tbuckley/cabot-search huggingface dataset:
Abstract 17185: Modest Performance of Heart Failure Clinical Prediction Models: A Systematic External Validation Study
Authors: Jenica N Upshaw, Jason Nelson, Benjamin Wessler, Benjamin Koethe, Christine Lundquist, Jennifer Lutz, David van Klaveren, Ewout Steyerberg, David M Kent
Journal: Circulation (2018)

Introduction: Most heart failure (HF) clinical prediction models (CPMs] have not been independently externally validated. We sought to test the performance of HF models in a diverse population using a systematic approach. Methods: A systematic review identified CPMs predicting outcomes for patients with HF. Individual patient data from 5 large publicaly available clinical trials enrolling patients with chronic HF were matched to published CPMs based on similarity in populations and available outcome and predictor variables in the clinical trial databases. CPM performance was evaluated for discrimination (c-statistic, % relative change in c-statistic) and calibration (Harrell’s E and E 90 , the mean and the 90% quantile of the error distribution from the smoothed loess observed value) for the original and recalibrated models. Results: Out of 135 HF CPMs reviewed, we identified 45 CPM-trial pairs including 13 unique CPMs. The outcome was mortality for all of the models with a trial match. During external validations, median c-statistic was 0.595 (IQR 0.563 to 0.630) with a median relative decrease in the c-statistic of -57 % (IQR, -49% to -71%) compared to the c-statistic reported in the derivation cohort. Overall, the median Harrell’s E was 0.09 (IQR, 0.04 to 0.135) and E 90 was 0.11 (IQR, 0.07 to 0.21). Recalibration of the intercept and slope led to substantially improved calibration with median change in Harrell’s E of -35% [IQR 0 to -75%] for the intercept and -56% [IQR -17% to -75%] for the intercept and slope. Refitting model covariates improved the median c-statistic by 38% to 0.629 [IQR 0.613 to 0.649]. Conclusion: For HF CPMs, independent external validations demonstrate that CPMs perform significantly worse than originally presented; however with significant heterogeneity. Recalibration of the intercept and slope improved model calibration. These results underscore the need to carefully consider the derivation cohort characteristics when using published CPMs.
<i>Pseudomonas aeruginosa</i>membrane vesicles cause endothelial barrier failure and lung injury
Authors: Mark J. McVey, Mazharul Maishan, Anna Foley, Razan Turki, Elyse J. Roach, Rose Deschler, Sarah Weidenfeld, Neil M. Goldenberg, Cezar M. Khursigara, Wolfgang M. Kuebler
Journal: European Respiratory Journal (2022)

<b>Membrane vesicles released by <i>Pseudomonas aeruginosa</i> PA14 can elicit septic acute lung injury due to loss of endothelial barrier integrity and inflammasome activation</b>https://bit.ly/3gMnkPu
IgG Anti–Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross‐Sectional Study Encompassing ~1,500 Samples
Authors: Theresa Kissel, Lise Hafkenscheid, Tineke J. Wesemael, Mami Tamai, Shin‐ya Kawashiri, Atsushi Kawakami, Hani S. El‐Gabalawy, Dirkjan van Schaardenburg, Solbritt Rantapää‐Dahlqvist, Manfred Wuhrer, Annette H. M. van der Helm‐van Mil, Cornelia F. Allaart, Diane van der Woude, Hans U. Scherer, Rene E. M. Toes, Tom W. J. Huizinga
Journal: Arthritis & Rheumatology (2022)

The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages.Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up.IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). In patients in whom DFR was later achieved, IgG ACPA VDG was already reduced at the time of RA onset.The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development.
Abstract 17193: Effect of Long Term Canagliflozin Use on Body Weight and Blood Pressure: A Systematic Review and Meta-Analysis
Authors: Muhammad S Khan, Tariq J Siddiqi, Muhammad S Usman, Muhammad M Memon, Sadiya S Khan, Sanjiv J Shah
Journal: Circulation (2018)

Introduction: Although Canagliflozin, an FDA-approved sodium-glucose cotransporter 2 inhibitor (SGLT2i), is known to reduce body weight and blood pressure (BP) in the short-term, it is unclear whether this effect persists in the long-term. Furthermore, it remains uncertain whether the reduction in BP and body weight is dose-dependent. Objective: To conduct a meta-analysis to study the effects of long term Canagliflozin use on BP and body weight in type 2 diabetes mellitus (T2DM) patients and stratify the results by dosage. Methods: MEDLINE and Scopus were queried in May 2018 for randomized controlled trials (RCTs) of Canagliflozin that had a follow-up period of at least one year and reported change in BP and percentage change in body weight. Data from included studies were pooled using a random effects model and results were presented as weighted mean differences (WMDs) with 95% confidence intervals (CIs). Subgroup analysis according to dosage (100mg/300mg) was performed. Chi-squared test was conducted to test for subgroup differences. Results: Five RCTs (N=15,230 participants) were included in the final analysis. Canagliflozin also led to significant reduction in body weight when compared to controls (WMD: -3.32% [-4.04, -2.60]; p&lt;0.001); however, this effect was not found to be dose-dependent (p=0.76). Both systolic (WMD: -4.40 mmHg [-5.18, -3.62]; p&lt;0.001) and diastolic (WMD: -1.68 mmHg [-2.14, -1.23]; p&lt;0.001) BP were significantly lower with long-term canagliflozin use, when compared to placebo (Figure 1). This effect was significantly stronger in the 300mg subgroup, when compared to the 100mg subgroup for both systolic (p=0.02) and diastolic (p=0.01) BP. There was no significant change in the risk of hypotension with the use of canagliflozin (Odds ratio: 1.59 [0.80, 3.19]; p=0.19). Conclusion: Long-term Canagliflozin is associated with reduced body weight and may be one mechanism for the beneficial BP response observed . Favorable changes in body weight and BP may be responsible for improved cardiovascular outcomes in T2DM patients with Canagliflozin.
Real-world experience with relugolix.
Authors: Saro Kasparian, Oren Wei, Christopher Lehmer, Sumanta K. Pal, Yung Lyou, Tanya B. Dorff
Journal: Journal of Clinical Oncology (2022)

57 Background: Gonadotropin-releasing hormone (GnRH) antagonists were developed in part to avoid testosterone flare to achieve faster and more consistent testosterone suppression. Relugolix (Rel) was given FDA approval for use in prostate cancer (PCa) based on the phase 3 HERO trial but some real-world concerns include compliance, affordability, and performance in patients transitioning from another GnRH agent or in combination with other therapeutic agents. The aim of our study was to evaluate the real-world implications of prescribing and/or switching to Rel. Methods: A single institution retrospective study was conducted on patients prescribed Rel. Treatment data including concomitant therapeutic agents were collected. Compliance data was measured via chart review and pharmacy dispensary records. Patients were classified as either newly castrated or transitioning from another agent. PSA and testosterone levels were tabulated. Reported adverse effects (AE), and reasons for discontinuation if applicable including financial toxicity were noted. Results: 50 patients were reviewed; 15 (30%) treated for adjuvant, 18 (36%) for biochemical recurrence, and 17 (34%) for metastatic PCa. 12% were on concomitant therapy with abiraterone, 4% with enzalutamide, and 2% with apalutamide. 80% reported compliance to Rel. 5 (10%) never filled the prescription. 30 (60%) were newly castrated (castration restart or naïve) while 16 (36%) were transitioned from another GnRH. No changes in PSA or testosterone were noted in patients switched form injected GnRH to Rel. The most common documented AE effects included hot flashes 24%, fatigue, 29%, and weight gain 9%. No unexpected toxicity was reported in combination with abiraterone. Of 11 patients who discontinued therapy, 45% did so due to cost, 36% due to AE, and 27% due to therapy completion. 4 of 16 (25%) of those who transitioned from injection GnRH felt symptoms were worse on Rel. Conclusions: In our early experience with Rel, patients did comply to therapy based on self-reporting, pharmacy fill dates, and laboratory evidence of castration. However, financial toxicity was and remains a significant barrier both accessing Rel and remaining on Rel therapy. While a differential toxicity was reported by those who switched from injection GnRH, sometimes leading to discontinuation, there were no new safety signals reported, especially in combination with abiraterone.
Abstract 17112: Transgenic Endothelial-Specific HIV-Nef Expression Induces Pulmonary Hypertension and Systemic Vascular Dysfunction, Which Can Be Reverted by Treatment With Statin
Authors: Natalia Bogatcheva, Sarvesh Chelvanambi, Xingjuan Chen, Alexander Obukhov, Matthias Clauss
Journal: Circulation (2018)

Introduction: HIV patients on ART perplexingly remain at higher risk for developing cardiovascular diseases including acute peripheral arterial disease and pulmonary hypertension. A likely culprit for observed vascular changes is HIV protein Nef, detected both intracellularly and extracellularly in the absence of HIV RNA or DNA. Nef is known to induce endothelial dysfunction through the activation of NADPH; statins are known to inhibit NADPH activation. Hypothesis: Nef expression in endothelial cells will trigger cardiopulmonary and vascular pathology; Nef effects will be reversed by statin. Methods: Endothelial-specific expression of HIV-Nef was achieved by mating the VE-Cadherin-Tet off mice with TRE-Nef mice. The resulting Nef+ double transgenics and their Nef- negative littermates were maintained without doxycycline to induce Nef expression. Changes in pulmonary acceleration and ejection times were analyzed by ultrasound (INVEVO2100). Additionally, we assessed the ability of bradykinin-preconstricted aortic rings to dilate in response to acetylcholine in NO-dependent manner. Results: Between week 10 and week 13 of age, Nef expressing mice displayed gradual reduction of PAT/PET ratio (down to the 75% of the original PAT/PET ratio at week 10), indicative of developing pulmonary hypertension (N=6). PAT/PET ratio in Nef-negative mice did not change significantly between week 10 and 13 of age. Importantly, statin treatment initiated at week 10 completely suppressed PAT/PET changes developing in Nef-expressing mice. Arterial rings from Nef expressing mice (n=4) showed significantly impaired dilatation in response to acetylcholine (10% relaxation in Nef+ mice vs 40% relaxation in Nef-negative littermates, p=0.03), indicative of changes in systemic circulation. This difference was significantly attenuated in Nef+ mice receiving statin treatment. Conclusions: Our data suggests that mice with endothelial expression of HIV-Nef display pathological changes in pulmonary and systemic circulation. Statin treatment significantly attenuates changes in parameters indicative of pulmonary and systemic hypertension, suggesting that statin will be beneficial for patients with HIV-induced cardiopulmonary and vascular diseases.
Malabsorption.
Authors: G. C. Cook
Journal: BMJ (1967)

Malabsorption implies a defect in the absorption of one or more nutritive substances, due to an abnormality either in the intestine or in one of the digestive organs.Impaired absorption of several substances, such as fat, protein, fat-soluble vitamins, vitamin B12, folic acid, and iron, is often present (Table I).Selective malabsorption of a single substance may, however, occur, as in vitamin-B12 malabsorption in pernicious anaemia or disaccharide malabsorption in disaccharidase deficiency.Malabsorption syndromes are present throughout the world.The main causes tend to be different numerically in tropical zones compared with temperate zones.As work in the field increases, however, it becomes abundantly obvious that the geographical distribution of aetiological factors is not as clear- cut as was formerly supposed.* Enzyme defects-e.g., disaccharidase deficiencies.Coeliac disease, adult coeliac disease (gluten-induced enteropathies).* Resection of part of the small intestine (i.e., absorptive-surface deficiency).
Glue ear.
Authors: I Friedmann
Journal: BMJ (1970)

Twenty-eight years agol I descrbed experiments in which I self-administered 1-2 mg. of nicotine hypodermically three or four times a day, with some smoking, for a month.I actually took over 150 doses by various routes.After a month I preferred a hypodermic of nicotine to a cigarette in- haled.I also found that 0.1 mg. of nicotine intravenously had exactly the same subjective action as one deep inhalation of cigarette smoke.Clearly therefore smoking is essentially a means of taking doses of nicotine and is governed not by a psychophysiological, but by a (psycho-)pharnfa- cological mechanism or, in simple language, by recurrent craving for tobacco.-Iam, etc.,
Postprandial blindness.
Authors: C F Pantin, R A Young
Journal: BMJ (1980)

Postprandial blindnessWe describe a patient in whom a common condition produced unusual symptoms. Case reportA 73-year-old man presented with a four-month history of blurred vision and diplopia while resting after meals.A quarter of an hour after a meal he developed blurring of vision and diplopia which worsened over the next 15 minutes.For the next half to two hours he was able to distinguish only light and dark.He complained of dizziness and slight nausea during this period, but had no loss of consciousness or sweating.The duration of the symptoms was proportional to the size of meal.Between meals his visual acuity was 6/9 bilaterally.For the two years before admission he had complained of dizziness, diplopia, and blurred vision after walking a decreasing distance (about 100 yards on admission) or on rising abruptly from a supine to standing position.These symptoms lasted for about 15 minutes on resting.In 1951 he had had a partial gastrectomy for duodenal ulcer from which he had noted no long-term problems.He smoked 20 cigarettes a day.The only palpable pulses in the limbs were the right femoral and popliteal with a femoral bruit.The right carotid pulse was very weak.The left carotid pulse was easily palpable with a bruit high in the neck.His blood pressure, measured with a large cuff on the right thigh, was 140/90 mm Hg (lying and standing) with a heart rate of 80/min in sinus rhythym.An electrocardiogram, chest radiograph, and 50-g glucose tolerance test (blood glucose and insulin) were within normal limits.After admission his symptoms occurred after eating a meal.His visual acuity was reduced to perception of finger movements.After a meal given under test conditions, however, his visual acuity, pulse, blood pressure (lying and standing), and electrocardiogram remained stable with blood glucose, insulin, pancreatic, and small intestinal enzyme profiles within normal limits.Arch aortography showed occlusions of the innominate artery and the proximal left subclavian artery.The right common carotid artery was patent but the right internal carotid was stenosed at its origin; both were filled only on late films via collaterals.Thus all the circulation to the brain passed through the patent left common carotid to the also stenosed left internal carotid, and through collaterals from the thorax to the vertebral and right internal carotid arteries.A left carotid endarterectomy was per- formed.The stump pressure in the intemal carotid artery was only 28 mm of blood.A Javid shunt was used for cerebral protection.Histology of the arterial wall showed atherosclerosis and calcification.His recovery was uncomplicated and he is now free of his postprandial symptoms.Selective left carotid angiography showed that the proximal segment of the internal carotid artery appeared normal.
Tuberculous Pericarditis
Authors: E. Montuschi, T. L. Reeves
Journal: BMJ (1947)

JOURNAL693it, and the basic neglect.The opportunity which this chal- lenge presented came with the introduction of the National Health Service, which promised to every citizen the treatment he needed, but the opportunity was also a heavy responsibility for medicine.Even with present knowledge, if there were suffi- cient hospital beds and adequate treatment facilities the invalidism resulting from rheumnatism could be greatly lessened.
Eosinophilic fasciitis.
Authors: S L Stubbs, G R Hughes
Journal: BMJ (1977)

Acute anuric glomerulonephritis in monoclonal cryoglobulinaemiaWhile proliferative glomerulonephritis with progressive renal failure is a common and often fatal complication of primary mixed cryo- globulinaemia,l the presence of monoclonal cryoglobulins is not usually associated with glomerular proliferative lesions.Nevertheless, a few well-documented cases of glomerulonephritis in patients with essential monoclonal IgG cryoglobulinaemia have been reported.-4In these cases the outcome of glomerulonephritis was generally favourable or very slowly progressive.We describe a further case of a woman with a primary monoclonal IgG cryoglobulinaemia who developed a diffuse proliferative glomerulonephritis.In this patient renal damage was particularly severe and prolonged anuria complicated the outcome.Despite the ominous prognosis attributed to acute renal failure in cryoglobulin- aemic nephritis, this patient's renal function recovered. Case reportA 42-year-old woman was admitted to our unit in December 1972.In July 1971 she had had a normal pregnancy, and in February 1972 she developed skin eruptions on her legs and arms, without fever or other symptoms.The skin lesions spontaneously disappeared but reappeared in subsequent episodes.In December 1972, during one of these episodes, we found that she had proteinuria and hypertension.After a few days she became oliguric and oedematous, and on admission she was pale, febrile, with oedema and haemorrhagic-papulo-necrotic lesions of the legs.Blood pressure was 165/100 mmHg.Serum creatinine was 831 tumol/l (9-4 mg/100 ml), blood urea 30 4 mmol/l (183 mg/100 ml), packed cell volume 28 %, haemo- globin 8-9 g/dl, white blood count 8-3 x 109/1, platelets 220 x 109/1.Serum C3 was 0-43 g/l, and tests for ANF and LE cells were negative.Her proteinuria amounted to 6 g daily and haematuria was present.In the serum cryo-
Functional role of the epicardium in postinfarction ventricular tachycardia: Observations derived from global epicardial activation mapping, entrainment, and epicardial laser photoablation
Authors: Laszlo Littmann, Robert H. Svenson, John J. Gallagher, Jay G. Selle, Marie-Claire Marroum, Chi Hui Chuang, Kathleen Seifert, George P. Tatsis
Journal: Journal of the American College of Cardiology (1990)
Abstract 17060: Effect of Septal Myectomy on Obstructive Sleep Apnea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy
Authors: Wang shengwei, Wang shuiyun
Journal: Circulation (2018)

Introduction: Hypertrophic cardiomyopathy (HCM) has a higher prevalence of OSA. The impact of obstructive sleep apnea on perioperative complications in hypertrophic obstructive cardiomyopathy (HOCM) patients undergoing septal myectomy and the impact of septal myectomy on OSA are not yet clear. Therefore, we sought to examine the association between HOCM and OSA before and after septal myectomy. Methods: We studied 69 consecutive patents with a confirmed diagnosis of HOCM who underwent septal myectomy. All patients performed polysomnography before and three months after operation. Results: Of all the patients, 41 (59.4%) were diagnosed with OSA. Compared to patients without OSA, patients with OSA were significantly older. The incidence of atrial fibrillation increased significantly during perioperative period in patients with OSA (31.7% vs 10.7%, p=0.048). Three months after operation, the severity of OSA increased significantly, as reflected by AHI, OAI and HI (11.7[7.2-22.1] vs 25.6(17.7-33.8), p&lt;0.001; 11.6[6.8-17.6] vs 15.1[9.5-20.8], p=0.024;) 4.4[2.5-7.1] vs 8.3[4.1-12.0], p=0.003) while the CAI decreased (0.4[0.0-2.1] vs 0.2[0.0-0.8], p=0.008). In a multivariate linear regression analysis, mean oxygen desaturation and time% with Spo2 &lt;90% during sleep were significantly associated with an increased AHI independently of sex, BMI and gender (p=0.026 and p=0.007, adjusted R 2 =0.365). Conclusions: The severity of OSA increased significantly three months after septal myectomy as reflected by AHI, OAI and HI. The mean oxygen saturation and time% with Spo2 &lt;90% during sleep are independently associated with the increase of AHI.
Percutaneous cholecystolithotomy
Authors: A G Johnson, B. Ross, P. Milner
Journal: BMJ (1988)

of single fibre electromyographic findings in the right extensor digitorum communis muscle of 10 patients with postviralfatigue syndrome % Fibre pairs with Mean Fibre Age abnormal overall Jitter Mean density Case and jitter jitter abnor-fibre abnor- No Sex (>55 ps)* ([ts)t mality densityl mality
Glue ear.
Authors: P W Alberti
Journal: BMJ (1970)

atrium.A convenient external reference point for this in a supine patient is the mid axillary point.This level was presumably used by A. E. Baue, whose review we quoted.Some prefer to use the sternal angle as a reference level, in which case the recorded pressures will, of course, be lower.Since the usefulness of C.V.P. measurements is not in their absolute values but in changes of C.V.P. that take place it is of little importance which reference point is chosen, provided the same point is used consistently.-ED., B.