Clinical Medicine最新文献

Atypical haemolytic-uraemic syndrome (aHUS) is a rare disease associated with uncontrolled activation of the alternative complement pathway, leading to thrombotic microangiopathy (TMA). Early diagnosis and treatment with eculizumab, a monoclonal antibody targeting the complement component C5, are crucial to improve outcomes and prevent renal failure and mortality. Current recommendations include lifelong eculizumab therapy, yet this practice presents challenges including high treatment costs and increased infection risks from prolonged complement inhibition. We hypothesise that a personalised eculizumab dosing strategy tailored to individual patient responses could optimise therapy, reduce costs and improve safety. This hypothesis was evaluated through a presentation of a patient who was managed with a specific eculizumab treatment approach. The patient's condition improved significantly, allowing for a gradual reduction in eculizumab dosage based on clinical response and drug level monitoring. Throughout treatment, the patient's complement activity and eculizumab levels were closely monitored, showing that lower doses maintained therapeutic efficacy without evident TMA recurrence. This case supports the feasibility of transitioning from fixed regimens to personalised dosing strategies in managing aHUS. Such approaches could mitigate the risks and costs associated with lifelong therapy while maintaining disease control, especially considering the variability in relapse risk among different genetic mutations. This personalised treatment model might significantly impact the management of aHUS, aligning clinical care with individual patient needs and economic considerations. Further research should relate drug pharmacokinetics/pharmacodynamics to clinical/genetic setting to identify milestones of individual patient treatment approach.

Background: Corticosteroids raise blood glucose concentrations; however, it remains unknown which form of administration, oral or intravenous, is associated with the greatest degree of blood glucose rise in hospitalised patients. Furthermore, it is not known whether the pattern of the associated hyperglycaemia throughout the day differs depending on the route of administration.

Methods: This was a single centre retrospective study of 384 adult inpatients receiving oral or intravenous hydrocortisone and dexamethasone. Data on capillary glucose concentrations and time taken over 7 days were collected. A mixed model for repeated measures was applied to compare changes in glucose concentration over time for oral and intravenous corticosteroids. An auto-regressive covariance structure was employed to model correlations between repeated measurements. This was adjusted for age, sex, pre-admission diabetes, and/or pre-admission corticosteroid status.

Results: No significant difference was found between oral and intravenous hydrocortisone on day 1 or across all 7 days (mean difference 0.17 mmol/L (-1.39, 1.75), p = 0.827, and mean difference 0.20 mmol/L (-0.61, 1.01), p = 0.639 respectively). There were no differences in mean glucose concentrations between those on oral or intravenous dexamethasone on day 1 or across all 7 days (mean difference 0.41 mmol/L (-0.55, 1.38), p = 0.404 and mean difference -0.09 mmol/L (-1.05,0.87), p = 0.855, respectively).

Conclusion: This study found that oral and intravenous administration of hydrocortisone and dexamethasone do not have a significantly differing impact on blood glucose levels. Capillary glucose monitoring is strongly recommended in all individuals who are on either oral or intravenous corticosteroids.

Background: Minimal residual disease (MRD) testing is a promising approach to tailor the treatment of multiple myeloma (MM). However, several major concerns remain to be addressed before moving it into daily practice, most of which stem from the dynamic nature of the MRD status. Thus, it is crucial to understand the MRD dynamics and propose its clinical implications.

Methods: We retrospectively analysed the data of patients with newly diagnosed MM (NDMM) who had flow cytometry-based MRD tests at multiple time points after initiation of therapy. The impact of undetectable MRD (including attainment, duration and loss) on clinical outcomes was analysed.

Results: In a cohort of 220 patients with NDMM, attainment of MRD^- offered favourable outcomes (P < 0.0001 for both progression-free survival (PFS) and overall survival (OS)), regardless of baseline risk factors. Notably, MRD^- duration ≥12 months was associated with an 83 % (95 % confidence interval (CI), 0.09-0.34; P < 0.0001) or 69 % (95 % CI, 0.13-0.76; P = 0.0098) reduction in risk of progression/death or death, while the longer MRD^- was sustained, the better the outcome was. Loss of MRD^- led to poor PFS (hazard ratio (HR) 0.01, 95 % CI 0-0.06, P < 0.0001) and OS (HR 0.03, 95 % CI 0-0.24, P = 0.0008). Most patients (70 %) who lost MRD^- status carried high-risk cytogenetic abnormalities (HRCAs). While MRD^- was temporally inconsistent with conventional therapeutic responses (eg ≥ complete remission or very good partial response), it predicted disease progression or recurrence more robustly than the latter. Last, the predictive value of the MRD status was independent of baseline risk factors (eg high-risk cytogenetic abnormality, International Staging System (ISS) or Revised (R-)ISS staging).

Conclusions: Longitudinal assessment of MRD during the treatment course and follow-up is required for monitoring disease progression or relapse, to guide treatment decisions. Accordingly, a prospective study is currently ongoing to investigate the feasibility and benefit of the MRD-tailored therapy according to the longitudinal changes of the MRD status.

Sarcoidosis is an inflammatory disease characterised by non-caseating granulomas of unclear aetiology. Isolated cardiac sarcoidosis (ICS) is rare and occurs when there is granulomatous infiltration of myocardial tissue without evidence of extracardiac sarcoidosis. The heterogeneity in clinical manifestations often presents a diagnostic challenge which leads to delays in treatment initiation. Our case highlights the often quiescent presentation of ICS, the importance of early treatment and the diagnostic challenges that contribute to its underdiagnosis.

Multidisciplinary meetings (MDMs) are central to clinical decision-making in many areas of cardiology. This study assessed current provision and structure of cardiology MDMs in England in comparison with national guidelines. British Cardiovascular Society (BCS) members were surveyed regarding frequency, core attendees, and organisational aspects of cardiology MDMs for myocardial revascularisation, endocarditis, heart failure, aortic valve, mitral and tricuspid valve MDMs, whether local, regional or outside of the region. Access to electrophysiology (EP), inherited cardiac conditions, and adult congenital heart disease (ACHD) MDMs was also assessed. Survey responses were received from 64 hospitals across England, of which 40 (62%) were secondary care centres and 24 (38%) were tertiary care centres. All units had access to revascularisation MDMs, although 6% of them (all in secondary care centres) lacked any surgical representation. Heart failure MDMs were available in 94% of centres, but 7% reported no attendance by a cardiologist with specialist interest in heart failure, and 23% reported no attendance by a device specialist. 61% of centres had access to dedicated endocarditis MDMs; however, 11% were not attended by a microbiologist or infectious disease physician, and 22% were not attended by a surgeon. Aortic valve MDMs were available in 69% of centres, while mitral and tricuspid valve MDMs were available in 56% of centres. One quarter of centres reported no access to EP, and one third of centres reported no access to ICC or ACHD MDMs. Substantial improvements in provision and structure of cardiology MDMs in England are needed in order to meet national guidance.

Pancytopenia is an uncommon abnormality detected on a full blood count. Features of presentation tend to be non-specific, and are due to impaired functions of the cell lines involved. These can include fatigue, infection and bleeding. However, the aetiology of pancytopenia is extensive. This narrative review aims to provide a minimally invasive diagnostic algorithm for generalist clinicians to approach pancytopenia, including investigations into the underlying aetiology, and when a referral to the haematologist is warranted for further investigations such as bone marrow aspiration and trephine biopsy.

For patients who may lack capacity, the Mental Capacity Act 2005 requires capacity to be assessed for each decision at the time that treatment is offered, but this is not practical for every element of basic care and intervention delivered to patients undergoing rehabilitation following acquired brain injury, especially if their needs are changing. In this quality improvement project, we introduced a system for screening Mental Capacity and documentation to identify patients with a) largely intact cognition for whom capacity may be reasonably be presumed, and b) those in prolonged disorders of consciousness who clearly lacked capacity for all decisions. This enabled the multidisciplinary team to concentrate on evaluation of capacity in the third group who had more nuanced ability and required detailed assessment or support for decision-making. Two rounds of audit demonstrated that implementation improved the consistency of assessment and documentation. Multicentre roll-out of this approach is now required.

Measles is a highly contagious but vaccine-preventable airborne-transmitted viral infection of which there has been a recent resurgence of cases worldwide over the past year, including in countries such as the UK, which had previously successfully achieved endemic measles elimination through vaccination programmes. Measles is typically a self-limiting illness, but can rarely cause severe, life-threatening disease, particularly when complicated by respiratory or neurological involvement. These severe complications are not typically seen in the absence of immunosuppression. We describe a rare case of severe measles with pneumonitis in an immunocompetent adult necessitating admission to an intensive care unit (ICU).

The protracted form of COVID-19 known as 'long covid' was first described in 2020. Its symptoms, course and prognosis vary widely; some patients have a multi-system, disabling and prolonged illness. In 2021, ring-fenced funding was provided to establish 90 long covid clinics in England; some clinics were also established in Scotland and Wales. The NIHR-funded LOCOMOTION project implemented a UK-wide quality improvement collaborative involving ten of these clinics, which ran from 2021 to 2023. At regular online meetings held approximately 8-weekly, participants prioritised topics, discussed research evidence and guidelines, and presented exemplar case histories and clinic audits. A patient advisory group also held a priority-setting exercise, participated in quality meetings and undertook a service evaluation audit. The goal of successive quality improvement cycles aimed at changing practice to align with evidence was sometimes hard to achieve because definitive evidence did not yet exist in this new condition; many patients had comorbidities; and clinics were practically constrained in various ways. Nevertheless, much progress was made and a series of 'best practice' guides was produced, covering general assessment and management; breathing difficulties; orthostatic tachycardia and other autonomic symptoms; fatigue and cognitive impairment; and vocational rehabilitation. This paper summarises key findings with the frontline clinician in mind.