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Objectives: Cases of fulminant myocarditis after mRNA COVID-19 vaccination have been reported. The most severe may need venoarterial extracorporeal membrane oxygenation (V-A ECMO) support. Here we report two cases successfully rescued with V-A ECMO. Method(s): We included all the cases supported with V-A ECMO for refractory cardiogenic shock due to myocarditis secondary to a mRNA SARS-COV2 vaccine in the high-volume adult ECMO Program in Vall Hebron University Hospital since January 2020. Result(s): We identified two cases (table). One of them was admitted for out-of-hospital cardiac arrest. In both, a peripheral V-A ECMO was implanted in the cath lab. An intra-aortic balloon pump was needed in one case for left ventricle unloading. Support could be successfully withdrawn in a mean of five days. No major bleeding or thrombosis complications occurred. Definite microscopic diagnosis could be reached in one case (Image, 3). Treatment was the same, using 1000mg of methylprednisolone/day for 3 days. A cardiac magnetic resonance 10 days after admission showed a significant improvement in systolic function and diffuse oedema and subepicardial contrast intake in different segments (Image, 1-2). Both patients were discharged fully recovered. Conclusion(s): V-A ECMO should be established in cases of COVID-19 vaccine-associated myocarditis with refractory cardiogenic shock during the acute phase. (Table Presented).
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Aims: The DisCOVery study sought to better understand the experiences of young people with complex emerging mental health problems over the longer-term social restrictions related to the COVID-19 pandemic. A key focus investigated young people's attitudes and experiences of social connection, and how they perceived this to be related to their mental health and future recovery needs. Method(s): Semi-structured interviews were completed with 16 young people (aged 20 to 25) with pre-existing and complex mental health and social problems, between January to December 2021. N = 6 completed follow up interviews approximately 6 months after their initial interview. Interviews were analysed using thematic analysis. Results and Conclusion(s): Four themes were identified. These centred around a preference for balancing solitude and quality relationships within small social worlds, the complex role of in-person versus online connection and interaction, how the COVID-19 lockdowns were a facilitator of both social connection and disconnection, and the importance of relationships, talking and being listened to for well-being. The findings suggest that in-person, and to some extent online connection, is a key component of well-being, and is an active recovery goal that socially withdrawn young people with complex pre-existing mental health problems would like to work on.
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Objectives: Investigate the utilization of cycled antineoplastic therapies (where dosages vary per monthly supply) for various cancers among Medicare-eligible patients, and medical costs and outcomes associated with discontinuation gaps in monthly adherence. Method(s): This retrospective study used the MarketScan Supplemental and Coordination of Benefits Design databases from 2019-2020. Discontinuations were calculated for 2020 utilizing cycled medications (8 generic products) from 6 therapeutic categories, where discontinuation was defined as the first gap in medication supply during the last 6 months of the year at intervals of >=1.5*prior supply. Continuous enrollment was required, as were ICD oncology diagnosis codes for those at least 65 years of age. New to therapy/diagnosis was inferred from 2019 metric files. Patients were excluded if hospice care and inpatient transplant services were indicated. Models examined adherence level (discontinued or not) and 10 covariates (including COVID-19 indications), with interaction terms, for significant associations with medical costs (inpatient and outpatient), hospitalizations, and length of hospital stay (LOS). Result(s): Patients who met metric criteria (n=1,357;Mean age 73.9) had a discontinuation rate of 16.7%. A total of 64.0% were new to therapy/diagnosis and 5.2% were identified having COVID-19 in 2020. However, COVID-19 was not significantly correlated with a discontinuation. Hospitalization rate was at 30.3% with mean LOS=9.8. Models found significant discontinuation effects with increased total medical costs ($11,977, p<.03), odds of hospitalization (2.7, p<.0001), and LOS (5.4, p<.03). COVID-19 patients had significantly higher total medical costs ($18,145, p<.007), odds of hospitalization (6.3, p<.0001), and non-oncology LOS (4.6, p<.009). Significant covariate interactions are discussed in the poster. Conclusion(s): Medication adherence (fewer gaps in medication coverage) on cycled oral antineoplastics can lead to lower medical costs and fewer hospitalization events or LOS as compared to lower adherence levels. This was independent of COVID-19 indications that were associated with increased costs, hospitalization, and non-cancer LOS.Copyright © 2023
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The patient presented with nausea, appetite loss, and fatigue. She had received two doses of Pfizer/BioN-Tech BNT162b2 mRNA vaccine (COMIRNATY) for coronavirus disease 2019 (COVID-19). Acute liver injury was noted 14 days after the first dose of the vaccine. Re-exposure through the second dose worsened the liver injury. After liver biopsy on the third day of admission, methylprednisolone (1000 mg) was administered. Liver histology showed acute hepatitis with diffuse lobular inflammation/necrosis and lymphocyte-dominant infiltra-tion in the portal areas. The patient was diagnosed with drug-induced liver injury due to the COVID-19 vaccine based on the Digestive Disease Week Japan 2004 (DDW-J) scale, which assesses the temporal relationship, liver biopsy, and laboratory findings. With improvements in the blood test parameters, prednisolone was gradually tapered and stopped. One month later, no biochemical signs of relapse were noted. To our knowledge, this is the first report describing liver injury after the administration of the Pfizer COVID-19 vaccine in Japan.Copyright © 2022 The Japan Society of Hepatology.
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Aims: Children and adolescents were affected in various ways by the measures due to COVID-19 pandemic. The aims of this study were to investigate and compare the effects on mental health across age, to identify latent class trajectories of emotional and behavioural problems over 12-months and to examine the association of classes of trajectories with baseline demographic and clinical predictors. Method(s): Children (n = 1854) and adolescents (n = 1243) from the general population were assessed baseline, at 6-, 9-, and 12-month follow-up. They were eligible if they were residents in Austria, Germany, or Switzerland, were parents/caregivers of a child aged between 7 and 10 years or adolescents >=11 years, had sufficient German language skills and provided informed consent. Results and Conclusion(s): Significant age-effects were found regarding type and frequency of problems. While children had the largest increase in aggressive behaviours, adolescents reported the largest increase in emotional problems. Sociodemographic variables, exposure to and appraisal of COVID-19, psychotherapy before COVID-19 and parental mental health significantly predicted change in problemscores (F >= 3.69, p <= .001). Using growth mixture modelling, a oneclass solution was detected for the trajectory of aggressive behaviours and a two- and three-class solution for withdrawn/depression and anxiety/depression. A substantial proportion of children and adolescents experienced age-related mental health problems during the different stages of the COVID-19 pandemic. These results suggest that psychological problems of specific sub-groups should be monitored over the longer-term and interventions to improve communication, emotion regulation, and appraisal style should be offered to risk groups.
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Burkholderia pseudomallei is soil saprophytic Gram-negative bacilli that cause a fatal disease called melioidosis. Melioidosis is capable of causing cutaneous infection and systemic infections in the respiratory tract, cardiovascular, gastrointestinal, urinary, skin and soft tissue, and musculoskeletal and central nervous systems. Here, we report rare forms of pulmonary, cerebral, and splenic abscess case series of melioidosis caused by B. pseudomallei. Imported cases have been reported among tourists, immigrants, and soldiers who returned from endemic areas. The acquisition of infection is through percutaneous, inhalation, and ingestion of contaminated water;person-to-person transmission is very rare. Melioidosis cases are primarily found in the rainfall season and are usually associated with risk factors such as diabetes, alcoholism, and chronic renal diseases. However, 20-26% of cases were not associated with predisposing conditions. The identification is based on colony morphology, Gram stain, antibiotic susceptibility testing, and other supportive automated and molecular assays when we suspect B. pseudomallei. There are two phases, the intensive and eradication phases, in managing melioidosis. In the intensive phase, ceftazidime for 2 weeks showed efficacy in almost 50% of cases, and the eradication phase treatment with co-trimoxazole and doxycycline or amoxicillin/clavulanic acid for 3-6 months showed an excellent response. The improper clinical diagnosis and management of B. pseudomallei can lead to complications. Hence, early diagnosis with microbiological approaches such as culture, biochemical reactions, or automated systems available and antimicrobial sensitivity testing will cure the patient quickly without mortality.Copyright © 2023 The Authors.
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In phase 1 of CC-92480- MM- 001 (NCT03374085), the recommended phase 2 dose (RP2D) of mezigdomide plus dexamethasone (MEZI-d) was selected at 1 mg once daily for 21/28 days. Here we report preliminary results from the MEZI-d dose-expansion cohort in patients with heavily pretreated RRMM. Key eligibility criteria were: RRMM;>=3 prior lines of therapy;disease progression <=60 days of last myeloma therapy;refractoriness to lenalidomide/pomalidomide, a proteasome inhibitor, a glucocorticoid, and an anti-CD38 monoclonal antibody. Oral mezigdomide 1 mg was given on days 1-21 of each 28-day cycle, plus weekly dexamethasone (40 mg;20 mg if >75 years of age). Primary objective was to evaluate efficacy (overall response rate [ORR]);secondary objectives included safety/tolerability and additional efficacy assessments. Pharmacodynamics was an exploratory objective. As of 16/Sep/2022, 101 patients had received MEZI-d at the RP2D. Median age was 67 (range 42-85) years, median time since initial diagnosis was 7.4 (1.1-37.0) years;39.6% of patients had plasmacytomas and 37/101 patients had high-risk cytogenetics (56/101 not evaluable). Median number of prior regimens was 6 (3-15);prior therapies included stem cell transplantation (77.2%) and anti-BCMA therapy (29.7%). All patients were refractory to last myeloma regimen and triple-class refractory. Median follow-up was 7.5 (0.5-21.9) months, with a median of 4 (1-20) cycles;10.0% of patients continued treatment;progressive disease was the main reason for discontinuation (60.4%). ORR was 40.6% for all patients. Whilst data are not mature yet, median PFS was 4.4 (95% CI 3.0-5.5) months and median duration of response was 7.6 (95% CI 5.4-9.5) months. ORR was 30.0% in patients with plasmacytomas (N = 40) and 50.0% in patients with prior anti-BCMA therapy (N = 30). Ninety-one (91.1%) patients experienced a grade 3/4 treatment-emergent adverse event (TEAE). Most frequent hematologic grade 3/4 TEAEs were neutropenia (75.2%), anaemia (35.6%), and thrombocytopenia (27.7%);34.7% of patients had grade 3/4 infections, including grade 3/4 pneumonia (15.8%) and COVID-19 (7.0%). Occurrence of other grade 3/4 non-hematologic TEAEs was generally low. Due to TEAEs, 76.2% and 29.7% of patients had mezigdomide dose interruptions and reductions, respectively;90.1% of patients discontinued mezigdomide. Mezigdomide induced substrate degradation and increases in activated and proliferating T cells in patients, including those directly refractory to pomalidomide-based therapies. MEZI-d had a manageable safety profile with encouraging efficacy in patients with triple-class refractory RRMM, including patients with prior BCMA-targeted therapies. These results strongly support the continued development of mezigdomide in MM, and especially in combination.
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Timely, effective, and safe antiviral therapy in COVID-19 patients reduces complications, disability and mortality rates. The greatest concern with remdesivir is the risk of drug-induced liver injury, including in patients whose liver function is compromised by COVID-19. The aim of the study was to investigate the efficacy and safety of remdesivir in patients with confirmed SARSCoV-2 infection who had been admitted to an infectious diseases hospital in the Volgograd region in March 2022. Material(s) and Method(s): the authors carried out an open, non-randomised, single-arm study using medical records of 234 patients who had been diagnosed with "U07.1 COVID-19, virus identified" and prescribed remdesivir upon admission. The effectiveness of therapy was evaluated using two criteria: the need for oxygen supplementation or ventilatory support, or mortality. The authors conducted the evaluation on days 7, 14, and 28 using the six-point ordinal severity scale by Y. Wang et al. The safety of therapy was assessed on the basis of complaints and changes in laboratory findings. Result(s): for the patients prescribed remdesivir at admission, the 7-day mortality rate was 3.0%, the 14-day mortality rate was 5.6%, and the 28-day mortality rate was 7.3%. With the exception of a patient with myocardial infarction, all the patients who had been hospitalised with mild COVID-19 and prescribed remdesivir did not require oxygen therapy and/or transfer to intensive care and were discharged following recovery. The patients with moderate to severe COVID-19 had the 14-day mortality rate of 6.4% and the 28-day mortality rate of 8.6%. 17 patients (7.2%) discontinued remdesivir prematurely for various reasons, including adverse drug reactions. Remdesivir therapy of 5-10 days was associated with an increase in ALT activity by 2.7 +/- 0.8 times in 15.9% of patients with mild COVID-19, by 3.8 +/- 1.8 times in 20.4% of patients with moderately severe COVID-19, and by 4.8 +/- 2.7 times in 24% (12/50) of patients with severe COVID-19. In two patients (0.9%), the increase exceeded 10-fold the upper limit of normal. Conclusion(s): the obtained results support recommending remdesivir to patients with mild, moderate and severe COVID-19, including those with moderately elevated baseline activity of hepatic transaminases.Copyright © NEICON ISP LLC. All rights reserved.
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Objectives: Assessment of the literature on the ProtekDuo cannula when used as venopulmonary (V-P) extracorporeal membrane oxygenation (ECMO) in ARDS secondary to COVID-19. Method(s): Systematic literature search in EMBASE, Medline (Pubmed) and NHS library using appropriate keywords as well as PICOS and PRISMA approach. Result(s): We found 285 publications, of which 5 publications met the search criteria and were included in this review. A total of 194 patients with COVID-19 related ARDS had a ProtekDuo placed to establish venovenous (V-V) ECMO and right ventricular (RV) support. Patients treated with the ProtekDuo cannula had survival rates between between the studies of 59 and 89%, with a significant survival compared to an invasive ventilation group or when compared to dual site V-V ECMO or other double lumen ECMO cannulas. One of the studies focused on extubation and early discontinuation of ventilator support, which the authors achieved in 100% of ProtekDuo patients. The incidence of acute kidney injury (AKI) and use of continuous renal replacement therapy (CRRT) was significantly reduced in the ProtekDuo versus other groups. Conclusion(s): The ProtekDuo displayed lower mortality rates, AKI occurrence and CRRT need as compared to other respiratory support modalities and has shown to be a game changer for ECMO support in patients suffering from COVID-19 ARDS. Many authors suggested the ProtekDuo for first line use in these patients.
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The phase 3 MOMENTUM study (NCT04173494) of the ACVR1/JAK1/JAK2 inhibitor momelotinib (MMB) vs. danazol (DAN) in patients with myelofibrosis (MF) previously treated with a JAK inhibitor (JAKi) met the primary endpoint and all key secondary endpoints at week 24 (W24). We provide updated results from week 48 assessments. Eligible patients had primary or post-ET/ PV MF;DIPSS high, Int-2, or Int-1 risk;Total Symptom Score (TSS) >=10;haemoglobin (Hb) <10 g/dL;platelets >=25 x 109/L;prior JAKi for >=90 days (>=28 days if red blood cell [RBC] transfusions >=4 units in 8 weeks or grade 3/4 thrombocytopenia/anaemia/ hematoma);and palpable spleen >=5 cm. Randomisation was 2:1 to MMB 200 mg/day or DAN 600 mg/day for 24 weeks, followed by open-label (OL) MMB. Week 48 endpoints included durations of response (TSS, transfusion independence [TI], splenic) and overall and leukaemia-free survival (OS, LFS). As of 17 May 2022, 93/130 (72%) MMB -> MMB and 41/65 (63%) DAN -> MMB patients received OL MMB;mean MMB durations were 48 weeks and 24 weeks, respectively. Analyses for W24 responders showed the following: of TSS responders, 31/32 (97%) MMB -> MMB and 6/6 DAN -> MMB patients had TSS < baseline;of TI responders, 36/40 (90%) and 10/13 (77%) had no RBC transfusions or Hb <8 g/dL;and of spleen responders, all patients had splenic volume < baseline. In the OL phase, the most common grade >=3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (MMB -> MMB, 9%;DAN -> MMB, 15%) and anaemia (MMB -> MMB, 9%;DAN -> MMB, 2%). Grade >=3 infections occurred in 19% of MMB -> MMB and 10% of DAN -> MMB patients, including grade >=3 (nonfatal) COVID-19. Peripheral neuropathy (PN) occurred in 2% of patients in each arm, and none discontinued MMB due to PN. TEAEs led to MMB discontinuation in 18% (MMB -> MMB) vs. 10% (DAN -> MMB). A trend towards improved OS up to W24 was previously observed with MMB vs. DAN (hazard ratio [HR], 0.506;p = 0.0719);after all patients crossed over to OL MMB, OS and LFS curves for both arms converged (HR, 0.945, 95% CI, 0.528-1.693;HR, 0.830, 95% CI, 0.473-1.4555). Sixty of 81 (74%) MMB -> MMB and 29 of 43 (67%) DAN -> MMB patients with baseline platelets <=150 x 109/L entered the OL phase. Efficacy and safety results in thrombocytopenic subgroups in the OL period were consistent with the intent-to- treat (ITT) population. OL MMB maintained symptom, TI, and spleen responses with continued good survival and safety in the ITT and low platelet populations. MMB may address an unmet need in anaemic patients with MF.
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Background: The interaction between checkpoint inhibitors (CPI) and Sars-COV-2 vaccines has been understudied. One potential complication in pts receiving CPI is immune-mediated adverse events (irAEs) resulting from overactivation of the immune system. It is unknown whether concurrent CPI and Sars-COV-2 vaccine administration increases the risk of irAEs. This retrospective study examined the incidence of severe irAEs in cancer patients receiving CPI therapy at the time of vaccination against Sars CoV-2. Method(s): Following IRB approval, pts with solid tumors who received any approved CPI since FDA authorization of the COVID-19 vaccine in December 2020 were identified via institutional electronic health record. Pts who received one or more doses of an authorized vaccine within 60 days of CPI treatment were included. The primary endpoint was to evaluate the incidence of severe irAE (one or more of the following: grade 3 AE or above, multi-system involvement, need for hospitalization). Secondary endpoints included time between CPI and vaccination, need for immunosuppressive therapy, and rate of discontinuation of CPI due to irAE. Data was analyzed using descriptive statistics. Result(s): 290 pts with bladder, head/neck, liver, skin (melanoma, SCC), renal, and gynecologic cancer were included in analysis. The median age was 67 years (IQR: 59.0-74.0) and 66% pts were male. At the time of vaccination, 201 pts (69.3%) received CPI monotherapy, 53 pts (18.3%) received combination (combo) CPI therapy, and 36 pts (12.4%) received other therapies (chemo, TKIs, etc.) with CPI. The vaccine manufacturer was Pfizer Bio-N-Tech in 162 pts (55.9%), Moderna in 122 pts (42.1%), and Johnson and Johnson in 6 pts (2.1%). The number of vaccinations received was >/= 3 in 214 pts, 2 in 64 pts, and 1 in 11 pts. 30 pts (11.5%) experienced severe irAEs following vaccination. The rate of severe irAEs was 10.3% (30/290) in the total population [6% (12/201) with CPI monotherapy, 19% (10/53) with combo CPI, and 22% (8/36) in the combo CPI-other group]. Severe irAEs occurred after the first vaccine dose in 5 pts (16.7%), second dose in 16 pts (53.3%), and third dose in 9 pts (30%) pts. The median time between CPI treatment and vaccination in pts who experienced irAE was15.5 days (IQR: 10.2-23.0). Hospitalization was required for 19 patients (63.3%). 24 pts (80.0%) required immunosuppressive therapy with a median therapy duration of 98.5 days (IQR 40.2-173.0). 16 pts (53.5%) discontinued CPI therapy following severe irAEs Conclusion(s): In this retrospective study, we observed a 10.3% rate of severe irAE in cancer pts receiving CPI concurrently with COVID-19 vaccines. Further investigation in pts with additional cancer types is warranted to help determine best practice guidelines for COVID-19 vaccination in cancer patients receiving CPI.
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Objectives: Death from SARS-CoV-2 pneumonia resulted from progressive respiratory failure in most patients. Whenever accessible, venovenous extracorporeal membrane oxygenation (VVECMO) was implemented to rescue patients with refractory hypoxemia. Reported mortality in this population reached values from 20 to 50 percent, but the direct causes of death were not so widely acknowledged. The aim of our study was to characterize mortality in patients treated with VVECMO support. Method(s): Retrospective review of a prospectively collected database in an ECMO referral centre. All patients with diagnosis of SARS-CoV-2 infection treated with VVECMO support were included. Survivors and nonsurvivors were compared using t-student and chi2 methods. A Cox regression analysis was performed to identify predictors of mortality at admission. Result(s): Ninety-three patients were included (29% female). Median age was 54+/-12 years, mean SOFA was 5.7+/-2.9 and SAPS II was 35.6+/-13.6. Hospital mortality was 24.7%. Main causes of death were septic shock in 39.1% (9 patients), irreversible lung fibrosis 30.4% (7 patients) and catastrophic hemorrhage in 4.3% (4 patients). End-of-life care measures (withdrawal or withholding) were adopted in 65.2% of non-survivals. Patients who died were older (55 vs 48 years, p<0.05), had longer disease course (19 vs 15.3 days, p<0.05), longer invasive mechanical ventilation course before cannulation (8.5 vs 5 days, p<0.05), lower static lung compliance (25.5 vs 31.8 mL/cmH2O, p<0.05) and were ventilated with lower PEEP (8 vs 10 cmH2O, p<0.05) on cannulation. On a Cox-regression model, only prone ventilation before cannulation (HR 9,7;CI 95% 1,4- 68,6;p<0.05) and SAPS II (HR 1.04;CI 95% 1,001- 1,083;p<0.05) predicted mortality. Conclusion(s): Mortality in patients with severe SARSCoV-2 pneumonia treated with VVECMO was exceedingly low in our study, when compared with other series. Only one-third died from progressive lung disease, which suggests that protocol improvement can further reduce mortality.
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Introduction: Over 200,000 patients survive an intensive care admission each year in the United Kingdom (UK). For patients, survival is frequently beset by a range of chronic disabilities. Approximately 50% must navigate an often complex convalescence, while suffering serious and persistent symptoms of post-traumatic stress disorder (PTSD), anxiety and/or depression.1 Eye-movement desensitisation and reprocessing (EMDR) is a trauma-focussed psychological therapy, recommended for treating PTSD by the International Society for Traumatic Stress Studies2 and NICE.3 However, EMDR has never been systematically investigated for patient benefit following intensive care admission. Objective(s): CovEMERALD4 evaluated the feasibility of delivering a randomised controlled trial (RCT), testing the effect of EMDR on the psychological health of intensive care survivors, following COVID-19 related critical illness. We also provide preliminary evidence of the effect on clinically relevant outcomes. Findings will inform the design of a subsequent fully-powered RCT. Method(s): This feasibility RCT was conducted at a single-centre, teaching hospital in the UK (University Hospital Southampton). Patients were eligible if they were admitted to intensive care for over 24-hours with confirmed COVID-19, were above 18 years of age, were recruited within 3-months of hospital discharge, and had no cognitive impairment or pre-existing psychotic diagnosis. Participants were randomised (1:1) to receive either up to 8 sessions of remotely-delivered EMDR (Recent traumatic events protocol) or standard care alone as the control group (CG). Psychometric evaluation was undertaken at Baseline and 6-months after hospital discharge. Result(s): Seventy-five consecutive patients were screened at hospital discharge, from October 2020 to April 2021. 51 eligible patients approached. 26 (51%) provided consent. Reasons for declining participation were;no psychological distress (n=16), no internet access (n=7) and being physically unready (n=2). Demographic variables were balanced between groups. Of the 13 patients randomised to EMDR, one withdrew prior to intervention: the remaining attended all sessions recommended by the psychological therapists (mean of 3-4 sessions per patient), giving an overall adherence of 93%. One patient from each group declined the 6-month follow-up evaluation, so trial completion was possible in 23 of 26 (88%) participants. No reasons for trial withdrawal were given. There were no attributable adverse events. Mean change in PTSD score (PTSD Checklist-Civilian) from Baseline to 6-months, was -8 (SD=10.49) in the EMDR group vs. +0.75 (SD=15.17) in CG (p=0.126). Mean change in anxiety (Hospital Anxiety and Depression Scale-Anxiety) was -0.45 (SD=2.3) following EMDR vs. -0.83 (SD=4.0) in the CG (p=0.787), and median change in depression (HADS-D) was -2(IQR:-3.0,1.0) following EMDR vs. +1(IQR-1.5,2.0) in the CG (p=0.263). Figure 1. Box-plot of change in PTSD symptoms (PCL-C) from baseline to 6-months post-hospital discharge for control group and EMDR intervention group. Conclusion(s): EMDR can improve psychological recovery following an intensive care admission for COVID-19, and appeared feasible and safe. Although not powered to determine clinical effectiveness, this single-centre feasibility study returned a positive signal, in reducing PTSD and depressive symptoms. A full results manuscript will be submitted prior to congress. CovEMERALD has supported a successful NIHR doctoral fellowship application, during which protocol refinements will be tested, within existing, and recommended rehabilitation pathways. Trial activity and progression will be consistent with the Medical Research Council framework for developing and evaluating complex healthcare interventions.5.
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The proceedings contain 9 papers. The topics discussed include: dulaglutide and NAFLD risk reduction;correlation between plasmatic long pentraxin PTX3 and nodular thyroid disease: a preliminary report;the fructose-bisphosphate aldolase a act as autoantigen in primary autoimmune hypophysitis;cortisol deficiency in Lenvatinib treatment;side effects of mitotane treatment: a retrospective study in 35 patients with adrenocortical carcinoma in adjuvant therapy;non-functioning pituitary adenoma: do predictor factors exist?;incidence and features of adrenal crisis in a series of 133 patients with Addison's disease;serological evidence and self-reported outcomes in patients with adrenal insufficiency during the first waves of COVID-19 in the North-East Italy;and persistent effects of spironolactone after its withdrawal in patients with hyperandrogenic skin disorders.
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Introduction: Bruton's tyrosine kinase inhibitors (BTKi) are used extensively within the NHS to treat specific B-cell malignancies with patients stopping BTKi usually due to adverse events or disease progression. The objective of this study was to analyse effectiveness of BTKi therapy for chronic lymphocytic leukaemia (CLL) at our centre compared to previously published real-world data from the UKCLL Forum (Follows et al, Blood 2019). In addition, we investigated treatment-related adverse events (AE) and second malignancies. Method(s): This is a single-centre retrospective study of 112 CLL patients treated with a BTKi for a minimum of 4 weeks between 2014 and 2022 (ibrutinib n = 71, acalabrutinib n = 38, zanubrutinib n = 3). Treatment was first line (n = 39), second line (n = 44) and 3+ line (n = 29). Patient demographics, duration of BTKi therapy, Aes, discontinuation reasons and second malignancies were collected. Aes were compared with a parallel cohort of 53 non-CLL BTKi-treated patients. Result(s): Median age starting treatment was 73 years, and 71% were male. Primary outcomes were discontinuation-free survival (DFS) and overall survival (OS). With a median follow-up of 3.90 years, the median DFS was 4.18 years (95% CI: 3.52-4.91) with a median OS of 6.35 years (95% CI: 5.52-NA). These compare favourably with previous UKCLL forum data (median DFS = 2.79 years;median OS = 4.66 years), although our patients were more likely to receive BTKi earlier in treatment (3rd line or beyond: 26% of our patients vs. 78% in the UKCLL Forum). The most common Aes included bleeding, cytopenia, infection, cardiac events and mouth ulcers, with 21% stopping BTKi for CLL due to Aes whilst 15% of non-CLL BTKi patients stopped due to an AE. Second malignancies were reported in 49% of CLL patients, yet only 34% of non-CLL patients. Among patients with a confirmed cause of death, infection was the most common cause (39%), followed by CLL (33%), then second malignancy (18%). Of the 31 deaths in 2020 and 2021, 7/31 (23%) were due to, or in association with COVID-19 infection. No COVID-19 deaths were associated with BTKi in non-CLL patients. Conclusion(s): We demonstrate a favourable real-world DFS and OS for BTKi-treated CLL patients although a high number of patients still stop BTKi due to Aes. The very high incidence of second malignancies for all BTKi-treated patients and COVID-19 and infection-related deaths for CLL patients is concerning. As CLL is known to associate with high levels of second cancers, it remains unclear whether BTKi use increases this risk further.
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Background/Aims Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to >=1 biologic disease modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. We aimed to evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECTPsA 2. Methods Pts were randomized to UPA 15mg (UPA15), UPA 30mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatmentemergent adverse events (TEAEs) were summarized for pts who received >=1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received >=1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks. Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 were consistent with that reported at wk 56. Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and two with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion In PsA pts with prior inadequate response or intolerance to>=1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to two years of treatment. No new safety signals were identified in this long-term extension.
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Introduction: Children requiring venoarterial (VA) extracorporeal membrane oxygenation for long durations may have increased risk of complications compared to venovenous (VV) ECMO. The purpose of this study was to evaluate the feasibility and safety of conversion from VA to VV ECMO. Method(s): This is a retrospective review of all children requiring VA ECMO who underwent conversion to VV ECMO at a single institution, from 2015- 2022. Indications for and methods of conversion were examined as well as adverse events including re-operation, ischemic complications, renal failure, and mortality. Descriptive statistics were calculated. Result(s): Of 422 pediatric patients on initial VA ECMO, only three children (0.7%) underwent conversion from VA to VV support, ages 10-19: for hypoxic respiratory failure due to COVID19, for cardiac dysfunction following orthotopic heart transplant, and for sepsis with associated left ventricular dysfunction. The indications for conversion were bleeding from cannulation site (n=2, 66%) and an anticipated prolonged ECMO run (n=1, 33%). For all three patients, the method of conversion was cutdown with femoral arterial repair followed by placement of additional jugular venous cannulas (n=2, 66%) or insertion of a singular jugular bicaval venous cannula with removal of the femoral cannulas (n=1, 33%). The median time on VA ECMO prior to conversion was 8 days (range 4-54 days). All 3 patients were managed with renal replacement therapy with 1 patient (33%) progressing to long term dialysis. There were no significant ischemic limb complications although one (33%) patient developed a femoral artery pseudoaneurysm that required re-operation. Two of the three patients (66%) were able to be decannulated at a median of 23.5 days (range 8-39 days) following conversion to VV ECMO and survived to discharge. The other patient was unable to be decannulated after successful conversion and care was withdrawn. Conclusion(s): Based on this small pilot study, conversion to VV ECMO from initial femoral VA ECMO cannulation is safe and feasible. Indications for conversion include coagulopathy and need for extended ECMO run after recovery of cardiac function.
ABSTRACT
Introduction: Drug-induced liver injury (DILI) is defined as hepatic dysfunction caused by prescription medications, supplements, or xenobiotics after alternative causes have been excluded. As one of the leading causes of acute liver failure, DILI should be considered when patients present with hepatic dysfunction. We present a case of symptomatic DILI secondary to artemisinin use. Case Description/Methods: A 78-year-old Chinese man with no medical history presented to the hepatology clinic with 10 weeks of jaundice, weakness, and pruritis. He started taking Artemisinin/ Bioperine 12 weeks ago to prevent COVID-19 but stopped 3 weeks ago. He denied abdominal pain, a family history of liver disease, substance/alcohol use, and taking other concomitant drugs. Physical examination revealed scleral icterus and no other signs of chronic liver disease. Laboratory studies showed total bilirubin 11 mg/dL, alkaline phosphatase 293 U/L, aspartate transaminase 170 U/L, and alanine transaminase 196 U/L with negative workup for hepatitis A, B, and C. CT abdomen and MRCP were unremarkable for liver or biliary pathology. Further serological workup was negative and follow-up labs revealed normalization of liver enzymes and bilirubin. Given the patient's improvement, liver biopsy was not pursued. The patient was instructed to avoid supplements unless prescribed by a physician. Discussion(s): DILI is a global issue with an estimated annual incidence rate of 13.9 to 24.0 per 100,000 persons. Diagnosing DILI is important as it can cause acute liver injury and liver failure in certain cases. Since COVID-19 emerged, supplement use has increased given claims of boosting the immune system. Artemisinin is an herb used in traditional Chinese medicine with antimalarial activity investigated to be a possible COVID-19 treatment, but no current evidence exists to support it being effective against COVID-193. Our patient's supplement also contained Bioperine, a black pepper extract, which is likely benign. Contrarily, artemisinin is a well-described cause of idiosyncratic acute liver injury and hepatotoxicity, causing self-limited mild to moderate transaminitis but also severe cases requiring emergent livertransplantation. Our patient's unrevealing workup, his spontaneous improvement correlating with supplement discontinuation, and RUCAM score of 7 led to high suspicion of DILI secondary to artemisinin. Providers should always ask patients about supplement use and consider DILI when patients present with liver injury. (Table Presented).
ABSTRACT
History: Twenty-two year old male basic trainee was brought to the ED after collapsing during a routine ruck march. At mile 8/12, soldier was noted to develop an unsteady gate and had witnessed loss of consciousness. A rectal core temperature was obtained and noted to be >107degreeF. Cooling initiated with ice sheets and EMS was activated. On arrival to the ED, patient demonstrated confusion and persistently elevated core temperatures despite ice sheeting, chilled saline and cold water bladder lavage. Cooling measures were discontinued after patient achieved euthermia in the ED;however, his temperatures subsequently spiked>103degreeF. Given rebound hyperthermia, an endovascular cooling (EVC) device was placed in the right femoral vein and patient was transferred to the ICU. Multiple attempts to place EVC device on standby were unsuccessful with subsequent rebound hyperthermia. Prolonged cooling was required. Physical Exam: VS: HR 121, BP 85/68, RR 22 SpO2 100% RA, Temp 102.4degreeF Gen: young adult male, NAD, shivering, A&Ox2 (person and place only) HEENT: Scleral anicteric, conjunctiva non-injected, moist mucus membranes Neck: Supple, no LAD Chest: CTAB, no wheezes/rales/rhonchi CV: tachycardia, regular rhythm, normal S1, S2 without murmurs, rubs, gallops ABD: NABS, soft/non-distended, no guarding or rebound EXT: No LE edema, tenderness SKIN: blisters with broad erythematous bases on bilateral heels Neuro: CN II-XII grossly intact, 5/5 strength in all extremities. Differential Diagnosis: 216. Septic Shock 217. Hypothalamic Stroke 218. Exertional Heat Stroke (EHS) 219. Neuroleptic Malignant Syndrome 220. Thyroid Storm Test Results: CBC: 18.2>14.5/40.6<167 CMP: 128/3.5 88/1831/2.7<104, AST 264, ALT 80, Ca 8.8 Lactate: 7.1 CK: 11 460 Myoglobin: 18 017 TSH: 3.16 CXR: No acute cardiopulmonary process Blood Cx: negative x2 CSF Cx: Negative COVID/Influenza/EBV: Negative Brain MRI: wnl. Final Diagnosis: Exertional Heat Stroke. Discussion(s): No EVC protocols exist for the management of EHS or rebound/refractory hyperthermia. As a result, the protocol used for this patient was adapted from post-cardiac arrest cooling protocols. It is unclear if this adapted protocol contributed to his delayed cooling and rebound hyperthermia as it was not intended for this patient demographic/ pathophysiology. Furthermore, despite initiating empiric antibiotics upon admission, delayed recognition and tailored therapy for his bilateral ankle cellulitis may have contributed to the difficulty in achieving euthermia. In summary, more research needs to be done to evaluate and develop an EVC protocol for EHS. Outcome(s): Euthermia was achieved and maintained after 36 hours of continuous EVC, at which point it was discontinued. His CK, AST/ALT, creatinine and sodium down-trended after discontinuation of EVC. Patient's antibiotics were transitioned to an oral formulation for treatment of ankle cellulitis and he was prepared for discharge. He was discharged with regular follow-up with the Fort Benning Heat Clinic. Follow-Up: After discharge, patient had regularly scheduled visits with the Fort Benning Heat Clinic. His typical lab markers for exertional heat stroke were regularly monitored. He had continued resolution of his Rhabdomyolysis, acute kidney injury and hyponatremia with typical treatment. Soldier returned to duty after 10 weeks of close monitoring and rehabilitation.