Diagnosis and investigation of suspected haemophagocytic lymphohistiocytosis in adults: 2023 Hyperinflammation and HLH Across Speciality Collaboration (HiHASC) consensus guideline.

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome characterised by persistently activated cytotoxic lymphocytes and macrophages, which, if untreated, leads to multiorgan dysfunction and death. HLH should be considered in any acutely unwell patient not responding to treatment as expected, with prompt assessment to look for what we term the three Fs-fever, falling blood counts, and raised ferritin. Worldwide, awareness of HLH and access to expert management remain inequitable. Terminology is not standardised, classification criteria are validated in specific patient groups only, and some guidelines rely on specialised and somewhat inaccessible tests. The consensus guideline described in this Health Policy was produced by a self-nominated working group from the UK network Hyperinflammation and HLH Across Speciality Collaboration (HiHASC), a multidisciplinary group of clinicians experienced in managing people with HLH. Combining literature review and experience gained from looking after patients with HLH, it provides a practical, structured approach for all health-care teams managing adult (>16 years) patients with possible HLH. The focus is on early recognition and diagnosis of HLH and parallel identification of the underlying cause. To ensure wide applicability, the use of inexpensive, readily available tests is prioritised, but the role of specialist investigations and their interpretation is also addressed.

Pembrolizumab for the treatment of progressive multifocal leukoencephalopathy following anti-CD19 CAR-T therapy: a case report.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection with few treatment options and poor survival when reversal of the underlying immune dysfunction is not achievable. JC polyomavirus reactivation resulting in PML can rarely complicate chimeric antigen receptor T-cell (CAR-T) therapy. We describe successful treatment of PML with Programmed death-1 (PD-1) blockade using pembrolizumab, 4 months following axicabtagene ciloleucel. Radiological features of immune reconstitution inflammatory syndrome without clinical deterioration were seen. Evidence of anti-viral immune reconstitution by in vitro detection of JC-specific T-cells and sustained neurological recovery in this patient suggest PD-1 blockade may be an effective treatment approach for PML post-CAR-T.

COVID-19 in the act: incidental 18F-FDG PET/CT findings in asymptomatic patients and those with symptoms not primarily correlated with COVID-19 during the United Kingdom coronavirus lockdown.

PURPOSE: The emergence of the novel SARS-CoV-2 pathogen and lethal COVID-19 disease pandemic poses major diagnostic challenges. The study aims to describe the spectrum and prevalence of thoracic and extrathoracic incidental findings in patients who have undergone 18F-FDG PET/CT during the first 3 weeks of the COVID-19 UK lockdown. METHODS: This is a single-centre retrospective controlled observational study. 18F-FDG PET/CT scans (n = 160) acquired from 23/3/2020 to 9/4/2020 were retrospectively reviewed for incidental findings in the lungs and extrapulmonary sites (heart, nasal sinuses, parotid and salivary glands, colon, large vessels, renal cortex, brain, spleen and testes). A date-matched control group (n = 205) of patients from 2019 was used for comparison. RESULTS: The total prevalence of suspicious findings was 26/160 (16.25%). Fifteen patients presented with incidental findings in the lungs, while eleven patients had only non-pulmonary incidental findings. There was a significant increase in the appearance of incidental 18F-FDG PET/CT findings during the 2nd week (OR = 3.8) and 3rd week (OR = 7.6) in relation to the 1st week. There was a significant increase in the average maximum standardised uptake values (SUVmax) in the parotid/salivary glands of patients scanned during week 2 in relation to week 1 (p = 0.036). There was no significant difference in the prevalence of incidental findings compared to the control group, but the number of pulmonary vs. extrathoracic findings was different between the two populations. CONCLUSION: The study provides a novel base of evidence to identify asymptomatic patients and those without symptoms strongly associated with COVID-19 with incidental 18F-FDG PET/CT findings suspicious of SARS-CoV-2 infection during the initial stages of the pandemic.

PEACE in the midst of an emergency: a rash not to miss.

We present the case of a 29-year-old woman who initially presented to her GP with a short history of non-pruritic annular skin lesions with central clearing. A month later, she developed signs and symptoms of bone marrow failure with bruising, epistaxis and fatigue. After urgent review of a blood film, she was diagnosed with acute promyelocytic leukaemia (APML), which is a haematological emergency. Treatment with all-trans retinoic acid (ATRA) was commenced immediately and she was subsequently treated with arsenic trioxide (ATO). The annular rash was subsequently diagnosed as paraneoplastic erythema annulare centrifugum (PEACE), which resolved with treatment. This case demonstrates the importance of the urgent diagnosis of APML and highlights PEACE as a rash that clinicians should be aware of, as it can be the initial manifestation of a number of both haematological and non-haematological malignancies.

CAR T Cell Therapy-Related Cardiovascular Outcomes and Management: Systemic Disease or Direct Cardiotoxicity?

CD19-specific chimeric antigen receptor (CAR) T cell therapies have shown remarkable early success in highly refractory and relapsing hematological malignancies. However, this potent therapy is accompanied by significant toxicity. Cytokine release syndrome and neurotoxicity are the most widely reported, but the true extent and characteristics of cardiovascular toxicity remain poorly understood. Thus far, adverse cardiovascular effects observed include sinus tachycardia and other arrhythmias, left ventricular systolic dysfunction, profound hypotension, and shock requiring inotropic support. The literature regarding cardiovascular toxicities remains sparse; prospective studies are needed to define the cardiac safety of CAR T cell therapies to optimally harness their potential. This review summarizes the current understanding of the potential cardiovascular toxicities of CD19-specific CAR T cell therapies, outlines a proposed cardiac surveillance protocol for patients receiving this new treatment, and provides a roadmap of the future direction of cardio-oncology research in this area.

Recording inpatient weight: implications for medicines administration.

AIM: To identify the proportions of hospital inpatients with recorded weights: among all patients, and among those receiving weight-dosed drug therapy. METHOD: Survey of clinical notes of hospital inpatients across a convenience sample of 11 secondary and tertiary referral hospitals in England and Wales in November 2011. RESULTS: 1068 patients were included, and 1061 patient clinical notes were available (99.3%). Nearly all paediatric patients had recorded weights (77/78; 98.7%). Half of adult inpatients had recorded weights (503/983, 51.2%). The proportion of adult inpatients with recorded weights varied by hospital, ranging from 13.5% to 92.5% (p<0.0001). In those receiving gentamicin or therapeutic-dose low molecular weight heparin (t-LMWH), only 64.5% (71/110) had a recorded weight. CONCLUSIONS: Half of adult inpatients, and two-thirds of those receiving gentamicin or t-LMWH, had recorded weights. There was significant variation in rates of weighing adult inpatients across hospitals. This may put patients at increased risk of side effects and problems resulting from malnutrition.