miracle here, we are asking for human intervention,” the foundation’s executive director Jayasree Iyer told The BMJ .

The findings show that 10 companies have now …
Helen Salisbury: The gaps in our knowledge
Authors: Helen Salisbury
Journal: BMJ (2020)

OxfordAt medical school we learn to recognise the patterns of symptoms and physical signs that add up to predefined diagnoses.They appear in the textbooks and again in exam scenarios, but many of the real patients we meet in the clinic don't fit neatly into diagnostic boxes.Sometimes they're just variants on a theme (the pneumonia without a cough, the painless heart attack), but a sizeable minority of patients in both primary and secondary care have symptoms we can't explain.Estimates vary, but this is said to be a feature of 20-50% of consultations in primary and secondary care. 1 2
Intergenerational Transmission of Depression
Authors: Sherryl H. Goodman
Journal: Annual Review of Clinical Psychology (2020)

The study of depression in mothers in relation to transmission of risk for the development of psychopathology in their children relies on solid foundations in the understanding of psychopathology, of development, and of developmental psychopathology per se. This article begins with a description of the scope of the problem, including a summary of knowledge of how mothers' depression is associated with outcomes in children and of moderators of those associations. The sense of scope then informs a theoretical and empirical perspective on knowledge of mechanisms in those associations, with a focus on what has been learned in the past 20 years. Throughout the article, and in conclusions at the end, are suggestions for next steps in research and practice.