Nature Reviews Disease Primers最新文献

Rotator cuff tears are the most common upper extremity condition seen by primary care and orthopaedic surgeons, with a spectrum ranging from tendinopathy to full-thickness tears with arthritic change. Some tears are traumatic, but most rotator cuff problems are degenerative. Not all tears are symptomatic and not all progress, and many patients in whom tears become more extensive do not experience symptom worsening. Hence, a standard algorithm for managing patients is challenging. The pathophysiology of rotator cuff tears is complex and encompasses an interplay between the tendon, bone and muscle. Rotator cuff tears begin as degenerative changes within the tendon, with matrix disorganization and inflammatory changes. Subsequently, tears progress to partial-thickness and then full-thickness tears. Muscle quality, as evidenced by the overall size of the muscle and intramuscular fatty infiltration, also influences symptoms, tear progression and the outcomes of surgery. Treatment depends primarily on symptoms, with non-operative management sufficient for most patients with rotator cuff problems. Modern arthroscopic repair techniques have improved recovery, but outcomes are still limited by a lack of understanding of how to improve tendon to bone healing in many patients.

Ischaemic or haemorrhagic perioperative stroke (that is, stroke occurring during or within 30 days following surgery) can be a devastating complication following surgery. Incidence is reported in the 0.1-0.7% range in adults undergoing non-cardiac and non-neurological surgery, in the 1-5% range in patients undergoing cardiac surgery and in the 1-10% range following neurological surgery. However, higher rates have been reported when patients are actively assessed and in high-risk populations. Prognosis is significantly worse than stroke occurring in the community, with double the 30-day mortality, greater disability and diminished quality of life among survivors. Considering the annual volume of surgeries performed worldwide, perioperative stroke represents a substantial burden. Despite notable differences in aetiology, patient populations and clinical settings, existing clinical recommendations for perioperative stroke are extrapolated mainly from stroke in the community. Perioperative in-hospital stroke is unique with respect to the stroke occurring in other settings, and it is essential to apply evidence from other settings with caution and to identify existing knowledge gaps in order to effectively guide patient care and future research.

Pulmonary hypertension encompasses a range of conditions directly or indirectly leading to elevated pressures within the pulmonary arteries. Five main groups of pulmonary hypertension are recognized, all defined by a mean pulmonary artery pressure of >20 mmHg: pulmonary arterial hypertension (rare), pulmonary hypertension associated with left-sided heart disease (very common), pulmonary hypertension associated with lung disease (common), pulmonary hypertension associated with pulmonary artery obstructions, usually related to thromboembolic disease (rare), and pulmonary hypertension with unclear and/or multifactorial mechanisms (rare). At least 1% of the world’s population is affected, with a greater burden more likely in low-income and middle-income countries. Across all its forms, pulmonary hypertension is associated with adverse vascular remodelling with obstruction, stiffening and vasoconstriction of the pulmonary vasculature. Without proactive management this leads to hypertrophy and ultimately failure of the right ventricle, the main cause of death. In older individuals, dyspnoea is the most common symptom. Stepwise investigation precedes definitive diagnosis with right heart catheterization. Medical and surgical treatments are approved for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. There are emerging treatments for other forms of pulmonary hypertension; but current therapy primarily targets the underlying cause. There are still major gaps in basic, clinical and translational knowledge; thus, further research, with a focus on vulnerable populations, is needed to better characterize, detect and effectively treat all forms of pulmonary hypertension.

Central neuropathic pain arises from a lesion or disease of the central somatosensory nervous system such as brain injury, spinal cord injury, stroke, multiple sclerosis or related neuroinflammatory conditions. The incidence of central neuropathic pain differs based on its underlying cause. Individuals with spinal cord injury are at the highest risk; however, central post-stroke pain is the most prevalent form of central neuropathic pain worldwide. The mechanisms that underlie central neuropathic pain are not fully understood, but the pathophysiology likely involves intricate interactions and maladaptive plasticity within spinal circuits and brain circuits associated with nociception and antinociception coupled with neuronal hyperexcitability. Modulation of neuronal activity, neuron-glia and neuro-immune interactions and targeting pain-related alterations in brain connectivity, represent potential therapeutic approaches. Current evidence-based pharmacological treatments include antidepressants and gabapentinoids as first-line options. Non-pharmacological pain management options include self-management strategies, exercise and neuromodulation. A comprehensive pain history and clinical examination form the foundation of central neuropathic pain classification, identification of potential risk factors and stratification of patients for clinical trials. Advanced neurophysiological and neuroimaging techniques hold promise to improve the understanding of mechanisms that underlie central neuropathic pain and as predictive biomarkers of treatment outcome.

Typhoid fever is an invasive bacterial disease associated with bloodstream infection that causes a high burden of disease in Africa and Asia. Typhoid primarily affects individuals ranging from infants through to young adults. The causative organism, Salmonella enterica subsp. enterica serovar Typhi is transmitted via the faecal–oral route, crossing the intestinal epithelium and disseminating to systemic and intracellular sites, causing an undifferentiated febrile illness. Blood culture remains the practical reference standard for diagnosis of typhoid fever, where culture testing is available, but novel diagnostic modalities are an important priority under investigation. Since 2017, remarkable progress has been made in defining the global burden of both typhoid fever and antimicrobial resistance; in understanding disease pathogenesis and immunological protection through the use of controlled human infection; and in advancing effective vaccination programmes through strategic multipartner collaboration and targeted clinical trials in multiple high-incidence priority settings. This Primer thus offers a timely update of progress and perspective on future priorities for the global scientific community.