tbuckley/cabot-search huggingface dataset:
ABC of arterial and venous disease: Swollen lower limb---1: General assessment and deep vein thrombosis
Authors: W P Gorman, K R Davis, R Donnelly
Journal: BMJ (2000)

The most common cause of leg swelling is oedema, but expansion of all or part of a limb may be due to an increase in any tissue component (muscle, fat, blood, etc). A correct diagnosis requires consideration of whether the swelling is acute or chronic, symmetrical or asymmetrical, localised or generalised, and congenital or acquired. Chronic swelling, particularly if asymmetrical, is usually a sign of chronic oedema arising from venous or lymphatic disease, whereas symmetrical lower limb swelling suggests a systemic or more central cause of oedema, such as heart failure or nephrotic syndrome. Oedema develops when the rate of capillary filtration (lymph formation) exceeds lymphatic drainage, either because of increased capillary filtration, inadequate lymphatic flow, or both. Extracellular fluid volume is controlled prinicpally by the lymphatic system, which normally compensates for increases in capillary filtration. Most oedemas arise because filtration overwhelms the lymph drainage system. Increased capillary filtration may occur because of raised venous pressure, hypoalbuminaemia, or increased capillary permeability due to local inflammation. The two main causes of a swollen lower limb are deep vein thrombosis and lymphoedema (a failure of the lymph drainage system). This article concentrates on deep vein thrombosis and next week's article on lymphoedema.

#### Causes of swelling of lower limb

##### Acute

##### Chronic

###### Congenital vascular abnormalities

###### Venous disease

###### Lymphoedema

###### Other

Thrombosis usually develops as a result of venous stasis or slow flowing blood around venous valve sinuses; extension of the primary thrombus occurs within or between the deep and superficial veins of the leg and the propagating clot causes venous obstruction, damage …
MKRN3 inhibits the reproductive axis through actions in kisspeptin-expressing neurons
Authors: Ana Paula Abreu, Carlos A. Toro, Yong Bhum Song, Victor M Navarro, Martha A. Bosch, Aysegul Eren, Joy N. Liang, Rona S. Carroll, Ana Claudia Latronico, Oline K. Ronnekleiv, Carlos F Aylwin, Alejandro Lomniczi, Sergio R. Ojeda, Ursula B Kaiser
Journal: Journal of Clinical Investigation (2020)

The identification of loss-of-function mutations in MKRN3 in patients with central precocious puberty in association with the decrease in MKRN3 expression in the medial basal hypothalamus of mice before the initiation of reproductive maturation suggests that MKRN3 is acting as a brake on gonadotropin-releasing hormone (GnRH) secretion during childhood. In the current study, we investigated the mechanism by which MKRN3 prevents premature manifestation of the pubertal process. We showed that, as in mice, MKRN3 expression is high in the hypothalamus of rats and nonhuman primates early in life, decreases as puberty approaches, and is independent of sex steroid hormones. We demonstrated that Mkrn3 is expressed in Kiss1 neurons of the mouse hypothalamic arcuate nucleus and that MKRN3 repressed promoter activity of human KISS1 and TAC3, 2 key stimulators of GnRH secretion. We further showed that MKRN3 has ubiquitinase activity, that this activity is reduced by MKRN3 mutations affecting the RING finger domain, and that these mutations compromised the ability of MKRN3 to repress KISS1 and TAC3 promoter activity. These results indicate that MKRN3 acts to prevent puberty initiation, at least in part, by repressing KISS1 and TAC3 transcription and that this action may involve an MKRN3-directed ubiquitination-mediated mechanism.
A RANDOMIZED TRIAL OF RECTAL INDOMETHACIN TO PREVENT POST-ESWL PANCREATITIS (THE RIPEP TRIAL)
Authors: Y Qian, N Ru, H Chen, Z Li, Z Liao
Journal: Endoscopy (2020)

Aims Pancreatic extracorporeal shock wave lithotripsy (ESWL) is the first-line therapy for large pancreatic duct stones, and pancreatitis is the most common complication. Non-steroidal anti-inflammatory drugs (NSAIDs) proved to be an effective prophylactic medication for post-ERCP pancreatitis while little research focused on the incidence and none on the effective prevention for post-ESWL pancreatitis. The aim of the study is to explore the effect of rectal indomethacin for post-ESWL pancreatitis.
Measured haplotype analysis of the angiotensin-I converting enzyme gene
Authors: B D Keavney, C A McKenzie, J M Connell, C Julier, P J Ratcliffe, E Sobel, M Lathrop, M Farrall
Journal: Circulation (1999)

Linkage and segregation analysis have shown that circulating angiotensin-I converting enzyme (ACE) levels are influenced by a major quantitative trait locus that maps within or close to the ACE gene. The D variant of a 287 bp insertion/deletion (I/D) polymorphism in intron 16 of the gene is associated with high ACE levels and may also be related to increased risk of cardiovascular disease. Multiple variants that are in linkage disequilibrium with the I/D polymorphism have been described, but it is unknown if any of these are directly implicated, alone or in combination with as yet undiscovered variants, in the determination of ACE levels. An analysis of 10 polymorphisms spanning 26 kb of the ACE gene revealed a limited number of haplotypes in Caucasian British families due to strong linkage disequilibrium operating over this small chromosomal region. A haplotype tree (cladogram) was constructed with three main branches (clades A-C) which account for 90% of the observed haplotypes. Clade C is most likely derived from clades A and B following an ancestral recombination event. This evolutionary information was then used to direct a series of nested, measured haplotype analyses that excluded upstream sequences, including the ACE promoter, from harbouring the major ACE-linked variant that explains 36% of the total trait variability. Residual familial correlations were highly significant, suggesting the influence of additional unlinked genes. Our results demonstrate that a combined cladistic/measured haplotype analysis of polymorphisms within a gene provides a powerful means to localize variants that directly influence a quantitative trait.
BAY-299, a novel chemical probe for in-depth analysis of the function of the bromodomain proteins BRPF2 and TAF1
Authors: L Bouche, C D Christ, S Siegel, C Tallant, A E Fernandez-Montalvan, K V Huber, V Putter, S Mueller, O Fedorov, A ter Laak, T Sugawara, D Stockigt, J Meier, S J Holton, I V Hartung, B Haendler
Journal: Cancer Research (2017)
INCREASING PREVALENCE OF ANXIETY AND DEPRESSION DISORDERS AFTER DIAGNOSIS OF CHRONIC PANCREATITIS: A 5 YEAR UNITED STATES POPULATION BASED STUDY
Authors: M Alkhayyat, MA Saleh, M Abureesh, G Khoudari, E Mansoor, C Roberto Simons-Linares, T Stevens, P Chahal
Journal: Endoscopy (2020)

Aims Few studies have shown an increased risk of certain psychiatric conditions as well as substance abuse disorders in CP, however; these were limited by sample size. Using a large database, we sought to describe the epidemiology and risk association of several psychiatric diseases in patients with CP.
IT IS SO USEFUL TO KNOW GASTRIC CANCER RISK AT GASTRIC ENTRANCE (CARDIA) WITH THE PRESENCE OF AN EASY SIMPLE SIGN
Authors: T Yamasaki, Y Kinoshita, Y Akita, H Miyashita, Y Maruyama, R Miyazaki, T Sakurai, M Mitsunaga, M Saruta
Journal: Endoscopy (2020)

Aims We have confused with various newly endoscopic findings (patchy redness and map-like redness etc.) after H.pylori（HP）eradication. On this time, we have found out a new other ultimate useful finding showing HP related gastritis at gastric cardia including present and post HP infection. Our aim of this study is to elucidate the possibility of judgement with only this cardiac endoscopic view about presence or absence with HP infection.
Assessing risk factors for SARS-CoV-2 infection in patients presenting with symptoms in Shanghai, China: a multicentre, observational cohort study
Authors: Bei Mao, Yang Liu, Yan-Hua Chai, Xiao-Yan Jin, Hai-Wen Lu, Jia-Wei Yang, Xi-Wen Gao, Xiao-Lian Song, Hong Bao, An Wang, Wen-Chao Gu, Lei Zhao, Jie-Ping Pan, Fan Li, Tie-Feng Zhang, Ye-Chang Qian, Chun-Ling Du, Wei Ding, Chun-Lin Tu, De-Jie Chu, Chun Li, Ling Ye, Yong Luo, Cui-Xia Zheng, Rong-Huan Yu, Zhong-Min Qiu, Hui-Fang Cao, Jia-Wei Ren, Jing-Ya Zhao, Chang-Hui Wang, Hong-Zhou Lu, Jun Li, Yang Hu, Shuo Liang, Zhi-Jun Jie, Jie-Ming Qu, Jin-Fu Xu
Journal: The Lancet Digital Health (2020)

SummaryBackgroundThe outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19.MethodsWe did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19.FindingsWe enrolled patients visiting fever clinics from Jan 17 to Feb 16, 2020. Among 53 617 patients visiting fever clinics, 1004 (1·9%) were considered as suspected cases, with 188 (0·4% of all patients, 18·7% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4·16, 95% CI 2·74–6·33; p<0·0001), fatigue (OR 1·56, 1·01–2·41; p=0·043), white blood cell count less than 4 × 109 per L (OR 2·44, 1·28–4·64; p=0·0066), lymphocyte count less than 0·8 × 109 per L (OR 1·82, 1·00–3·31; p=0·049), ground glass opacity (OR 1·95, 1·32–2·89; p=0·0009), and having both lungs affected (OR 1·54, 1·04–2·28; p=0·032) were independent risk factors for confirmed COVID-19.InterpretationThe screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease.FundingNational Natural Science Foundation of China.
RISK FACTORS FOR MORTALITY AMONG PATIENTS ADMITTED TO HOSPITAL FOR LOWER GASTROINTESTINAL BLEEDING: A PREDICTIVE MODEL
Authors: CD Bono, L Frazzoni, F Radaelli, A Mussetto, C Spada, G Manes, A Repici, MG Vassallo, S Segato, A Musso, ED Giulio, P Soriani, GD Nucci, V Festa, AD Leo, M Marini, L Ferraris, C Hassan, S Paggi, L Fuccio, A Andrealli
Journal: Endoscopy (2020)

Aims Lower GI bleeding (LGIB) is a common cause of hospitalization and death. A recent UK multicenter study has developed and validated a risk score for safe outpatient management. However, data on factors associated with mortality in higher risk patients are lacking. Aim of this study was to assess factors associated with mortality and to derive and validate a predictive model.
THE SUMP SYNDROME: AN UNUSUAL CAUSE OF ACUTE CHOLANGITIS
Authors: Z Bouabane, A Zazour, AE Mekkaoui, G Kharrasse, W Khannoussi, Z Ismaili
Journal: Endoscopy (2020)

Sump syndrome is recognized as a rare and long term complication of biliary enteric anastomosis. It results from the reflux of biliary and enteric contents into the distal segment of the common bile duct leading to biliary and or pancreatic complications. We report the case of a 90-years-old woman who presented to our department with an acute cholangitis. Her past medical history included a cholecystectomy with side-to-side choledochoduodenostomy performed 30 years ago. Imaging showed pneumobilia and a grossly dilated bile ducts. She was successfully treated by ERCP with multiple food debris and stones extraction as described in the video case.
Preliminary Estimate of Excess Mortality During the COVID-19 Outbreak — New York City, March 11–May 2, 2020
Authors: Donald R. Olson, Mary Huynh, Annie Fine, Jennifer Baumgartner, Alejandro Castro, Hiu Tai Chan, Demetre Daskalakis, Katelynn Devinney, Kevin Guerra, Scott Harper, Joseph Kennedy, Kevin Konty, Wenhui Li, Emily McGibbon, Jaimie Shaff, Corinne Thompson, Neil M. Vora, Gretchen Van Wye
Journal: MMWR Morbidity and Mortality Weekly Report (2020)
Pseudomonas aeruginosa Utilizes Host-Derived Itaconate to Redirect Its Metabolism to Promote Biofilm Formation
Authors: Sebastián A. Riquelme, Kalle Liimatta, Tania Wong Fok Lung, Blanche Fields, Danielle Ahn, David Chen, Carmen Lozano, Yolanda Sáenz, Anne-Catrin Uhlemann, Barbara C. Kahl, Clemente J. Britto, Emily DiMango, Alice Prince
Journal: Cell Metabolism (2020)
Stimulating pro-reparative immune responses to prevent adverse cardiac remodelling: consensus document from the joint 2019 meeting of the ESC Working Groups of cellular biology of the heart and myocardial function
Authors: Sabine Steffens, Sophie Van Linthout, Joost P G Sluijter, Carlo Gabriele Tocchetti, Thomas Thum, Rosalinda Madonna
Journal: Cardiovascular Research (2020)

Abstract Cardiac injury may have multiple causes, including ischaemic, non-ischaemic, autoimmune, and infectious triggers. Independent of the underlying pathophysiology, cardiac tissue damage induces an inflammatory response to initiate repair processes. Immune cells are recruited to the heart to remove dead cardiomyocytes, which is essential for cardiac healing. Insufficient clearance of dying cardiomyocytes after myocardial infarction (MI) has been shown to promote unfavourable cardiac remodelling, which may result in heart failure (HF). Although immune cells are integral key players of cardiac healing, an unbalanced or unresolved immune reaction aggravates tissue damage that triggers maladaptive remodelling and HF. Neutrophils and macrophages are involved in both, inflammatory as well as reparative processes. Stimulating the resolution of cardiac inflammation seems to be an attractive therapeutic strategy to prevent adverse remodelling. Along with numerous experimental studies, the promising outcomes from recent clinical trials testing canakinumab or colchicine in patients with MI are boosting the interest in novel therapies targeting inflammation in cardiovascular disease patients. The aim of this review is to discuss recent experimental studies that provide new insights into the signalling pathways and local regulators within the cardiac microenvironment promoting the resolution of inflammation and tissue regeneration. We will cover ischaemia- and non-ischaemic-induced as well as infection-related cardiac remodelling and address potential targets to prevent adverse cardiac remodelling.
Treatment of Shigellosis: III. Comparison of One- or Two-Dose Ciprofloxacin with Standard 5-Day Therapy
Authors: Michael L. Bennish, Mohammed Abdus Salam, Wasif Ali Khan, Ali Miraj Khan
Journal: Annals of Internal Medicine (2020)

Abstract ▪Objective:To determine whether a single dose, or 2 doses, of ciprofloxacin are as effective as 5-day, 10-dose therapy for the treatment of shigellosis in adult men who are moderately to s...
ARTIFICIAL INTELLIGENCE IN ENDOSCOPY FOR GASTRIC CANCER ASSESSMENT: MACHINE OVER MAN OR PERFECT HARMONY?
Authors: IF Cherciu Harbiyeli, IM Cazacu, ET Ivan, MS Serbanescu, B Hurezeanu, A Saftoiu
Journal: Endoscopy (2020)

Aims Artificial intelligence (AI) is likely to execute roles currently performed by humans, being essential for endoscopists to focus on this novel technology for avoiding to miss and mischaracterize malignant change in the stomach. The aim of our study was to assess the advances of AI-based medicine and the involvement in rectifying current limitations of gastroscopy.
Prevalence of COVID-19 among patients with rheumatic diseases: the need to await results from large collaborative studies. Response to: ‘COVID-19 pneumonia in a large cohort of patients treated with biological and targeted synthetic antirheumatic drugs’ by Conticini <i>et al</i>
Authors: Sara Monti, Carlomaurizio Montecucco
Journal: Annals of the Rheumatic Diseases (2020)

Prevalence of COVID-19 among patients with rheumatic diseases: the need to await results from large collaborative studies.Response to: 'COVID-19 pneumonia in a large cohort of patients treated with biological and targeted synthetic antirheumatic drugs' by Conticini et alWe thank Dr Conticini et al 1 for their comment on our previously published paper describing the course of COVID-19 in a cohort of patients treated with biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). 2The authors commented on the low prevalence of subjects treated with bDMARDs in our cohort of patients affected by COVID-19; however, our paper actually described the course of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection in the cohort of patients attending our biologic clinic rather than the opposite.Nonetheless, assessing the prevalence of COVID-19 in patients treated with b/tsDMARDs was out of the scope of our study. 2The main message that can be drawn by observational studies on our and other smaller cohorts of patients with rheumatic diseases such as the one reported by Conticini et al 1 is that, in our limited series of patients, SARS-CoV-2 infection did not seem to have a worse course or outcome compared with the general population.We have previously highlighted how a high degree of caution should be applied when interpreting these results and when assessing an immunocompromised patient with COVID-19.Large, multicentre, national and international cohorts have been launched to actively recruit patients such as the Italian Society of Rheumatology-sponsored registry (COVID-19-RMD) or the European EULAR-COVID-19 Database. 3The results from these large cohorts are awaited to properly assess the incidence and prevalence of COVID-19 among rheumatological patients and the clinical implications on this susceptible population.The evaluation of the epidemiology of COVID-19 among patients with rheumatic diseases will need to take into account the potential impact that the use of immunomodulatory drugs may have both on the course of the infection and on the careful preventive behavioural changes that our patients affected by chronic conditions might have adopted to protect themselves during the pandemic.The geographical differences of COVID-19 distribution among different Italian regions and in Europe should also be considered when evaluating the impact of the infection on rheumatological diseases populations.
Alanine Aminotransferase and Gamma‐Glutamyl Transpeptidase Predict Histologic Improvement in Pediatric Nonalcoholic Steatohepatitis
Authors: Kimberly P. Newton, Joel E. Lavine, Laura Wilson, Cynthia Behling, Miriam B. Vos, Jean P. Molleston, Philip Rosenthal, Tamir Miloh, Mark H. Fishbein, Ajay K. Jain, Karen F. Murray, Jeffrey B. Schwimmer
Journal: Hepatology (2020)

Background and Aims Predictive, noninvasive tools are needed to monitor key features of nonalcoholic fatty liver disease (NAFLD) in children that relate to improvement in liver histology. The purpose of this study was to evaluate the relationship between liver chemistries and liver histology using data from the CyNCh (Cysteamine Bitartrate Delayed‐Release for the Treatment of NAFLD in Children) clinical trial. Approach and Results This study included 146 children. Improvement in liver histology, defined as decrease in nonalcoholic fatty liver disease (NAFLD) Activity Score ≥2 points without worsening of fibrosis, occurred in 43 participants (30%). There were 46 participants with borderline zone 1 nonalcoholic steatohepatitis (NASH) at baseline, with resolution in 28% (12 of 46). Multivariate models were constructed using baseline and change in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma‐glutamyl transferase (GGT) at 52 weeks, for improvement in (1) liver histology primary outcome, (2) borderline zone 1 NASH, and (3) fibrosis. For improvement in histology, the model ( P &lt; 0.0001) retained baseline and change in GGT (area under the receiver operating characteristic [AUROC], 0.79; 95% confidence interval [CI], 0.71‐0.87). For borderline zone 1 NASH, the model ( P = 0.0004) retained baseline and change in ALT (AUROC, 0.80; 95% CI, 0.67‐0.93). For fibrosis, the model ( P &lt; 0.001) retained baseline and change in ALT (AUROC, 0.80; 95% CI, 0.67‐0.93). Additional clinical parameters were added to the models using Akaike’s information criterion selection, and significantly boosted performance: improvement in histology with AUROC of 0.89 (95% CI, 0.82‐0.95), borderline zone 1 NASH with AUROC of 0.91 (95% CI, 0.83‐0.99), and fibrosis with AUROC of 0.89 (95% CI, 0.82‐0.94). Models were validated using data from the TONIC (Treatment of Nonalcoholic Fatty Liver Disease in Children) trial. Conclusions In children with NAFLD, dynamic changes in serum ALT and GGT are associated with change in liver histology and appear to be powerful indicators of histological response.
Type 1 Treg cells promote the generation of CD8+ tissue-resident memory T cells
Authors: Cristina Ferreira, Leandro Barros, Marta Baptista, Birte Blankenhaus, André Barros, Patrícia Figueiredo-Campos, Špela Konjar, Alexandra Lainé, Nadine Kamenjarin, Ana Stojanovic, Adelheid Cerwenka, Hans C. Probst, Julien C. Marie, Marc Veldhoen
Journal: Nature Immunology (2020)
Judith Darmady: supercharged childcare visionary
Authors: John Illman
Journal: BMJ (2020)

It is hard to imagine how a consultant paediatrician from Basingstoke initially reacted to the horror of seeing children so undernourished it was hard to tell how old they were. There was only one spoon in each room, meaning that the strongest children had the most food. The weakest were left to grab at titbits on a floor wet with urine. Toddlers with bone stick arms and legs were tied to their beds. Starving babies were unattended. Naked older children had shaved heads. The death rate was inevitably high.

This is what Judith Darmady found in 1990 in the remote village of Ungureni, north of Bucharest, in one of Romania’s 29 infamous orphanages for “incurables.” She had answered an appeal from the Romanian Orphanage Trust for a consultant paediatrician who specialised in caring for children with special needs.

How did Darmady react to the legacy of the 25 year regime of repression by Romania’s communist leader Nicolae Ceausescu? Did she wilt? She did not. A nursing friend, Jane Waldram, described Darmady as being “mentally built like a tank.” It was hard to reconcile her irrepressible energy with her plump, short stature (she was less than five feet tall) and her age. Most of her 100 or so Romanian trips were made in her retirement. She also had a formidable reputation for rising to challenges.



Few challenges were more daunting than the 100 000 abandoned Romanian children classified as incurable. Fired by the Stalinist theory that a large population would generate rapid economic growth, Ceausescu outlawed contraception and abortion, except …
Deepening the Talent Pool
Authors: S Colloca, E Barnes, A Folgori, V Ammendola, S Capone, A Cirillo, L Siani, M Naddeo, F Grazioli, M L Esposito, M Ambrosio, A Sparacino, M Bartiromo, A Meola, K Smith, A Kurioka, G A O'Hara, K J Ewer, N Anagnostou, C Bliss, Hill Avs., C Traboni, P Klenerman, R Cortese, A Nicosia
Journal: Science Translational Medicine (2012)
EUS-GUIDED LEFT HEPATICO-DUODENOSTOMY (L-HDS): A NOVEL OPTION FOR EUS-GUIDED BILIARY DRAINAGE (EUS-BD) OF THE LEFT BILE-DUCT WHEN HEPATICOGASTROSTOMY (EUS-HGS) IS NOT FEASIBLE
Authors: I Fanjul Yanicelli, G Salazar, R Sanchez-Ocana, C Chavarría Herbozo, M de Benito, C De la Serna-Higuera, M Perez-Miranda
Journal: Endoscopy (2020)

Introduction: We describe L-HDS as alternative to EUS-HGS in left biliary exclusion when transgastric access is precluded.
ENDOSCOPIC ULTRASOUND-GUIDED ANGIOTHERAPY WITH COMBINED COILS AND GLUE INJECTION FOR GASTRIC VARICES: AN EUROPEAN PILOT STUDY
Authors: J Privat, H Demmak, BA Keita
Journal: Endoscopy (2020)

Nevertheless, it´s associated with more than 25% of re-bleeding and serious adverse events, mainly glue embolization. Endoscopic ultrasound (EUS)-guided and combined coil and glue injection provide a new alternative treatment for bleeding varices.