bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute respiratory failure
Authors: Leaver Susannah , Cordingley Jeremy , Finney Simon , Griffiths Mark 
Published: February 2020

Abstract
Acute respiratory failure is defined clinically by hypoxaemia with (type 2) or without (type 1) hypercapnia. It is one of the most common problems afflicting critically ill patients and is a common indication for transfer to an intensive care unit. Critical illness may be manifest solely as respiratory insufficiency, especially in patients with covert infection. Acute respiratory failure frequently coexists with other organ system failures in the critically ill, and delayed recognition of the condition adversely affects outcome. The signs of critical illness tend to be similar whatever the precipitating cause and are manifest in failure of the respiratory, cardiovascular, and neurological systems. Full and repeated physical examination may be required to assess the cause and severity of acute respiratory failure and its associated complications, but in severe cases should not delay the instigation of life-saving support and treatment.
Bronchiectasis
Authors: Wilson R. , Bilton D. 
Published: February 2020

Abstract
A bronchiectatic lung contains permanently dilated subsegmental airways that are inflamed, tortuous, and often partially or totally obstructed with secretions. Pathogenesis involves airway inflammation which can cause further bacteria-driven host-mediated lung damage. Causes include developmental defects, damage caused by previous infection, immune deficiency, mucociliary clearance defects, and mechanical obstruction, but in many cases (40–60%) the cause is unknown. Bronchiectasis should be suspected when there is a history of persistent cough productive of sputum throughout the year, with chest infections leading to increased symptoms. About 80% of patients have upper respiratory tract symptoms. Clinical examination is often normal, although ‘classical’ severe cases show finger clubbing and widespread coarse crackles. Management involves the treatment of the specific underlying cause (when possible) and treatment of the bronchiectasis itself, with the most important elements being sputum clearance by physiotherapy and antimicrobials, which need to be given in high dose.
Pulmonary Langerhans’ cell histiocytosis
Authors: Bourke S. J. 
Published: February 2020

Abstract
Pulmonary Langerhans’ cell histiocytosis is characterized by a reactive monoclonal proliferation of activated histiocytes in the distal bronchioles, resulting in inflammatory nodules, cyst formation, and fibrosis. Langerhans’ cells are a particular type of histiocyte derived from dendritic cells in the bone marrow. They normally migrate in the blood to the squamous epithelium of the skin, lungs, gastrointestinal, and female genital tract, where they are involved in antigen presentation to T cells. It presents with cough, breathlessness, and (sometimes) systemic symptoms. Chest radiography and CT typically show nodules which then cavitate and may rupture, causing pneumothorax. Corticosteroids and/or cytotoxic drugs are of some benefit, and lung transplantation is an option for progressive disease.
Pulmonary alveolar proteinosis
Authors: Bourke S. J. 
Published: February 2020

Abstract
In 90% of cases pulmonary alveolar proteinosis is caused by autoimmune antibodies to GM-CSF which impair the function of alveolar macrophages in clearing surfactant from the alveoli, giving rise to impaired gas exchange, breathlessness, and respiratory failure. Chest radiography shows extensive alveolar shadowing simulating pulmonary oedema, and CT scanning shows a characteristic ‘crazy paving’ pattern. The presence of GM-CSF antibodies in the serum is useful in diagnosis. Bronchoalveolar lavage or lung biopsy demonstrates alveolar secretions that are strongly PAS-positive. Treatment is by physical removal of the lipoproteinaceous material from the alveoli by whole-lung lavage. Massive inhalation of dust and fumes may overwhelm macrophage function, giving rise to secondary pulmonary alveolar proteinosis.
Toxic gases and aerosols
Authors: Stenton Chris 
Published: February 2020

Abstract
Acute exposure to noxious agents causes pulmonary effects that are determined by the size of aerosol particles and by the solubility of gases. Large particles (&gt;10 um) and soluble agents such as CS gas, ammonia, or sulphur dioxide affect primarily the upper respiratory tract, causing lacrimation, blepharospasm, rhinitis, cough, and breathlessness. Nitrogen oxides, ozone, and other agents of low solubility affect mainly the lungs, with pneumonitis and pulmonary oedema that can develop 24 hours or more after exposure. Smoke inhalation, intermediate solubility gases such as chlorine, and overwhelming exposures have effects throughout the respiratory tract. Some inhaled gases such as carbon monoxide and methane act as simple asphyxiants. Other reactions occur, such as metal fume fever with zinc and cadmium, and pulmonary haemorrhage with crack cocaine. Management is essentially supportive. Carboxyhaemoglobin and lactate levels should be measured with smoke inhalation.
Lung transplantation
Authors: Hopkins P. , Fisher A.J. 
Published: February 2020

Abstract
Lung transplantation offers the only therapeutic option for many patients with end-stage pulmonary and cardiopulmonary diseases, but donors are scarce and the major challenge facing lung transplantation (as with all solid organ transplants) is the shortage of donor organs.
Emphysema/chronic obstructive pulmonary disease, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary vascular disease are the main disease groups referred for lung transplantation. Most suitable patients are listed for transplantation when their 2-year survival is estimated to be less than 50% without transplantation. Almost all organs come from cadaveric donors who have sustained brainstem death, but an increasing proportion come after withdrawal of life support leads to cardiac death in those who have sustained irreversible cardiac or neurological injury. Ideal donors have satisfactory lung function and are free of systemic infection and disease. Donor/recipient matching is on the basis of ABO blood group, and size.
Pulmonary metastases
Authors: Spiro S.G. 
Published: February 2020

Abstract
Malignant metastasis to the lung is common. It may present as a solitary enlarging nodule, as multiple nodules ranging enormously in size and number, and/or with diffuse lymphatic involvement. Diagnosis can usually be secured by percutaneous CT-guided biopsy and most suspicious lesions will be PET positive. Resection remains the treatment of choice, and good prognostic factors include the time from treatment of the primary tumour to the development of lung metastases, the fewer the number, the absence of extrapulmonary metastases, and the longer the tumour doubling time. The most favourable group are younger patients with a good performance status, with sarcomas who present with lesions a year or more after successful treatment of the primary disease. Factors including older age, male sex, and more lung metastases predict poorer survival after resection of any initial pulmonary metastases.
Infection and arthritis
Authors: Raftery Graham , Shaikh Muddassir 
Published: February 2020

Abstract
Septic arthritis (or infective arthritis) is the most serious cause of one or more hot swollen joints. A causative organism can be identified in about 80% of cases, with Staphylococcus aureus the most common, followed by Streptococcus and gram-negative organisms. The key diagnostic investigation is microscopy and culture of aspirated joint fluid. Management is with drainage of bacteria, pus, and debris from the joint, along with antibiotics. Consensus is that these should be given intravenously for up to two weeks, or until clinical signs improve, followed by oral antibiotics for four weeks. Prosthetic joint infection is a particular challenge requiring specialist care. Arthralgia and/or arthritis are common occurrences with many viral infections, particularly parvovirus, hepatitis B and C, rubella, HIV, alpha (including chikungunya) and dengue viruses. Joint manifestations are usually sudden in onset, correlate with the onset of clinical illness, and generally self-limiting, but can persist following infection.
Crystal-related arthropathies
Authors: Roddy Edward , Doherty Michael 
Published: February 2020

Abstract
Many crystals have been associated with arthropathies or periarticular syndromes: only monosodium urate (gout), calcium pyrophosphate (acute calcium pyrophosphate crystal arthritis, chondrocalcinosis), and basic calcium phosphates (mainly hydroxyapatite) are common. Crystals implicated in joint disease are stable, hard particles that exert biological effects via surface-active (activation of humoral and cell-derived mediators, interaction with cell membranes) and mechanical properties. In general, smaller particle size, marked surface irregularity, and high negative surface charge correlate with inflammatory potential. A ‘crystal deposition disease’ is defined as a pathological condition associated with mineral deposits that contribute directly to the pathology. This is probably the situation for all manifestations of gout, for acute syndromes associated with calcium pyrophosphate, and for acute apatite periarthritis.
Systemic sclerosis (scleroderma)
Authors: Denton Christopher P. , Black Carol M. 
Published: February 2020

Abstract
The scleroderma spectrum of disorders includes several diseases that have Raynaud’s phenomenon or skin sclerosis in common, comprising (1) localized cutaneous scleroderma; (2) systemic sclerosis (SSc)—the most important form of scleroderma—limited cutaneous SSc, diffuse cutaneous SSc, and overlap syndromes (with features of another autoimmune rheumatic disease, e.g. systemic lupus erythematosus); (3) Raynaud’s phenomenon—autoimmune (with antinuclear or other SSc-associated antibodies) or primary. These conditions affect women four times as often as men, most often beginning in the fifth decade. The cause of SSc is not known: an attractive hypothesis is that the disease represents a syndrome of dysfunctional connective tissue repair with associated immunological, epithelial, and vascular pathology, triggered by some environmental factor(s) in a genetically and immunologically susceptible individual.
Kawasaki disease
Authors: McCrindle Brian W. 
Published: February 2020

Abstract
Kawasaki disease is an acute, self-limited, inflammatory vasculitis of unknown aetiology, with a peak incidence under five years of age. Coronary complications can present in adults. Its diagnosis requires persistent fever for five days or more and at least four of the following five clinical signs: (1) non-purulent conjunctivitis, (2) oropharyngeal inflammation, (3) cervical lymphadenopathy, (4) polymorphous exanthem, and (5) erythema of the palms and soles with subsequent desquamation. Coronary artery dilation and aneurysms occur in 15–25% of untreated patients. Its primary therapy is with intravenous gammaglobulin. Persistent and resolving coronary artery aneurysms are the predominant long-term morbidity. In adults, new presentations of myocardial ischaemia with coronary artery aneurysms may suggest a previous episode of Kawasaki disease during childhood.
Antiglomerular basement membrane disease
Authors: Segelmark Mårten , Hellmark Thomas 
Published: February 2020

Abstract
Antiglomerular basement membrane (anti-GBM) disease, also known as Goodpasture’s disease, is a rare autoimmune kidney and/or lung disease caused by autoantibodies directed against the noncollagenous, C-terminal domain of the α3 chain of type IV collagen (α3(IV)NC1). Epidemiology—bimodal age distribution with peaks in the third and sixth/seventh decades; incidence 0.5 to 2/million population/year. Clinical features—typically presents as a renopulmonary syndrome with the combination of rapidly progressive glomerulonephritis and lung haemorrhage, but can present with isolated glomerulonephritis. Pathology—light microscopy typically reveals crescent formation, often in more than 80% of glomeruli, with linear staining of IgG along the GBM. Management—aside from supportive care, this typically consists of (1) stopping the inflammatory process with high doses of corticosteroid, (2) removal of the pathogenic antibodies by plasma exchange, and (3) stopping production of new antibodies with cyclophosphamide. It is controversial whether patients presenting with dialysis dependency and no pulmonary disease benefit from immunosuppression. Prognosis—recent series report mortality at 6 to 12 months of 7 to 36%, with patients’ survival mainly dependent on age and renal function at diagnosis. The most important factor in renal prognosis is the glomerular filtration rate at diagnosis, which is strongly correlated to the proportion of crescents seen in the renal biopsy. Very few patients with dialysis dependency at diagnosis regain enough function to become dialysis independent (0–7% most series). Patients do not need long-term immunosuppression, and the disease rarely recurs. Renal transplantation is safe if performed after autoantibodies have been suppressed or naturally disappeared.
Acute interstitial nephritis
Authors: Roger Simon D. 
Published: February 2020

Abstract
Acute interstitial nephritis (AIN) is an inflammation of the tubules and interstitium within the kidney, associated with a relatively sudden onset and rapid decline in renal function. It is usually secondary to drugs (antibiotics, nonsteroidal anti-inflammatory drugs, and proton pump inhibitors being most commonly incriminated), with other causes being infections (classically streptococcal, but this is now less common) and immune disorders (systemic lupus erythematosus, sarcoidosis, and tubulointerstitial nephritis with uveitis). Clinical features—the diagnosis of AIN should be considered in any patient with unexplained acute kidney injury. Drug-induced AIN may present with a classic allergic response, including arthralgias, fever, rash, loin pain, and eosinophilia/eosinophiluria, but these are not invariable and their absence does not exclude the diagnosis. The urine typically shows low-grade proteinuria (&lt;1 g/day). Renal biopsy is the only way to confirm or exclude the diagnosis. Management and prognosis—treatment is by ceasing the offending agent, treating the concurrent infectious cause, or managing the immune aetiology with steroids (typically prednisolone 1 mg/kg per day, tapered to zero over 6–8 weeks). Most patients with drug-induced AIN recover renal function, but some are left with chronic renal impairment and a small proportion progress to endstage chronic kidney disease.
The kidney in systemic vasculitis
Authors: Jayne David 
Published: February 2020

Abstract
Systemic vasculitis can occur as a primary autoimmune disorder, or as a secondary manifestation of another disease process (related to infection, malignancy, chronic inflammatory disorder, or drugs). Primary systemic vasculitis is classified according to the predominant size of the blood vessel involved and the presence of circulating antineutrophil cytoplasm autoantibodies (ANCA). Incidence and prevalence rates are between 15 and 20 per million and 200 to 400 per million population, respectively. Vasculitic syndromes frequently involve the kidney, causing tissue infarction, loss of function, and rapid progression to endstage renal disease within weeks or months. They account for 5% of cases of endstage renal failure. ANCA-associated vasculitis is the most common cause of renal vasculitis and has been the focus for most research. Management aims for an early diagnosis, recovery of renal function, and prevention of renal relapse. Small-vessel vasculitides—renal disease is common. There are two subgroups: ANCA-associated vasculitis that comprises three syndromes: granulomatosis with polyangiitis (formerly Wegener’s granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with angiitis (formerly Churg–Strauss syndrome). The second subgroup is immune complex vasculitis and comprises IgA vasculitis (formerly Henoch–Schönlein purpura), antiglomerular basement membrane disease, and cryoglobulinaemia: these are ANCA negative and characterized by immune complex deposition. Medium- and larger-vessel vasculitides—renal disease is uncommon in the medium-vessel disorders polyarteritis nodosa (ANCA negative) and Kawasaki’s disease, and rare in the large-vessel disorders, giant cell arteritis and Takayasu’s arteritis. This chapter discusses the aetiology and pathogenesis, pathology, clinical presentation, diagnosis, management, disease relapse, and prognosis of systemic vasculitis in detail.
Haemolytic uraemic syndrome
Authors: Wong Edwin K.S. , Kavanagh David 
Published: February 2020

Abstract
Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy characterized by the triad of thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. It is most often caused by Shiga toxin-producing Escherichia coli (STEC-HUS), and any HUS not caused by this is often termed atypical HUS (aHUS). aHUS may be caused by an underlying complement system abnormality (primary aHUS) or by a range of precipitating events, such as infections or drugs (secondary aHUS). Management of STEC-HUS is supportive. In aHUS, plasma exchange is the initial treatment of choice until ADAMTS13 activity is available to exclude thrombotic thrombocytopenic purpura as a diagnosis. Once this has been done, eculizumab should be instigated as soon as possible.
Infection-associated nephropathies
Authors: Turner A. Neil 
Published: February 2020

Abstract
Infection may be a primary cause of renal disease (e.g. postinfectious glomerulonephritis) or affect the kidneys on a background of debilitating illnesses and previous medical interventions. Renal disease may arise as a consequence of immune responses to a pathogen, direct invasion by the microorganism, or the effects of infection on the systemic or local circulations. Glomerulonephritis—associated with chronic and acute bacterial infections. Shunt nephritis follows colonization of a ventriculoatrial shunt, most commonly with Staphylococcus epidermidis, leading to constitutional symptoms, an acute inflammatory response, and (most characteristically) a type 1 mesangiocapillary glomerulonephritis. Infective endocarditis and other deep-seated bacterial infections may produce a similar renal picture, but they can mimic vasculitic syndromes and outcome is dependent on the response of the infection to treatment. Interstitial nephritis—bacteria that can cause this include leptospira (Weil’s disease), Rickettsia rickettsii (Rocky Mountain spotted fever), legionella, and mycobacteria. Viral infections include hantaviruses (haemorrhagic fever with renal syndrome and nephropathia epidemica) and, almost exclusively following renal transplantation, cytomegalovirus and polyomavirus hominis type 1 (BK) virus. HIV-associated renal disorders—these include HIV nephropathy, which is a focal segmental glomerulosclerosis of ‘collapsing’ form, occurring almost exclusively in black patients. Other morphologies are more common in other races, but interstitial disease is also common as a manifestation of infection or of drug toxicity. Hepatitis B virus—chronic infection is strongly associated with membranous nephropathy; affected individuals are HBeAg and HBsAg positive, usually with coexistent hepatitis; seroconversion from HBeAg positive to HBeAb positive (naturally or induced by treatment) is associated with remission of the renal lesion. Hepatitis C virus—chronic infection is the commonest cause of mixed essential (type II) cryoglobulinaemia in most populations.
Granulocytes in health and disease
Authors: Sinning Joseph , Berliner Nancy 
Published: February 2020

Abstract
White cells (leucocytes) mediate inflammatory and immune responses and are key to the defence of the host against microbial pathogens. Subpopulations of leucocytes include granulocytes—neutrophils, eosinophils, and basophils; monocytes; and lymphocytes. Neutrophils comprise half the peripheral circulating leucocytes and are characterized by heterogeneous primary and secondary granules and a segmented nucleus. Maturation from the haematopoietic stem cell occurs in the bone marrow and takes 10 to 14 days. Neutrophilia—defined as an increase in the circulating neutrophil count to greater than 7.5 × 106/µl, usually occurs as an acquired reactive response to underlying disease. Causes include infection, particularly bacterial; drugs; malignancies, and hereditary conditions. Neutropenia—defined as a reduction in the absolute neutrophil count to less than 1.5 × 106/µl, is of particular importance because, when severe (&lt;0.5 × 106/µl), it markedly increases the risk of life-threatening infection. Causes include drugs and toxins, postinfectious, nutritional deficiencies, autoimmune, large granular lymphocytosis, and congenital. Disorders of neutrophil function include chronic granulomatous disease, leucocyte adhesion deficiency, myeloperoxidase deficiency, and Chediak–Higashi syndrome. Monocytes share a common myeloid precursor with granulocytes, present antigens to T cells, produce several important cytokines with immunomodulatory and inflammatory functions, and are the precursors to resident tissue macrophages. They are especially important in defence against intracellular pathogens. Causes of monocytosis (&gt;0.9 × 106/µl) include chronic infection, autoimmune diseases, and malignancy. Basophils are nonphagocytic granulocytes that function in immediate-type hypersensitivity. Basophilia (&gt; 0.2 × 106/µl) is seen in myeloproliferative disorders, hypersensitivity reactions, and with some viral infections.
Inherited bone marrow failure syndromes
Authors: Roberts Irene , Dokal Inderjeet S. 
Published: February 2020

Abstract
Inherited forms of bone marrow failure may involve all haematopoietic lineages or a single lineage. They are rare, but collectively account for 20 to 30% of patients presenting with aplastic anaemia. They may present at birth or in infancy or childhood, but also sometimes in adults. Associated somatic abnormalities may be helpful in diagnosis. Two of the best characterized syndromes are Fanconi’s anaemia and dyskeratosis congenita, both frequently associated with generalized bone marrow failure. Other well-recognized disorders lead to much more specific abnormalities affecting a single cell type (e.g. impaired red cell production in Diamond–Blackfan anaemia and impaired neutrophil production in Shwachman–Diamond syndrome) and reduced platelet production in thrombocytopenia with absent radii syndrome. Advances in understanding the genetics of inherited bone marrow failure syndromes have provided valuable insight into their pathophysiology, and also into normal haematopoiesis.