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Vaccine-induced thrombosis and thrombocytopenia (VITT) may follow immunisation with the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2. Autoantibodies to platelet factor 4 (PF4) may mediate VITT through antibody-dependent platelet activation, though the underlying etiology is uncertain. Anti-PF4 antibodies are also seen in heparin-induced thrombocytopenia, though most cases of VITT do not have prior heparin exposure. More than 20 million people in the United Kingdom (UK) have received the ChAdOx1 nCoV-19 vaccine.

Cytomegalovirus (CMV) disease caused by genetically resistant CMV poses a major challenge in solid organ transplant recipients, and the development of resistance is associated with increased morbidity and mortality. Antiviral resistance affects 5%-12% of patients following ganciclovir (GCV) therapy, but is more common in individuals with specific underlying risk factors. These include the CMV D+R- serostatus, type of transplanted organ, dose and duration of (Val)GCV ([V]GCV) prophylaxis, peak viral loads, and the intensity of immunosuppressive therapy. Guideline recommendations for the management of GCV resistance (GanR) in solid organ transplant recipients are based on expert opinion as there is a lack of data from controlled trials. Second-line options to treat GanR include foscarnet (FOS) and cidofovir (CDV), but these drugs are often poorly tolerated due to high rates of toxicity, such as renal dysfunction and neutropenia. Here, we report seven cardiothoracic transplant recipients with GCV resistance CMV infection from our centre treated with CMV immunoglobulin (CMVIG) +/- leflunomide (LEF) and reviewed the literature on the use of these agents in this therapeutic setting.

Cytomegalovirus (CMV) is the most important infectious agent in solid organ transplant recipients and has a major impact on morbidity and mortality. Most cases are well managed with antiviral agents, but CMV hyperimmune globulin (CMVIg) can be used alongside antiviral therapy for prophylaxis in high-risk thoracic organ recipients and to treat life-threatening CMV infection or disease. CMVIg may also improve antiviral host defences when genetic resistance to antivirals or unwanted side effects occur. In this single-center, retrospective study, we reviewed the CMVIg use to supplement antiviral therapy as a "rescue therapy" in cardiothoracic transplant recipients. These comprised 12 single lung, 11 double lung, and 12 heart transplant recipients. Patients received a median of 2 doses of CMVIg, most often in combination with ganciclovir or valganciclovir, and reduced immunosuppression. One week after rescue therapy was initiated, CMV DNA levels were significantly reduced, and after four weeks, CMV DNA was undetectable in 73% patients. Only one patient died as a result of CMV-related disease. No significant adverse effects were observed. We conclude that CMVIg rescue therapy is safe, well tolerated, and effective at controlling viral replication in cardiothoracic transplant recipients.

Introduction UK guidelines for LTx and HTx candidate referral require a minimum of 6 months abstinence from smoking and ALL forms of nicotine replacement before patients can be formally assessed. Our unit adopted this principle and we aimed to investigate smoking habits in a consecutive cohort of such referrals. Methods Prospectively collected urine cotinine levels were used as a patient engagement tool. LTx referrals from August 2010 to April 2018 and HTx referrals from September 2015 to April 2018 who clearly stated they had met the smoking/nicotine abstinence criterion were asked to submit an on-the-spot urine sample at outpatient consultations and inpatient assessments. Cotinine>50 ng/ml indicated active smoking/nicotine use (liquid chromatography mass spectrometry, lower detection limit 5 ng/ml). Results 499 LTx and 149 HTx candidates submitted ≥1 sample during this period; total 977 and 220 samples, mean (range): 2 (1–14) and 1 (1–8)/patient; median self-reported nicotine abstinence 1.9 years (IQR 0.8–4.9) and 1.1 (0.2–2.5) respectively. 25.8% (LTx) and 27.5% (HTx) had elevated first sample cotinine [LTx: mean (range) 171 (6–2100) ng/ml, 102/129>50 ng/ml; HTx 111 (6–1100), 30/41>50 ng/ml]. Smokers were predominantly male (LTx-57.4%; HTx-71%, p Conclusion We found a high prevalence of nicotine ‘mis’-use in patients with advanced pulmonary and cardiac disease selected by referring physicians for consideration of organ transplant having declared long abstinence. Smoking habits changed in both directions with a clear risk of relapse on the waiting list; implications for relapse post-operatively require further study. Urinary cotinine targets can be used to incentivise patients’ behavioural change and set clear expectations within the contract governing relationship with the transplant team.

Introduction Total Lung capacity (TLC) is often measured in patients with advanced lung disease to help inform diagnosis, severity and management. However, some may not manage or tolerate the technical aspects of the gold standard test: whole body plethysmography (Pleth-TLC). N2 washout (N2W-TLC) is often used in lieu but it is unreliable in obstructive conditions and some still find it challenging. As all potential lung transplant candidates undergo thoracic CT during their workup, we hypothesised that CT estimates of total lung volume (CT-TLV) could substitute Pleth-TLC and are superior to N2W-TLC. Methods Prospectively collected data between April 2015–2018. 1–2 mm CT slices were analysed using Vitrea software (version 6.1.1169.10077, Vital Solutions, Toshiba Medical Systems Europe) by a single radiologist. Descriptive statistics were compared with parametric tests. Agreement and bias between methods were examined with Pearson’s correlation and Bland and Altman analysis. Results 202 patients were studied (94 female, mean [SD] age 52 [11] yrs, BMI 25.0 [4.2] kg/m2, COPD/IPF/CF/other n=72/45/21/64). 37 (18.3%) and 50 (24.8%) were unable to perform Pleth and N2W respectively. Paired data were available for comparison of CT vs Pleth (n=160), CT vs N2W (147) and Pleth vs N2W (131), with subgroup analysis into obstructive, restrictive and normal ventilation. Mean [SD] CT-TLV, Pleth-TLC and N2W-TLC were 4.69 [1.95], 5.20 [2.06] and 4.32 [1.71] L respectively, p Conclusion CT estimates of TLC reliably approximate Pleth-TLC and could replace body box measurement in practice, for patient convenience and cost containment. Gastro-oesophageal air, captured by Pleth but not CT, accounts for some of the underestimation. The consistent small bias with a reliable homoscedastic difference between these methods may allow incorporation of a correction factor and wider application of this CT algorithm.

Hypereosinophilic syndrome is a disease characterised by a persistently elevated eosinophil count. The syndrome can be reactive to infections, autoimmune disease, cancers, etc. Multiple organ involvement can occur including cardiomyopathies, pulmonary involvement and neuropathies. We describe a case of a patient who presented with signs and symptoms of asthma with recurrent asthma exacerbations, but in fact proved to be hypereosinophilic syndrome secondary to strongyloides infection.

Sirolimus is a potent immunosuppressant agent that has utility in solid-organ transplantation (SOT), particularly for its renal-sparing effects. However, lung toxicity can be a significant issue and a variety of different lung injury patterns have been described. We report an unrecognized association of sirolimus with lung cavitation in patients who have undergone cardiothoracic transplantation. Between 1996 and 2010, lung and heart transplant patients received sirolimus-based immunosuppression as a second-line agent after initial therapy with calcineurin inhibitors. All cases of sirolimus-induced lung cavities were recorded and a retrospective review of the case notes of these patients was undertaken. A total of 9 patients were identified. Clinical symptoms, time to first cavity and mean levels were variable. Some patients showed complete resolution, whereas others had persistent cavitatory lung lesions. Patients who developed persistent lung cavities had a worse outcome than those who did not have cavitation.