bluuebunny/crossref_metadata_2025 huggingface dataset:
Scoring systems in acute kidney injury patients
Authors: Candela-Toha Angel , Tenorio Teresa , Lietor Aurora , Liaño Fernando
Published: November 2015

The development of severity of illness scoring systems in the intensive care unit was prompted by the high mortality of patients in this setting. The great changes in the field of intensive care medicine have fostered new and more complex generations of scoring systems. There are several versions of the three major models used, APACHE, SAPS, and MPM. Among them, APACHE II remains the most frequently used. When these generic models are applied to acute kidney injury (AKI) patients, their discrimination ability measured by the area under the receiver operating characteristic curve is about 0.8. Another approach to prognosis of AKI patients was the development of specific scoring systems. While initial models were flawed by methodological problems, a second generation of prognosis systems for AKI patients is now available. Their discriminatory power goes beyond that of generic scores. However, some of them are awaiting external validation. Specific scoring systems for AKI patients must show their usefulness in future early-therapy trials. While we await effective therapies for AKI, the role of these systems is to improve risk stratification by the addition of new untested variables.
Viral infections in patients on dialysis
Authors: Jadoul Michel , Labriola Laura , Goffin Eric
Published: November 2015

From the early days of hemodialysis, viral hepatitis has been recognized as common in dialyzed patients.

The prevalence and incidence of HBV infection have decreased markedly over the last decades in HD units. Still, the infectivity of HBV is very high. Vaccinating HD patients, preferably prior to starting dialysis, together with the strict application of hygienic precautions and adequate screening of blood donors remains required, together with the segregation of infective (HBV+) patients in a separate dialysis ward. The level of aminotransferases is markedly lower in HD patients than in the general population: any level above the normal range should thus trigger the suspicion of acute hepatitis (viral or not). The treatment of HBV infection in HD patients is rarely required, unless they are scheduled for a kidney transplant.

Screening for HCV infection usually relies on a modern ELISA test. The prevalence and incidence of HCV infection in HD patients has also decreased substantially but remains higher than in the general population. The risk of post-transfusional HCV is currently extremely low, at least in western countries. The actual application of basic hygienic precautions is crucial if nosocomial transmission of HCV is to be prevented. These include optimal hand hygiene practices (hydroalcoholic solution use before contact with patient and after gloves withdrawal), the systematic wearing of gloves, to be changed between patients/stations, an adequate separation of the clean and contaminated items and circuits within the HD unit, and regular cleaning/disinfection of potentially contaminated surfaces. The necessity and usefulness to isolate HCV positive patients in a separate dialysis ward has not been demonstrated and is not recommended by current KDIGO guidelines. The field of the treatment of HCV infection is changing rapidly with many orally active drugs, some of which can be used even in dialysis patients.
Cardiovascular disease
Authors: McQuarrie Emily P. , Holdaas Hallvard , Fellström Bengt , Jardine Alan G.
Published: November 2015

Premature cardiovascular disease is much more common in renal transplant recipients than the general population, although less common than in patients relying on maintenance haemodialysis. Cardiovascular disease in renal transplant recipients differs from the traditional atherosclerotic model. Although ordinary risk factors such as age, gender, diabetes, hypertension, and smoking still apply, others such as left ventricular hypertrophy and uraemic cardiomyopathy are relevant. Transplantation also adds specific risks such as immunosuppressive therapies and acute rejection. Understanding and managing the cardiovascular risk in this population is limited by a lack of large-scale randomized trials. The approach to managing the cardiovascular risk profile of these patients should be multifactorial and start even before transplantation.
Cancer after kidney transplantation
Authors: Wong Germaine , Webster Angela C.
Published: November 2015

Cancer is a major cause of mortality and morbidity after transplantation. The overall risk of cancer among transplant recipients is at least 2.5–3-fold greater than that of the age- and gender-matched general population. The increased risk is also type specific, and is greatest among virus-related neoplasms such as Kaposi sarcoma, post-transplant lymphoproliferative disease, and vulvovaginal cancers, with an excess risk of at least 9–20 times greater than that of the general population. Cancer prognoses are also poor in transplant recipients, with less than 10% surviving 5 years after initial diagnoses. Despite the increased cancer risk, little is known about the efficacy of treatment, the screening strategies, and the outcomes of patients with cancer and kidney transplants. Uncertainties also exist as to how the various types of modern immunosuppression impact on recipients’ overall long-term survival and quality of life. This chapter discusses the incidence and prognoses of patients with de novo cancer after transplantation, the epidemiology of donor cancer transmission, the outcomes of transplanting patients with a prior history of cancer, as well as the different approaches to cancer screening and management after kidney transplantation.
Metabolic bone disease after renal transplantation
Authors: Elder Grahame J.
Published: November 2015

Patients who undergo kidney transplantation have laboratory, bone, and soft tissue abnormalities that characterize chronic kidney disease mineral and bone disorder (CKD-MBD). After successful transplantation, abnormal values of parathyroid hormone, fibroblast growth factor 23, calcium, phosphate, vitamin D sterols, and sex hormones generally improve, but abnormalities often persist. Cardiovascular risk remains high and is influenced by prevalent vascular calcification, and fracture risk increases due to a combination of abnormal bone ‘quality’, compounded by immunosuppressive drugs and reductions in bone mineral density. Patients with well managed CKD-MBD before transplantation generally have a smoother post-transplant course, and it is useful to assess patients soon after transplantation for risk factors relevant to the general population and to patients with CKD. Targeted laboratory assessment, bone densitometry, and X-ray of the spine are useful for guiding therapy to minimize post-transplant effects of CKD-MBD. To reduce fracture risk, general measures include glucocorticoid dose minimization, attaining adequate 25(OH)D levels, and maintaining calcium and phosphate values in the normal range. Calcitriol or its analogues and antiresorptive agents such as bisphosphonates may protect bone from glucocorticoid effects and ongoing hyperparathyroidism, but the efficacy of these therapies to reduce fractures is unproven. Alternate therapies with fewer data include denosumab, strontium ranelate, teriparatide, oestrogen or testosterone hormone replacement therapy, tibolone, selective oestrogen receptor modulators, and cinacalcet. Parathyroidectomy may be necessary, but is generally avoided within the first post-transplant year. A schema is presented in this chapter that aims to minimize harm when allocating therapy.
The child with renal cysts
Authors: Bergmann Carsten , Ortiz-Brüchle Nadina , Frank Valeska , Zerres Klaus
Published: November 2015

Renal cysts of different aetiology are a common diagnosis in paediatric nephrology. The classification is usually based on the clinical picture, morphology, and family history. In syndromic forms, additional features have to be evaluated. Most common are cystic dysplastic kidneys with a broad phenotypic spectrum ranging from asymptomatic clinical courses in unilateral cases to severe, lethal manifestations in patients with considerable bilateral involvement. Simple cysts are rare. Polycystic kidneys are usually subdivided according to the mode of inheritance into autosomal recessive and autosomal dominant polycystic kidney disease. The most useful investigation in order to distinguish between these two types is the family history with parental ultrasound and demonstration of polycystic kidneys in one parent in the majority of cases with dominant polycystic kidney disease. Finally, cystic kidneys are associated with a variety of hereditary, usually recessive syndromes affecting cilia.
Autosomal dominant polycystic kidney disease in children and young adults
Authors: Bergmann Carsten , Zerres Klaus
Published: November 2015

Many children with autosomal dominant polycystic kidney disease have renal cysts on ultrasound, some are even being diagnosed antenatally, although the statistics on this are not well understood. Most are asymptomatic but hypertension may be more common than generally appreciated, and a minority of patients develop early renal failure. The cause of early presentations is probably often inheritance of a hypomorphic allele on another gene implicated in cyst formation, or in cilia. Extrarenal manifestations of polycystic kidney disease are very rare in childhood.
Bardet–Biedl syndrome and other ciliopathies
Authors: Foggensteiner Lukas , Beales Philip
Published: November 2015

Ciliopathies encompass a genotypically complex and phenotypically variable and overlapping series of disorders that makes the general term ‘ciliopathies’ very useful. The genes behind these conditions encode parts of the machinery of the primary cilium. This is also true of the major cystic kidney disorders autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease, but the ‘long tails’ of other ciliopathies are characterized by variable nephropathy (often without cyst formation), retinopathy, and effects on brain and skeletal development. Not all have substantial renal phenotypes. Bardet–Biedl syndrome (BBS) is an autosomal dominant condition characterized by obesity, retinopathy, nephropathy, and learning difficulty, but renal abnormalities are varied and end-stage renal failure occurs in only a minority. Many BBS genes have been described. Alström syndrome is a rare recessive disorder again associated with obesity and retinopathy, but also deafness and dilated cardiomyopathy. Renal failure is a common but later feature. Joubert syndrome is an autosomal dominant condition but can arise from mutations in at least 10 genes. It has a wide phenotypic variation with a common link being hypodysplasia of the cerebellar vermis and other abnormalities giving rise to the ‘molar tooth sign’ on cerebral magnetic resonance imaging scanning, associated with hypotonia in infancy, central ataxia, ocular apraxia, developmental delay, and varying degrees of cognitive impairment. Jeune syndrome is a recessive condition characterized by osteochondrodysplasia which can give rise to hypodevelopment of the chest wall known as suffocating thoracic dystrophy, in addition to other manifestations.
Tuberous sclerosis complex renal disease
Authors: Dixon Bradley P. , Christopher Kingswood J. , Bissler John J.
Published: November 2015

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting almost all organs. It has wider phenotypic variation than often appreciated, with less than half showing the combination of characteristic facial angiofibromas, epilepsy, and mental retardation. Renal angiomyolipomata or cysts are found in 90% and renal failure was historically a common mode of adult death from the disease. Pulmonary lymphangioleiomyomatosis is restricted to females. Angiomyolipomata or cystic disease, or both, may cause renal failure. Angiomyolipomata may also haemorrhage, especially from larger lesions. Manifestations of brain involvement substantially complicate management of many patients with TSC. The causative genes TSC1 and TSC2 encode tuberin and hamartin which are involved in control of the mammalian target of rapamycin pathway. Inhibitors of that pathway, such as sirolimus and everolimus, are therefore logical approaches to therapy and have been shown to be effective in reducing angiomyolipomata volume. It remains to be seen whether they can protect renal function.
Von Hippel–Lindau disease
Authors: Connor Thomas , Maxwell Patrick H.
Published: November 2015

Von Hippel–Lindau (VHL) disease is a dominantly inherited familial cancer syndrome caused by germline mutations in the VHL tumour suppressor gene. The most frequent manifestations of VHL disease are retinal and central nervous system haemangioblastomas, clear cell renal cell carcinomas, and phaeochromocytomas. Genetic testing and active screening for clinical manifestations is now started in childhood and has greatly improved the prognosis for patients with VHL disease. The VHL protein plays a critical role in regulating the cellular response to changes in oxygen tension. Loss of VHL function results in constitutive activation of a range of angiogenic and metabolic pathways. New drug therapies have been developed that reverse some of the cellular consequences of VHL loss of function in kidney cancer.
Anatomical types of congenital anomalies
Authors: Schreuder Michiel F.
Published: November 2015

Antenatal hydronephrosis is the most common abnormality detected during antenatal ultrasound screening (1 in 100–500 pregnancies). Depending on the degree of dilatation, postnatal evaluation with ultrasound and/or renography is indicated to detect urinary tract obstruction. Obstruction can be found at various levels of the urinary tract such as the pyeloureteric junction, vesicoureteric junction (resulting in a megaureter), and lower urinary tract (most commonly posterior urethral valves). The decision to surgically correct obstruction can be challenging to make, and additional markers (both radiological as urinary) are needed but are not yet available in daily practice.
Duplex, ectopic, and horseshoe kidneys
Authors: Schreuder Michiel F.
Published: November 2015

A duplex urinary tract, irrespective of the degree of duplication, is present in 0.8% at autopsy, of which about 20–35% is bilateral. The majority of duplex systems are incomplete, indicating that the ipsilateral ureters fuse before entering the bladder. A complete duplex system shows anomalies of the upper moiety, with associated ureterocele or ectopic ureter, and of the lower moiety, frequently associated with vesicoureteral reflux. Renal ectopia is a rare (1/1000) congenital defect where the kidney is not located in the renal fossa, and is associated with a high rate of hydronephrosis, vesicoureteral reflux, and abnormal contralateral kidney. In a horseshoe kidney (present in 1/400 to 1/1800), fusion of the two kidneys takes place, but the two renal moieties are still located on both sides of the midline. As the lower poles are fused in the midline, a horseshoe kidney is usually located lower than normal and orientation of the renal axis is shifted, which may guide diagnosis during abdominal ultrasound.
Biologics registries
Authors: Isenberg David , Zink Angela
Published: November 2015

Double-blind controlled trials undertaken over the past two decades have established the short-term effectiveness and side-effect profile of biologic drugs for patients with rheumatoid arthritis and related diseases. However, the development of biologics registers to capture ’real-life experience’ and explore long-term effectiveness and complications is equally important. In this chapter, we demonstrate how these registers have identified long-term joint benefits, a reduction in cardiovascular mortality, reassurance concerning fears about cancer development, and a balanced view of the risk of infection.
Genetics of connective tissue diseases
Authors: Lewis Myles , Vyse Tim
Published: November 2015

The advent of genome-wide association studies (GWAS) has been an exciting breakthrough in our understanding of the genetic aetiology of autoimmune diseases. Substantial overlap has been found in susceptibility genes across multiple diseases, from connective tissue diseases and rheumatoid arthritis (RA) to inflammatory bowel disease, coeliac disease, and psoriasis. Major technological advances now permit genotyping of millions of single nucleotide polymorphisms (SNPs). Group analysis of SNPs by haplotypes, aided by completion of the Hapmap project, has improved our ability to pinpoint causal genetic variants. International collaboration to pool large-scale cohorts of patients has enabled GWAS in systemic lupus erythematosus (SLE), systemic sclerosis and Behçet’s disease, with studies in progress for ANCA-associated vasculitis. These ’hypothesis-free’ studies have revealed many novel disease-associated genes. In both SLE and systemic sclerosis, identified genes map to known pathways including antigen presentation (MHC, TNFSF4), autoreactivity of B and T lymphocytes (BLK, BANK1), type I interferon production (STAT4, IRF5) and the NFκ‎‎B pathway (TNIP1). In SLE alone, additional genes appear to be involved in dysregulated apoptotic cell clearance (ITGAM, TREX1, C1q, C4) and recognition of immune complexes (FCGR2A, FCGR3B). Future developments include whole-genome sequencing to identify rare variants, and efforts to understand functional consequences of susceptibility genes.
Putative environmental triggers for connective tissue diseases include infectious agents, especially Epstein-Barr virus; cigarette smoking; occupational exposure to toxins including silica; and low vitamin D, due to its immunomodulatory effects. Despite numerous studies looking at toxin exposure and connective tissue diseases, conclusive evidence is lacking, due to either rarity of exposure or rarity of disease.
Haematology
Authors: Kesteven Patrick
Published: November 2015

This chapter describes the common haematological abnormalities seen in rheumatic conditions with special reference to laboratory findings and diagnostic traps. The chapter is organized into sections dealing with red cell abnormalities (and the distinction between anaemia of chronic disease and iron deficiency); white cell abnormalities (neutrophilia and neutropenia); platelets (thrombocytosis, idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura); and finally coagulation abnormalities (lupus anticoagulant).
Glucocorticoids
Authors: Jacobs Johannes W. G. , Spies Cornelia M. , Bijlsma Johannes W. J. , Buttgereit Frank
Published: November 2015

Glucocorticoids are anchor drugs of therapeutic regimens in most inflammatory and autoimmune rheumatic conditions and vasculitides, for reasons of effectiveness, versatility, and low cost. In this chapter on glucocorticoid therapy in rheumatology, basic mechanisms and pharmacological effects, indications, adverse advents, monitoring, and new developments are discussed. Throughout, emphasis is placed on clinically relevant implications for daily clinical practice.
Vaccination in immunocompromised adults
Authors: van Assen Sander , Bijl Marc
Published: November 2015

This chapter addresses all important questions regarding vaccination of patients with autoimmune inflammatory rheumatic diseases (AIIRD). First, the incidence of vaccine-preventable infections in these patients is discussed. Pulmonary infections, including influenza and pneumococcal infection, occur more often in AIIRD patients; herpes zoster and human papillomavirus are also more frequent.
The efficacy of vaccination for all European registered vaccines is discussed. Treatment with disease-modifying anti-rheumatic drugs (DMARDs) and biologicals (in particular TNFα‎‎-blocking agents) do not hamper, or only slightly hamper, the immune responses to most vaccines. Rituximab is an exception, severely reducing humoral responses following influenza and pneumococcal vaccination, at least during the first 6 months after administration.
Safety of vaccination is an important issue in patients with autoimmune diseases, since increased disease activity of the underlying disease as a result of vaccination is theoretically possible. The available evidence is summarized, suggesting that vaccination is safe in AIIRD patients. Live vaccines, however, are contraindicated in immunosuppressed patients with AIIRD. Finally, the European League Against Rheumatism (EULAR) recommendations are highlighted, summarizing the ’do’s’ and ’don’ts’ of vaccination in adults with AIIRD.
Brucellar arthritis
Authors: Merino Esperanza , Pascual Eliseo
Published: November 2015

Joint infection is the most common local complication of brucellosis and is a frequent cause of infectious arthritis in endemic areas. Brucellosis is prevalent in countries of the Mediterranean basin, the Near East, South America, and possibly sub-Saharan Africa. Brucella melitensis and B. abortus are the most common species. Arthralgia occurs in 70% of patients with brucellosis, Large peripheral joints are a common site of localized infection. The sacroiliac joint is frequently involved (30–75%) in recent series. First-line treatment is with doxycycline combined with either streptomycin or gentamycin.
Rheumatoid arthritis—clinical features
Authors: Feist Eugen , Burmester Gerd-R.
Published: November 2015

Rheumatoid arthritis (RA) presents with variable clinical features, making this most frequent chronic systemic autoimmune disease with characteristic joint involvement a diagnostic and therapeutic challenge. This chapter describes in detail the different clinical, laboratory and imaging findings in patients with RA. In addition to the characteristic arthritic involvement, which can lead to severe joint changes with progressive destruction and loss of function, other systemic disease manifestations as well as an increased risk for cardiovascular events and non-Hodgkin’s lymphoma with relevance for patients’ prognosis are described. Recent approaches to early diagnosis and stratification of patients by predictive factors for a severe course of disease are discussed. These patient profiles include increased inflammatory markers, the presence of autoantibodies, and erosive changes at the time of diagnosis. The novel classification criteria for RA and the significance of autoantibody status, namely seropositivity for antibodies against citrullinated antigens as highly specific diagnostic markers, are highlighted to further promote early differentiation of RA from other arthritic disease entities.
Anti-phospholipid antibody syndrome
Authors: Khamashta Munther A. , Hughes Graham R. V. , Ruiz-Irastorza Guillermo
Published: November 2015

The anti-phospholipid syndrome (APS) described almost 30 years ago, is now recognized as a major cause of deep vein thrombosis, stroke, and heart attacks in young people (<45 years of age). It is also the commonest treatable cause of recurrent miscarriages and a major cause of late fetal death. Other clinical manifestations are cardiac valvular disease, livedo reticularis, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, epilepsy, and cognitive impairment.
The presence of anti-phospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop the clinical features. Lupus anticoagulant is generally thought to be more strongly associated with the risk of clinical manifestations of APS than anticardiolipin and anti ?2-glycoprotein I antibodies.
The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Therapy of thrombosis is based on long-term oral anti-coagulation and patients with arterial events should be treated aggressively. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin.
Osteoarthritis—management
Authors: Wenham Claire Y. J. , Conaghan Philip G.
Published: November 2015

Osteoarthritis (OA) is a common condition which often causes pain and functional limitation, significantly impacting on a person’s quality of life. A comprehensive assessment of the impact of OA should be performed before selecting therapies and treatment goals. Current recommended therapies include a combination of pharmacological and non-pharmacological therapies, which should be considered for all people with OA, regardless of anatomical site of involvement. Non-pharmacological treatments include education, muscle strengthening and aerobic exercises, weight loss if appropriate, splints and devices, and aids. Pharmacological therapies include paracetamol, oral and topical non-steroidal anti-inflammatory drugs, topical capsaicin, intra-articular corticosteroid injections, and opioids. Many existing therapies have only a small analgesic effect size and, in the case of drug therapies, may be associated with important side effects, so an individual’s symptoms and comorbidities must be taken into account when selecting therapies. For those who do not respond to these treatments, surgery such as a total joint arthroplasty may be required. There is a strong need for new analgesic treatments for OA. As it is becoming increasingly clear that the sources of pain in OA are complex and multifactorial, future treatments for OA will need to target both peripheral and central pain mechanisms.
Renal osteodystrophy
Authors: Bardin Thomas , Drüeke Tilman
Published: November 2015

Renal osteodystrophy (ROD) is a term that encompasses the various consequences of chronic kidney disease (CKD) for the bone. It has been divided into several entities based on bone histomorphometry observations. ROD is accompanied by several abnormalities of mineral metabolism: abnormal levels of serum calcium, phosphorus, parathyroid hormone (PTH), vitamin D metabolites, alkaline phosphatases, fibroblast growth factor-23 (FGF-23) and klotho, which all have been identified as cardiovascular risk factors in patients with CKD.
ROD can presently be schematically divided into three main types by histology: (1) osteitis fibrosa as the bony expression of secondary hyperparathyroidism (sHP), which is a high bone turnover disease developing early in CKD; (2) adynamic bone disease (ABD), the most frequent type of ROD in dialysis patients, which is at present most often observed in the absence of aluminium intoxication and develops mainly as a result of excessive PTH suppression; and (3) mixed ROD, a combination of osteitis fibrosa and osteomalacia whose prevalence has decreased in the last decade.
Laboratory features include increased serum levels of PTH and bone turnover markers such as total and bone alkaline phosphatases, osteocalcin, and several products of type I collagen metabolism products. Serum phosphorus is increased only in CKD stages 4-5. Serum calcium levels are variable. They may be low initially, but hypercalcaemia develops in case of severe sHP. Serum 25-OH-vitamin D (25OHD) levels are generally below 30 ng/mL, indicating vitamin D insufficiency or deficiency.
The international KDIGO guideline recommends serum PTH levels to be maintained in the range of approximately 2-9 times the upper normal normal limit of the assay and to intervene only in case of significant changes in PTH levels. It is generally recommended that calcium intake should be up to 2 g per day including intake with food and administration of calcium supplements or calcium-containing phosphate binders. Reduction of serum phosphorus towards the normal range in patients with endstage kidney failure is a major objective. Once sHP has developed, active vitamin D derivatives such as alfacalcidol or calcitriol are indicated in order to halt its progression.
Foot and ankle
Authors: Redmond Anthony C. , Helliwell Philip S.
Published: November 2015

Foot and ankle problems have been the subject of major advances in the rheumatology in recent years. This chapter reviews the anatomy of the foot and covers the manifestations of foot pathology for the major conditions: rheumatoid arthritis, osteoarthritis, the seronegative arthritides, connective tissue disease, crystal diseases, and miscellaneous conditions including hypermobility syndrome. Relevant local conditions including plantar fasciitis, tendinopathy, and neuroma are addressed separately. The principles of assessing and treating the foot and ankle in rheumatology are covered, along with the relevant specific approaches best suited to dealing with problems associated with the major conditions.
Cervical and lumbar spine
Authors: Walsh David A.
Published: November 2015

Cervical and lumbar spine pain are major causes of disability and distress. Careful assessment is needed of the nature and extent of the problem, for diagnosis and exclusion of important (treatable) differential diagnoses, and for the formulation and engagement of the patient in an appropriate treatment plan. Acute spinal pain frequently does not indicate underlying joint pathology. Chronic spinal pain is often associated with intervertebral disc disease or which is often classified together with facet joint osteoarthritis as spondylosis. Sciatica, brachalgia, or spinal claudication may each be a consequence of either spondylosis or intervertebral disc prolapse. Simple mechanical low back and neck pain may respond well to conservative management with analgesics and physiotherapy. Specific spinal problems, such as neuronal compromise, may require additional treatments. The roles of injections and surgery in the management of spinal pain continue to evolve. Although ongoing management is largely determined by the individual’s clinical response, comprehensive health economic analyses inform healthcare policies which may limit treatment availability. Many people with spinal problems suffer long-term or recurrent pain and disability, with significant psychological and social impact. Multidisciplinary approaches are needed to facilitate pain management and enable people with spinal pain to lead fulfilling lives when the underlying condition cannot be cured.
Sarcoidosis
Authors: Müller-Quernheim Joachim , Zissel Gernot , Prasse Antje
Published: November 2015

Sarcoidosis is a systemic disease characterized by non-necrotizing granulomata and manifestations in almost any organ. Diagnosis relies on the exclusion of other granulomatous disorders and a compatible pattern of symptoms and clinical findings. Inflammatory lesions and granulomata may undergo spontaneous resolution or persist in chronic disease with eventual fibrosis and permanent organ damage. Immunological disease mechanisms are linked to severe derangements of the cytokine network. In systemic resolution or under prednisolone therapy of symptomatic disease pro-inflammatory cytokines are downregulated and histological lesions may completely vanish. Corticosteroid-resistant disease, however, requires treatment with an immunosuppressive regimen consisting of prednisolone and an immunosuppressive agent or anti-tumour necrosis factor (TNF) monoclonal antibodies.
Rheumatological manifestations of endocrine disorders
Authors: Sharma Sanjeev , Rayman Gerry
Published: November 2015

There is considerable overlap of musculoskeletal manifestations of both rheumatological and endocrine disorders. Apart for the well-described autoimmune basis governing the aetiopathogenesis of clinical states pertaining to specific conditions affecting both systems, there is more recent evidence on the overlapping biology and genetics of these organ systems. Not uncommonly, endocrine manifestations can herald the initial presentation of rheumatological illnesses and the converse holds true for endocrinopathies. Rheumatologists and physicians alike need to be astutely aware of this overlap of symptomatology and also the physiology linking both groups of clinical conditions.
This review discusses the common endocrine presentations associated with rheumatic illnesses in relation to newer information gleaned from population studies, genetic studies, and clinical presentations. A comprehensive list of rheumatological conditions found in endocrine states is also tabulated at the end.
Iliac artery occlusions: surgical bypass, covered and uncovered stents
Authors: Christie Andrew , Robertson Iain
Published: November 2015

The Trans-Atlantic Intersociety Consensus (TASC) is the landmark publication offering guidance on endovascular versus surgical treatment of iliac disease. The discussion is based upon a patient with TASC C occlusive morphology. The technical aspects of endovascular treatment and their potential complications are discussed, as well as variations in practice. Emphasis is also placed on outcome measures with comparison to standard surgical alternatives for bypassing complex iliac lesions. A comprehensive review of the literature is provided, and the potential pitfalls of pre-procedure imaging are highlighted.
Thrombolysis for acute lower limb ischaemia
Authors: Diamantopoulos Athanasios , Gkoutzios Panos
Published: November 2015

Since its introduction by Dotter, catheter directed thrombolysis has been established as an effective treatment option for patients suffering from acute limb ischaemia (ALI). We present the case of a 57-year-old female patient who was admitted with ALI symptoms in her left leg with moderate motor and sensory loss. Her previous medical history included a right common iliac artery to right common femoral artery (CFA) bypass followed by right CFA to left CFA and a left CFA to left popliteal artery bypass using a synthetic graft one year prior to admission. Pre-procedural imaging with computer tomography angiography revealed that both the right to left femoral-femoral bypass graft and the femoral-popliteal bypass grafts were thrombosed, with flow reconstituting at the popliteal artery. After establishment of endovascular access, thrombolysis was initiated as per the institutional protocol and the patient was then transferred to a high dependency unit for monitoring. After 24 hours, digital subtraction angiography showed satisfactory flow in both the right to left femoral-femoral graft and the left side femoral-popliteal graft with no significant underlying lesions being present. The anterior tibial artery was patent to the foot. The patient had regained full motion and sensory feeling of the previous ischaemic limb and the distal foot was significantly warmer than before the procedure. Catheter-directed thrombolysis techniques and results are discussed.
Renal artery stenosis: angioplasty or stent?
Authors: Prabhudesai Shirish , Gupta Yuri , Karunanithy Narayan
Published: November 2015

Renal artery stenosis impedes blood flow and can result in refractory hypertension, congestive heart failure, and progressively worsening renal function. This case discusses the indications for treatment, endovascular technique, and procedural considerations, and provides a literature review of currently available evidence.
IVC filters and anticoagulation
Authors: Burke Christopher , Krokidis Miltiadis , Hoppe Hanno
Published: November 2015

Inferior vena cava (IVC) filters, which are usually deployed via the common femoral or internal jugular veins, were initially intended for use in patients who had venous thromboembolism (VTE) and a contraindication to anticoagulation, a complication of anticoagulation, inability to achieve adequate anticoagulation, or recurrent pulmonary embolism despite anticoagulation. These indications have been expanded to include some patients with high VTE risk but no evidence of VTE. The development of retrievable filter designs has extended the clinical utility for IVC filters. This case demonstrates the decision-making process in filter deployment, describes some technical aspects of the procedure, and discusses the current literature on the use of IVC filters.
TIPS and TIPS revision for Budd–Chiari patients
Authors: Pavlidis Vyzantios , Brountzos Elias
Published: November 2015

Budd-Chiari syndrome (BCS) is a relatively rare condition, with potentially life-threatening outcomes in untreated patients. Although transjugular intrahepatic portosystemic shunt (TIPS) with the use of PTFE-covered stent-grafts is an efficient minimal invasive treatment, variations of the technique have been described according to the degree of hepatic vein thrombosis. However, the underlying thrombotic tendency in such patients may cause a high rate of shunt restenosis or occlusion. Interventional recanalization of the shunt is possible, but is not always successful. Management of such cases of total shunt occlusion may involve the creation of a new shunt. This challenging procedure is technically feasible and seems to prolong survival as well as being an alternative to early transplantation.
Lung tumour radiofrequency ablation: what are the success factors?
Authors: St Noble Victoria , Fotiadis Nicos
Published: November 2015

Radiofrequency ablation (RFA) is an increasingly used minimally invasive treatment option for patients with pulmonary metastatic disease or inoperable non-small-cell lung cancer. We describe a case of RFA in a female patient who underwent multiple ablation sessions for pulmonary metastatic disease. The case highlights some of the issues regarding lesion suitability for RFA, technical considerations, and potential complications. In our experience RFA is an effective treatment option when applied to appropriately selected patients. Careful follow-up is critical for early detection of incomplete treatment or recurrence.
Parkinson Disease
Authors: Barton Brandon R. , Hall Deborah A.
Published: November 2015

Parkinson disease (PD) is a multisystemic neurodegenerative disease that causes progressive deterioration of motor, autonomic, and neuropsychiatric functions. The cardinal motor features of Parkinsonism include bradykinesia, rigidity, rest tremor, and postural instability. Patients commonly also have masked facial features, flexed posture, hypophonic speech, and slowed eye movements. Rest tremor and dyskinesia are particularly enhanced during difficult, distracting cognitive or motor tasks; therefore, it is important to include these in any protocol. Special precautions must be taken so that the patient does not fall. Other special considerations for videotaping PD patients are related to the stage of the disease and the predominant symptoms.
Dystonia
Authors: Barton Brandon R. , Hall Deborah A.
Published: November 2015

Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation in the primarily activated muscles as well as the surrounding muscles. The filming of the dystonia patient is challenging given the protean nature of the disease: dystonia may occur in any body part, either isolated or more diffusely as part of a more generalized syndrome. A general video protocol is suggested with further suggestions for specific, common dystonic syndromes. For dystonia in the neck (spasmodic torticollis or cervical dystonia), a particular focused protocol is used based on the TWSTRS (Toronto Western Spasmodic Torticollis Rating Scale).
Tics
Authors: Barton Brandon R. , Hall Deborah A.
Published: November 2015

Tics are repetitive, stereotyped sounds (vocal tics) or movements (motor tics). They may be simple or complex in nature, are often preceded by a premonitory urge, and are usually suppressible. The tic protocol is the shortest and least complicated of all video protocols. The videographer simply leaves the patient in the room alone, which frequently increases the presence of tics on the video as the patient no longer feels a need to suppress them in front of medical personel. Other movement disorders are rarely present, so observation alone is the highest-yield to capture the tics. Also included in this chapter are tips for taping small children, and discussing triggers of the tics.
Functional Movement Disorders
Authors: Barton Brandon R. , Hall Deborah A.
Published: November 2015

Many phenomenologies may be seen in patients with functional movement disorders, including shaking of the arms, parkinsonism, dystonia, and gait disorders. However the movements will be more variable and inconsistent with classic presentations of common movement disorders. A single phenomenology or multiple ones can be seen in one patient. The functional protocol is a variation of the general protocol with taping of movement in all areas of the body. Flexibility of the videographer is important because some patients may have triggers that bring out the movements, and the movements could occur only occasionally, at unexpected times, and sometimes home videos need to be requested. Efforts to distract the movements can show their variability.
Tax Farming Redux: Experimental Evidence on Performance Pay for Tax Collectors
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Authors: Khan Adnan Q. , Khwaja Asim I. , Olken Benjamin A.
Published: November 2015

Performance pay for tax collectors has the potential to raise revenues, but might come at a cost if it increases the bargaining power of tax collectors vis-à-vis taxpayers. We report the first large-scale field experiment on these issues, where we experimentally allocated 482 property tax units in Punjab, Pakistan, into one of three performance pay schemes or a control. After two years, incentivized units had 9.4 log points higher revenue than controls, which translates to a 46% higher growth rate. The scheme that rewarded purely on revenue did best, increasing revenue by 12.9 log points (64% higher growth rate), with little penalty for customer satisfaction and assessment accuracy compared to the two other schemes that explicitly also rewarded these dimensions. The revenue gains accrue from a small number of properties becoming taxed at their true value, which is substantially more than they had been taxed at previously. The majority of properties in incentivized areas in fact pay no more taxes, but instead report higher bribes. The results are consistent with a collusive setting in which performance pay increases collectors’ bargaining power over taxpayers, who have to either pay higher bribes to avoid being reassessed or pay substantially higher taxes if collusion breaks down.
Epigenetic Mechanisms: An Emerging Player in Plant-Microbe Interactions
Authors: Zhu Qian-Hao , Shan Wei-Xing , Ayliffe Michael A. , Wang Ming-Bo
Published: November 2015

Plants have developed diverse molecular and cellular mechanisms to cope with a lifetime of exposure to a variety of pathogens. Host transcriptional reprogramming is a central part of plant defense upon pathogen recognition. Recent studies link DNA methylation and demethylation as well as chromatin remodeling by posttranslational histone modifications, including acetylation, methylation, and ubiquitination, to changes in the expression levels of defense genes upon pathogen challenge. Remarkably these inducible defense mechanisms can be primed prior to pathogen attack by epigenetic modifications and this heightened resistance state can be transmitted to subsequent generations by inheritance of these modification patterns. Beside the plant host, epigenetic mechanisms have also been implicated in virulence development of pathogens. This review highlights recent findings and insights into epigenetic mechanisms associated with interactions between plants and pathogens, in particular bacterial and fungal pathogens, and demonstrates the positive role they can have in promoting plant defense.
Virulence Characterization and Identification of Maize Lines Resistant to Puccinia sorghi Schwein. Present in the Argentine Corn Belt Region
Authors: Darino M. A. , Rochi L. , Lia V. V. , Kreff E. D. , Pergolesi M. F. , Ingala L. R. , Dieguez M. J. , Sacco F.
Published: November 2015

Puccinia sorghi Schwein., the causal agent of maize common rust, is an endemic disease in the Argentine Corn Belt region. Virulence surveys of the pathogen population within the region have not been performed; thus, the understanding of the pathogen population is low and it is difficult to deploy resistance genes that could be effective at controlling the disease. In total, 58 single-uredinial isolates derived from infected maize leaves collected in different locations throughout the Argentine Corn Belt region during 2010 to 2012 were tested on a set of 25 maize lines carrying different Rp genes. Maize lines Rp3-A and PIO19802 showed the lowest virulence frequencies (3.4 and 1.7%, respectively) for all tested isolates. Moreover, the combination in a single genotype of the resistance genes carried by lines Rp3-A and PIO19802 or either of these lines combined with the resistance genes from PIO12345 would confer resistance to all isolates tested. Virulent isolates on maize lines Rp-G, Rp1-K, and Rp-GI were most frequent in 2012. Twenty-four virulence phenotypes were identified, with phenotypes TCCG (17.2%), TTBB (15.5%), and TCFG (10.3%) being the most common throughout the region. Adult plant resistance associated with hypersensitive response was identified at vegetative stage 6 in maize lines PIO68752, PIO28427, and PIO36420.
Isolation, Identification, Storage, Pathogenicity Tests, Hosts, and Geographic Range of Fusarium solani f. sp. pisi Causing Fusarium Root Rot of Pea
Authors: Porter Lyndon D. , Pasche Julie S. , Chen Weidong , Harveson Robert M.
Published: November 2015

Fusarium root rot caused by Fusarium solani f. sp. pisi is a major pea disease worldwide. This diagnostic guide characterizes disease symptoms on pea plants and signs of the pathogen produced on artificial media. Hosts, geographic distribution of the pathogen, and techniques effective in isolating, storing, and inoculating with the pathogen are described.

Accepted for publication 8 September 2015. Published 15 September 2015.
Genome-Wide Analysis of Small Secreted Cysteine-Rich Proteins Identifies Candidate Effector Proteins Potentially Involved in Fusarium graminearum−Wheat Interactions
Authors: Lu Shunwen , Edwards Michael C.
Published: November 2015

Pathogen-derived, small secreted cysteine-rich proteins (SSCPs) are known to be a common source of fungal effectors that trigger resistance or susceptibility in specific host plants. This group of proteins has not been well studied in Fusarium graminearum, the primary cause of Fusarium head blight (FHB), a devastating disease of wheat. We report here a comprehensive analysis of SSCPs encoded in the genome of this fungus and selection of candidate effector proteins through proteomics and sequence/transcriptional analyses. A total of 190 SSCPs were identified in the genome of F. graminearum (isolate PH-1) based on the presence of N-terminal signal peptide sequences, size (≤200 amino acids), and cysteine content (≥2%) of the mature proteins. Twenty-five (approximately 13%) SSCPs were confirmed to be true extracellular proteins by nanoscale liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) analysis of a minimal medium-based in vitro secretome. Sequence analysis suggested that 17 SSCPs harbor conserved functional domains, including two homologous to Ecp2, a known effector produced by the tomato pathogen Cladosporium fulvum. Transcriptional analysis revealed that at least 34 SSCPs (including 23 detected in the in vitro secretome) are expressed in infected wheat heads; about half are up-regulated with expression patterns correlating with the development of FHB. This work provides a solid candidate list for SSCP-derived effectors that may play roles in mediating F. graminearum−wheat interactions. The in vitro secretome-based method presented here also may be applicable for identifying candidate effectors in other ascomycete pathogens of crop plants.
Preparation of Urogenital Sinus Mesenchymal Cells for Prostate Tissue Recombination Models
Authors: Zong Yang , Goldstein Andrew S. , Witte Owen N.
Published: November 2015

An appropriate microenvironment provided by the mesenchyme is important for establishing tissue recombination models for epithelial cancer. Urogenital sinus mesenchymal (UGSM) cells derived from embryonic rodent show potent inductive effects for prostate regeneration. Genetic manipulation of these mesenchymal cells allows us to define the contribution of the tumor microenvironment to prostate cancer development. This protocol describes preparation and propagation of murine UGSM cells in culture.