INTRODUCTION:Therapeutic apheresis (TA) is an important treatment for certain conditions. TA refers to various procedures in which either plasma (plasmapheresis) or specific blood cell fractions (cyta-pheresis) are removed. These include, among others, extracorporeal photopheresis (EP), erythrocytapheresis (EA), therapeutic plasma exchange (TPE), and therapeutic erythrocyte exchange (TEE). The indications for these procedures in specific diseases are published by the American Society for Apheresis (ASFA) as well as by hematology societies such as the American Society of Hematology (ASH) and the British Society of Haematology (BSH). There are only a few indications for therapeutic apheresis as first-line therapy for hematologic diseases, either as primary treatment or in combination with other therapies, for which strong evidence (Grade 1A-1C) exists. These indications include TPE for symptomatic hyperviscosity syndrome, hyperviscosity syndrome prophylaxis during rituximab therapy for Waldenström's macroglobulinemia, TEE for acute complications of sickle cell disease such as stroke and for the prophylaxis of such events, as well as the use of TPE for thrombotic thrombocytopenic purpura. Less well-known indications with strong evidence include the treatment of erythrocytosis in polycythemia vera and the treatment of iron overload in hereditary hemochromatosis using EA. Similarly, EP is an established treatment option for mycosis fungoides and Sézary syndrome. The aim of this paper is to summarize these indications.
INTRODUCTION:Immune checkpoint inhibitors have fundamentally transformed the treatment of numerous malignant diseases and are now part of standard therapy plans across many tumor entities. With their increasing use, physicians outside specialized oncology centres are more frequently confronted with immune-related adverse events. These adverse events result from enhanced immune activity and can, in principle, affect any organ system. The clinical presentation is often non-specific and ranges from mild symptoms to potentially life-threatening conditions. Moreover, immune-related adverse events may occur not only during treatment but also with a delayed onset after therapy has been disconti-nued. In clinical practice, the early recognition of immune-related adverse events represents a key challenge, particularly in general practice and internal medicine settings. This review provides an overview of the pathophysiology, typical clinical manifestations, and important warning signs of immune-related adverse events. Its aim is to raise awareness of these complications and to promote timely referral for specialized evaluation.
INTRODUCTION:Historically, the discovery of new pharmaceutical therapies has constituted a lengthy and cost-intensive process. Between the initial identification of a drug candidate and successful regulatory approval, 10 to 15 years commonly elapse, with development costs reaching the order of billions of dollars. Research activities, which are still largely empirical in nature, are frequently marked by setbacks, for example due to toxicological findings or insufficient efficacy in preclinical disease models. Technological breakthroughs, such as the sequencing of the human genome, have given rise to largely unmet expectations that medicines could be developed more rapidly and efficiently. Accordingly, expectations for the application of artificial intelligence (AI) in pharmaceutical research and development are high. Indeed, workflows in the preclinical phase are currently being fundamentally transformed by AI. In the following, the individual stages of preclinical research are analysed, and the potential applications of AI are described. In addition, selected critical aspects are discussed to realistically contextualize expectations regarding AI. As a result of the integration of AI, both preclinical and clinical research are undergoing profound transformation. There is justified hope that effective and safe therapies can finally be developed more rapidly and cost-efficiently.
INTRODUCTION:Drug development is undergoing profound change. Accelerated regulatory processes, gene and cell therapies, the use of artificial intelligence, and the increasing use of real-world evidence are fundamentally transforming the pharmaceutical innovation system. These developments offer patients faster access to effective therapies, but at the same time raise significant ethical and regulatory questions: How can the protection of trial participants be reconciled with the desire for rapid innovation transfer? How can an evidence-based risk-benefit assessment be successful when pivotal trials are small and short? What mechanisms ensure the equitable distribution of high-cost therapies in a solidarity-based healthcare system such as Switzerland's? This overview outlines the key trends and provides guidance for practising doctors on the use of innovative medicines.
INTRODUCTION:This review summarizes the immunologic approach to systemic sarcoidosis and presents the use of novel, targeted therapies such as TNF-alpha inhibitors and Janus kinase (JAK) inhibitors. Sarcoidosis is a granulomatous multisystem disease with diverse clinical manifestations that requires differentiated diagnostic and therapeutic strategies. The recommendations presented here are based on extensive clinical experience and expert opinion from the certified sarcoidosis center of excellence at University Hospital Zurich. The article provides an overview of immunopathogenesis, immunoserologic and imaging diagnostic pathways, as well as an evaluation of established and novel therapeutic concepts. Practical guidance for the use of TNF-alpha and JAK inhibitors, for adverse effect management, and for therapy escalation is presented. A focus is also placed on the indication for consultation in difficult cases to support primary care physicians in the effective and individually tailored care of patients with systemic sarcoidosis.
INTRODUCTION:Melanoma arises from malignant transformation of melanocytes and accounts for approximately 3500 new cases per year in Switzerland. The most important risk factors include intermittent UV exposure, fair skin, a high number of nevi, five or more atypical nevi, and a positive family history. The most common type is the superficial spreading melanoma, followed by the nodular type. Diagnosis is primarily clinical, for example using the ABCDE rule, and is supported by dermoscopy performed by dermatologists. If there is a suspicion, a narrow complete excision should be performed to confirm the diagnosis. Treatment options have improved drastically over the years, so nowadays there are indeed good chances of cure, even in a metastatic setting. Immunotherapy as well as targeted therapies have led to major breakthroughs. While adjuvant or neoadjuvant therapy is recommended in earlier stages of disease, PD-1 blockage plays a central role in metastatic disease, preferably in combination with anti-CTLA-4-antibody or, according to more recent data, with an anti-LAG-3-antibody. Targeted therapy also has an established role today in treatment, both in the adjuvant and curative settings. After successful treatment, regular follow-ups should be performed to detect relapses at an early stage.
INTRODUCTION:Myocarditis and pericarditis represent a broad spectrum of inflammatory heart diseases and are important differential diagnoses in patients presenting with chest pain, heart failure, or arrhythmias. Diagnosis is often challenging due to non-specific clinical presentation and biomarkers. Growing recognition of the clinical relevance of myocardial inflammation, together with accumulating evidence, has led to increased scientific and clinical attention. This is reflected in emerging concepts such as the introduction of the new term "inflammatory myocardial syndrome (IMPS)" in the recently published guidelines of the European Society of Cardiology (ESC). Notably, these are the first ESC guidelines to cover the full spectrum of inflammatory diseases of the myocardium and pericardium - marking an important paradigm shift in the field. Current ESC guidelines highlight the central role of multimodality cardiac imaging in the evaluation of myocardial inflammation. While echocardiography serves as a first-line tool, cardiac magnetic resonance imaging (CMR) is considered the non-invasive gold standard for tissue characterization. Nuclear imaging techniques such as positron emission tomography (PET) are increasingly relevant, particularly in specific entities such as cardiac sarcoidosis. This review highlights the practical role of multimodality imaging in the diagnostic work-up of myocardial inflammation, with emphasis on clinically relevant decision-making.
INTRODUCTION:Sudden cardiac death (SCD) in athletes is usually the result of an undetected underlying heart disease, with physical exertion acting as the trigger. Commotio cordis is a rare cause of SCD. In young athletes, genetically determined cardiomyopathies predominate, while in older athletes coronary artery disease remains the most important differential diagnosis. Regular screening programs - consisting of medical history, physical examination, and resting ECG - can detect over 90 % of relevant conditions, particularly when international ECG criteria are applied correctly. However, these assessments are not always sufficient, as some pathologies may manifest later in life and/or require additional diagnostic tests to be recognized. The main task of screening athletes is to distinguish physiological adaptations of the athlete's heart from pathological changes. Echocardiography, MRI, and CT play a central role here.
INTRODUCTION:Cardiac amyloidosis and cardiac sarcoidosis can be classified as infiltrative cardiomyopathies. Although the aetiology and underlying pathophysiology of these two conditions differ substantially, imaging techniques are becoming increasingly important for both. Only a decade ago myocardial biopsy used to be essential for establishing the diagnosis, contemporary diagnostic algorithms for both diseases now rely predominantly on non-invasive cardiac imaging, enabling not only accurate diagnosis but also guiding therapeutic decision-making. In this review, we aim to highlight the respective strengths and limitations of the available cardiac imaging modalities as they relate to these disorders. Particular emphasis will be placed on disease detection and the differential diagnosis between amyloidosis and sarcoidosis, and its value for prognostic assessment. Where appropriate, we will also discuss recent advances in multimodality imaging and how they have reshaped clinical pathways and management strategies.
INTRODUCTION:Coronary angiography has evolved from the first cardiac catheterization performed by Werner Forssmann into a highly precise imaging modality of the coronary arteries. Modern techniques such as intravascular ultrasound, optical coherence tomography, and physiological measurements including FFR and iFR enable combined structural and functional assessment of coronary stenoses. At the same time, non-invasive coronary computed tomography, particularly with photon-counting technology, is gaining importance for diagnosis and procedural planning. Cardiovascular imaging is therefore becoming central to personalized management of coronary artery disease.
INTRODUCTION:Artificial intelligence (AI) has rapidly gained importance in medicine over recent years, particularly in medical imaging. AI is transforming cardiac imaging along the entire workflow - from image acquisition and reconstruction to interpretation and diagnosis. In echocardio-graphy, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine, AI systems have the potential to automatically capture and standardize measurements, reduce noise and artifacts, shorten acquisition and analysis times, and improve reproducibility. Applications range from real-time automated analysis of transthoracic echocardiograms and CT-based calcium scoring and plaque quantification to the detection of rare coronary anomalies, AI-assisted MRI planning and the identification of subtle pathological patterns of cardiac amyloidosis. In the future, multimodal AI models combining imaging, clinical, laboratory, and genetic data will enable highly precise risk stratification and individualized therapies. However, challenges remain in terms of generalizability, prospective validation, explainability, and integration into real-world workflows. Clinical validation, quality control, and physician oversight remain essential cornerstones for the responsible use of AI in cardiac imaging.
INTRODUCTION:Coronary artery disease (CAD) remains one of the leading causes of morbidity and mortality worldwide. Accurate, patient-centered, and efficient diagnostic strategies are therefore essential. Beyond clinical history, physical examination, and laboratory testing, cardiac imaging has become increasingly central to both diagnostic evaluation and risk stratification. In recent years, non-invasive imaging modalities for CAD have undergone remarkable technological and methodological advancements. They now play a pivotal role in confirming or excluding obstructive CAD, assessing the functional significance of coronary stenoses, and supporting individualized treatment decision-making. Selecting the most appropriate imaging modality is thus crucial for achieving diagnostic precision and optimal patient management. This article provides a comprehensive overview of the currently available non-invasive imaging techniques, highlights their respective strengths and limitations, and offers practical guidance on choosing the most suitable modality for different patient groups. Particular emphasis is placed on their application in routine clinical practice in Switzerland.
INTRODUCTION:Valvular heart disease is common in an aging population and is associated with substantial morbidity and mortality. Modern cardiovascular imaging is central to diagnosis, therapeutic decision-making, and longitudinal follow-up of aortic, mitral, and tricuspid valve disease throughout the entire care pathway - from initial evaluation to specialized intervention. Transthoracic echocardiography (TTE) remains the first-line modality for initial diagnosis and follow-up assessment. Transesophageal echocardiography (TEE) provides detailed morphological evaluation of the valves and is indispensable for surgical and interventional planning, particularly of the atrioventricular valves. Cardiac CT is the current standard for planning transcatheter aortic valve implantation (TAVI) and is gaining importance in percutaneous mitral and tricuspid valve replacement, including simulation-based planning and risk assessment. Cardiac MRI contributes primarily to precise volume quantification and the assessment of ventricular function and myocardial structure. Peri-interventional TEE has become an essential real-time guidance tool in the catheter laboratory, enabling precise device navigation and immediate evaluation of procedural success. The targeted use of complementary imaging modalities is crucial for accurate assessment of valvular pathology, optimal planning and guidance of interventions, and long-term patient follow-up. Imaging is therefore not merely a diagnostic aid but the foundation of modern, increasingly catheter-based valve therapy.
INTRODUCTION:Heart failure is clinical syndrome with many different underlying cardiac diseases. The definition of heart failure includes the presence of typical symptoms and the proof of a structural cardiac abnormality, which is responsible for a reduced cardiac output and/or elevated cardiac filling pressures at rest or on exertion. The identification and exact description of the main mechanism of heart failure is key for the introduction of an appropriate treatment, which when appropriately selected improves symptoms and prognosis. In patients with suspected heart failure, a basic assessment including history, physical examination, ECG, measurement of natriuretic peptides, and a comprehensive transthoracic echocardiogram should always be performed. Based on the finding of this initial assessment additional imaging modalities are selected on a case-to-case basis. In this review, we discuss the role of advanced echocardiography techniques, cardiac magnetic resonance imaging, computed tomography, cardiac catheterization and nuclear medicine examinations in this context.
INTRODUCTION:The effect of a (neuro-)psychopharmacological drug is determined by its interaction with its target structure in the brain (pharmacodynamics). A number of pharmacokinetic factors determine whether a drug is capable of reaching its site of action in a sufficient concentration. The concentration of the active compound can be significantly affected by its metabolism, which is genetically determined in each individual (known as the pharmacokinetic genotype), and by potential interactions with other prescribed drugs (known as the pharmacokinetic phenotype). For example, changes in drug metabolism inevitably lead to changes in the concentration of active compounds and thus to changes in the exposure of the drug. Therapeutic drug monitoring (TDM) is a tool for individualized pharmacotherapy that helps to optimize pharmacological treatment. On the one hand, TDM helps to detect deviations from expected drug concentrations and individualize treatment by adjusting doses. On the other hand, looking at the ratio of the parent compound and its metabolite (known as the metabolic ratio) helps to identify any abnormalities or peculiarities in drug metabolism supporting dose adjustments. This article provides a clinically oriented overview of how changes in drug metabolism can lead to treatment failure and which tools can be used to optimize treatment.
INTRODUCTION:Depressive syndromes are among the most common mental conditions in primary care. They are associated with high morbidity and relevantly reduced quality of life. General practitioners (GPs) play a central role in early detecting and diagnosing depression as well as in initial treatment. This paper summarises the new Swiss treatment recommendations and gives an overview of evidence-based treatment algorithms with a focus on applicability in primary care. Diagnosis is based on core symptoms of depression. In addition to a structured anamnesis, validated instruments for screening and development of symptoms should be used. Further, somatic causes should be excluded using basic laboratory tests and, if indicated, neuroimaging. Treatment depends on the severity of depression: In mild depression, active monitoring, low-intensity interventions (e. g. self-help strategies, activation, sleep and circadian strategies, physical activity, etc.) and psychotherapy are indicated. In moderate episodes, psychotherapy or antidepressants are indicated; severe episodes require a combination of psychotherapy and antidepressants. First-line antidepressants are SSRIs and SNRIs and other modern antidepressants. In case of non-response, a combination of antidepressants or augmentation with atypical antipsychotics or Lithium is recommended. Psychotherapy has proven efficacy across all severity levels, and it should be combined with antidepressants in severe episodes. In severe, psychotic and difficult to treat depressive episodes, strategies from the field of interventional psychiatry (ECT, rTMS, Esketamine) are effective. Complementary approaches such as physical activity/exercise, light therapy, or social therapy further enhance treatment outcomes. In conclusion, guideline-based multimodal care for patients starting in primary care improves outcome and prognosis for patients with depression and can reduce the risk of chronification and relapses. Key elements are structured diagnostics, early initiation of evidence-based therapy with regular valid monitoring within a strong doctor-patient-relationship.
