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1.
Critical Care Medicine ; 51(1 Supplement):17, 2023.
Article in English | EMBASE | ID: covidwho-2190458

ABSTRACT

INTRODUCTION: Multisystem Inflammatory Syndrome in Children (MIS-C) after SARS-CoV-2 infection is often complicated by ventricular dysfunction. Our prior work suggests that strain echocardiography (SE) detects abnormalities in cardiac function in ICU patients unrecognized by conventional echocardiography (CE). This study compares the relative strengths of CE and SE in predicting needs for ICU level therapies in MIS-C patients. METHOD(S): A retrospective, single center analysis was performed on patients admitted to a quaternary-care children's hospital with the diagnosis of MIS-C from March 2020 to January 2022. Only patients with CE and SE measured prior to initiation of vasoactives were included. Abnormal LVEF was defined as < 55% and abnormal strain as <= -17.2%. Clinical metrics included use of positive pressure ventilation (PPV), vasoactives, or any ICU level care. RESULT(S): Of 90 patients diagnosed with MIS-C, median LVEF was normal in both normal (64.0%) and abnormal strain (57.2%) groups. We found 97.6% of patients with normal strain had normal LVEF but only 57.1% of those with normal LVEF had normal strain. Median LVEF was normal in both those who did and did not require ICU level care (63% vs 57.1%), and those who did and did not require vasoactives (62.4% vs 56.5%). Strain was abnormal in patients who required ICU level care, PPV, and vasoactives (-13.8%, -12.9%, -13.8% respectively), compared to those who did not (all -19.3%, p all < 0.001). Sensitivity analysis showed strain was superior to LVEF in identifying need for ICU level care (75.8% vs 39%), PPV (88% vs 48%), and vasoactives (90% vs 55%). Negative predictive value of strain was superior to LVEF for similar outcomes (ICU level care (80.9% vs 72%), PPV (92.7% vs 81.9%) and vasoactives (95.1% vs 87.2%)). CONCLUSION(S): We demonstrate that SE detects abnormalities in cardiac function in MIS-C patients unrecognized by CE. In both ICU and non-ICU patients, we found compared to LVEF, detection of abnormal strain better identifies patients who will need ICU level therapies. Similarly, a measurement of normal strain is superior to a normal LVEF in predicting those who will not need these interventions.

2.
Gut ; 71:A196, 2022.
Article in English | EMBASE | ID: covidwho-2005403

ABSTRACT

Introduction During the first wave of the COVID- 19 pandemic many elective procedures were postponed including venesection for the treatment of haemochromatosis. On resumption of venesection, limited capacity offered the opportunity to observe the effect of prolonged cessation of maintenance in non-cirrhotic patients over 70 years who guidelines suggest should undergo lifelong venesection. Methods 40 HFE haemochromatosis patients aged 70+ at Royal Derby Hospital (RDH) (25 C282Y homozygotes, 11 compound heterozygotes (CH) and 4 C282Y heterozygotes- 3 mutually exclusive groups) who had a SF< 150mg/L at the point of venesection cessation were identified. SF levels at venesection cessation and resumption were collected and the time interval used to express the change in SF over 12 months. Statistical analyses were conducted using STATA. Results The median projected increase in SF in 1 year in C282Y homozygotes was 40.8(-40.9-490.2)mg/L, in C282Y heterozygotes was 36.4(11.5-157.5) mg/L, and in compound heterozygotes was 74.1(-58.2-170.5) mg/L. There was no significant difference between the projected median increase in SF in 1 year between C282Y homozygotes compared to C282Y heterozygotes (p=0.95, p>0.05), between C282Y homozygotes compared to compound heterozygotes (p=0.72, p>0.05) or between all patients with a single C282Y mutation (compound heterozygotes and C282Y heterozygotes) compared to C282Y homozygotes (p=0.75,p>0.05). Considering all patients requiring venesection, the proportion of patients whose ferritin increased over 12 months by less than 50 was 50%, < 100 was 80% and 98% remain within normal range. Conclusions In non-cirrhotic HFE patients age 70+ the majority of patients can safely suspend venesection for at least 1 year and continued ferritin monitoring would likely reduce the burden on the service without clinically significant consequences as long as a threshold for resumption were agreed. Since evidence suggests that reduced iron absorption may be a physiological result of ageing, some patients may not require further venesection.

3.
Gut ; 71:A73, 2022.
Article in English | EMBASE | ID: covidwho-2005356

ABSTRACT

Introduction NICE guidelines (2017) recommend offering 6 monthly surveillance with USS for all cirrhotic patients with exception for patients identified for end of life care. But surveillance intervals are often missed where care is delivered through Consultant-led clinics. Having introduced a nurse-led stable cirrhosis clinic in 2016, we assessed whether the recommended interval was being achieved, and what impact the 'aMAP' score stratifying annual HCC risk as low(<0.2%), medium( 1%) and high(4%) might have on service utilisation. Methods A retrospective review of all patients attending our nurse-led stable cirrhosis clinic. Review included demographic data, aetiology of liver disease, calculation of Child and aMAP (age, gender, albumin-bilirubin) scores using parameters from initial clinic visits. We assessed adherence to the twice yearly US scan since our adaptation of NICE guidelines in 2018. Results Between 2016-2018, 117(49 female) cirrhotic patients were enrolled in the clinic. Majority of the patients had ALD (55) and NASH(24). Other aetiologies included HCV, HFE and PBC. All patients had Child A disease except 7 with Child B (B7:3;B8:4). 13/117 patients were excluded from the surveillance program mainly because other co-morbidities and age. of the remaining 104 enrolled in surveillance, 90(87%) patients had their USS at 6 months interval, 2(2%) missed only one scan (not requested by clinician), 7(7%) failed to attend their appointments, 5(4%) either declined surveillance or were lost to follow up. aMAP score identified 70/104 (67%) high risk, 29 (28%) medium risk and only 5(5%) low risk for HCC. HCC was diagnosed in 4/104 patients after 3 years follow up (2 medium risk;2 high risk).Death was reported in 10/104 patients (1 HCC;4 liver failure;3 other cancers;1 post-operative complications following orthopaedic surgery;1 2ry to sepsis). Despite interruptions caused by COVID-19 pandemic, no HCC was diagnosed in 1st US scan after restarting the services. Conclusions HCC surveillance organised through a dedicated nurse-led stable cirrhosis clinic can achieve excellent adherence to planned USS intervals. Only a small number were identified as low risk within our cohort using the aMAP score offering limited opportunity to reduce the volume of USS for this indication in Derby.

4.
American Journal of Respiratory and Critical Care Medicine ; 205:2, 2022.
Article in English | English Web of Science | ID: covidwho-1880368
5.
British Journal of Haematology ; 197(SUPPL 1):80, 2022.
Article in English | EMBASE | ID: covidwho-1861230

ABSTRACT

COVID-19 has had a profound impact on the delivery of healthcare services within the NHS. To relieve burden, elective procedures were ceased. This included venesection, the treatment for haemochromatosis, a disease characterised by excessive dietary iron absorption. Evidence suggests that a physiological result of ageing is reduced iron absorption. Therefore, an arbitrary cut-off age for venesection cessation was established at over 70, in attempt to limit adverse outcomes. However, management guidelines state that treatment is required lifelong, though there is no evidential basis for this. Therefore, the purpose of this study is to explore the effect of cessation of venesection on serum ferritin (SF) level and liver function in patients aged over 70 at the Royal Derby Hospital (RDH). Primarily, it was to assess whether venesection cessation was safe. Haemochromatosis patients, aged over 70 at RDH were the group of interest. Only those who were receiving maintenance venesection at the time of treatment cessation (SF < 150 μg/l) were included. Using the software CITO, their genotypes were identified and only those with HFE mutation were selected. The sample group was composed of 44 patients with conventional HFE hereditary haemochromatosis (biallelic HFE mutation) and seven with monoallelic HFE mutation, who were used as a comparator. SF, ALT, ALP and GGT levels before and after venesection cessation were collected. Statistical analyses were conducted using STATA, to test for a significant difference between blood test parameters before versus after treatment cessation. The rate of change in SF per day was calculated for both groups. Patients did not receive treatment for a median of 403 days (1 year and 38 days). No significant difference was noted between GGT, ALT and ALP levels before versus after treatment cessation. There was a statistically significant increase in SF before versus after treatment cessation ( z = -4.532), p < 0.001) at the 99% confidence level. The median SF before treatment cessation was 74 μg/l compared to 124.5 μg/l just before treatment re-initiation. However, this did not prove to be clinically significant, as only 1/44 patients had a SF that rose above the normal reference range of 30-400 μg/l. There was a statistically significant difference in the rate of change in SF per day between patients with biallelic HFE mutation (median = was 0.14 μg/l/day) compared to patients with monoallelic HFE mutation (median = 0.10 μg/l/day) at the 95% confidence level. Venesection cessation was safe for patients aged over 70 with HFE haemochromatosis at RDH. The results suggest that venesection does not need to be lifelong, but can safely be paused-not ceased, after the age of 70 for 5-year intervals. Results can facilitate the establishment of new clinical guidelines for the treatment of haemochromatosis. (Table Presented).

6.
PeerJ ; 9: e12159, 2021.
Article in English | MEDLINE | ID: covidwho-1436350

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) is the cell receptor that the coronavirus SARS-CoV-2 binds to and uses to enter and infect human cells. COVID-19, the pandemic disease caused by the coronavirus, involves diverse pathologies beyond those of a respiratory disease, including micro-thrombosis (micro-clotting), cytokine storms, and inflammatory responses affecting many organ systems. Longer-term chronic illness can persist for many months, often well after the pathogen is no longer detected. A better understanding of the proteins that ACE2 interacts with can reveal information relevant to these disease manifestations and possible avenues for treatment. We have undertaken an approach to predict candidate ACE2 interacting proteins which uses evolutionary inference to identify a set of mammalian proteins that "coevolve" with ACE2. The approach, called evolutionary rate correlation (ERC), detects proteins that show highly correlated evolutionary rates during mammalian evolution. Such proteins are candidates for biological interactions with the ACE2 receptor. The approach has uncovered a number of key ACE2 protein interactions of potential relevance to COVID-19 pathologies. Some proteins have previously been reported to be associated with severe COVID-19, but are not currently known to interact with ACE2, while additional predicted novel ACE2 interactors are of potential relevance to the disease. Using reciprocal rankings of protein ERCs, we have identified strongly interconnected ACE2 associated protein networks relevant to COVID-19 pathologies. ACE2 has clear connections to coagulation pathway proteins, such as Coagulation Factor V and fibrinogen components FGA, FGB, and FGG, the latter possibly mediated through ACE2 connections to Clusterin (which clears misfolded extracellular proteins) and GPR141 (whose functions are relatively unknown). ACE2 also connects to proteins involved in cytokine signaling and immune response (e.g. XCR1, IFNAR2 and TLR8), and to Androgen Receptor (AR). The ERC prescreening approach has elucidated possible functions for relatively uncharacterized proteins and possible new functions for well-characterized ones. Suggestions are made for the validation of ERC-predicted ACE2 protein interactions. We propose that ACE2 has novel protein interactions that are disrupted during SARS-CoV-2 infection, contributing to the spectrum of COVID-19 pathologies.

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