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1.
Egypt Heart J ; 73(1): 108, 2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-2098510

ABSTRACT

BACKGROUND: Myocardial damage worsens the clinical course and prognosis of coronavirus disease 2019 (COVID-19) patients. High total bilirubin levels have been associated with a poor prognosis in COVID-19. This study aimed to investigate the predictive value of the total bilirubin level, a marker of heme oxygenase-1 enzyme activity, in determining myocarditis in patients with COVID-19. RESULTS: A total of 190 patients diagnosed with COVID-19 were enrolled in the study. The patients were divided into two groups based on their troponin positivity. The study group (n = 95) consisted of patients with high troponin, and the control group (n = 95) consisted of patients without high troponin levels. The D-dimer (727 [572-995] vs. 591 [440-790], p = 0.001), C-reactive protein (CRP) (30.0 [10-48] vs. 10.3 [5.8-15.9], p < 0.001), and total bilirubin (9.5 [8.2-12.1] vs. 7.0 [5.3-8.0], p < 0.001) levels were significantly higher in the study group. In multivariate analysis, CRP (odds ratio [OR]: 1.103; 95% confidence interval [CI]: 1.060-1.148; p < 0.001) and total bilirubin (OR: 1.612; 95% CI: 1.330-1.954; p < 0.001) levels were independent predictors of myocarditis in COVID-19. CONCLUSIONS: Total bilirubin levels can be used as an early predictor of myocarditis in COVID-19 and can contribute to therapy management.

2.
Chemistry of Materials ; 2022.
Article in English | Web of Science | ID: covidwho-2096612

ABSTRACT

Interest in developing and applying emerging biomaterials to sensing and energy devices' frameworks has dramatically climbed in recent years. The world has been recently threatened by the COVID-19 pandemic, generating a sprint for reliable manufacturing and analysis, low-cost detection methods. The challenge is implied in the elaboration of innovative materials and the design of biointerfaces to thrive in the sensing objectives. Concomitantly, the global search for economic growth and recovery is rebounding on energy demand, surpassing growth in energy generation from renewable sources. Therefore, efforts are being focused on the conception and application of biomaterials for the eco-friendly generation, storage, and conversion of energy. Here, we offer some highlights of the rational design of biomaterials and challenges to be overcome in the near future for the commercial consolidation of biodevices in these two segments.

3.
Int J Immunopathol Pharmacol ; 36: 3946320221133952, 2022.
Article in English | MEDLINE | ID: covidwho-2064535

ABSTRACT

OBJECTIVES: To evaluate the ABO blood type and indirect bilirubin to predict early mortality in adults with severe COVID-19. METHODS: This retrospective observational study was conducted on 268 adult patients with laboratory-confirmed COVID-19 who had attended the intensive care unit (ICU), Quena general hospital and Luxor International Hospital, and other hospitals or centers for the treatment of COVID-19, during the period from January 2021 till December 2021. RESULTS: Relation between mortality and ABO group were highly significant, as we found non-O blood group with more risk of early mortality and intensive care unit admission ICU. There were significant differences between dead and alive cases as regards platelets, white blood cells WBCs (neutrophil, lymphocyte), albumin, liver enzymes aspartate transeferase (AST), alanine transferase (ALT), total direct and indirect bilirubin, creatinine, and urea. CONCLUSION: There was a highly significant relation between dead cases and ABO blood group as between the O and non-O groups; also, group O was associated with less severe manifestations and or ventilation and less mortality in patients with severe COVID-19 infection. Direct bilirubin >0.5 was found to be the best predictor for mortality in cases with COVID-19 so indirect bilirubin may be considered a good protector against complications of the infection.


Subject(s)
COVID-19 , ABO Blood-Group System , Alanine , Alanine Transaminase , Albumins , Aspartic Acid , Bilirubin , Creatinine , Humans , Phenotype , Retrospective Studies , SARS-CoV-2 , Urea
4.
Liver Int ; 42(11): 2453-2465, 2022 11.
Article in English | MEDLINE | ID: covidwho-2063872

ABSTRACT

BACKGROUND & AIMS: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy. METHODS: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs). RESULTS: One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37, 1.00-1.87), Child-Pugh score (1.79, 1.28-2.50), MELD (1.17, 1.04-1.30) and bilirubin (1.83, 1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10-3.36), lower albumin levels (0.18, 0.06-0.51), Child-Pugh score (2.43, 1.50-4.04), history of ascites (3.5, 1.85-6.5) and bilirubin (1.30, 1.05-1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. CONCLUSIONS: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use.


Subject(s)
Liver Cirrhosis, Biliary , Albumins/therapeutic use , Ascites/drug therapy , Ascites/etiology , Bilirubin , Chenodeoxycholic Acid/analogs & derivatives , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Liver Cirrhosis, Biliary/complications , Liver Cirrhosis, Biliary/drug therapy , Male
5.
Gut ; 71(Suppl 3):A83, 2022.
Article in English | ProQuest Central | ID: covidwho-2064233

ABSTRACT

P69 Table 1Demographic and transplant data for all 14 prioritised patientsPatient/Sex Centre Age at registration (yrs) Primary liver disease Registered prior to Prioritisation Indication of Prioritization LT Waiting time on prioritised tier/Time on list prior to prioritisation 1/M 1 0 CDG Yes Acute decompensation with presence of encephalopathy Yes/LLS 5/27 2/M 2 1 Cryptogenic Cirrhosis Yes CLD with nodular lesions s/o HCC Yes/LLS 16/48 3/F 1 15 AILD Yes Chronic rejection Yes/whole liver 3/4 4/M 2 0 Biliary Atresia Yes PTLD/HAT/Sepsis Yes/LLS 14/71 5/F 2 4 IFALD No Coagulopathy with active bleeding/Renal impairment Yes/LLS 15/820 6/F 2 0 Biliary Atresia Yes Acute decompensation due to portal hypertension Yes/LLS 37/405 7/M 2 10 NSC Yes Decompensated chronic liver disease/Renal impairment Yes/reduced R lobe 4/7 8/M 3 8 PFIC3 Yes Acute decompensation of Chronic liver disease Yes/LLS 6/51 9/F 1 0 Other (Hepatoblastoma) Intestinal Tx prioritized Acute decompensation of Chronic liver disease Yes/LLS 11/ 10/F 2 0 Biliary atresia Yes Decompensated Chronic Liver Disease with Severe Coagulopathy Yes/LLS 10/120 11/M 1 0 Biliary atresia (Hepatoblastoma) Yes Acute decompensation of Chronic liver disease Yes/LLS 9/4 12/F 3 0 Biliary atresia Yes Acute decompensation of Chronic liver disease Yes/LLS 12/323 13/F 1 17 Hepatic Artery thrombosis Yes Hepatic Artery thrombosis Yes/whole liver 2/ 14/F 2 0 Biliary atresia Yes Acute decompensation of Chronic liver disease Suspended 12/65 PFIC3;Progressive Familial Intrahepatic Cholestasis type 3, LT;Liver transplantation, HCC;Hepatocellular Carcinoma NSC;Neonatal Sclerosing Cholangitis, CDG;Congenital Disorder of Glycosylation, AILD;Autoimmune Liver Disease, IFALD;Intestinal Failure Associated Liver Disease,PTLD;Center 1-Kings;Center2-Birmingham;Center3-Leeds.ConclusionThe national paediatric prioritization tier, introduced during the COVID19 pandemic, has been a pivotal initiative for the UK paediatric LT program, showcasing national collaboration. All patients underwent a LT successfully within a short time from prioritization with 100% patient and graft survival. The intention is to maintain this prioritized paediatric tier beyond the pandemic.

6.
Gut ; 71(Suppl 3):A13-A14, 2022.
Article in English | ProQuest Central | ID: covidwho-2064219

ABSTRACT

OP06 Table 1Demographics of patients Valid (n=) Missing (n=) Mean Std. Deviation Minimum Maximum Age (years) 134 0 55.522 15.111 17 87 Metabolic risk factors BMI in kg/m2 129 5 34.875 7.168 21.5 59.3 HbA1c (mmol/mol) 118 16 47.398 14.793 27 94 Total cholesterol (mmol/L) 119 15 4.646 1.195 1.9 7.4 Triglyceride level (mmol/L) 104 30 2.117 1.211 0.6 7.1 Blood tests AST U/L 116 18 48.621 36.672 14 318 ALT U/L 134 0 61.515 49.304 8 367 Bilirubin umol/L 134 0 11.261 9.398 3 59 Albumin g/L 133 1 44.12 4.624 21 53 Platelet count (x10*9/L) 134 0 229.343 83.631 23 509 INR 98 36 1.052 0.22 0.9 2.5 Fibrosis assessment Enhanced liver fibrosis (ELF) 16 118 9.671 0.754 8.31 11.06 Elastography (kPa) 79 55 10.944 7.049 2.5 39 CAP score 78 56 315.808 59.388 104 400 ConclusionOur study showed that patients with underlying metabolic risk factors were treated in 80% of cases. TE is not performed in all patients due to social isolation limitation imposed by covid-19 infection. In those who had TE;the index diagnosis of cirrhosis was seen in around 20% at the time of TE.

7.
American Journal of Transplantation ; 22(Supplement 3):971, 2022.
Article in English | EMBASE | ID: covidwho-2063416

ABSTRACT

Purpose: Despite known increases in alcohol use, changes in alcohol-associated liver disease rates during COVID-19 have not been well characterized. We compared the incidence and outcomes of hospitalized patients with acute alcoholic hepatitis (AH) before and during COVID-19. Method(s): We identified patients admitted with AH at two tertiary care centers by retrospective chart review in pre-COVID-19 (4/1-6/31/2019) and during COVID-19 (4/1-6/31/2020) time periods using strict criteria (total bilirubin>3.0, AST 35-500, ALT 49-500, and heavy drinking within 60 days of admission). Severe AH was defined as Maddrey's discriminant function (MDF) >= 32. Univariable comparisons were performed using Chi-square and Wilcoxon rank sum tests as appropriate. Result(s): Inpatient admissions for AH increased from 0.13% (90 of 69610) pre- COVID-19 to 0.25% (160 of 63021) during COVID-19 (P<.001). During COVID-19, AH patients had lower rates of polysubstance abuse (40% vs 18%, P<.001) compared to pre-COVID-19 (Table 1). Mental health and substance abuse (MHSA) consult rate was 52% pre- and during COVID-19. Relapse medication use rate was 8% and did not differ significantly between time periods. In severe AH (N=127) frequency of steroid treatment (39% vs 48%, P=0.31), evaluation for (12% vs 16%, P=0.61) or receipt of liver transplant (2% vs 4%, P=1.00) were similar pre- and during COVID-19. Compared to pre-COVID-19, AH patients during COVID-19 had significantly lower rates of all-cause 90-day readmission (59% vs 42%, P=0.02), but there was no difference in rates of 90-day readmission for AH (27% vs 22%, P=0.47), inpatient mortality (11% vs 9%, P=0.66) and 12-month mortality (30% vs 23%, P=0.23). Conclusion(s): Inpatient admission rates for AH nearly doubled during COVID-19. Polysubstance abuse was less common among patients with AH during COVID-19, but 90-day readmission rates remained high pre- and during COVID-19. Low rates of both MHSA consult and relapse medication use indicate a need for greater attention to inpatient alcohol treatment. (Table Presented).

8.
Chest ; 162(4):A1071, 2022.
Article in English | EMBASE | ID: covidwho-2060764

ABSTRACT

SESSION TITLE: Critical Renal and Endocrine Disorders Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Sickle Cell Disease (SCD) is an autosomal recessive disease characterized by an abnormal beta-globin chain of hemoglobin (Hb) that leads to malformed sickled cells with a multitude of downstream microvascular occlusions and anemia. While splenic infarction is by far the most common gastrointestinal (GI) manifestation, vaso-occlusion may occur in the liver, leading to an acute hepatic crisis. Acute hepatic sequestration of sickled erythrocytes is an exceedingly rare manifestation. CASE PRESENTATION: A 43-year-old man with homozygous sickle cell disease complicated by End-Stage renal disease was admitted with generalized malaise, right upper quadrant (RUQ) abdominal pain, nausea and vomiting. He was febrile with a temperature of 38.1°C, hypotensive with a blood pressure of 93/61 mmHg and tachycardic with a heart rate of 120 bpm. He was lethargic and uncomfortable with diffuse abdominal tenderness without guarding. Due to concern for septic shock, blood cultures, COVID PCR and influenza were obtained, and the patient was rapidly transferred to the intensive care unit for closer monitoring. Empiric vancomycin and cefepime were started promptly. The initial hemoglobin level was 6.1mg/dL with a leukocytosis of 31.2 K/CUMM and absolute neutrophil count of 21.8 K/CUMM;total hyperbilirubinemia of 17.45 mg/dL, direct hyperbilirubinemia of 11.46mg/dL and elevated INR at 1.66. Computed tomography of the abdomen and pelvis without contrast showed a known 4 cm cystic lesion of the right hepatic lobe and atrophic kidneys. Duplex flow of the abdomen and pelvis showed no portal vein thrombosis and patent flow in the portal vein and artery. Over the course of several hours, the patient's hemoglobin dropped to 3.8mg/dL with a steep rise in LDH and total bilirubin to 632 U/L and 27.04 mg/dL, respectively consistent with hepatic sequestration crisis. Patient was transfused with two units of packed red blood cells, fluid hydration and initiation of erythrocyte exchange transfusion. Prior to receiving exchange transfusion, the patient experienced rapid clinical deterioration with subsequent pulseless electrical activity. Return of spontaneous circulation was achieved transiently however patient's family at this point opted for palliative measures and the patient passed away shortly thereafter. DISCUSSION: Complications of SCD manifest in multiple organ systems. One of the few acute manifestations, hepatic sequestration crisis, is often unfamiliar to many clinicians and left unrecognized, results in poor clinical outcomes. It is rarely encountered and treatment options with blood and, more importantly, exchange transfusion remains often underutilized. CONCLUSIONS: Acute hepatic sequestration crisis is an often-unrecognized manifestation of SCD in which delay in diagnosis and prompt treatment with exchange and blood transfusions may impart a significant risk of mortality in an already prone patient population. Reference #1: Shah R, Taborda C, Chawla S. Acute and chronic hepatobiliary manifestations of sickle cell disease: a review World J Gastrointestinal Pathophysiology 2017;8(3): 108-116 Reference #2: Norris W. Acute hepatic sequestration in sickle cell disease. J of the National Medical Association 2004;96: 1235-1239 Reference #3: Praharaj D, Anand A. Sickle Hepatopathy J of Clinical and Experimental Hepatology 2021;11: 82-96 DISCLOSURES: No relevant relationships by Karim Dirani No relevant relationships by Georgiana Marusca No relevant relationships by Aryan Shiari

9.
Chest ; 162(4):A895, 2022.
Article in English | EMBASE | ID: covidwho-2060719

ABSTRACT

SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: SARS-CoV-2 related autoimmune and thrombotic complications due to vigorous immune system stimulation and induction of hypercoagulable state are not uncommon. Two hypotheses have been proposed for thrombotic microangiopathy associated with low ADAMTS13 levels in patients with COVID-19 disease. First underscores a significant increase in von Willebrand factor (vWF), likely due to endothelial activation, that overwhelms ADAMTS13. It is observed in the absence of thrombocytopenia or ADAMTS13 inhibitor. The second highlights the formation of autoantibodies against ADAMTS13 because of an immunological trigger (SARS-CoV-2), resulting in the diagnosis of TTP. CASE PRESENTATION: This is a case of a 72-year-old Caucasian man with a history of hypertension, diabetes, chronic obstructive lung disease, and asymptomatic SARS-CoV-2 infection three weeks ago who was transferred to our institution to initiate plasmapheresis for suspected TTP due to new-onset confusion, anemia and worsening renal function. Patient had presented with confusion a day before transfer. Vital signs were remarkable for tachycardia (heart rate of 105 beats/min). Labs were significant for anemia (hemoglobin:6.7 g/dL), thrombocytopenia (platelet count:13 K/µL), acute kidney injury (creatinine:1.8 mg/dL), elevated lactate dehydrogenase (1983 IU/L), high bilirubin (2.3 mg/dL), low haptoglobin (<4 mg/dL), and demonstration of schistocytes on peripheral smear. The coagulation profile was normal. On arrival, he required emergent intubation due to multiple seizures. Computed tomography scan of the head was normal. SARS-CoV-2 molecular testing was negative. Given a PLASMIC score of six, urgent plasmapheresis and high-dose methylprednisolone were started. Screening for human immunodeficiency virus, hepatitis viruses, Epstein-Barr virus, and Cytomegalovirus were negative. Subsequently, his ADAMTS13 activity resulted as being ≤5% with an elevated inhibitor Bethesda titer of 0.9 (normal < 0.4). The patient completed six sessions of plasmapheresis. He was discharged on steroid taper and weekly rituximab. DISCUSSION: COVID-19 associated de-novo TTP has been mostly reported with typical COVID-19 symptoms within a few days of a positive test. One report described presentation with only neurological symptoms 19 days after a positive test with low autoantibody titers, favoring the hypothesis of consumption of ADAMTS13. To the best of our knowledge, this is the first case of new, late-onset immune TTP developing three weeks after asymptomatic COVID-19 infection with a robust positive inhibitor screen and infinitesimal ADATMS13 levels. The temporal sequence of events and lack of other plausible causes aided in the diagnosis of COVID-19 induced TTP. CONCLUSIONS: Our report aims to make clinicians aware of ruling out TTP as a cause of thrombocytopenia and/or altered mental status in patients with past COVID-19 infection, aiding in early management. Reference #1: 1. Mancini I, Baronciani L, Artoni A, Colpani P, Biganzoli M, Cozzi G, Novembrino C, Boscolo Anzoletti M, De Zan V, Pagliari MT, Gualtierotti R, Aliberti S, Panigada M, Grasselli G, Blasi F, Peyvandi F. The ADAMTS13-von Willebrand factor axis in COVID-19 patients. J Thromb Haemost. 2021 Feb;19(2):513-521. doi: 10.1111/jth.15191. Epub 2020 Dec 18. PMID: 33230904;PMCID: PMC7753796. Reference #2: 2. Tehrani HA, Darnahal M, Vaezi M, Haghighi S. COVID-19 associated thrombotic thrombocytopenic purpura (TTP);A case series and mini-review. Int Immunopharmacol. 2021;93:107397. doi:10.1016/j.intimp.2021.107397 Reference #3: 3. Beaulieu, M.-C., Mettelus, D.S., Rioux-Massé, B. and Mahone, M. (2021), Thrombotic thrombocytopenic purpura as the initial presentation of COVID-19. J. Thromb. Haemost., 19: 1132-1134. https://doi-org.libproxy.uams.edu/10.1111/jth.15231 DISCLOSURES: No relevant relationships by Harmeen Goraya No relevant relationships by PRACHI SALUJA

10.
Chest ; 162(4):A883, 2022.
Article in English | EMBASE | ID: covidwho-2060717

ABSTRACT

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: COVID-19 is a systemic infectious and inflammatory disease, with multifactorial immunosuppression during the recovery phase which predisposes to serious infections. Although the gastrointestinal (GI) system is often affected in post-acute COVID-19 patients, liver abscess formation is rare. Here, we present a case of septic shock caused by a bacterial liver abscess in a survivor of severe COVID-19. CASE PRESENTATION: 78-year-old man with no past medical or surgical history was admitted to an outside hospital (OSH) with severe COVID-19 pneumonia and discharged after 14 days. He required high flow nasal cannula and was treated with Remdesevir, Dexamethasone, and Baricitinib. D-dimer was elevated without evidence of acute venous thromboembolism. Four weeks later he returned to the OSH due to dyspnea and was found to be hypotensive and hypoxemic. Laboratories showed leukocytosis, hyperlactatemia, and mild elevation of total bilirubin and transaminases. Whole-body CT scan revealed a small RUL pulmonary embolus and a 7cm multifocal loculated complex fluid collection indicative of a left hepatic lobe abscess. He was managed with supplemental oxygen, anticoagulation, broad-spectrum antibiotics, IV fluids, and vasopressors and transferred to our hospital for abscess drainage. The liver abscess was aspirated after an abdominal MR confirmed the findings and the septic shock subsequently resolved. Body fluid and blood cultures grew pan-sensitive Klebsiella pneumoniae. Antibiotics were narrowed to levofloxacin. He remained hemodynamically stable and was discharged home. DISCUSSION: In our patient, the underlying cause of bacterial inoculation of the liver and abscess formation remains unclear and is not fully explained by drug-induced immunosuppression given the frequency with which these medications are used. Hepatic abscesses often develop after liver injury and, in COVID-19, multiple mechanisms of liver injury have been proposed which may predispose to abscess formation. Specifically, in our case, it is likely that hypoxic hepatitis and arterial/venous thrombosis from hypercoagulability played a role in abscess formation given the need for supplemental oxygen and the presence of a pulmonary embolism. Additionally, in COVID-19, increased hepatobiliary expression of ACE2 may contribute to direct viral cytotoxicity of the liver and substantial dysbiosis may lead to cholestasis and bacterial translocation. CONCLUSIONS: Our case is unique and underlines the importance of having a high index of suspicion and monitoring for "occult infections,” such as liver abscesses in the COVID-19 recovery phase, even in those without prior GI medical history and with non-specific signs and symptoms. Further elucidation of the cause of liver injury and abscess formation are warranted;however, early identification and treatment can reduce morbidity and mortality. Reference #1: Nalbandian, A., et al, 2021. Post-acute COVID-19 syndrome. Nat Med, 27(4): 601–615. Reference #2: Liemarto, A.K., et al, 2021. Liver abscess with necrosis in post COVID-19: A case report. Ann Med Surg (Lond), 72: 103107. Reference #3: Alhaddad O., et al, 2022. A case report of COVID-19 evoked cholangitic liver abscess. Egypt Liver J, 12(1):5. DISCLOSURES: No relevant relationships by Christian Ascoli No relevant relationships by Anna Duchnowska No relevant relationships by Tirsa Ferrer Marrero No relevant relationships by Manasa Reddy

11.
Chest ; 162(4):A858, 2022.
Article in English | EMBASE | ID: covidwho-2060710

ABSTRACT

SESSION TITLE: Management of COVID-19-Induced Complications SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Up to 17% of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to develop pancreatic lesions (1). We present 2 cases of coronavirus disease 2019 (COVID-19) patients that presented with pancreatic lesions. CASE PRESENTATION: Case1 A 47-year-old lady with a history of type 2 diabetes mellitus present to the emergency department (ED) with complaints of flu-like symptoms for ten days. She tested positive for COVID-19 by rapid PCR. Computed tomography (CT) scan without contrast on admission shows an incidental finding of a pancreatic mass (see Figure 1). Abdominal CT with contrast shows a large, multiloculated cystic mass in the pancreatic tail (see Figure 2). Laboratory examination depicted lipase: 27 U/L, CA19-9: 72 U/mL, CEA: 6.5 ng/mL, CA125: 24 U/mL, erythrocyte sedimentation rate (ESR):2 mm/h, Total Bilirubin: 0.6 mg/dl, Direct Bilirubin: 0.1 mg/dl. Following treatment, the patient recovered fully and is discharged from the hospital 10 days later with home oxygen therapy. Case2 An 81-year old Caucasian lady presented to the outpatient clinic with complaints of fecal incontinence. She tested positive for COVID-19, four months before her visit. CT scan of the abdomen with oral contrast revealed multiple hypodense masses on the pancreas measuring 0.3cm in diameter (see Figure 3). Laboratory tests reveal CA19-9: 57 U/mL, CA125: 8 U/mL, CEA: 1.9 ng/mL, erythrocyte sedimentation rate (ESR):11 mm/h, C-reactive protein: 0.7 mg/L, Total Bilirubin: 1.5 mg/dl, Direct Bilirubin: 1.3 mg/dl. Following outpatient treatment and follow-up, the patient's symptoms were relieved. DISCUSSION: Pancreatic lesions in COVID-19 patients can be caused directly by the cytopathic effects of the viral infection, or indirectly by systemic responses to inflammation or respiratory failure. Several studies have shown that ACE2 is the functional receptor used by SARS-CoV-2 to gain access to target cells (2) and ACE-2 receptors are expressed in significant amounts in the pancreas (3). In the first case, an incidental finding of a multi-cystic pancreatic mass on admission was reported. There was no pancreatic ductal dilation on the CT scan, which may indicate a direct injury caused by cytopathic effects of the virus rather than inflammation resulting in exocrine secretions forming cysts. In the second case, multiple masses on the pancreas were found after recovering from COVID-19. These lesions could be remnants of a previous pancreatic injury during the acute phase of the infection. CONCLUSIONS: COVID-19 infection may trigger pancreatic injury in some patients. Reference #1: Yong, Shin Jie. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infectious diseases. 2021 Oct;53(10): 737–754. Reference #2: Ma C, Cong Y, Zhang H. COVID-19, and the Digestive System. Vol. 115, American Journal of Gastroenterology. Wolters Kluwer Health;2020. p. 1003–6. Reference #3: Liu F, Long X, Zhang B, Zhang W, Chen X, Zhang Z. ACE2 Expression in Pancreatic Damage After SAERS-CoV-2 Infection. Gastroenterology. 2020 Aug 1;18(9): 2128 – 2130.e2. DISCLOSURES: No relevant relationships by Ailine Canete Cruz No relevant relationships by Claudia Ramirez No relevant relationships by Joseph Varon No relevant relationships by Mohamed Ziad

12.
Chest ; 162(4):A854, 2022.
Article in English | EMBASE | ID: covidwho-2060707

ABSTRACT

SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Drug-induced hepatotoxicity is a well-known occurrence from a variety of different medications. However, phenobarbital (PHB) induced hepatotoxicity has not been well studied, and acute liver injury from PHB even less so. In this case, although our patient had many reasons to develop acute liver failure, including alcohol and toluene exposure, timing and investigations seem to point to PHB being responsible. CASE PRESENTATION: Patient is a 39 y.o male with past medical history significant for hepatitis A and B, hyperlipidemia and alcohol abuse who was found unresponsive by EMS after friends reported witnessing patient drinking alcohol and sniffing paint thinner. Patient remained unresponsive on arrival and was intubated and transferred to the MICU. Patient was afebrile with BP 100/55 and otherwise normal vital signs. Significant labs on presentation included a WBC of 8.15, CO2 of 16, lactic acid of 3.6 and mildly elevated transaminases (ALT: 59, AST: 48). Urine toxicology was positive for marijuana. EKG, chest x-ray and CT Head without contrast unremarkable. COVID negative. Video EEG was negative except for generalized slowing. On hospital day 3, patient was increasingly agitated, at which point phenobarbital was started due to concerns for alcohol withdrawal. Hepatic function panel the following mornings showed significant increases in transaminases (ALT: 972 and 5,746, AST: 790 and 4,805) and total bilirubin (6.8 and 11.4), and mild increase in alkaline phosphatase (112 and 125), respectively. Hepatitis panel, acetaminophen level and salicylate level were unremarkable. RUQ ultrasound was also negative for pathology. Gastroenterology was consulted, who recommended starting NAC protocol. Phenobarbital was discontinued. Hepatic function panel the following morning showed significant improvement. Liver transplant was considered, however LFTs continued to downtrend and remainder of hospital course was unremarkable. DISCUSSION: PHB is an anticonvulsant developed primarily for seizure management. However its use has expanded to alcohol withdrawal and even sedative withdrawal. Studies have demonstrated in vitro liver toxicity as well as idiosyncratic reactions and acute liver failure in children (1) (2), with minimal documentation in adults. And while there has even been histological analysis with linkage of chronic phenobarbital use to hepatic necrosis and granulomatous formation (3), there has been minimal documentation regarding acute liver failure in an adults taking phenobarbital. CONCLUSIONS: In conclusion, it is clear that phenobarbital played a significant role in this patient's liver injury and may need to be considered in future episodes of acute liver injury with unclear etiology. Reference #1: Li AM, Nelson EA, Hon EK, Cheng FW, Chan DF, Sin NC, Ma KC, Cheung KL, Fok TF. Hepatic failure in a child with anti-epileptic hypersensitivity syndrome. J Paediatr Child Health. 2005 Apr;41(4):218-20. doi: 10.1111/j.1440-1754.2005.00591.x. PMID: 15813878;PMCID: PMC7166358. Reference #2: Roberts EA, Spielberg SP, Goldbach M, Phillips MJ. Phenobarbital hepatotoxicity in an 8-month-old infant. J Hepatol. 1990 Mar;10(2):235-9. doi: 10.1016/0168-8278(90)90058-y. PMID: 2332596. Reference #3: Di Mizio Di Mizio, G., Gambardella, A., Labate, A., Perna, A., Ricci, P., & Quattrone, (2007). Hepatonecrosis and cholangitis related to long-term phenobarbital therapy: An autopsy report of two patients. Seizure, 16(7), 653–656. https://doi.org/10.1016/j.seizure.2007.05.008 DISCLOSURES: No relevant relationships by Zachary Banbury No relevant relationships by Michael Basir No relevant relationships by Inessa Bronshteyn No relevant relationships by Kyle Foster No relevant relationships by Anna-Belle Robertson

13.
Chest ; 162(4):A833, 2022.
Article in English | EMBASE | ID: covidwho-2060699

ABSTRACT

SESSION TITLE: COVID-Related Critical Care Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: Multisystem Inflammatory Syndrome in Adult (MIS-A) is a rare hyperinflammatory response occurring 2 to 6 weeks after COVID-19 resembling Kawasaki disease. CASE PRESENTATION: A 23-year-old male presented to the emergency room with fevers, cough, shortness of breath, fatigue and painful rashes all over his body. 3 weeks prior, he was diagnosed with COVID-19 which was managed conservatively at home. He recovered within 3 days. He had received 2 doses of Moderna COVID-19 vaccine 6 months prior. He denied recent drug intake. Vitals were BP 116/78 mmHg, heart rate 164/min, temperature 97.3℉, SpO2 96% on room air. Physical exam revealed macular erythematous rash in his trunk and extremities. Leukocyte count was 4 k/uL, hemoglobin 15.5 g/dL, platelets 99 k/uL, sodium 126 mmol/L, bicarbonate 20 mmol/L, BUN 30 mg/dL, creatinine 2.2 mg/dL, lactate 5.1 mmol/L, ferritin >7500 ng/mL, total bilirubin 7.6 mg/dL, AST 298 U/L, ALT 291 U/L, ALP 106 U/L, procalcitonin 14.71 ng/mL, D-dimer 11.98 FEUug/mL. Troponin-I peaked at 1359 pg/mL. CT angiography of the chest showed clear lung fields without pulmonary embolism. Venous doppler was negative. Echocardiogram showed normal biventricular function and valves. An extensive infectious disease workup was negative. He was suspected to have MIS-A from recent COVID-19. He was started on methylprednisolone 1g/day, intravenous immunoglobulin (IVIG), anakinra and empiric antibiotics. Over the next 2 days, there was progression of rash with sloughing of skin in his trunk, back and extremities with bullae on his legs, and thigh sparing the face (figures). Skin biopsy revealed epidermal necrobiosis with apoptosis consistent with Toxic Epidermal Necrolysis (TEN). On day 3, he had a cardiac arrest from ventricular fibrillation but was successfully resuscitated. Subsequently, he was intubated, and required escalating vasopressor support for shock. On day 5, he also developed non-purulent conjunctivitis. On day 6, he was transferred to a higher center with a burns unit. However, despite aggressive supportive measures he succumbed to refractory shock the following day. DISCUSSION: Our patient fit the criteria for MIS-A outlined by CDC (1) with age ≥21 years, fevers, rash with non-purulent conjunctivitis for primary clinical criteria, hypotension and thrombocytopenia for secondary clinical criteria, several laboratory criteria, negative infectious work-up with a history of recent COVID-19. It is unclear if the COVID-19 vaccine increased his risk of MIS-A. There have been case reports of MIS-A presenting as TEN following COVID-19 and COVID-19 vaccines in the absence of typical triggering drugs. (2,3) MIS-A is treated with high dose steroids, IVIG, tocilizumab and supportive measures. Anakinra was used for our patient because of liver dysfunction. CONCLUSIONS: MIS-A following COVID-19 can also present as life-threatening skin reactions like TEN in the absence of triggering drugs. Reference #1: Retrieved from https://www.cdc.gov/mis/index.html Reference #2: Narang I, Panthagani AP, Lewis M, Chohan B, Ferguson A, Nambi R. COVID-19-induced toxic epidermal necrolysis. Clin Exp Dermatol. 2021;46(5):927-929. Reference #3: Kherlopian A, Zhao C, Ge L, Forward E, Fischer G. A case of toxic epidermal necrolysis after ChAdOx1 nCov-19 (AZD1222) vaccination. Australas J Dermatol. 2022;63(1):e93-e95. DISCLOSURES: No relevant relationships by Fady Jamous No relevant relationships by Swaminathan Perinkulam Sathyanarayanan

14.
Chest ; 162(4):A773-A774, 2022.
Article in English | EMBASE | ID: covidwho-2060686

ABSTRACT

SESSION TITLE: COVID-Related Critical Care Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: We present a case of diffuse alveolar hemorrhage (DAH) secondary to Immune Thrombocytopenia (ITP) temporally related to SARS-CoV-2 (CoV) vaccine. CASE PRESENTATION: An 80-year-old female presented with dyspnea, hemoptysis, diffuse petechiae, and ecchymosis;no focal neurological deficits or hepatosplenomegaly. She had no history of bleeding or autoimmune disorders;no recent respiratory or gastrointestinal infections;but received Moderna CoV vaccine 4 weeks prior to presentation. Chest X-ray (CXR) and CTA of chest demonstrated multifocal bilateral patchy airspace opacities. Initial platelet was 1 x 109/L with normal morphology of platelet and WBC, and no schistocytes. Coagulation panel, LDH, haptoglobin, and bilirubin were all normal. CoV NAAT was negative. Dexamethasone and IVIG for high suspicion of ITP was initiated. Supportive care including platelet transfusion and oxygen via nasal cannula was maintained. Platelets were severely consumed in spite of treatment with platelets undetectable at nadir and rapid decrease of hemoglobin, approximately 6 g/dL, within 24 hours of admission. IgM and IgG plasma platelet autoantibodies returned positive, confirming ITP diagnosis. Additional workup was unremarkable for infections, rheumatologic disorders, and malignancy. Respiratory state rapidly declined with worsening hemoptysis and significant increase of bilateral airspace opacities on repeat CXR, indicative of DAH. Lung protective mechanical ventilation protocol was initiated on day 2 with medically induced deep sedation and paralysis to minimize hemorrhage exacerbation. Rituximab, romiplostim, and nebulized tranexamic acid were added for severe and refractory ITP, which eventually slowed platelet consumption, reduced pulmonary hemorrhage, and stabilized hemoglobin. Platelets recovered above 30 x 109/L on day 9, and subsequent bronchoscopy showed persistent blood on bronchoalveolar lavage. She was successfully extubated after prolonged 14-day intubation. Platelet normalized before discharge. DISCUSSION: Incidence of ITP related to CoV vaccine is approximately 0.8-0.9 case per million vaccinated. Most cases present with superficial bleeding and respond to first-line agents with rapid recovery. GI bleeding and intracranial hemorrhage, but not DAH, have been reported in several cases, requiring third-line agents to promote platelets recovery and achieve hemostasis. We report a case of DAH secondary to ITP following CoV vaccine. Temporal relationship and severe presentation are consistent with other reports of ITP with life-threatening internal bleeding probably secondary to CoV vaccine. CONCLUSIONS: When DAH is suspected, rapid escalation of treatment to include third-line agents is desired. If intubated, lung protective ventilation with paralysis is preferred to minimize further lung injury due to DAH. Reference #1: Lee EJ, Cines DB, Gernsheimer T, et al. Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination. Am J Hematol. 2021;96(5):534-537. doi:10.1002/ajh.26132 doi:10.1016/J.VACCINE.2021.04.054 Reference #2: Welsh KJ, Baumblatt J, Chege W, Goud R, Nair N. Thrombocytopenia including immune thrombocytopenia after receipt of mRNA COVID-19 vaccines reported to the Vaccine Adverse Event Reporting System (VAERS). Vaccine. 2021;39(25):3329-3332. Reference #3: Tarawneh O, Tarawneh H. Immune thrombocytopenia in a 22-year-old post Covid-19 vaccine. Am J Hematol. 2021;96(5):E133-E134. doi:10.1002/ajh.26106 DISCLOSURES: No relevant relationships by Timothy Barreiro No relevant relationships by Tiewei Cheng No relevant relationships by Zeina El Amil No relevant relationships by Jin Huang No relevant relationships by Sanaullah Khalid

15.
Chest ; 162(4):A698, 2022.
Article in English | EMBASE | ID: covidwho-2060670

ABSTRACT

SESSION TITLE: Shock and Sepsis in the ICU Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: The Lazarus Phenomenon, also known as auto-resuscitation, is a rare event where cessation of CPR results in a delayed return of spontaneous circulation (ROSC). The phenomenon was named after the story of Lazarus, who was restored to life four days after death. We present a case of a 78-year-old male who presented to the hospital for septic shock and had intra-hospital cardiac arrest with ROSC after cessation of CPR. CASE PRESENTATION: 78 year old male with a medical history of paroxysmal atrial fibrillation, stage IIIA NSCLC and COPD, presented for progressive dyspnea. He complains of feeling weak with loss of appetite and had a recent mechanical fall. Initial vital signs were temperature 96F, BP 141/78, HR 75 bpm, RR 18/min, SaO2 100% on 2LNC. Initial labs showed lactic acid 11.6, BUN 55, creatinine 3.7, CO2 9, anion gap 25, AST 2654, ALT 2120, ALP 159, total bilirubin 0.8, troponin <0.1, CK 399, INR 4.2, PTT 36, WBC 16.5, Hb 10.8, and plt 202. COVID-19 testing was negative. CXR demonstrated a retro-cardiac opacity consistent with previous diagnosis of lung cancer versus a dense consolidation. He was started on antibiotics for sepsis and admitted to the ICU for his metabolic status and shock liver. He remained hemodynamically stable for a few hours until a he had sudden onset of unresponsiveness with asystole. Code blue was called. Repeat labs demonstrated lactic acid 15.5, potassium 6.3, CO2 9. He underwent resuscitation for 32 minutes when compressions were stopped. Within 5 minutes post arrest, sinus activity was noted on the cardiac monitor. The patient had a radial pulse on evaluation. Manual blood pressure measurement was 119/71 with a HR of 99. Arterial blood gas after ROSC showed a pH 7.0, pCO2 68, pO2 273, HCO3 16, lactic acid 19. A few hours later, the patient rapidly de-compensated and underwent resuscitation for a second time. Efforts were deemed futile and the patient expired. DISCUSSION: The physiologic description of the Lazarus phenomenon is yet to be fully elucidated. Hypotheses include auto-PEEP due to rapid manual ventilation generating increased intrathoracic pressure and decreased venous return, delayed drug effect and stunned myocardium during active chest compressions (1). Once chest compressions and positive pressure ventilation via manual bag-mask stops, sudden decrease in intrathoracic pressure allows for sudden venous return and re-perfusion of cardiac tissue, resulting in ROSC in some cases. A recent literature review cited 65 published cases over the past 30 years with the most common rhythm being asystole (2). Most cases of auto-resuscitation occurred between 5-10 minutes post stopping of chest compressions (2). Mortality of these cases were 70% post resuscitation (2). CONCLUSIONS: It is important for clinicians to be aware of the Lazarus phenomenon post resuscitative efforts and to observe patients carefully post resuscitation. Reference #1: Adhiyaman V, Adhiyaman S, Sundaram R. The Lazarus phenomenon. J R Soc Med. 2007;100(12):552-557. doi:10.1177/0141076807100012013 Reference #2: Gordon, L., Pasquier, M., Brugger, H. et al. Autoresuscitation (Lazarus phenomenon) after termination of cardiopulmonary resuscitation - a scoping review. Scand J Trauma Resusc Emerg Med 28, 14 (2020). https://doi.org/10.1186/s13049-019-0685-4 DISCLOSURES: No relevant relationships by Vincent Chan No relevant relationships by Mackenzie Kramer No relevant relationships by Nathaniel Rosal No relevant relationships by Laura Walters No relevant relationships by William Ward

16.
Chest ; 162(4):A566, 2022.
Article in English | EMBASE | ID: covidwho-2060633

ABSTRACT

SESSION TITLE: Imaging Across the Care Spectrum SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) has led to approximately 474 million cases and a devastating 6 million deaths worldwide, to date. Despite a relatively low incidence of secondary bacterial infections in COVID-19 patients, the frequency of empiric treatment with antibiotics is as high as 60 to 100%, highlighting a lack of stringent antibiotic stewardship. This promotes the development of multidrug resistant microorganisms. The purpose of this study was to evaluate the utility of the procalcitonin (PCT) biomarker in identifying the development of hospital acquired pneumonia (HAP) in COVID-19 patients. METHODS: We conducted a single center retrospective study of COVID-19 patients admitted between March 2020 to March 2021. COVID-19 patients who developed HAP during their index hospitalization were compared to those who did not develop HAP. Included in the study were COVID-19 positive patients who received empiric antibiotics for < 48 hours and had at least one PCT value ≥ 48 hours since admission. Exclusion criteria included patients with conditions that could affect PCT values including chronic kidney disease stage 5 and above, malignancy and elevated bilirubin levels. Patients with positive microbiology data < 48 hours of admission and those receiving antibiotic therapy prior to admission were excluded as well. All data was analyzed via SPSS. RESULTS: The median age of the cohort was 65 years. There was no difference in demographics in those who had HAP compared to those who did not. Median Charlson comorbidity index (CCI) (3,2;p=0.6) PCT (0.16, 0.13;p=0.91), ferritin (707, 659.5;p=0.48), and C-reactive protein (CRP) (10.56, 6.78;p=0.19) within 48 hours of admission did not differ significantly between the groups either. Notably, PCT (0.09,0.47;p=0.01) and CRP (3.37, 6.59, p=0.01) 48 hours after admission were significantly higher in COVID-19 patients who developed HAP. However, when PCT and CRP were included in multivariate logistic regression, neither remained a significant predictor of HAP. The odds ratios of PCT and CRP 48 hours after admission were 1.25 (95% CI:0.85-1.8;p=0.27) and 1.08 (95% CI:0.95-1.23;p=0.22), respectively. CONCLUSIONS: Our study did not show a significant difference in the median CCI, PCT, CRP and ferritin obtained within 48 hours of admission in patients who developed HAP versus those who did not. However, PCT and CRP obtained 48 hours after admission, were higher in patients who developed HAP. CLINICAL IMPLICATIONS: The data support the use of PCT and CRP as potential tools to predict the development of concomitant HAP in COVID-19 patients and as guides for antibiotic stewardship in this patient population. DISCLOSURES: No relevant relationships by Mythri Anil Kumar No relevant relationships by Tara McLaughlin No relevant relationships by Raj Parikh No relevant relationships by Meher Singha

17.
Chest ; 162(4):A559, 2022.
Article in English | EMBASE | ID: covidwho-2060630

ABSTRACT

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder that can lead to thrombosis, hemolytic anemia and leukemia. Though there are documented relationships between autoimmune hemolytic anemia (AIHA) and COVID-19 infection, this is the first to highlight aa potential association between PNH exacerbations and COVID vaccinations. CASE PRESENTATION: A 38 year-old female with a history of chronic paroxysmal nocturnal hemoglobinuria (PNH) currently on maintenance ravculizumab therapy presented with 3 days of generalized fatigue, chills, and worsening scleral icterus. She reports being unable to move out of the bed with concomitant somnolence. Of note, she received her second dose of the Moderna COVID-19 vaccine 2 days prior to symptom onset and not had any similar symptoms prior to this episode. Patient was hemodynamically stable on admission and afebrile. Physical exam revealed generalized lethargy/weakness and jaundice. Chest x-ray did not demonstrate any evidence of infection or pleural effusions. Initial complete blood count showed a hemoglobin of 5.9 g/dL, compared to her baseline of 9 without any evidence of bleeding. Absolute reticulocyte and bilirubin levels were elevated to 295.2 x 109 and 4.7 mg/dL respectively with a haptoglobin of <20 mg/dL. She received a total of 3 units of packed red-blood cells with subsequent stable hemoglobin levels and did not require emergent use of glucocorticoids or plasma exchange. Her lethargy improved slowly, and within a week, she returned back to her baseline functional status. She was ultimately stable and discharged for follow up with her hematologist without any complications. DISCUSSION: Though the sequelae of COVID-19 infections and associated hematologic diseases have been extensively established, the pathogenesis of COVID-19 vaccinations associated exacerbations remain unclear. Given the timing of the onset of our patient's symptoms, it is highly suggestive that her second COVID-19 vaccination was the inciting factor for her acute hemolytic anemia. It is crucial to be cognizant of the potential hematologic side effects in individuals with rare auto-immune disorders such as PNH and take into consideration the timing of vaccination or booster administrations. CONCLUSIONS: While COVID-19 vaccination benefit most likely outweighs the risks for this specific patient population, our case raises the question about the need for extra precautions in patients with known PNH associated AIHA including the timing of PNH treatment before receiving the vaccination. Reference #1: Algassim AA, Elghazaly AA, Alnahdi AS, Mohammed-Rahim OM, Alanazi AG, Aldhuwayhi NA, Alanazi MM, Almutairi MF, Aldeailej IM, Kamli NA, Aljurf MD. Prognostic significance of hemoglobin level and autoimmune hemolytic anemia in SARS-CoV-2 infection. Annals of Hematology. 2021 Jan;100(1):37-43. DISCLOSURES: No relevant relationships by Suhwoo Bae No relevant relationships by Edward Bae No relevant relationships by Joseph You

18.
HemaSphere ; 6:2622-2623, 2022.
Article in English | EMBASE | ID: covidwho-2032155

ABSTRACT

Background: Etavopivat, an investigational, once-daily, selective, activator of erythrocyte pyruvate kinase (PKR) increases PKR activity, resulting in decreased 2,3-DPG and increased ATP in red blood cells (RBCs) of healthy volunteers and patients (pts) with sickle cell disease (SCD).1,2 Aims: We report results of an open-label (OL) extension cohort from a Phase 1 study (NCT03815695) designed to characterize the safety and clinical activity of etavopivat at a maximal pharmacodynamic dose in pts with SCD. Methods: 15 pts were enrolled to receive etavopivat 400 mg once daily for 12 wks, followed by a 4-wk follow-up. Assessments included safety, pharmacokinetics, pharmacodynamics, RBC health parameters and systemic markers of SCD pathophysiology. Results: Of 15 pts (age 32.3 ±10.1 yr;HbSS/SC n=13/2), 14 completed 12-wks of treatment (tx);1 pt discontinued tx after ∼2 wks. Etavopivat 400 mg once daily was generally well tolerated. Adverse events (AEs) reported during tx and follow-up were commonly low grade (Gr) and consistent with pts' SCD. Gr1-2 AEs in >2 pts (n [%]) were sickle cell pain events (9 [60%]);headache (5 [33%]);and upper respiratory tract infection (3 [20%]). The Gr3-4 AE in >1 pt was sickle cell vaso-occlusion (VOC;4 [27%]). On-tx serious adverse events (SAEs;1 pt each) were Gr3 VOC post Gr3 COVID (not tx-related) and Gr3 left femoral deep vein thrombosis (possibly related, resulting in tx discontinuation as stated above). SAEs (1 pt each) during the 4-wk follow-up were Gr3 acute chest syndrome + Gr3 VOC, Gr3 non-cardiac chest pain and Gr3 syncope (all unrelated). Observed increases in ATP and decreases in 2,3-DPG were durable over 12 wks of etavopivat tx. Etavopivat tx normalized hemoglobin (Hb)S-oxygen affinity to that of HbA. Etavopivat tx over 12 wks improved overall sickle RBC health, demonstrated by a reduction in point of sickling as well as improved measures of deformability and hydration of sickle RBCs (all P<0.01;Figure). Etavopivat tx over 12 wks was associated with a sustained significant increase in Hb compared with baseline (BL;P<0.0001), with mean maximal increase of 1.5 (range 0.7-2.3) g/dL. Ontx increase in Hb >1g/dL was achieved in 11 (73%) pts, for whom the mean maximal Hb increase was 1.8 (1.2-2.3) g/dL. Absolute reticulocytes, indirect bilirubin and lactate dehydrogenase significantly decreased from BL and were sustained over the 12wk period (all P<0.05), indicative of increased RBC lifespan and decreased hemolysis. Several markers of disease activity significantly decreased from BL during daily etavopivat tx, including the inflammatory marker tumor necrosis factor-α , which decreased by 35% (P<0.001). Based on preliminary exploratory analysis with an aggregate duration of etavopivat exposure of 3.32 pt-yrs in the OL cohort, a decrease in the trend for VOC Hospitalizations was observed: annualized historical and on-tx VOC Hospitalization rates were 0.93 and 0.30, respectively;the 1 on-tx VOC Hospitalization was COVID-related. Summary/Conclusion: Etavopivat 400 mg once daily for up to 12 wks demonstrated a tolerable safety profile and showed improvements in various markers of RBC health in pts with SCD. Rapid and sustained increases in Hb were associated with decreases in reticulocyte counts and markers of hemolysis, supporting increased sickle RBC lifespan and improved anemia. Together, these results support further evaluation of etavopivat in the Phase 2/3 Hibiscus Study (NCT04624659) currently enrolling pts. (Figure Presented).

19.
Gut ; 71(Suppl 2):A91-A92, 2022.
Article in English | ProQuest Central | ID: covidwho-2020126

ABSTRACT

IDDF2022-ABS-0185 Table 1Clinical characteristics of patients with Giloy-induced liver injuryCharacteristics Number of patients (Total-16 patients) Gender Male 7 (43.75%) Female 9 (56.25%) Age (mean ± SD) 48.3±14 years Presentation type Acute hepatitis 6 (37.5%) ACLF 10 (62.5%) Mean duration for symptom onset after consumption of giloy 84.3±35 days Mean BMI 23.23±3 kg/m2 Comorbidities Type 2 diabetes 9 (56.25%) Interstitial lung disease (on inhalational steroids) 2 (12.5%) Hypertension 1 (6.25%) None 5 (31.25%) NAFLD 2 (6.25%) Symptoms Jaundice 16 (100%) Ascites 8 (50%) Fatigue 12 (75%) Pruritus 4 (25%) Liver function tests Peak total bilirubin (Mean ± SD) 17 ± 9.4 mg/dl Peak ALT (mean ± SD) 365± 219 U/L Peak AST (mean ± SD) 558 ± 475 U/L Peak ALP (mean ± SD) 186 ± 114 U/L Peak serum IgG (mean ± SD) 2400 ± 1213 mg/dl Peak INR (mean ± SD) 2.63 ± 1.05 AIH serology ANA 1(6.25%) ASMA - Anti LKM1 - AMA - Seronegative (biopsy proven) - Liver biopsy 10 (62.5) Drug induced liver injury 5 (31.25%) Features of AIH 5 (31.25%) Treatment N-Acetyl Cysteine infusion+Ademetionine 3 (18.75%) Steroids 10 (62.5%) Plasma Exchange 3 (18.75%) Outcome Alive 16 (100%) One listed for liver transplant Mean duration for recovery 37 ± 16 days IDDF2022-ABS-0185 Figure 1ConclusionsGiloy, a commonly used immunity booster, can produce drug-induced liver injury, which often mimics autoimmune hepatitis and responds to steroids.

20.
Gut ; 71(Suppl 2):A85-A87, 2022.
Article in English | ProQuest Central | ID: covidwho-2020125

ABSTRACT

IDDF2022-ABS-0170 Table 1Demographics, comorbidities, laboratory investigations and clinical outcomes of COVID-19 patients stratified by ALT All (n=163) Status of ALT P-value¶ Characteristics Abnormal (n=50) Normal (n=113) Age in years, median (IQR) 56 (43–65) 60 (50–67) 55 (37–64) 0.022 Gender, n (%) 0.124 Male 96 (58.9) 34 (68.0) 62 (54.9) Female 67 (41.1) 16 (32.0) 51 (45.1) Ethnic group, n (%) 0.520 Chinese 98 (60.1) 34 (68.0) 64 (56.6) Malay 18 (11.0) 4 (8.0) 14 (12.4) Indian 20 (12.3) 6 (12.0) 14 (12.4) Others 27 (16.6) 6 (12.0) 21 (18.6) Comorbidities, n (%) Diabetes 32 (19.6) 13 (26.0) 19 (16.8) 0.201 Hyperlipidemia 57 (35.0) 24 (48.0) 33 (29.2) 0.032 Hypertension 61 (37.4) 26 (52.0) 35 (31.0) 0.014 Ischemic heart disease 15 (9.2) 7 (14.0) 8 (7.1) 0.238 Chronic liver disease 4 (2.5) 1 (2.0) 3 (2.7) 1.000 Charlson Comorbidity Index, median (IQR) 0 (0–1) 0 (0–1) 0 (0–1) 0.400 BMI, kg/m2, median (IQR), n=46 24.3 (23.2–27.9) 22.9 (22.1–24.2) 24.6 (23.6–28.7) 0.011 GI symptoms, n (%) Diarrhoea 29 (17.8) 12 (24.0) 17 (15.0) 0.186 Abdominal pain 4 (2.5) 0 (0.0) 4 (3.5) 0.313 Nausea/vomiting 10 (6.1) 0 (0.0) 10 (8.8) 0.032 Abnormal chest radiography on admission 55 (33.7) 22 (44.0) 33 (29.2) 0.074 Laboratory investigations on admission, median (IQR) ALT, U/L 23 (18–31) 29 (22–33) 21 (17–26) <0.0005 ALT/LDH ratio, n=162 0.05 (0.04–0.07) 0.06 (0.04–0.07) 0.05 (0.03–0.06) 0.039 ALP 72 (60–89) 72 (61–90) 72 (60–89) 0.700 R factor 0.94 (0.70–1.26) 1.15 (0.86–1.49) 0.87 (0.63–1.19) <0.0005 WBC, x109/L 4.70 (3.80–5.70) 4.75 (3.80–5.83) 4.70 (3.85–5.70) 0.844 Lymphocyte, x109/L 1.11 (0.84–1.49) 0.99 (0.74–1.23) 1.20 (0.87–1.65) 0.002 PLT, x 109/L 188 (150–225) 177 (142–223) 193 (155–226) 0.306 CRP, mg/L, n=162 10.75 (3.15–39.40) 30.10 (11.28–50.65) 6.85 (1.95–23.88) <0.0005 LDH, U/L, n=162 420 (350–547) 482 (378–572) 408 (342–525) 0.033 Creatinine, μmol/L 72 (61–87) 76 (65–88) 71 (59–87) 0.288 Albumin, g/L, n=156 39 (37–42) 39 (37–41) 40 (37–43) 0.044 BIL, μmol/L, n=152 11 (9–14) 11 (9–14) 12 (9–15) 0.555 Medication used, n (%) NSAIDs 22 (13.5) 4 (8.0) 18 (15.9) 0.218 β-lactam 47 (28.8) 22 (44.0) 25 (22.1) 0.008 Hydroxychloroquine 7 (4.3) 1 (2.0) 6 (5.3) 0.677 Lopinavir/Ritonavir (Kaletra) 25 (15.3) 16 (32.0) 9 (8.0) <0.0005 Remdesivir 12 (7.4) 5 (10.0) 7 (6.2) 0.516 Interferon 9 (5.5) 6(12.0) 3 (2.7) 0.025 Days of symptoms before admission, median (IQR) 4 (3–7) 4 (2–7) 5 (3–7) 0.396 Length of stay in days, median (range) 13(8–17) 16(13–24) 11 (7–16) <0.0005 Clinical severity HDU/ICU, n (%) 29 (17.8) 16 (32.0) 13 (11.5) 0.003 Required supplementary oxygen, n (%) 50 (30.7) 29 (58.0) 21 (18.6) <0.0005 Days on supplementary oxygen, median (IQR), n=50 11 (6–18) 12 (6–21) 8 (5–15) 0.15 Intubated, n (%) 13 (8.0) 10 (20.0) 3 (2.7) <0.0005 Death, n (%) 5 (3.1) 3 (6.0) 2 (1.8) 0.169 Sample size, n=163, except where indicated.¶ P values are from Fisher’s exact test or chi-square test for categorical variables and Mann-Whitney U test for continuous variables. P values< 0.05 are in bold.ALP, alkaline phosphatase;ALT, alanine aminotransferase;AST, aspartate aminotransferase;BIL, bilirubin;BMI, body mass index;CRP, c-reactive protein;GI, gastrointestinal;ICU, intensive care unit;IQR, interquartile range;LDH, lactate dehydrogenase;HDU, high dependency unit;PLT, platelet count;WBC, white blood cell.Results30.7% of patients developed abnormal ALT: they were more likely to be older and had comorbidities of hyperlipidaemia and hypertension. Multivariate logistic regression (IDDF2022-ABS-0170 Table 2) showed that R-factor ≥1 on admission (aOR 3.13, 95%CI 1.41–6.95) and hypoxia (aOR3.54, 95%CI 1.29–9.69) were independent risk factors for developing abnormal ALT, but not medications or comorbidities. The R-factor on admission trended higher for patients who developed abnormal LFT as compared to those who didn’t, regardless of the day of illness (IDDF2022-ABS-0170 Figure 1. R-factor). The patients who developed abnormal ALT also ran a more severe course of illness with a greater proportion needing supplementary oxygen (58%vs18.6%, p <0.0005), admission to Intensive Care/High Dependency Unit (32%vs11.5%, p=0.003) and intubation (20%vs2.7%, p<0.0005). The death rate between the 2 groups was similar. IDDF2022-ABS-0170 Table 2Odds ratio of risk factors for development of abnormal ALTVariable Univariable model Multivariable model ‡ cOR (95% CI) P value aOR (95% CI) P value Age in years <45 1.00 Referent 1.00 Referent 45–64 3.42 (1.28–9.11) 0.014 2.69 (0.84–8.47) 0.096 65+ 4.31 (1.49–12.42) 0.007 2.84 (0.66–12.19) 0.160 Gender Male 1.00 Referent Female 0.57 (0.28–1.15) 0.118 Diabetes 1.74 (0.78–3.87) 0.176 Hyperlipidemia 2.24 (1.13–4.45) 0.022 1.14 (0.43–3.00) 0.796 Hypertension 2.41 (122–4.78) 0.0110.89 (0.31–2.58) 0.835 Ischemic heart disease 2.14 (0.73–6.26) 0.166 Presence of GI symptom(s) on admission 1.17 (0.53–2.58) 0.695 Abnormal chest x-ray on admission 1.90 (0.96–3.80) 0.067 0.91 (0.36–2.25) 0.833 R factor on admission <1 1.00 Referent 1.00 Referent ≥1 3.12 (1.56–6.24) 0.001 3.13 (1.41–6.95) 0.005 Use of acetaminophen No 1.00 Referent Yes, <2 g/day 1.48 (0.39–5.65) 0.567 Yes, ≥2 g/day 2.86 (0.71–11.46) 0.139 Use of β-lactam 2.77 (1.35–5.65) 0.005 1.12 (0.38–3.24) 0.840 Use of Hydroxychloroquine 0.36 (0.04–3.11) 0.355 Use of Lopinavir/Ritonavir (Kaletra) 5.44 (2.20–13.43) <0.0005 2.20 (0.57–8.45) 0.252 Use of Remdesivir 1.68 (0.51–5.58) 0.395 Use of interferon 5.00 (1.20–20.88) 0.027 0.80 (0.12–5.22) 0.813 Hypoxia 6.05 (2.9–12.62) <0.0005 3.54 (1.29–9.69) 0.014 ‡ Variables in the multivariable logistic regression model were age group, hyperlipidemia, hypertension, whether there was abnormal chest x-ray on admission, R factor on admission, use of β-lactam, use of LPV/r, use of interferon, and hypoxia, P values<0.05 are in bold, aOR, adjusted odds ratio, cOR, crude odds ratio IDDF2022-ABS-0170 Figure 1ConclusionsLiver injury is associated with poorer clinical outcomes in COVID-19 patients. R-factor ≥1 on admission and hypoxia are independent risk factors for developing abnormal ALT in COVID-19. More studies are required to see if the incorporation of the R-factor into conventional clinical risk scores can improve the performance in predicting disease progression/discriminating disease severity and applicability in emerging virus variants.

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