bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial overgrowth of the small intestine
Authors: Middleton Stephen J. , Playford Raymond J. 
Published: February 2020

Abstract
Small intestinal bacterial overgrowth can be defined as the presence of excessive bacteria in the small intestine which can interfere with digestion and absorption. Predisposing causes include sustained hypochlorhydria induced by proton pump inhibitors, small intestinal dysmotility and stasis due to anatomical or motor abnormalities, and reduced antibacterial activity as seen in immunological deficiency and chronic pancreatitis. Presentation is predominantly from consequences of malabsorption, including gastrointestinal symptoms (e.g. diarrhoea or steatorrhoea) and features of specific nutrient malabsorption (e.g. osteoporosis, anaemia, neuropathy, and night blindness). Definitive diagnosis is difficult, requiring a properly collected and appropriately cultured aspirate from the proximal small intestine revealing a total concentration of a mixed growth of bacteria generally greater than 105 organisms/ml. Alternative investigations frequently used include glucose/lactulose breath tests or either the 13C- or 14C-xylose breath test, with elevated levels of 13CO2 or 14CO2 found in the breath. There may be low levels of cobalamin (metabolized by Gram-negative anaerobes), increased serum folate (synthesized by overgrowth flora), and increased urinary indicans (intraluminal product of bacterial tryptophan metabolism). Aside from treatment of any nutritional deficiencies, specific treatment is with an antimicrobial that is effective against both aerobic and anaerobic enteric bacteria (e.g. doxycycline, amoxicillin–clavulanic acid, rifaximin, or ciprofloxacin), which can be administered in rotation to reduce antibiotic resistance. Where possible and appropriate, correction of any underlying cause should also be performed.
Whipple’s disease
Authors: Fenollar Florence , Raoult Didier 
Published: February 2020

Abstract
Whipple’s disease is an uncommon infection caused by the actinomycete Tropheryma whipplei, most commonly diagnosed when overt small intestinal disease leads to malabsorption, but with protean other clinical manifestations (e.g. systemic, neurological, or cardiological). Diagnosis usually depends upon demonstration of classical histological features in the small intestine, and positive identification of T. whipplei DNA by polymerase chain reaction. Treatment is with antibiotics, initially doxycycline and hydroxychloroquine followed by long-term therapy with doxycycline. Clinical improvement occurs within a few weeks, but prolonged treatment for at least a year is recommended. Relapse can occur, even after many years, especially when progressive central nervous system disease occurs in the absence of other systemic manifestations.
Miscellaneous disorders of the bowel
Authors: Gimson Alexander 
Published: February 2020

Abstract
A wide range of miscellaneous disorders can affect the bowel. Those discussed in this chapter include cystic disorders (colitis cystica profunda and pneumatosis cystoides intestinalis), protein-losing enteropathy, vascular disorders of the intestine (spontaneous intramural haemorrhage and ortoenteric fistulas), intestinal pseudo-obstruction (acute colonic pseudo-obstruction, chronic intestinal pseudo-obstruction), various disorders of the colon and rectum (including microscopic, collagenous, and lymphocytic colitis, malakoplakia, solitary rectal ulcer syndrome, and stercoral ulcers), complications of parenteral nutrition and intestinal failure, peritoneal disorders, and endometriosis.
Cirrhosis and ascites
Authors: Fernández Javier , Arroyo Vicente 
Published: February 2020

Abstract
Ascites is the accumulation of fluid in the peritoneal cavity and the most common complication of cirrhosis, when it is associated with a poor prognosis. It occurs only when portal hypertension has developed and is mainly due to renal sodium retention secondary to splanchnic arterial vasodilation that leads to homeostatic activation of vasoconstrictor and sodium-retaining systems. Clinical presentation is with abdominal distension. The initial evaluation of a patient with ascites must include (1) history and physical examination; (2) liver and renal function tests including serum and urine electrolytes; (3) analysis of ascitic fluid (diagnostic paracentesis) for cell count and culture, and protein/albumin concentration; other tests such as cytology (suspicion of malignancy), amylase (pancreatic disease), and polymerase chain reaction and culture for mycobacteria (tuberculosis) should be done only when the diagnosis is unclear; (4) abdominal ultrasonography for evidence of cirrhosis, portal hypertension, or malignancy. First-line manoeuvres include dietary salt restriction, and therapeutic or total paracentesis. Water restriction is only recommended if there is severe dilutional hyponatraemia. Refractory ascites is managed by repeated paracentesis or insertion of a transjugular intrahepatic portosystemic shunt. Cirrhotic patients with ascites should be considered for liver transplantation. All patients with cirrhosis and ascites are at risk of spontaneous bacterial peritonitis (SBP). Typical symptoms are abdominal pain and fever, but the condition may be asymptomatic. Treatment with appropriate antibiotics should be started as soon as a presumptive diagnosis is made following diagnostic paracentesis. Mortality is around 10% for the acute episode and 75% at 1 year; hence (unless contraindicated), all patients with SBP should be considered for liver transplantation. Patients with cirrhosis and ascites are also at high risk of other complications.
Liver transplantation
Authors: O’Grady John G. 
Published: February 2020

Abstract
Liver transplantation is an established treatment for liver conditions that broadly fall into the categories of acute liver failure, end-stage chronic liver disease, primary hepatic malignancy, and metabolic disease. The expected 1-year survival rate is over 90% and some patients are alive more than 40 years after transplantation. Disease severity scores for cirrhosis heavily influence selection of patients with cirrhosis for transplantation. The prototype is the MELD (Model for End-Stage Liver Disease) score, based on serum bilirubin, serum creatinine, and INR: a score of 16 is considered the threshold that confers benefit from liver transplantation. Hepatocellular carcinoma accounts for most of the malignancy group and selection is largely determined by tumour bulk assessed by the number and size of lesions. Immunosuppression strategies based on tacrolimus, with or without other drugs including mTOR (mechanistic target of rapamycin) inhibitors, antiproliferative agents, or prednisolone, are highly effective in preventing loss of the graft through classical rejection processes. Recurrence of original disease is the main cause of loss of graft function, with recurrence of hepatitis C a particularly challenging problem, although new direct-acting antiviral agents are likely to radically improve outcomes. Technical problems can also result in graft loss due to hepatic artery thrombosis or diffuse ischaemic cholangiopathy, especially in livers harvested from donors after cardiac death. Anastomotic biliary strictures are the commonest technical complication, with 15 to 20% of patients requiring some form of endoscopic or surgical intervention. There is a considerably increased risk of myeloproliferative disease and skin cancers in transplant recipients, as well as aetiology-specific risk. Many patients die having achieved a normal life expectancy, and death with a functioning graft is the commonest terminal scenario.
Primary biliary cholangitis
Authors: Dyson Jessica K. , Jones David E.J. 
Published: February 2020

Abstract
Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a chronic, cholestatic liver disease in which the biliary epithelial cells lining the small intrahepatic bile ducts are the target for immune-mediated damage, leading to progressive ductopenia and cholestasis. The cause is unknown but presumed to be autoimmune. The disorder affects women (&gt;90% of cases) and usually has an insidious onset in middle age. Younger patients are less common but have a more aggressive disease course. Fatigue and pruritus are the most common presenting symptoms. Findings on examination vary widely, ranging from no abnormality to jaundice with hyperpigmentation, scratch marks, and rarely the features of advanced liver disease. Diagnosis of PBC is based on three criteria: (1) cholestatic liver function tests, with increases in serum alkaline phosphatase and γ-glutamyl transferase, (2) presence of serum antimitochondrial antibodies (found in more than 95% of cases), and (3) compatible liver histology. Many asymptomatic patients are recognized following the incidental discovery of antimitochondrial antibodies or elevated levels of serum alkaline phosphatase. First-line treatment is with ursodeoxycholic acid which can lead to significant improvement in liver biochemical values. Second-line treatment is with obeticholic acid. No immunosuppressive drug regimen has been proven effective. Progression may be slow, but eventually patients can develop cirrhosis. Cholestyramine is used as first line to treat pruritus. There is no recognized treatment for fatigue. Liver transplantation is indicated in some cases.
Diseases of the gallbladder and biliary tree
Authors: Johnson Colin , Wright Mark 
Published: February 2020

Abstract
Diseases of the gallbladder and bile ducts are common, with gallstones and their complications being most frequent. Less common are biliary strictures, usually malignant, which are caused by adenocarcinomas of the pancreas, bile ducts, ampulla of Vater, and gallbladder. Rarely encountered are sclerosing cholangitis and a variety of congenital disorders. Disorders of the biliary system include gallstones, which cause biliary colic and cholecystitis by obstruction of the cystic duct, and bile duct obstruction (cholestasis), with jaundice, dark urine, and pale stools, itching, and sometimes constant right hypochondrial pain. Fevers and rigors may indicate bacterial infection of the biliary tract (cholangitis), which frequently accompanies partial obstruction. Weight loss may be due to fat malabsorption but can also be caused by malignancy. Prolonged biliary obstruction leads to skin changes of increased pigmentation (due to melanin) and cholesterol deposition (xanthelasma and xanthoma). Biliary cirrhosis can cause portal venous hypertension and liver cell failure. Disorders of the biliary system generally give rise to the biochemical picture of cholestasis: the serum (conjugated) bilirubin concentration may be normal or raised; serum alkaline phosphatase, γ-glutamyl transferase, and bile acids are elevated; serum transaminases show only modest elevation. Bilirubinuria is present, with the disappearance of urobilinogen from the urine indicating complete biliary obstruction. Imaging is critical in the diagnosis of biliary disease, initially by ultrasonography, with CT and MRI in more complicated cases. However, these investigations sometimes provide insufficient anatomical detail for diagnosis or planning of treatment, and further imaging with the cholangiographic techniques of magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) are required. ERCP and PTC can be used to place biliary stents.
Acute pancreatitis
Authors: Carter R. , Dickson Euan J. , McKay C.J. 
Published: February 2020

Abstract
Acute pancreatitis affects 300 to 600 new patients per million population per year and is most commonly caused by gallstones or alcohol. Careful imaging reveals that most so-called idiopathic acute pancreatitis is due to small (1–3-mm diameter) gallstones. Diagnosis is made by a combination of a typical presentation (upper abdominal pain and vomiting) in conjunction with raised serum amylase (more than three times the upper limit of normal) and/or lipase (more than twice the upper limit of normal). Several other acute abdominal emergencies can mimic acute pancreatitis and may be associated with a raised serum amylase. In equivocal cases, a CT scan is indicated to exclude other causes and confirm the diagnosis. Initial management is with (1) analgesia, (2) ensuring adequate oxygenation, and (3) intravenous fluid administration. The revision of the Atlanta classification separates patients clinically into (1) mild—with early resolution without complications, (2) moderate—local complications without organ failure, and (3) severe—complications associated with organ failure. Mild acute pancreatitis responds to analgesia and intravenous fluids. If gallstones have been identified, then cholecystectomy (or endoscopic retrograde cholangiopancreatography (ERCP) sphincterotomy where clinically appropriate) should be performed during the same admission, or at least within 2 to 4 weeks to prevent recurrent attacks. Severe acute pancreatitis carries a high mortality (up to 20%). Management in the early stages is centred on organ support (respiratory, circulatory, and renal failure). Later management involves surgical or radiological intervention for sepsis, usually within a specialist pancreatic unit.
Chronic pancreatitis
Authors: Bruno Marco J. , Cahen Djuna L. 
Published: February 2020

Abstract
Chronic pancreatitis is a major source of morbidity, loss in quality of life, and healthcare expenditure. It is most commonly caused by chronic alcoholism in adults and cystic fibrosis in children, but there are many other causes. Patients typically present with severe abdominal pain, but this may vary and even be absent. Exo- and endocrine insufficiency usually occur late in the disease course and reflect permanent loss of pancreatic parenchyma due to ongoing inflammation and fibrosis, exocrine insufficiency manifesting as steatorrhea and weight loss due to fat maldigestion and endocrine insufficiency as diabetes mellitus. Diagnosis is confirmed by imaging investigations such as CT, MRI, and endoscopic ultrasonography. Endoscopic retrograde cholangiopancreatography to diagnose chronic pancreatitis is obsolete. Hormone stimulation tests (e.g. secretin–cholecystokinin stimulation test) to diagnose exocrine insufficiency are largely abandoned because of their complexity and burden to patients. They are replaced by faecal elastase testing, even though this test is less sensitive. Management focuses on the treatment of pain using a stepwise approach. Initially, nonopioid analgesics are prescribed. Next, when feasible, endoscopic therapy is initiated, including pancreatic stone fragmentation by extracorporeal shock-wave lithotripsy, endotherapy to remove stone fragments, and placement of plastic stents to dilate any concomitant pancreatic duct stricture. If that fails or when, for example, the pancreatic head is enlarged, surgical intervention is indicated. Medical management includes enteric-coated pancreatic enzyme preparations and treatment of diabetes mellitus, usually by means of insulin. Abstinence from alcohol and smoking cessation are important predictors of disease and treatment outcome.
Syncope and palpitation
Authors: Rajappan K. , Rankin A.C. , McGavigan A.D. , Cobbe S.M. 
Published: February 2020

Abstract
Syncope is a transient episode of loss of consciousness due to cerebral hypoperfusion. Its causes can be subdivided on the basis of pathophysiology, including neurally mediated—or reflex—syncope; orthostatic hypotension; cardiac causes; and cerebrovascular or psychogenic causes. Neurocardiogenic syncope, or simple faint, is the commonest cause and is benign, but it is always important to exclude or establish the diagnosis of cardiac syncope, because this has an adverse prognosis that may be improved with appropriate treatment. Meanwhile, palpitation is the awareness of one’s heart beating—it may be due to an awareness of an abnormal cardiac rhythm, or an abnormal awareness of normal rhythm. It is most commonly due to premature beats (ectopics) and is benign. Correlation between symptoms and cardiac rhythm is the initial aim of investigations in patients presenting with palpitations.
Myocarditis
Authors: Mason Jay W. , Schultheiss Heinz-Peter 
Published: February 2020

Abstract
Myocarditis can be acute, subacute, or chronic and may affect either focal or diffuse areas of the myocardium. It has many infectious and non-infectious aetiologies, but viral infections are the main cause in most regions, with notable exceptions such as Chagas myocarditis in South America. The condition often results in congestive heart failure and is a common cause of chronic dilated cardiomyopathy, also called inflammatory cardiomyopathy. It can present with (a)typical chest pain, palpitations, ventricular arrhythmias, syncope, or even fulminant heart failure. Patients with lymphocytic myocarditis are usually young (average age in the forties) and often report an antecedent viral illness. The disease can be diagnosed by demonstration of lymphocyte infiltration and adjacent myocyte damage on endomyocardial biopsy, and molecularly by the detection of viral genomic material and tissue markers of immune activation in biopsy specimens.
The cardiomyopathies: Hypertrophic, dilated, restrictive, and right ventricular
Authors: Guttmann Oliver P. , Elliott Perry 
Published: February 2020

Abstract
The term cardiomyopathy is used to describe heart muscle disease unexplained by abnormal loading conditions (hypertension, valve disease, and others), congenital cardiac abnormalities, and ischaemic heart disease. The current classification is based on the predominant phenotype, that is, hypertrophic, dilated, arrhythmogenic right ventricular, restrictive, and unclassifiable (including left ventricular non-compaction), and— where possible— incorporating inheritance and genotype. The diagnosis of hypertrophic cardiomyopathy is based on the demonstration of unexplained myocardial hypertrophy, defined as a wall thickness measurement exceeding two standard deviations above normal for gender and age. In practice, in an adult of normal size, the presence of a left ventricular myocardial segment of 1.5 cm or greater in thickness is diagnostic. Less stringent criteria should be applied to first-degree relatives of an unequivocally affected individual.
Specific heart muscle disorders
Authors: Guttmann Oliver P. , Elliott Perry 
Published: February 2020

Abstract
Systemic immune-mediated diseases are autoimmune and autoinflammatory diseases affecting at least two-organ systems. Autoinflammatory diseases are a family of conditions characterized by episodes of unprovoked inflammation in the absence of high autoantibody titres or autoreactive T lymphocytes, reflecting a primary dysfunction of the innate immune system. Autoimmune diseases are characterized by aberrant B, T, and dendritic cell responses with predominantly cell-mediated or autoantibody-mediated responses to self-antigens in genetically susceptible individuals. Cardiovascular involvement is systemic immune-mediated diseases may be occult and often goes undetected, but is associated with a poor prognosis. As any anatomical structure in the heart may be involved, patients can present with one or more features consistent with pericarditis, myocarditis, endocarditis, and vasculitis. There is often no correlation between the extent of systemic disease and cardiac involvement.
Congenital heart disease in the adult
Authors: Thorne S.A. 
Published: February 2020

Abstract
Adults with congenital heart disease are a growing population, and now outnumber children with congenital heart disease in the United Kingdom. Many patients with repaired hearts can now, with specialist care, expect to live a normal or near normal lifespan. Other survivors have complex, surgically altered hearts and circulations that reflect the surgical and interventional practices of the preceding two decades. Their long-term outlook is unknown and they remain at lifelong risk of complications that may require further intervention. The organization of services to provide specialist care is key to their long-term survival. As the population of adults with congenital heart disease ages, so the number developing heart failure increases. Services caring for patients need to develop a robust end-of-life pathway that focuses on symptoms and quality of life, and runs in parallel with other therapies.
Pulmonary hypertension
Authors: Morrell Nicholas W. 
Published: February 2020

Abstract
Symptoms of unexplained exertional breathlessness or symptoms out of proportion to coexistent heart or lung disease should alert the clinician to the possibility of pulmonary hypertension, and the condition should be actively sought in patients with known associated conditions, such as scleroderma, hypoxic lung disease, liver disease, or congenital heart disease. Heterozygous germ-line mutations in the gene encoding the bone morphogenetic protein type II receptor (BMPR2) are found in over 70% of families with pulmonary arterial hypertension. Pulmonary hypertension is defined as a mean pulmonary arterial pressure greater than 25 mm Hg at rest, and may be due to increased pulmonary vascular resistance (e.g. pulmonary arterial hypertension), increased transpulmonary blood flow (e.g. congenital heart disease), or increased pulmonary venous pressures (e.g. mitral stenosis). Exercise tolerance and survival in pulmonary hypertension is ultimately related to indices of right heart function, such as cardiac output.
Deep venous thrombosis and pulmonary embolism
Authors: Stein Paul D. , Matta Fadi , Firth John D. 
Published: February 2020

Abstract
Deep venous thrombosis (DVT) and pulmonary embolism (PE) are sometimes described together using the term ‘thromboembolism’. PE is a complication of DVT, with thrombi in 80% or more of cases originating in the legs. Deep venous thrombosis (DVT) is diagnosed in 1–2% of hospitalized patients, but is often silent and is found much more frequently at autopsy. Patients typically complain of pain and/or swelling of the leg, but often the diagnosis will be considered only when the physician detects unilateral leg swelling. Management strategies of PE have been developed that are based on the diagnosis of either PE or DVT, provided the patient has good respiratory reserve. Treatment with anticoagulants is the same for both. Some physicians believe that patients can be managed better if it is known whether acute PE is present, even if a diagnosis of DVT is already established.
Anaphylaxis
Authors: Brown Anthony F.T. 
Published: February 2020

Abstract
The term anaphylaxis describes both immunoglobulin E (IgE) immune-mediated reactions, plus non-IgE immune-mediated, and non-allergic, non-immunologically triggered events. Comorbidities such as asthma or infection, exercise, alcohol, or stress and concurrent medications such as β-blockers and aspirin increase the risk, a concept known as ‘summation anaphylaxis’. Activated mast cells and basophils release preformed, granule-associated mediators and newly formed lipid mediators, and generate cytokines and chemokines. These cause vasodilatation, increased capillary permeability, and smooth muscle contraction, as well as attracting new cells to the area. Positive feedback enhancing mechanisms amplify the reaction in a ‘mast cell—leucocyte cytokine cascade’, although conversely reactions can be self-limiting. Parenteral penicillins, hymenopteran stings, and food are the most common causes of IgE immune-mediated fatalities, with radiocontrast media, aspirin, and other non-steroidal anti-inflammatory drugs most commonly responsible for non-IgE and non-allergic fatalities.