Nature Reviews Disease Primers最新文献

Podocytopathies are glomerular diseases caused by initial podocyte injury or dysfunction that lead to proteinuria and often nephrotic syndrome. The term encompasses characteristic histological patterns, most commonly focal segmental glomerulosclerosis, minimal changes, membranous nephropathy, diffuse mesangial sclerosis and collapsing glomerulopathy. However, proteinuria of glomerular origin is frequently managed without biopsy; importantly, when the protein loss is mostly albumin, it is a direct readout of podocyte injury and a strong predictor of cardiovascular events, kidney failure and reduced survival. Patients present with oedema and volume disturbances and are at risk of thromboembolism, serious infections and progressive kidney dysfunction. Aetiologically, podocytopathies arise from autoimmune, genetic, mechanical (hyperfiltration), infectious, toxic or monoclonal mechanisms, which may coexist and vary by age; this unifying, mechanism-based view bridges the historically divergent paediatric (response-based) and adult (histology-based) classifications. Diagnosis integrates clinical features with emerging serology for podocyte-directed autoantibodies, targeted genetic testing and kidney biopsy when required. Diagnostic workup has to delineate the causes of podocyte dysfunction. Management combines supportive care with aetiology-guided therapy aimed at minimizing steroid exposure and preventing relapses. Current advances in the field and their effects on diagnostic and therapeutic algorithms open the path towards personalized use of traditional treatments and newly available drugs, which should improve outcomes and quality of life for patients with podocytopathies.

Vitiligo is an acquired autoimmune depigmenting disorder that affects approximately 0.36% of the global population and presents in three forms based on lesion distribution: non-segmental, segmental and mixed vitiligo. Beyond its visible impact on the skin, vitiligo deeply affects mental well-being and quality of life. The pathogenesis of non-segmental vitiligo is influenced by genetic polymorphisms that are linked to immune response and melanogenesis pathways, whereas environmental factors contribute to disease onset. Diagnosis is generally clinical, with laboratory tests or biopsies rarely required. Melanocyte loss involves mechanisms, such as cellular stress, innate immune activation and adaptive immune responses, that specifically target melanocytes, with a central role for tissue-resident memory T cells. This cascade ultimately leads to the depletion of epidermal melanocytes and impairs melanocyte stem cell regeneration. Clinical management emphasizes shared decision-making with three primary objectives: halting depigmentation, initiating repigmentation and sustaining pigment restoration. Signs of active disease help clinicians to identify patients in need of intervention. Treatments approved in the past 2 years offer potential for reversing disease progression, and emerging therapies targeting key pathways to modulate immune activation and stimulate melanocyte regeneration and differentiation are being tested in clinical trials.

Schizophrenia is a challenging and diverse mental health condition with a lifetime prevalence of 0.4%. Schizophrenia usually manifests in late adolescence or early adulthood and is associated with high disability and a reduced life expectancy. Risk factors include genetic predisposition, prenatal and birth complications, infections and immune dysfunction, and cannabis use as well as psychosocial factors such as childhood trauma or migration. The first psychotic episode is often preceded by a long prodromal phase that can last for several years. No markers are yet available for clinical use that allow prediction of disease development or a diagnosis to be established. A leading theory postulates that excitatory-inhibitory (that is, glutamate-GABA) imbalance in the cortex ultimately leads to dysfunction of the dopaminergic system. Schizophrenia is a heterogeneous disease with different manifestations, including psychotic symptoms as well as negative symptoms and global cognitive deficit, that do not respond to antipsychotic drugs, making management very difficult. Pharmacological treatment coupled with psychotherapeutic interventions, such as cognitive behavioural therapy, cognitive remediation and psychoeducation, remains the mainstay of treatment; however, treatment resistance is frequent. The first medication that targets neurotransmitter systems other than dopamine has been approved for use. Current attempts to use virtual reality and avatars to improve psychotic symptoms and smartphone applications to prevent relapses seem promising.

Leishmaniasis is an endemic disease in Asia, Africa, the Americas and Southern Europe caused by Leishmania parasites and transmitted through the bite of female sandflies, resulting in Leishmania replication in macrophages. The condition manifests either as visceral leishmaniasis, a potentially fatal systemic disease that causes persistent fever, enlargement of the liver and spleen (hepatosplenomegaly), and a reduction in almost all blood cells (pancytopenia), or as cutaneous leishmaniasis, characterized by ulcerative or non-ulcerative skin lesions. Disease manifestation and severity are determined by parasite, host and vector characteristics, with a complex immunological interplay. The rK39 rapid diagnostic test is the primary diagnostic method for visceral leishmaniasis, while cutaneous leishmaniasis is commonly diagnosed by microscopy of skin samples. Visceral leishmaniasis and severe forms of cutaneous leishmaniasis are managed by systemic treatment. For localized cutaneous leishmaniasis, treatment involves topical therapies, including cryotherapy, thermotherapy and/or intralesional injections with antimonials. The WHO 2021-2030 roadmap of neglected tropical diseases aims to eliminate visceral leishmaniasis as a public health problem and to achieve enhanced control of cutaneous leishmaniasis. In South Asia, a regional visceral leishmaniasis programme has dramatically reduced the caseload. Eastern Africa has recently launched a similar initiative. Sustainable progress in the control and elimination of leishmaniasis will require better diagnostics, treatment and vector control interventions as well as progress in vaccine development, political commitment, improved surveillance and healthcare services.

The appendix is a small, worm-like diverticulum of the caecum, potentially having a role in regulating intestinal microbiota and immunology. Inflammation of the appendix, acute appendicitis, is one of the most common reasons for acute abdominal pain in children and adults and surgical emergency visits worldwide. The pathophysiology of appendicitis is still poorly understood. During the past decade, evidence has overturned the long-lasting dogma that all appendicitis cases have a clinical course inevitably progressing to perforation and life-threatening peritonitis unless operated upon in a timely manner. Instead, this natural course occurs only in a smaller proportion of patients, for whom emergency appendectomy remains mandatory. Advances in diagnostic accuracy following utilization of clinical scoring systems and imaging has enabled more accurate pre-interventional assessment of appendicitis disease severity. While some patients still require urgent surgery, the majority can be treated successfully with antibiotics, and in some the disease has even been shown to resolve spontaneously. This has confirmed the notion of at least two different forms of appendicitis: non-perforating and perforating, often referred to as uncomplicated and complicated appendicitis. Unified definitions of these forms are still undergoing rigorous research and debate, hampering both comparison of different studies and the establishment of unified treatment guidelines. The current knowledge on the safe and effective outcomes of non-operative treatment alternatives has further underlined the need for standardized uniform definitions of appendicitis severity and assessment of the success of two fundamentally different treatment options.