tbuckley/cabot-search huggingface dataset:
Skin toxicity of sunitinib: Prospective analysis in patients (pts) with metastatic renal cell carcinoma (mRCC)
Authors: B. Billemont, S. Barete, J. B. Méric, P. Moguelet, C. Francès, O. Chosidow, F. Goldwasser, O. Rixe
Journal: Journal of Clinical Oncology (2008)

16146 Background: Sunitinib (SU) is an angiogenesis inhibitor (AI) recently approved and widely used for the treatment of mRCC. This oral multi-targeted kinase inhibitor blocks the VEGF and PDGF receptors and c-kit. In clinical trials (phase II and III), cutaneous side effects such as acral syndrome, waxy skin and rash has been reported with a prevalence of less than 10%. The aim of this study was to investigate skin toxicity. Methods: From October 2005 to June 2007, pts with mRCC included in clinical trials and expanded access program with SU 50 mg daily for 4 weeks followed by a 2 week off period (4/2 schedule) were analyzed for relevant or unusaual dermatologic adverse event (DAE) as defined by the National Cancer Institute Common Toxicity Criteria 3.0. Grade 2 or 3 dermatologic toxicities with clinical or therapeutic consequences were photographed and biopsied. Results: Among 40 pts, with a median age of 58 years (range 39–78), median duration of SU therapy 115 days, 46 DAEs were reported: 12 hair depigmentations (30%), 11 hand-foot skin reactions (27%), 9 acral syndromes with circumscribed hyperkeratosis (22%), 6 scrotal erythemas (15%) with 3 inguinal area lesions and 5 mucositis (12%). DAEs increased and decreased with SU exposure, with median time of 2 weeks. Three pts had a severe scrotal squamous erythema with bleeding or pain. Biopsies of scrotal lesions revealed parakeratosis and epidermal hypertrophy. Clinical aspects and histopathology results corresponded to psoriasis feature. Conclusions: These findings reveal that the prevalence of relevant and severe skin toxicities is high, are different from previous reports and may interfere with both quality of life and treatment observance. Hypoxia inducing factor (HIF1alpha) and VEGF are upregulated in psoriasis disease. This psoriasic like scrotal erythema suggests that HIF and VEGF could play a putative role in the skin response to AI. No significant financial relationships to disclose.
Post Hoc Economic Analysis of Temozolomide Versus Dacarbazine in the Treatment of Advanced Metastatic Melanoma
Authors: Bruce E. Hillner, Sanjiv Agarwala, Mark R. Middleton
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the potential economic implications resulting from oral temozolomide (TEM) compared with intravenous (IV) dacarbazine (DTIC) for metastatic melanoma. PATIENTS AND METHODS: We performed a cost-effectiveness (CE) analysis using hazard ratios (HRs) from the phase III (Schering I95–018) trial comparing TEM 200 mg/m 2 /d orally for 5 days every 28 days with DTIC 250 mg/m 2 /d IV for 5 days every 21 days. Sensitivity analyses assessed a range of TEM’s efficacy and costs, direct nonmedical costs, and the DTIC schedule. RESULTS: The trial found an overall survival trend favoring TEM; median survival times of patients treated with DTIC and TEM were 6.4 and 7.7 months, respectively (HR = 1.18; 95% confidence interval [CI], 0.92 to 1.52; intention to treat, P = .20). The mean increase in survival of TEM over DTIC was 1.1 months. The projected average costs per patient were greater with TEM than DTIC ($6,902 v $3,697, respectively). The incremental CE ratio using TEM was $36,990 per life-year or $101 per day of life gained. The CE ratio’s 95% CI ranged from −$65,180 (DTIC is more effective) to $18,670 per year of life gained. The CE ratios decreased 50% if direct nonmedical costs were included and increased 50% if DTIC’s efficacy was unchanged if given as a single daily dosage. Sixty percent of simulations found TEM with a CE threshold of less than $50,000 per life-year gained. CONCLUSION: Although the base-case efficacy of TEM compared with DTIC was not statistically significant, its associated incremental CE would be comparable with many interventions. TEM for metastatic melanoma illustrates the tension confronting providers choosing between similar agents that markedly differ in convenience and costs.
High-Dose Therapy and Autologous Hematopoietic Progenitor Cell Transplantation for Recurrent or Refractory Hodgkin's Disease: Analysis of the Stanford University Results and Prognostic Indices
Authors: Sandra J. Horning, Nelson J. Chao, Robert S. Negrin, Richard T. Hoppe, Gwynn D. Long, Wendy W. Hu, Ruby M. Wong, Byron W. Brown, Karl G. Blume
Journal: Blood (1997)
Synovial Cysts and Rupture of the Knee Joint in Rheumatoid Arthritis: An Arthrographic Study
Authors: A.P. Hall, J.T. Scott
Journal: Annals of the Rheumatic Diseases (1966)

19th century descriptions of cysts in the popliteal region or calf communicating with the knee included those of Adams (1840) and Baker (1877, 1885), and these phenomena are often called Baker's cysts.Baker clearly recognized the possibility of acute rupture occurring in these cysts.Recently Dixon and Grant (1964) have described five patients with rheumatoid arthritis in whom they diagnosed acute synovial rupture of a knee effusion into the calf.The present paper describes the use of contrast arthrography in studying twenty patients who presented during the past 2 years with either intact cysts of the popliteal region or calf, or synovial rupture of the knee joint or of a popliteal cyst.This method of examination has been used in single patients or in small groups by Beatty (1959), Harvey and Corcos (1960), and Tait, Bach, and Dixon (1965).Method
Clinical applications of counterfactual thinking during memory reactivation
Authors: Felipe De Brigard, Eleanor Hanna
Journal: Behavioral and Brain Sciences (2015)

Abstract The Integrative Memory Model offers a strong foundation upon which to build successful strategies for clinical intervention. The next challenge is to figure out which cognitive strategies are more likely to bring about successful and beneficial modifications of reactivated memories during therapy. In this commentary we suggest that exercising emotional regulation during episodic counterfactual thinking is likely to be a successful therapeutic strategy to bring about beneficial memory modifications.
Abstract 3736: Glucose Lowering Treatment is Prognostically Important in Patients with Coronary Artery Disease and Newly Detected Diabetes Mellitus. A report from a Euro Heart Survey
Authors: Matteo Anselmino, John Öhrvik, Klas Malmberg, Lars Rydén
Journal: Circulation (2007)

Patients with coronary artery disease (CAD) and newly diagnosed diabetes mellitus (NDM) are at increased risk for cardiovascular events (CVE= death, myocardial infarction or stroke). This report from the Euro Heart Survey on Diabetes and the Heart relates glucose lowering (GL) treatment to cardiovascular prognosis. Methods 3940 patients with CAD were enrolled at 110 centers in 25 countries, of whom 1425 (36%) had known DM and 2515 (64%) were glucometabolically characterized with an oral glucose tolerance test (WHO 1999) or fasting blood glucose (ADA 2004) and followed for one-year with respect to CVE. Results 452 patients had NDM of whom 77 (17%) were started on pharmaceutical GL treatment (insulin 5%, oral glucose lowering drugs 94%, both 1%) while 375 (83%) not received any GL drugs. Baseline characteristics did not differ in patients receiving pharmaceutical GL treatment or not. None of the patients receiving pharmaceutical GL treatment died compared to 25 of those who did not (p=0.002). Myocardial infarction and stroke occurred in one vs. 13 and one vs. five patients respectively. Kaplan-Meier curves for CVE in patients receiving GL drugs (full) or not (empty) are shown in the figure . Adjusting for age, sex, previous cardiovascular disease and use of evidence based medications in a Cox proportional hazard regression, patients on pharmaceutical GL treatment had a lower CVE hazard ratio during follow-up (HR 0.22, 95%CI 0.05–0.97; p=0.041) compared to those not on GL therapy. Conclusion There was a striking decrease in event free survival in NDM patients prescribed pharmacological GL therapy following diagnosis underlining the importance to detect and treat such perturbations.
A stapled peptide antagonist of MDM2 carried by polymeric micelles sensitizes glioblastoma to temozolomide treatment through p53 activation
Authors: Xishan Chen, Lingyu Tai, Jie Gao, Jianchang Qian, Mingfei Zhang, Beibei Li, Cao Xie, Linwei Lu, Wuyuan Lu, Weiyue Lu
Journal: Journal of Controlled Release (2015)
The six minute walking test: Clinical predictors of survival in idiopathic pulmonary fibrosis
Authors: Giuseppe Brunetti, Veronica Rossi, Alberto Malovini
Journal: European Respiratory Journal (2013)

Aim : To identify clinical predictors of survival among 6MWT parameters in IPF patients.  Methods : 30 IPF underwent 6MWT, 16 in room air (RA) and 14 with oxygen supplementation (OX), at baseline (T0). 20 subjects repeated the test after 6-9 months (T1). Six-minute walk distance (6MWD), Distance-saturation product m% (DSP), 6MWD_m x Body weight_Kg(6MWD_mxKg), Peak heart rate %predicted (HR_%p), Borg scale and other parameters were measured using a standardized protocol. The difference of each parameter between T1 and T0 was also calculated (Δ). The relationship between 6MWT parameters and survival and the difference of each parameter between died and survivor at 18 months follow up, were estimated by non parametric statistic tests.  Results : In the whole group none of T0 variables was significantly correlated to the survival. A statistically significant relationship between survival and 6MWD_m (r=0,45,p  Conclusion : Change in 6MWD was highly predictive of mortality in IPF. The indicators related to the SatO2 are less sensitive. The oxygen supplementation may affect the prognostic value of 6MWT.
Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial
Authors: Ana Maria Henao-Restrepo, Ira M Longini, Matthias Egger, Natalie E Dean, W John Edmunds, Anton Camacho, Miles W Carroll, Moussa Doumbia, Bertrand Draguez, Sophie Duraffour, Godwin Enwere, Rebecca Grais, Stephan Gunther, Stefanie Hossmann, Mandy Kader Kondé, Souleymane Kone, Eeva Kuisma, Myron M Levine, Sema Mandal, Gunnstein Norheim, Ximena Riveros, Aboubacar Soumah, Sven Trelle, Andrea S Vicari, Conall H Watson, Sakoba Kéïta, Marie Paule Kieny, John-Arne Røttingen
Journal: The Lancet (2015)
Pulmonary hypertension in patients with infective endocarditis
Authors: Elena Yu Ponomareva, Elena E. Arkhangelskaya, Andrey P. Rebrov
Journal: European Respiratory Journal (2011)

Aim and methods: To study pulmonary hypertension (PH) in infective endocarditis (IE) pts with different localization, valve injury and activity of disease we have investigated 136 pts with native valve IE, in which 102 (75%) had left and 34 (25%) – sided IE. Diagnosis of IE was made according to Duke-criteria (ECS, 2009). Pulmonary artery systolic pressure (PASP) was measured using trans-thoracic EchoCG in dynamics taking into account the systolic tricuspid gradient and right atrium pressure.

Results: PH was revealed in 132 pts with IE (97%). Mean PASP was 53,7±16,2 mmHg. Pts with minimal and moderate PH prevailed (1st degree PH in 61 pts (45%), 2d degree – in 50 pts (37%)), only 15% pts (21) proved high degree PH (PASP> 70 mmHg). No significant differences of PH level were found depending on the gender, age, left or right-sided localization of IE, acute stage or 1-year or more advanced stage of disease duration. Nevertheless the PH degree was significantly higher in the group of pts with bi-valve or multiple valve injury in comparison with group of pts with mono-valve pathology (61,3±15,8 vs 49,3±14,9, p<0,001). Among haemodynamic factors influencing the PASP most possible were left atrium diastolic size (R=0,556386, p=0,00001) and myocardium mass index (R=0,47, p<0,0001).

Conclusions: So PH naturally develops in pts with IE and haemodynamic factors proved to be most significant in its development.
Variables responsible for tuberculin positivity of household contacts of sputum positive TB cases
Authors: Anishkumar Khan, Tushar Sahasrabudhe
Journal: European Respiratory Journal (2011)

In high TB endemic countries such as India, chemoprophylaxis is routinely offered only to contacts below 6 years of age. The possibility however remains that the index case may have transmitted the infection to other family members before the diagnosis of the disease. We evaluated this in the context of Indian patients. We did a cross sectional study of household contacts of the sputum positive TB patients diagnosed from our center that had no other index case at home in present or in the past. The contacts were tested for tuberculosis infection using 5 TU PPD (Purified Protein Derivative) immediately after the diagnosis of the index case. An induration of more than 10 mm was taken as a positive result. A total of 179 household contacts of 50 index cases were evaluated. 85/179 (47.48%) were tuberculin positive. 6/23 (26.08%) contacts below 6 years of age were infected. 31/44 spouses (70.45%) were tuberculin positive as against 39/87 (44.82%) first degree relatives and 15/48 (31.25%) second degree relatives. 61/112 (54.46%) contacts sharing same bedroom were infected as against 24/67 (35.82%) not sharing the bedroom. The prevalence of infection of contacts correlated with the grade of sputum positivity of the index case. The variables that did not show any statistically significant correlation were presence of lung cavity, hemoptysis, literacy level and gender. This study suggests the need for offering chemoprophylaxis to the contacts sharing bedroom including spouses in addition to contact children below 6 years of age.
Experts disagree over necessity of hepatitis E vaccine in Nepal
Authors: S. Cousins
Journal: BMJ (2015)

A group of international doctors has called for the speedy introduction of a vaccine against hepatitis E infection in Nepal, which they said could prevent the deaths of more than 400 pregnant women. However, some experts in Nepal have cast doubt over the safety and necessity of the vaccine.

The virus, which spreads through contaminated water, is common in Nepal, and experts fear an outbreak is likely given the imminent monsoon season, which officially begins next week. Moreover, tens of thousands of Nepalese people are still living in makeshift camps with limited or no access to clean drinking water after the two earthquakes that killed more than 8000 people and destroyed 500 000 homes. …
New perspectives on the management of hepatocellular carcinoma with portal vein thrombosis
Authors: Hyun Young Woo, Jeong Heo
Journal: Clinical and Molecular Hepatology (2015)

Despite advances in the treatment of hepatocellular carcinoma (HCC), managing HCC with portal vein thrombosis (PVT) remains challenging. PVT is present in 10-40% of HCC cases at the time of diagnosis and its therapeutic options are very limited. Current guidelines mainly recommend sorafenib for advanced HCC with PVT, but surgery, transarterial chemoemolization, external radiation therapy, radioembolization, transarterial infusion chemotherapy, and combination therapy are also still used. Furthermore, several new emerging therapies such as the administration of immunotherapeutic agents and oncolytic viruses are under investigation. This comprehensive literature review presents current and future management options with their relative advantages and disadvantages and summary data on overall survival. Keywords: Management; Hepatocellular carcinoma; Portal vein thrombosis
X‐linked thrombocytopenia with thalassemia displays bone marrow reticulin fibrosis and enhanced angiogenesis: Comparisons with primary myelofibrosis
Authors: Maria Åström, Victoria Hahn‐Strömberg, Eva Zetterberg, Inger Vedin, Mats Merup, Jan Palmblad
Journal: American Journal of Hematology (2014)

X‐linked thrombocytopenia with thalassemia (XLTT) is caused by the mutation 216R &gt; Q in exon 4 of the GATA1 gene. Male hemizygous patients display macrothrombocytopenia, splenomegaly, and a β‐thalassemia trait. We describe two XLTT families where three males were initially misdiagnosed as having primary myelofibrosis (PMF) and all five investigated males showed mild‐moderate bone marrow (BM) reticulin fibrosis. Comparative investigations were performed on blood samples and BM biopsies from males with XLTT, PMF patients and healthy controls. Like PMF, XLTT presented with high BM microvessel density, low GATA1 protein levels in megakaryocytes, and elevated blood CD34+ cell counts. But unlike PMF, the BM microvessel pericyte coverage was low in XLTT, and no collagen fibrosis was found. Further, as evaluated by immunohistochemistry, expressions of the growth factors VEGF, AGGF1, and CTGF were low in XLTT megakaryocytes and microvessels but high in PMF. Thus, although the reticulin fibrosis in XLTT might simulate PMF, opposing stromal and megakaryocyte features may facilitate differential diagnosis. Additional comparisons between these disorders may increase the understanding of mechanisms behind BM fibrosis in relation to pathological megakaryopoiesis. Am. J. Hematol. 90:E44–E48, 2015. © 2014 Wiley Periodicals, Inc.
Azithromycin fails to restore apoptosis in cystic fibrosis airway epithelium post viral infection
Authors: Erika Sutanto, Clara Foo, Anthony Kicic, Stephen Stick, Arestcf
Journal: European Respiratory Journal (2011)

Rationale:  Airway epithelium is primary target for respiratory viruses, especially human rhinovirus (HRV). Apoptosis as early host defense mechanisms is induced in response to viral infection. We have previously observed damped apoptotic & increased viral replication in cystic fibrosis (CF) airway epithelium compared to healthy controls. Azithromycin induces innate immune responses in non-CF epithelium. We hypothesize that addition of azithromycin to HRV-infected CF cells may restore/elevate their current apoptotic response to viral insult.   Methods:  Airway epithelial cells (AEC) from healthy children (HNA) & those with CF were infected with HRV1b at various multiplicities of infection (MOI: 3-25). AECs were either pre-treated for 24hr or co-treated with azithromycin (1-10μM). Viral replication was determined using qPCR, apoptosis assessed using ssDNA apoptosis kit & IL-8 measured via ELISA.   Results:  HRV1b replication was 10-fold greater in CF compared to HNA despite the expression of HRV1b-specific receptor remaining the same between the two cohorts. Furthermore, CF exhibited a dampened apoptotic (∼2 fold) compared to the healthy counterparts. Pre- or co-treatment of CF AEC with azithromycin had little effect in restoring apoptosis to levels seen in healthy cells. Azithromycin also did not reduce the level of IL-8 in CF in response to HRV infection.   Conclusion:  Although CF are more susceptible to HRV1b infection, the dampened apoptotic response seen in CF epithelium after HRV infection cannot be restored with pre or co-treatment with azithromycin. The increased production of IL-8 observed post viral infection was not ameliorated following macrolide treatment.  Funding: NHMRC, ARC, ACFRT.
Abstract 13955: M-Atrial Natriuretic Peptide, a Novel Anti-Hypertensive Therapeutic Peptide, is Markedly Resistant to in vivo Intra-Nephron Degradation
Authors: Paul McKie, Tomoko Ichiki, Alessandro Catalioitti, S J Sangaralingham, Horng Chen, John Burnett
Journal: Circulation (2011)

Introduction M-atrial natriuretic peptide (M-ANP) is a novel 40 amino acid peptide based on the native 28 amino acid cardiac hormone atrial natriuretic peptide (ANP). In vitro studies suggest M-ANP...
Comparison of the Dermatology Life Quality Index and the Children's Dermatology Life Quality Index in assessment of quality of life in patients with psoriasis aged 16–17 years
Authors: M.J. Geel, M. Maatkamp, A.M. Oostveen, E.M.G.J. Jong, A.Y. Finlay, P.C.M. Kerkhof, M.M.B. Seyger
Journal: British Journal of Dermatology (2015)

Journal Article Comparison of the Dermatology Life Quality Index and the Children's Dermatology Life Quality Index in assessment of quality of life in patients with psoriasis aged 16–17 years Get access M.J. van Geel, M.J. van Geel Department of Dermatology Radboud University Medical Center PO Box 9101 6500 HB Nijmegen the Netherlands Correspondence Maartje J. van Geel. E‐mail: Maartje.vanGeel@radboudumc.nl Search for other works by this author on: Oxford Academic Google Scholar M. Maatkamp, M. Maatkamp Department of Dermatology Radboud University Medical Center PO Box 9101 6500 HB Nijmegen the Netherlands Search for other works by this author on: Oxford Academic Google Scholar A.M. Oostveen, A.M. Oostveen Department of Dermatology Radboud University Medical Center PO Box 9101 6500 HB Nijmegen the Netherlands Search for other works by this author on: Oxford Academic Google Scholar E.M.G.J. de Jong, E.M.G.J. de Jong Department of Dermatology Radboud University Medical Center PO Box 9101 6500 HB Nijmegen the Netherlands Search for other works by this author on: Oxford Academic Google Scholar A.Y. Finlay, A.Y. Finlay Department of Dermatology and Wound Healing Institute of Infection and Immunity Cardiff University School of Medicine Cardiff U.K Search for other works by this author on: Oxford Academic Google Scholar P.C.M. van de Kerkhof, P.C.M. van de Kerkhof Department of Dermatology Radboud University Medical Center PO Box 9101 6500 HB Nijmegen the Netherlands Search for other works by this author on: Oxford Academic Google Scholar M.M.B. Seyger M.M.B. Seyger Department of Dermatology Radboud University Medical Center PO Box 9101 6500 HB Nijmegen the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 1, 1 January 2016, Pages 152–157, https://doi.org/10.1111/bjd.14163 Published: 01 January 2016
Hyperkalaemia on the surgical ward
Authors: David P Baird, Robert W Hunter, John J Neary
Journal: BMJ (2015)

A 56 year old woman was admitted with an infected stump wound at the site of a below the knee amputation. Her medical history included type 2 diabetes, diabetic foot ulcer, and painful peripheral neuropathy. Her regular drugs were metformin, amitriptyline, lansoprazole, Humulin I and Novorapid SC insulin, aspirin, paracetamol, morphine sulfate, gabapentin, and carbamazepine. In hospital, she was also prescribed dalteparin 5000 units subcutaneously once daily, intravenous benzylpenicillin, and flucloxacillin. 

Before admission, serum potassium was 4.6-4.8 mmol/L (reference range 3.6-5.0). During admission, she had persistent hyperkalaemia peaking at 6.2 mmol/L and received repeated doses of insulin-dextrose and salbutamol over three days. Renal function was stable throughout (creatinine 60-85 μmol/L (60-120), estimate glomerular filtration rate >60 mL/min/1.73 m2). She was mildly acidotic (bicarbonate 18-20 mmol/L (22-30)) and serum lactate was 1.9 mmol/L (0.6-2.4). A paired sample of serum and urine showed serum: potassium 5.7 mmol/L, osmolality 312 mOsm (280-296); urine: sodium 69 mmol/L, potassium 18 mmol/L, osmolality 370 mOsm.



### 1. From the history, what are the likely causes of the hyperkalaemia?

#### Short answer

Potassium in intravenous penicillin preparations or release of intracellular potassium from necrotic muscle in the stump. Potassium excretion may be impaired due to type IV renal tubular acidosis associated with diabetes or dalteparin.

#### Discussion

Hyperkalaemia is common in patients in hospital, with a reported incidence of 1.3-10%.1 2 3 It is important to recognise and treat hyperkalaemia promptly because it can cause life threatening cardiac arrhythmias without warning.

Potassium is the principal intracellular cation; 98% of total body potassium is intracellular.4 Serum potassium levels are usually efficiently maintained within the normal range (3.6-5.0 mmol/L) because of buffering against the intracellular pool and by …