tbuckley/cabot-search huggingface dataset:
AB1316 Hospital admission trends and short-term outcome for iga vasculitis in children and adults in western australia
Authors: J. Nossent, W. Raymond, H. Keen, C. Inderjeeth, D. Preen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Immunoglobulin A vasculitis (IgAV), formerly called Henoch-Schönlein purpura, is an immune complex mediated small-vessel vasculitis that preferentially affects the skin, intestines and kidneys. While more common in children, IgAV is not unusual in adults, where it has been associated with worse outcomes. <h3>Objectives</h3> To compare hospital admission rates and outcomes over time between adult and paediatric inpatients with IgA vasculitis <h3>Methods</h3> Data were extracted from a state-wide registry for all hospital admissions in Western Australia (WA) between 1980 to 2015 for patients with a primary or secondary diagnosis of IgAV (ICD-9-CM code 287.0/ICD-10-AM code D69.0). Paediatric cases were defined as those ≤19 years at first diagnosis. <h3>Results</h3> From a total 764 patients admitted to hospital with an IgAV diagnosis 508 (66%) were paediatric and 256 (34%) adult cases. IgAV was the primary diagnosis in 463 (91.1%) paediatric and in 123 (48%) adult patients (p&lt;0.01). In children, mean age at primary diagnosis was 5.6 years of (range 0–19) versus 50.2 years (range 20–91) in adults. Both groups had similar proportions of Indigenous (3.5 vs 1.6%, p=0.4) and male patients (59 vs 51.2%, p=0.3). Over the observation period, the annual rates per 100.000 for a first admission for IgAV declined from 4.2 to 0.4 for children and from 0.42 to 0.2 for adults, while length of stay in days decreased from 5.8 to 1.8 for children and increased from 10.5 to 21.1 for adults. Three adults (2.4%) but no child required ICU admission, while one adult (0.7%) and no child died in hospital. Readmission rates for IgAV were considerable and higher in children than adults (25.6% vs 18.7%, p=0.1). <h3>Conclusions</h3> Admission rates for IgAV in children in WA have declined steeply over the last decades and now almost equate admission rates for adults. The reduction in length of stay and absence of in-hospital mortality support an increased willingness or necessity to manage children with IgAV outside the hospital setting despite a significant readmission rate. In contrast, hospital admission for IgAV in adults associates with prolonged lenth of stay and a slight risk for ICU admission and in-hospital mortality. <h3>Acknowledgements</h3> Supported by an unrestricted grant from the Arthritis Foundation of Western Australia. We acknowledge the contribution by Data Linkage WA staff and custodians. <h3>Disclosure of Interest</h3> None declared
Abstract P2-08-28: Relationship between FDG uptake and neutrophil/lymphocyte ratio in patients with breast invasive ductal cancer
Authors: T Fujii, K Yanai, S Tokuda, Y Nakazawa, S Kurozumi, S Obayashi, R Yajima, T Hirakata
Journal: Cancer Research (2019)

Abstract Background: 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) is used to evaluate the glucose metabolic rates of cancers. Several studies have reported that high FDG uptake is predictive of poor prognosis and aggressive features in patients with breast cancer. FDG uptake is influenced by many factors, including inflammation. In this study, we investigated the relationship between FDG uptake and neutrophil/lymphocyte ratio (NLR), which is an indicator of systemic inflammation. Patients and Methods: We retrospectively investigated the cases of 143 consecutive invasive ductal carcinoma patients who had undergone surgery and FDG-PET preoperatively.PET was evaluated using standardized uptake value max (SUVmax). The median SUVmax was 2.5 (range 0-10.5). Thus, we divided the cases into two groups based on the value of SUVmax; low (&amp;lt;2.5) and high (≥2.5). The relationships between SUVmax and clinicopathological features, including NLR, were investigated. Results: Among the143 patients, 73 (51.0%) had high SUVmax in the primary tumor. The analysis revealed that large tumor size (p&amp;lt;0.001), high nuclear grade (p&amp;lt;0.001), the presence of lymphovascular invasion (p&amp;lt;0.001), CRP (p=0.046) and high NLR (p&amp;lt;0.001) were significantly associated with high SUVmax in the primary tumor. There were associations between SUVmax and NLR (r=0.323, p&amp;lt;0.001). Among the 70 cases with low SUVmax, there was no recurrent disease, while 6 cases among the 73 cases with high SUVmax had disease recurrence. It is interesting to note that the group with high SUVmax and low NLR had no recurrent disease. Conclusions: To the best of our knowledge, this is the first report to describe the relationship between FDG uptake and NLR in breast cancer. The present study demonstrated that the finding of preoperative high FDG uptake in breast cancer may be reflective of poor prognosis and that high NLR may be predictive of aggressive features among patients with breast cancer. On the other hand, among breast cancer patients with high SUVmax in the primary tumor, it will be useful to identify the subset of patients with low NLR in order to improve prognostic accuracy. Citation Format: Fujii T, Yanai K, Tokuda S, Nakazawa Y, Kurozumi S, Obayashi S, Yajima R, Hirakata T. Relationship between FDG uptake and neutrophil/lymphocyte ratio in patients with breast invasive ductal cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-28.
The enhancer RNA ARIEL activates the oncogenic transcriptional program in T-cell acute lymphoblastic leukemia
Authors: Shi Hao Tan, Wei Zhong Leong, Phuong Cao Thi Ngoc, Tze King Tan, Fatima Carla Bertulfo, Mei Chee Lim, Omer An, Zhenhua Li, Allen Eng Juh Yeoh, Melissa J. Fullwood, Daniel G. Tenen, Takaomi Sanda
Journal: Blood (2019)
Dementia care: dispatches from the frontline
Authors: Anna Watkinson-Powell
Journal: BMJ (2013)

Dementia care is a UK government priority with an established place on medical school curriculums. After working as a hospital healthcare assistant and a carer in a residential home, however, I realise that doctors are removed from the reality of managing dementia on the front line.

It has always concerned me that those who, arguably, have the greatest impact on the wellbeing of patients with dementia have virtually no training. Society does not seem to appreciate that these patients can be extremely challenging to care for—physically and emotionally. People with dementia are often repetitive. They ask the same questions …
Big bad pharma
Authors: Jonathan Batty
Journal: BMJ (2013)

Every time a patient takes a tablet, this represents an implicit act of trust in the doctor who prescribed it. How can the doctor weigh up the benefits and harms to the patient without robust evidence that the drug works, and knowledge of its side effects? According to Ben Goldacre, author of Bad Science , and, latest work, Bad Pharma , the frightening truth is that doctors often make prescribing decisions without all the evidence to hand. Indeed, a doctor might be making decisions in accordance with the best evidence based practice guidelines, and still cause patients harm.

Bad Pharma is a 400 page declaration of war on the questionable practices of the $600bn behemoth that is big pharma, the drug industry. Goldacre argues that because of factors …
Assessing the nutritional status of an acutely ill patient
Authors: Francesca Moroni, Emma Metcalfe, Alastair McKinlay
Journal: BMJ (2017)

How to recognise and treat patients at risk of malnutrition #### Box 1: Quotes about nutrition “Nutrition is a basic human right, and a universal factor that defines the health of all people” Gro Harem Bruntsland, former director general of the World Health Organization 1 “Assistance was not provided with feeding for patients who could not eat without help. Water was left out of reach” Robert Francis, Report into the circumstances surrounding care at the Mid Staffordshire Hospital Trust 2 It is estimated that more than 33% of people over 65 years old are at high risk of malnutrition on admission to hospital in the United Kingdom.3 In patients admitted from care homes, the risk is higher, at 50%.4 Poor nutrition can lead to reduced immunity, increased susceptibility to disease and impaired physical and mental development,5 and longer stays in hospital.6 The Francis report, a public inquiry into failings in care at the Mid Staffordshire Hospital Trust in the late 2000s, highlighted how the nutrition of patients had been neglected in many cases.2 The term malnutrition encompasses under- and over-nutrition.7 Under-nutrition is common in the UK but is under-recognised, particularly in patients admitted to acute hospitals. At any given time in the UK, an estimated three million people are malnourished.89 In this article we provide guidance on how to recognise malnutrition early on and initiate appropriate investigations and management.10 The causes of under-nutrition in people living in developing countries and those living in Western nations differ greatly (see boxes 2 and 3). #### Box 2: Causes of malnutrition in the developing world11 ##### Environment ##### Appetite ##### Non-viable gut #### Box 3: Causes of malnutrition in the Western world11 ##### Environment
Abstract P4-01-24: S100A11 is a diagnostic marker and promotes cancer progression for luminal breast cancer
Authors: A Kwong, J Wang, J Chen, MT Siu, I Chuek, V Shin
Journal: Cancer Research (2019)

Abstract Background: S100A11, also known as calgizzarin, is a member of S100 calcium-binding protein family and is upregulated in various cancers including lung cancer, renal cell cancer, ovarian cancer and pancreatic cancer. Many studies have shown that S100A11 is related to cancer progression. However, the function of S100A11 in breast cancer remains largely unknown. In the present study, we aim to investigate the underlying mechanism(s) of S100A11 in cancer cell proliferation, invasion, migration, and evaluate the clinical association with breast cancer. Methods: The mRNA expression level of S100A11 in plasma samples from breast cancer patients and normal control individuals was detected with quantitative real-time PCR. Knockdown of S100A11 using small interfering RNA (siRNA) in luminal breast cancer cells (MCF-7 and T-47D) were used to study the biological function of S100A11 for the progression of breast cancer. Cell proliferation ability was analysed with MTT assay and colony formation assay. Cell invasion ability was analysed with transwell invasion assay. Cell migration ability was detected by wound healing assay. Cell cycle distribution and apoptosis were determined by flow cytometry. Results: The mRNA expression level of S100A11 was significantly increased in the plasma samples obtained from 182 breast cancer patients compared with 115 normal control individuals, and the area under curve was 0.83. In particular, higher expression was associated with luminal breast cancer subtype as well as respective cell lines. S100A11 siRNA effectively inhibited the proliferation, invasion, and migration abilities of MCF-7 and T-47D cells. Knockdown of S100A11 caused cell cycle G1 arrest and induced apoptosis. Silencing of S100A11 decreased the mRNA and protein expression levels of cyclin D1 and NF-κB p50 whereas increased the expression level of E-cadherin in MCF-7 and T-47D cells. Conclusion: These results suggest that S100A11 is upregulated in breast cancer and promoted cell proliferation, invasion and migration in MCF-7 and T-47D cells through the upregulation of NF-κB p50 and cyclin D1. Thus, S100A11 may be a potential diagnostic marker for luminal breast cancer subtype and also a therapeutic target for breast cancer. Citation Format: Kwong A, Wang J, Chen J, Siu MT, Chuek I, Shin V. S100A11 is a diagnostic marker and promotes cancer progression for luminal breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-24.
Abstract 2539: CTLA-4 blockade for hormone refractory prostate cancer: Dose-dependent induction of CD8+ T cell activation and clinical responses
Authors: Lawrence Fong, Serena Kwek, Brian Kavanagh, Shaun O'Brien, Douglas McNeel, Vivian Weinberg, Brian Rini, Eric J. Small
Journal: Cancer Research (2008)

Abstract CTLA-4 is a costimulatory molecule expressed on activated T cells that delivers an inhibitory signal to these T cells. CTLA4 blockade with antibody treatment has been shown to augment T cell responses and anti-tumor immunity in animal models and is being developed as an immunotherapy for cancer patients. We performed a phase I trial in patients with metastatic, hormone refractory prostate cancer (HRPC) where sequential cohorts of 3-6 patients were treated with escalating doses (0.5, 1.5 or 3 mg/kg) of ipilimumab, a fully human anti-CTLA-4 antibody (Medarex/BMS), given IV on day 1 of each 28-day cycle x 4 cycles. Patients also received GM-CSF (sargramostim, Berlex) 250 mg/m2/d SC on days 1-14 of the 28-day cycles. Patients were monitored for toxicity as well as for T cell activation. PSA and radiographic tests were performed at baseline and through therapy to evaluate for clinical response. 24 patients have been treated in the initial phase of this study. Of 6 patients treated on the highest dose level (3.0 mg/kg x 4), 3 (50%) had confirmed PSA declines of &amp;gt;50%, and one of these patients had a partial response in hepatic metastases. Immune-related adverse events associated with ipilimumab treatment were also seen more frequently at higher doses of treatment. Expansion of CD25+CD69+ CD8 T cells was also seem primarily at the highest dose level. The treatment also induced an antibody and CD8 T cell immune response to NY-ESO-1. These results demonstrate that CTLA-4 blockade induces not only the expansion of activated effector CD8 T cells in vivo in cancer patients, but also can induce from the endogenous T cell repertoire of these patients T cells that are specific for tumor-associated antigens. CD8 T cell activation, toxicity, and clinical responses also appear to be dose-dependent. Supported by NIH P50 CA89520.
How to Perform an Elliptical Excision of the Skin
Authors: Tomas J. Saun, Jessica Truong, Shelly P. Dev, Kyle Wanzel
Journal: New England Journal of Medicine (2019)

This video demonstrates elliptical excision of the skin, a procedure that can be used in the diagnosis and management of skin and subcutaneous lesions, may be performed with minimal risk in most patients, and may avert the need for other, more invasive procedures.
Prevalence of Alcoholic Fatty Liver Disease Among Adults in the United States, 2001-2016
Authors: Terrence Wong, Katherine Dang, Sanah Ladhani, Ashwani K. Singal, Robert J. Wong
Journal: JAMA (2019)

This national survey study uses National Health and Nutrition Examination Survey (NHANES) data to estimate the prevalence of alcoholic fatty liver disease (AFLD) overall and with stage 2 or greater and stage 3 or greater fibrosis among US adults from 2001 to 2016.
Abstract ES3-1: Brain metastases of breast cancer
Authors: P Steeg
Journal: Cancer Research (2019)

Abstract Brain metastases are devastating consequences of breast cancer. Both the lesions and their treatments cause physical and neurocognitive complications. Translational investigations have provided several new insights into the brain metastatic process which are hoped to lead to new preventive and therapeutic approaches. First, DNA sequencing of matched primary tumors and brain metastases revealed that nearly half of the brain lesions harbor potentially actionable mutations not present in the primary tumor. Second, model systems reveal that brain metastatic colonization arises through a complex interplay between the tumor cells and their microenvironment. Astrocytes are found in the normal blood-brain barrier and activate and surround a developing metastasis. They have been reported to modulate metastatic growth via several pathways. Additional investigations have uncovered other mechanistic contributions from activated microglia and other cells. The blood-brain barrier is also a contributor to heterogeneous and insufficient uptake of drugs to brain metastases. When a metastasis forms, the blood-brain barrier is termed a blood-tumor barrier (BTB). Multiple facets of the BBB are altered in the BTB. Alterations to the sphingosine-1 phosphate receptor 3 (S1P3) pathway in neuroinflammatory astrocytes of the BTB functionally altered BTB permeability. These data indicate that the BTB is a tractable structure to improve drug uptake and efficacy. Finally, investigators have identified brain permeable drugs and hormonal therapies that prevent the development of brain metastases in models, and which stand as support for new trials. Citation Format: Steeg P. Brain metastases of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES3-1.
Case 14-2019: A 44-Year-Old Man with Neck Pain and Swelling
Authors: Philip J. Saylor, David M. Dudzinski, Dexter P. Mendoza, Krzysztof Glomski
Journal: New England Journal of Medicine (2019)

A 44-year-old man was admitted to the hospital because of pain and swelling on the left side of the neck, which developed 12 weeks after placement of an implantable cardioverter–defibrillator. CT revealed a 4-cm heterogeneous soft-tissue mass located deep to the sternocleidomastoid muscle. Additional diagnostic tests were performed.
Fournier Gangrene Associated With Sodium–Glucose Cotransporter-2 Inhibitors
Authors: Susan J. Bersoff-Matcha, Christine Chamberlain, Christian Cao, Cindy Kortepeter, William H. Chong
Journal: Annals of Internal Medicine (2019)

Background: Use of sodium–glucose cotransporter-2 (SGLT2) inhibitors has been associated with Fournier gangrene (FG), a rare urologic emergency characterized by necrotizing infection of the external genitalia, perineum, and perianal region. Objective: To describe and compare reported cases of FG in diabetic adults receiving treatment with SGLT2 inhibitors or other antiglycemic agents. Design: Descriptive case series. Setting: U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and published case reports. Patients: Adults receiving SGLT2 inhibitors or other antiglycemic agents. Measurements: Clinical and laboratory data. Results: The FDA identified 55 unique cases of FG in patients receiving SGLT2 inhibitors between 1 March 2013 and 31 January 2019. The patients ranged in age from 33 to 87 years; 39 were men, and 16 were women. Time to onset after initiation of SGLT2-inhibitor therapy ranged from 5 days to 49 months. All patients had surgical debridement and were severely ill. Reported complications included diabetic ketoacidosis (n = 8), sepsis or septic shock (n = 9), and acute kidney injury (n = 4). Eight patients had fecal diversion surgery, 2 patients developed necrotizing fasciitis of a lower extremity that required amputation, and 1 patient required a lower-extremity bypass procedure because of gangrenous toes. Three patients died. For comparison, the FDA identified 19 FG cases associated with other antiglycemic agents between 1984 and 31 January 2019: metformin (n = 8), insulin glargine (n = 6), short-acting insulin (n = 2), sitagliptin plus metformin (n = 2), and dulaglutide (n = 1). These patients ranged in age from 42 to 79 years; 12 were men, and 7 were women. Two patients died. Limitation: Inability to establish causality or incidence, variable quality of reports, possible underreporting, and confounding by indication. Conclusion: FG is a newly identified safety concern in patients receiving SGLT2 inhibitors. Physicians prescribing these agents should be aware of this possible complication and have a high index of suspicion to recognize it in its early stages. Primary Funding Source: None.
Oligonucleotide Treatment for Huntington’s Disease
Authors: Kenneth H. Fischbeck, Nancy S. Wexler
Journal: New England Journal of Medicine (2019)

Huntington's disease is a severe autosomal-dominant neurodegenerative disorder that involves chorea, cognitive decline, and psychological problems such as depression, delusions, and impulsive behavior. Nowhere are the manifestations more striking than around Lake Maracaibo in northwestern Venezuela, where the disease is almost epidemic. The Huntington's disease kindreds in Venezuela encompass more than 18,000 persons spanning 10 generations. DNA samples from nearly 4000 patients and family members in this area were used to map the Huntington's gene to chromosome 4 in 19831 and to identify the disease gene in 1993.2 Subsequent studies in this population have discovered modifiers of age at onset.3 . . .
How to approach the mental state examination
Authors: Marina Soltan, Joseph Girguis
Journal: BMJ (2017)

What to look for and ask when assessing patients' emotions, thoughts, and behaviour #### Box 1: Learning points A mental state examination (MSE) gives you a snapshot of a patient's emotions, thoughts, and behaviour at the time of observation.1 It can help you identify the presence and severity of a variety of mental health conditions and the risk a patient poses to him- or herself, or to others. Performing an MSE is a skill you will need to be familiar with for psychiatry placements and for psychiatry objective structured clinical examinations at medical school. In this article, we use the structure of an MSE to give pointers on what you should look for and ask patients. ### Appearance and behaviour Observing patients' appearance and behaviour can give you clues about their mental state. #### Appearance
Gold-caged copolymer nanoparticles as multimodal synergistic photodynamic/photothermal/chemotherapy platform against lethality androgen-resistant prostate cancer
Authors: Qi Wang, Xiangyu Zhang, Ying Sun, Liting Wang, Li Ding, Wei-Hong Zhu, Wen Di, You-Rong Duan
Journal: Biomaterials (2019)