Key Advances in Medicine 2018

In 2017, a cluster of papers have provided strong evidence in favour of the inflammation hypothesis in cardiovascular disease. From fundamental observations on clonal haematopoiesis to clinical evidence indicating that blocking an inflammatory cytokine mitigates heart disease, 2017 has been a watershed year.

Important milestones in cardiac regenerative medicine that will define future research were reached in 2017: demonstration of adult cardiomyocyte renewal capacity, recognition of the importance of the extracellular matrix and the higher regenerative efficacy of repetitive dose protocols, and the publication of human data supporting paracrine effects of stem cell therapies and guidelines from TACTICS, the first international alliance on cardiac regenerative medicine.

In 2017, several high-impact studies in thrombosis were published. Refinements were made in the optimal therapy for patients with stable atherosclerosis or with atrial fibrillation undergoing percutaneous coronary intervention. Risk scores to determine duration of antiplatelet therapy were developed. The potential risk of subclinical valve leaflet thrombosis was identified.

In 2017, three groundbreaking immunotherapies for relapsed and/or refractory B-cell acute lymphoblastic leukaemia (ALL) were approved based on impressive outcomes observed in clinical trials. Additional breakthroughs included seminal research into ALL genomics and the importance of adherence to chemotherapy, which will have direct implications for clinical care.

In 2017, major advances in the treatment of non-small-cell lung cancer (NSCLC) continued to emanate from the fields of molecularly targeted therapy and immunotherapy. In the former, new drugs with improved efficacy and reduced toxicity entered the clinic; in the latter, immune-checkpoint inhibition proved efficacious after chemoradiotherapy for stage III disease, but had disparate results in the frontline treatment of stage IV disease.

2017 saw the publication of clinical trial data and the approval of new treatment approaches for metastatic urothelial carcinoma. Pembrolizumab is now a well-established treatment for patients with disease progression after cisplatin, with high-level evidence supporting its superiority over second-line chemotherapy. For patients ineligible for cisplatin, atezolizumab and pembrolizumab provide meaningful clinical benefit as frontline therapies.

Research on dyslipidaemias in 2017 reaffirmed the central role of reducing the levels of atherogenic apolipoprotein B-containing lipoproteins, predominantly LDL, in preventing ischaemic cardiovascular events. However, whether increasing HDL-cholesterol levels in isolation can reduce cardiovascular risk remains to be determined.

In 2017, genetic research on cardiovascular disease (CVD) produced seemingly paradoxical findings. Thanks to the continuous upscaling of genotyping and sequencing data, researchers have discovered that whereas numerous genetic variants among the general population can increase CVD risk, an individual can tolerate most severe genetic alterations.

The past year provided strong evidence on the use of the instantaneous wave-free ratio to determine the severity of coronary artery disease, the improving outcomes of contemporary percutaneous coronary intervention, the increased risk of thrombosis with bioresorbable vascular scaffolds, and the benefits of a simple revascularization strategy in cardiogenic shock.

In 2017, results from phase III trials demonstrated the impressive safety and efficacy of adjuvant targeted and immune therapies in patients with resectable stage III–IV melanoma, and raised questions about the surgical management of patients with microscopic sentinel-lymph-node metastases. For patients with unresectable disease, new overall survival data added to the debate about the relative benefits of single-agent anti-PD-1 versus combined anti-PD-1 and anti-CTLA-4 immunotherapy.

2017 has been full of new discoveries that will influence the treatment of colorectal cancer. In the adjuvant setting, 3 months of chemotherapy might now be considered a new standard of care. Various other new treatments and promising biomarkers have also become available that will improve survival outcomes and the quality of life of many patients with metastatic disease.

Data published in 2017 underscore the benefit of optimizing anti-HER2 therapy in early stage high-risk HER2-positive disease, and of capecitabine in patients with residual disease after optimal neoadjuvant therapy. In the advanced-stage setting, endocrine therapy combined with cyclin-dependent kinase 4/6 inhibitors, or olaparib could become the preferred option.

The risk of death from cardiovascular causes in people with type 2 diabetes mellitus remains around twice that in the general population, with heart failure a common event. In 2017, results from cardiovascular outcome trials in people with diabetes mellitus showed that some drugs have dual utility — reducing cardiovascular risk and improving glycaemic control.

Extracellular danger-associated molecular patterns signal to NOD-like receptors, but the exact signalling pathways remain unclear. The inflammasomes, a subgroup of these receptors, translate danger signals into inflammatory responses by maturing IL-1 and IL-18. In 2017, researchers reported novel functions of the mutual interaction between metabolism and the inflammasomes in health and disease.

The artificial pancreas — the automated closed-loop control of diabetes mellitus — made its first outpatient strides in 2011. In 2017, the results of long-term clinical trials on the artificial pancreas were published, the first hybrid commercial artificial pancreas system was approved and the artificial pancreas was tested under increasingly demanding conditions. Thus, artificial pancreas technology is here to stay.

2017 has witnessed key advances in knowledge about the metabolic capacities of the gut microbiota, enabling the progression of our understanding of the principles driving xenobiotic–bacteria–host interplay. This research paves the way for the long road towards personalized medicine and nutrition, which could be based on gut microbial metabolism.

In 2017, there have been substantial advances in our understanding of the immunological and endocrine mechanisms of disease progression in NAFLD, paving the way for novel therapeutic strategies.

2017 has witnessed major advances in gut stem cell and cancer stem cell research, delivering key insights into their regulation, more defined culture methods and novel stem cell markers that collectively drive us ever closer to breakthroughs for regenerative medicine and cancer treatment in the clinic.

Nutraceuticals are gaining legitimacy and their potential clinical role is expanding. Data from 2017 provides evidence for their possible use in type 2 diabetes mellitus, the metabolic syndrome, obesity, dyslipidaemia and osteoporosis. Ongoing high-quality research in this area might justify future selective implementation of nutraceuticals into general health practice.

Studies of rare growth disorders taken together with large-scale genetic studies of adult height variability have uncovered a large genetic network regulating childhood growth. Advances in technology and experimental model systems will help decipher the molecular mechanisms of this complex network and lead to novel treatment approaches for growth disorders.

High stromal cellularity in pancreatic cancer is an important factor for ineffective treatment and molecular studies. In 2017, major advancements were made in transcriptional characterization, treatment delivery and clinical regimes, raising hope for a breakthrough against this deadly disease.

The central studies published in 2017 address novel IBD therapeutic strategies and prediction of the future disease course or response to a distinct therapy. Together, these studies contribute to the understanding of the regulation of mucosal homeostasis and at the same time serve to develop novel personalized treatment algorithms in patients in whom a severe disease course can be predicted.

In 2017, the FDA approved regorafenib and nivolumab for the treatment of patients with hepatocellular carcinoma following prior sorafenib treatment, opening the door for an effective systemic second-line therapy in advanced disease. By contrast, the addition of sorafenib to transarterial chemoembolization with drug-eluting beads did not improve progression-free survival in the intermediate disease stage.

Studies of cellular energetics have revealed important roles of metabolic pathways in determining cell fate and response to injury. Insights from 2017 into the mechanisms underlying these pathways might identify therapeutic targets to minimize injury and promote repair.

2017 saw the emergence of a new era in renoprotective medicine for diabetic kidney disease with reports of promising renal outcomes with the sodium–glucose cotransporter 2 (SGLT2) inhibitors empagliflozin and canagliflozin from follow-up analyses of the EMPA-REG OUTCOME trial and the CANVAS Program, respectively, and with use of the glucagon-like peptide 1 (GLP1) agonist liraglutide in the LEADER trial.

New findings in 2017 enhanced our understanding of the mechanisms that regulate blood pressure. Key studies provided insights into immune mechanisms, the role of the gut microbiota, the adverse effects of perivascular fat and inflammation on the vasculature, and the contribution of rare variants in renin–angiotensin–aldosterone system genes to salt sensitivity.

In 2017, dramatic advances have been made in the treatment of motor neuron diseases. New therapies have been approved for spinal muscular atrophy and amyotrophic lateral sclerosis, and a host of other therapies that are currently under development are showing promising results.

2017 saw the publication of new classifications for epilepsy and seizure types, which emphasize the importance of understanding the underlying disease mechanisms. This aetiology-based approach is already beginning to inform developments in therapies and trial design in the epilepsies.

The past year saw advances in endovascular treatment for acute stroke, speech therapy for aphasia after stroke, and cardiac disease management to prevent stroke. These treatments were characterized by more intensive or more extensive effects than standard care, necessitating thoughtful translation of the clinical trial findings into routine clinical practice.

In 2017, progress was made in several aspects of immune-mediated kidney disease. Mechanistic studies provided new insights into the underlying signals that confer risk to, or protection from, immune pathways, whereas new approaches to the treatment of immunological kidney disease will hopefully translate into a move away from the use of toxic corticosteroids.

Technical advances in genome sequencing and association studies have yielded critical insights into the genetic architecture of kidney diseases. Here, I summarize four key studies from 2017 that deciphered the genetic basis of known and novel diseases and provided insights into the mechanisms of glomerular, developmental defects and manifestations of kidney disorders.

200 years after James Parkinson's An Essay on the Shaking Palsy, 2017 has seen important advances that are driving a shift towards a broader and more holistic understanding of Parkinson disease aetiology and progression. This shift might finally pave the way to entirely novel and more effective prevention and management strategies.

In 2017, extensive research into multiple sclerosis (MS) resulted in improved diagnostic criteria, development of biomarkers that enable monitoring of disease evolution and treatment response over time, and identification of novel genetic markers of disease susceptibility. In addition, 2017 saw the first successful clinical trials of remyelination strategies and treatments for progressive MS.

Multiple scientific fields pertaining to inflammation, including the fields of cardiovascular, infection and cancer research, are increasingly contributing to our understanding of rheumatoid arthritis (RA). In 2017, such research has helped develop our understanding of RA comorbidity, the link between RA pathogenesis and infection, and the effects of new therapies.

A large number of patients with osteoporosis are not receiving appropriate treatment, due in part to concerns regarding drug safety. Great progress has been made to address this crisis in therapy in 2017, including highlighting the patients' views, developing new therapies and treatment strategies and addressing these safety concerns.

The rarity, severity and complexity of paediatric rheumatic diseases make progress in treating these diseases a challenge. In 2017, a new series of recommendations for treatment, studies that unravel the complexity of juvenile idiopathic arthritis and clinical trials that tackle sight-threatening uveitis have helped to improve paediatric care.

Landmark papers published in 2017 have advanced our understanding of the molecular heterogeneity of urothelial cancer, provided insights into the genomic evolution of the disease in the context of metastasis and therapy, and established new treatment standards for patients with previously limited treatment options.

Treatment paradigms for advanced renal cell carcinoma (RCC) continue to be challenged and refined. Recent studies in metastatic RCC have demonstrated the efficacy of first-line cabozantinib and the safety and efficacy of dual checkpoint blockade; in the adjuvant setting, pazopanib failed to improve progression-free survival in high-risk localized RCC compared with placebo.

Major advances in the management of all stages of upper tract urothelial carcinoma have been made in 2017. Radical nephroureterectomy can be valuable in patients with metastatic disease and adjuvant platinum-based chemotherapy can improve outcomes in those with advanced disease. Kidney-sparing surgery with early follow-up ureterorenoscopy has shown benefit in patients with low-grade tumours. Avoiding unnecessary ureterorenoscopy might decrease intravesical tumour recurrence.

Tremendous progress has been made in the identification of rheumatoid arthritis (RA) risk factors in 2017. The results of epidemiological studies highlighted dietary and hormonal factors that are associated with slowing the transition from one preclinical phase of RA to another, potentially protecting individuals from developing RA.

Osteoarthritis research in 2017 provided new insights into the long-term effects of intra-articular glucocorticoids, and also led to the approval of a novel, longer-lasting glucocorticoid formulation. New drugs for the treatment of osteoarthritis also emerged this year, including a small-molecule inhibitor of the Wnt signalling pathway.

Implementing a successful penile transplantation programme requires a multidisciplinary approach to overcome social, institutional, and patient-related obstacles. The literature in 2017 presents controversial ethical solutions, novel research models to evaluate immunosuppression, and long-term patient reports that help advance the field towards developing successful penile transplantation programmes.

In the past year, the results of three studies in the field of prostate cancer imaging — the prostate MR imaging study (PROMIS), an analysis of the cost-effectiveness of various diagnostic strategies based on PROMIS data, and a retrospective analysis of a prostate-specific membrane antigen (PSMA)-directed PET radiopharmaceutical — have been published that could have lasting effects on clinical practice.

Our biological understanding of TGCTs has been improved using sequencing, and molecular profiles associated with the genomic evolution and development of cisplatin resistance have been identified. The genomics of variants underpinning TGCT predisposition is being delineated. Studies of circulating microRNAs have demonstrated their potential for noninvasive diagnosis and disease monitoring.