Volume 2 Issue 1, 22 December 2016

Erectile dysfunction is a multidimensional but common male sexual dysfunction involving an alteration in any of the components of the erectile response. This Primer highlights numerous aspects of the condition, summarizing various treatments and ongoing preclinical studies.

Calcific aortic stenosis (AS) involves fibro-calcific remodelling of the aortic valve that causes restriction of blood flow. Pibarot and colleagues discuss the mechanisms, diagnosis and management of AS and highlight how the introduction of transcatheter-based valve replacement has transformed patient outcomes.

Kidney stones form when the urine becomes supersaturated with respect to a mineral, leading to crystal formation, growth, aggregation and retention within the kidneys. In this Primer, Khan et al. describe the contributing pathways to stone formation and the available treatments, as well as highlight the emerging management strategies.

Cerebral palsy is the most common cause of movement and posture disorders caused by brain injury acquired during the antenatal, perinatal or early postnatal period. Here, Graham et al. describe this complex disease entity, the possible causes and the clinical management of the disorder.

Acute rheumatic fever (ARF) is caused by an autoimmune response to group A streptococcal infection. Severe and/or repeated episodes of ARF can lead to rheumatic heart disease (RHD). Both conditions predominantly affect those experiencing economic disadvantage.

Patent foramen ovale (PFO) is the most common congenital heart abnormality and is present in approximately ∼25% of the adult population. In this Primer, Homma et al. describe various aspects of PFOs, focusing on their potential relationship with stroke.

In this Primer, Dharnidharka et al. describe post-transplant lymphoproliferative disorders (PTLDs). PTLDs are a group of lymphoma-like conditions characterized by an uncontrolled proliferation of lymphoid cells as a consequence of therapeutic immunosuppression, following solid organ or haematopoietic stem cell transplantation.

Acute myeloid leukaemia is characterized by clonal proliferation of haematopoietic stem cells or progenitor cells, leading to fewer differentiated red blood cells, platelets and white blood cells. The disease presents with a rapid onset and may be fatal in weeks or months if left untreated.

Diabetic retinopathy is a common microvascular complication of diabetes and is a major cause of vision loss in middle-aged and elderly people. In this Primer, Wong et al. discuss the epidemiology, underlying pathophysiological mechanisms, classification and diagnosis and treatment options of this condition.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high prevalence. Enck et al. describe the association between IBS and other gastrointestinal, somatic and psychiatric conditions, as well as the current view on the pathophysiology, and diagnostic and management options.

Atrial fibrillation occurs when cardiac electrical impulses become disordered, leading to a rapid and irregular heartbeat. Lip and colleagues discuss the mechanisms that underlie this common arrhythmia and outline current strategies and potential future developments for its diagnosis and management.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and has well-known risk factors, including cirrhosis and viral hepatitis. Here, Llovet and colleagues discuss the challenges and recent advances in HCC molecular characterization, diagnosis and management.

This Primer describes the mechanisms underlying the serious effects of Clostridium difficile infection, which is the leading cause of health-care-associated infective diarrhoea. Strategies for diagnosis, prevention and management are also described, illustrating the burden that C. difficile infection places on patients and society.

In 2015, an estimated 367,000 new cases of pancreatic cancer were diagnosed worldwide; this disease is aggressive and patients face a dismal overall prognosis. In this Primer, the current understanding of pathophysiological, molecular, translational and clinical aspects of pancreatic cancer are described.

Gallstones are masses in the gallbladder or biliary tract. This Primer by Lammert et al. focuses on the formation of gallstones, summarizes the current principles of treatment of the stones and their potential complications and envisions future approaches for this widespread disease.

Meniere's disease is a disorder of the inner ear that causes vertigo attacks, fluctuating hearing loss, tinnitus and aural fullness. In this Primer, Nakashima et al. give an overview of the complex aetiology, classification systems, diagnostic tools and management strategies.

Benign prostatic hyperplasia, which causes lower urinary tract symptoms, is a common diagnosis among ageing men that is associated with many risks factors, including metabolic syndrome. In this Primer, these risk factors are described, as well diagnostic work-up and treatment options.

Primary hyperparathyroidism (PHPT) is characterized by excessive secretion of parathyroid hormone due to a single benign adenoma or multiglandular disease. In this Primer, Bilezikian et al. describe the epidemiology, clinical presentations, genetics, evaluation and guidelines for the management of PHPT.

Tuberous sclerosis complex (TSC) is a rare inherited disease caused by mutations in the tumour-suppressor genes TSC1 or TSC2. As a chronic disease that manifests as benign tumours in the brain, kidneys, lungs and skin, TSC requires lifelong treatment.

Disseminated intravascular coagulation can be caused by various infectious and non-infectious insults, such as sepsis and trauma, respectively. It is characterized by the widespread activation of coagulation and, depending on the underlying condition, can manifest as bleeding and/or thrombosis.

Systemic lupus erythematosus is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Here, Kaul et al. highlight the heterogeneity of the disease, the management approaches and provide an outlook on the future research directions.

Patients with cirrhosis can develop acute-on-chronic liver failure, a syndrome characterized by acute decompensation, organ failure and high short-term mortality. Arroyo et al. discuss the mechanisms, diagnosis and management of this evolving concept in the field of liver disease.

Uterine fibroids are benign neoplasms of the uterus and are a major source of morbidity in women of reproductive age. In this Primer, Stewart et al. discuss the epidemiology, pathophysiology and management of uterine fibroids, including both surgical and non-surgical therapies.

Sepsis is the dysregulated systemic inflammatory and immune response to infection that produces organ injury. Septic shock is characterized by persistent hypotension that substantially increases the risk of death. In this Primer, the authors outline the controversies in sepsis and septic shock, including the complex mechanistic factors and management of critically ill patients.

Sjögren syndrome (SjS) is a systemic autoimmune disease that primarily affects the exocrine glands, resulting in the development of sicca symptoms and systemic disease. In this Primer, the mechanisms as well as the diagnosis and management of SjS are described.

Measles is an infectious disease caused by the measles virus. In this Primer, Rota et al. cover the pathophysiology and management options, with a focus on the strategies to eliminate endemic transmission of the measles virus by achieving a high level of vaccination coverage

α1-Antitrypsin deficiency (A1ATD) is an inherited disorder caused by mutations in SERPINA1, leading to liver and lung disease. In this Primer by Greene et al., the classification of A1ATD is discussed, in addition to the mechanisms, diagnosis and management of this disease.

Aortic dissection is a medical emergency that occurs when the layers of the aortic wall are forced apart by bleeding, creating a false route of blood flow. Important risk factors for aortic dissection include hypertension and connective tissue disorders.

Infection with any one of the four dengue virus serotypes can cause disease that ranges from a mild febrile illness through to haemorrhagic fever and shock. This Primer outlines the epidemiology, pathogenesis, diagnosis and management of dengue infection.

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Here, Azziz et al. describe the current state of knowledge regarding the epidemiology, pathophysiology, diagnosis, management and future investigational directions of the disorder.

Infective endocarditis (IE) is caused by damage to the endocardium of the heart followed by microbial, usually bacterial, colonization. IE is a disease that affects multiple systems and can be fatal if left untreated, and antimicrobial prophylaxis strategies for IE remain controversial.

Ovarian cancer is a global health problem that is generally diagnosed at a late stage and has no effective screening strategy. This Primer by Matulonis et al. discusses the risk factors, genetics, diagnosis and management of ovarian cancer.

Otitis media (OM) or middle ear inflammation is a spectrum of diseases. In this Primer, Schilder et al. provide an overview of OM epidemiology, its underlying pathophysiology, diagnosis, impact on children and their families and preventive and treatment options, as well as an outlook on the future.

Major depressive disorder (MDD) is characterized by depressed mood, diminished interests and impaired cognitive function, among other symptoms. This Primer by Otte et al. discusses the epidemiology, pathophysiology, diagnosis and management of MDD.

Primary open-angle glaucoma (POAG) is the most common form of glaucoma and is characterized by deformation of the optic nerve head and vision loss. This Primer by Weinreb et al. discusses the risk factors, pathophysiology, diagnosis and management of POAG.

Osteoporosis is a metabolic bone disorder that is characterized by low bone mass and micro-architectural deterioration of bone tissue. In this Primer, Eastell et al. discuss the epidemiology and pathophysiology of postmenopausal osteoporosis and consider its diagnosis, prevention and treatment and its effect on quality of life.

Osteoarthritis (OA) is the most common degenerative joint disorder. In this Primer, Pelletier and colleagues provide an update on the progress made in the field of OA epidemiology, pathophysiological mechanisms, diagnosis, prevention, disease management and quality of life.

Community-acquired bacterial meningitis (inflammation of the meninges) is most commonly caused by Streptococcus pneumoniae or Neisseria meningitidis. Prevention (through vaccination) and early antibiotic treatment are essential to reduce morbidity and mortality of this medical emergency.

Tuberculosis (TB) is an airborne infectious disease with high morbidity and mortality rates, especially in low-income countries. Advances in diagnosis and treatment have been made, but new vaccines and drugs are needed to achieve the goal of the End TB Strategy by 2035.

Neuroblastoma is a neuroendocrine tumour that arises in the developing sympathetic nervous system and is the most common malignancy diagnosed in the first year of life. This Primer by Matthay et al. reviews the mechanisms, diagnosis and risk-stratified management of neuroblastoma.

Mitochondrial diseases are a group of genetic disorders that are characterized by mutations in nuclear or mitochondrial DNA. This Primer discusses the mechanisms underlying the development of mitochondrial diseases, in addition to the diagnosis, prevention and management of these disorders.

Psoriasis is a chronic, immune-mediated disease that can severely affect patient quality of life. Various kinds of skin manifestations are possible; psoriatic arthritis is a common but underdiagnosed comorbidity. Treatments for psoriasis include topical agents, phototherapy and systemic and biologic agents.

Traumatic brain injuries (TBIs) result from an external force and can result in a range of clinical manifestations and neuropathological changes, many of which are only beginning to be understood. Here, the authors argue that the cellular and molecular processes involved in TBIs of different severities are probably similar, just to different degrees.

Virtually all cervical cancers, a large fraction of other anogenital cancers and an increasing proportion of oropharyngeal cancers are caused by human papillomavirus (HPV) infection. Here, the authors describe HPV-driven carcinogenesis and discuss how developments in vaccines and screening tests could dramatically alter the landscape of HPV-related cancers worldwide.

Hookworm infection is a major neglected tropical disease that causes substantial disability and iron deficiency anaemia in at-risk populations. However, the ability of hookworms to regulate the host's inflammation to its advantage could prove useful in the treatment of autoimmune and allergic diseases.

Lyme borreliosis is a tick-borne disease that is caused by the bacteria Borrelia burgdorferi, Borrelia afzelii and Borrelia garinii. This Primer by Steere and colleagues discusses the epidemiology, mechanisms and management of Lyme borreliosis in North America and Europe.

Sheehan syndrome refers to postpartum hypopituitarism caused by necrosis of the pituitary gland as a consequence of severe hypotension owing to uterine bleeding during or soon after childbirth. In this Primer, Kelestimur and colleagues describe the epidemiology, mechanisms, diagnosis and treatment options of Sheehan syndrome.

IgA nephropathy is a common glomerulonephritis that is probably triggered by the aberrant glycosylation of IgA1, which is recognized as an autoantigen. This PrimeView highlights the plausible mechanisms underlying the disease, as well as how patients are managed.

Erectile dysfunction is the inability to achieve or maintain an erection for satifactory sexual performance, which as a considerable impact on quality of life. This PrimeView highlights the treatment options for this condition.

Calcific aortic stenosis (AS) results from the thickening and calcification of valve leaflets and subsequent obstruction of blood-flow across the aortic valve This PrimeView highlights the management of AS, for which the only treatment is aortic valve replacement.

This PrimeView highlights the surgical interventions to treat kidney stones, which can develop when the urine becomes supersaturated with respect to a given mineral.

Cerebral palsy is a clinical description of children and adults who share features of motor dysfunction as a consequence of a non-progressive brain injury. This PrimeView focuses on the heterogeneous presentation of the movement disorder, depending on the location of the brain injury.

A single episode or repeated episodes of acute rheumatic fever can severely damage the heart valves, leading to rheumatic heart disease — a chronic condition that can cause heart failure. This PrimeView highlights that these conditions are most common in developing countries and are strongly related to socioeconomic disadvantage.

Patent foramen ovale (PFO) is the consequence of failed closure of the foramen ovale, a normal structure that is present in the fetus to direct blood flow directly from the right to the left atrium, bypassing the pulmonary circulation.

Post-transplant lymphoproliferative disorders (PTLDs) show some similarities with classic lymphomas in the general population, but occur only in immunosuppressed individuals following transplantation. This PrimeView highlights the involvement of Epstein–Barr Virus infection as an aetiological trigger in many PTLDs.

Acute myeloid leukaemia is a malignant disorder that leads to an expansion of immature myeloid precursors at the expense of their differentiated counterparts. This PrimeView highlights how the disease can occur at all ages, but predominantly affects the elderly (>60 years of age).

One-third of people with diabetes develop diabetic retinopathy (DR). This PrimeView focuses on the pathophysiology of the different stages of DR, ranging from mild to severe non-proliferative DR and proliferative DR, with or without diabetic macular oedema.

Irritable bowel syndrome is a gastrointestinal disorder that can be mild in some patients, but debilitating in others. This PrimeView focuses on the complex aetiology and current understanding of the molecular pathophysiology, involving intestinal permeability, microbiota, inflammation and visceral sensitivity, among other factors.

Atrial fibrillation results from the disorganized propagation of electrical impulses in the heart. The subsequent ineffective pumping of blood increases the risk of coagulation and thrombosis, and stroke prevention is therefore the most important management priority for these patients.

Common risk factors for developing hepatocellular carcinoma (HCC) include cirrhosis, excessive alcohol consumption and viral hepatitis. This PrimeView highlights the management of HCC, for which there is only one systemic therapy and front-line treatment remains liver transplantation.

Clostridium difficile infection is an increasingly common infective healthcare-associated diarrhoea. This PrimeView highlights how the bacterium causes disease, which typically emerges after antibiotic-mediated dysbiosis of the gut.

This PrimeView highlights the interplay between genetic mutations, signalling pathway aberrations, microenvironmental disturbances and metabolic reprogramming that underlie the development of pancreatic cancer.

10–20% of adults will develop gallstones in their lifetime, and >20% of those will develop symptoms or complications. This PrimeView focuses on the most common risk factors, which include genetics, ethnicity, sex, age, drugs, parasites, overnutrition and pregnancy.

Meniere's disease is a multifactorial disorder of the inner ear. This PrimeView highlights its common symptoms including tinnitus (continuous ringing noise), aural fullness (feeling of pressure in the ear), vertigo (a spinning sensation) and fluctuating hearing loss.

Benign prostatic hyperplasia, in which the prostate gland becomes enlarged, is a major cause of lower urinary tract symptoms in ageing men. This PrimeView highlights the available treatment options for this condition.

Primary hyperparathyroidism (PHPT) is a common disorder characterized by an excessive secretion of parathyroid hormone. This PrimeView accompanies the Primer by Bilezikian and colleagues and shows that PHPT can be caused by a single benign adenoma, multiglandular disease and parathyroid carcinoma.

This PrimeView highlights the mechanisms underlying tuberous sclerosis complex (TSC), a lifelong chronic disease caused by mutations in either TSC1 or TSC2. These mutations lead to signalling changes that promote the growth of benign tumours in various organs.

Disseminated intravascular coagulation (DIC) is a medical emergency that can be caused by infectious or non-infectious conditions. The mechanisms underlying DIC — highlighted in this PrimeView — are an imbalance in the factors that control haemostasis.

Systemic lupus erythematosus (SLE) is a potentially fatal, chronic autoimmune disorder. This PrimeView illustrates that SLE is heterogeneous with considerable variability in clinical manifestations and disease severity. Early diagnosis and prevention of flares is important to reduce long-term morbidity and mortality.

This PrimeView highlights the pathophysiology of acute-on-chronic liver failure in cirrhosis. In patients with cirrhosis, triggers of inflammation, such as sepsis and alcoholic hepatitis, can cause acute liver decompensation and organ failure, resulting in high short-term mortality.

Uterine fibroids are common neoplasms of the uterus and can cause heavy or prolonged menstrual bleeding, as well as pain and urinary and gastrointestinal problems. This PrimeView focuses on the mechanisms underlying the development of uterine fibroids.

This PrimeView highlights the three main components of managing patients with sepsis: infection control, haemodynamic stabilization and modulation of the septic response.

Sjögren syndrome (SjS) is an autoimmune disease that is characterized by the development of sicca symptoms and, in some patients, systemic disease. This PrimeView focuses on the aetiopathogenetic mechanisms of SjS and also discusses the epidemiology, diagnosis and management of this disease.

Measles is caused by a highly infectious, airborne pathogen: measles virus. This PrimeView focuses on the transmission of this virus and explains how cheap and safe vaccines can be used to prevent transmission and eliminate measles globally.

This PrimeView highlights the mechanisms of α1-antitrypsin deficiency (A1ATD), an inherited disorder caused by mutations in SERPINA1. A1ATD leads to liver and lung disease and can be associated with substantial morbidity and increased mortality.

Aortic dissection is a medical emergency that requires prompt diagnosis and treatment to ensure patient survival. This PrimeView highlights the mechanisms and risk factors that contribute to aortic dissection, including hypertension, connective tissue disorders, inflammation and atherosclerosis.

Dengue is caused by infection with any of the four dengue virus serotypes. This PrimeView highlights the mechanisms underlying the clinical course of a dengue infection, which can range from mild febrile illness through to haemorrhagic fever and circulatory shock.

Polycystic ovary syndrome (PCOS) affects 5–20% of women of reproductive age. This PrimeView focuses on the complex aetiologies and interplay between mechanisms that result in and perpetuate the clinical features of PCOS, including hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology.

This PrimeView highlights the pathophysiology of infective endocarditis (IE), which results from infection usually bacterial of the endocardial surface of the heart. IE can have cardiac, pulmonary, renal and neurovascular manifestations, among others.

This PrimeView highlights the genetic alterations that are associated with the development of ovarian cancer, including genes that have a role in homologous recombination and DNA mismatch repair.

Otitis media (OM) or inflammation of the middle ear is an umbrella term that encapsulates acute OM, OM with effusion and chronic suppurative OM. This PrimeView focuses on the diagnosis of OM, which mainly depends on clinical signs and symptoms, accompanied by diagnostic modalities.

This PrimeView highlights the diagnostic criteria for major depressive disorder, a psychiatric condition that is characterized by persistent depressed mood, diminished interests, impaired cognitive function and vegetative symptoms.

This PrimeView highlights the mechanisms underlying the development of primary open-angle glaucoma, an optic neuropathy that is characterized by deformation of the optic nerve head and visual impairment.

Osteoporosis, which is characterized by low bone mass and micro-architectural deterioration of bone tissue, increases bone fragility and the risk of fractures. Half of women >50 years of age will experience an osteoporotic bone fracture during their lifetime, which has a considerable impact on quality of life.

Osteoarthritis (OA) is a joint disorder that results from a combination of risk factors, of which increasing age and obesity are the most important. This PrimeView focuses on the epidemiology, mechanisms, diagnosis and management of OA.

Community-acquired bacterial meningitis is an inflammation of the meninges and a medical emergency. This PrimeView focuses on its mechanisms, following the bacteria as they infect the host, migrate to the bloodstream and infiltrate the cerebrospinal fluid.

This PrimeView highlights the complex nature of Mycobacterium tuberculosis infection; it can remain latent and asymptomatic in the lungs or progress to active tuberculosis disease, which requires prolonged treatment with multiple antibiotics and has high morbidity and mortality in high-burden, resource-poor settings.

Neuroblastoma is a neuroendocrine tumour of early childhood and results in tumours in the adrenal glands and/or sympathetic ganglia. This PrimeView focuses on the diagnosis of neuroblastoma, which encompasses laboratory tests, radiographic imaging and tumour biopsy.

This PrimeView focuses on the mechanisms underlying the development of mitochondrial diseases, a group of genetic disorders caused by mutations in the mitochondrial or nuclear genomes that encode proteins involved in mitochondrial function.

Psoriasis is a chronic, immune-mediated disease characterized by cutaneous manifestations (often red, scaly plaques) and rheumatological complications (psoriatic arthritis). This PrimeView highlights the pathological mechanisms that lead to psoriatic lesions, in particular, the altered immune responses.

Traumatic brain injuries (TBIs) can affect people of all ages and are a major cause of disability and death worldwide. The mechanisms of TBIs, including axonal injury, inflammation and vascular disturbances, are highlighted in this PrimeView.

This PrimeView on carcinogenic human papillomavirus (HPV) infection highlights the need for more reliable tests and strategies to predict cancer risk of a given HPV lesion.

Hookworms are soil-transmitted human parasites that can survive and multiply in the small intestine for years. This PrimeView illustrates how hookworms feed on the host's blood and focuses on their complex interactions with the host's immune system and commensal microbiota.

Lyme borreliosis is a tick-borne disease, caused by three genospecies of Borrelia burgdorferi sensu lato, that can cause a distinctive skin lesion, and neurological and cardiovascular symptoms. This PrimeView focuses on the epidemiology of Lyme borreliosis.

Sheehan syndrome or postpartum hypopituitarism is a condition characterized by hypopituitarism due to necrosis of the pituitary gland. The initial insult is caused by massive postpartum haemorrhage, leading to impaired blood supply to the pituitary gland, which has become enlarged during pregnancy.