ABSTRACT
Background: To reduce the spread of coronavirus disease 2019 (COVID-19), many substance use disorder treatment programs have transitioned to telemedicine. Emergency regulatory changes allow buprenorphine initiation without an in-person visit. We describe the use of videoconferencing for buprenorphine initiation combined with street outreach to engage 2 patients experiencing homelessness with severe opioid use disorder (OUD). Case Presentation: Patient 1 was a 30-year-old man with severe OUD who had relapsed to injection heroin/fentanyl after incarceration. A community drop-in center outreach harm reduction specialist facilitated a videoconference with an addiction specialist at an OUD bridge clinic. The patient completed a community buprenorphine/naloxone initiation and self-titrated to his prior dose, 8/2 mg twice daily. One week later, he reconnected with the outreach team for a follow-up videoconference visit. Patient 2, a 36-year-old man with severe OUD, connected to the addiction specialist via a syringe service program harm reduction specialist. He had been trying to connect to a community buprenorphine/naloxone provider, but access was limited due to COVID-19, so he was using diverted buprenorphine/naloxone to reduce opioid use. He was restarted on his previous dose of 12/3 mg daily which was continued via phone follow-up 16 days later. Conclusion(s): COVID-19-related regulatory changes allow buprenorphine initiation via telemedicine. We describe 2 cases where telemedicine was combined with street outreach to connect patients experiencing homelessness with OUD to treatment. These cases highlight an important opportunity to provide access to life-saving OUD treatment for vulnerable patients in the setting of a pandemic that mandates reduced face-to-face clinical interactions.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.
ABSTRACT
Introduction: Wolman disease is a rare genetic disorder with an autosomal recessive inheritance. A mutation in the LIPA gene causes lysosomal acid lipase (LAL) deficiency results in lipid storage and adrenal insufficiency. Death in early infancy is due to liver failure. Patients and methods: We describe the clinical course of a three-month-old infant diagnosed with Wolman disease. A rapid mutational analysis confirmed a LIPA gene defect. Results: He underwent matched unrelated donor peripheral blood stem cell hematopoietic stem cell transplantation (HSCT) at 3 months of age, with a treosulfan-based conditioning, which resulted in engraftment with donor-derived hematopoietic cells. He required supportive care for sinusoidal obstruction syndrome and mucositis. He was administered low dose prednisolone for grade I skin graft versus host disease, and a complete donor chimerism was documented on several occasions. At one year post HSCT, his growth and development were optimal, and there was no hepatosplenomegaly. He is maintained on glucocorticoid and mineralocorticoid supplements for primary hypoaldosteronism. Conclusion: The case emphasizes the timely diagnosis and the potential for successful treatment of Wolman disease by HSCT. © 2022 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics
ABSTRACT
Objective: To describe a case of levo-dopa responsive parkinsonism secondary to combined COVID-19 and Enteric fever in a patient Background: The first link between viruses and parkinsonism comes from the possible relationship between lethargic encephalitis and the Spanish flu of 1918.In addition, other viruses, including West Nile virus, herpes viruses, influenza A virus, and human immunodeficiency virus (HIV), have been associated with parkinsonism Methods: A 31 years old presented with fever ,headache for 5 days followed by altered sensorium. At presentation he had neck rigidity ,was localizing to pain ,not fully oriented and not following verbal command but he had hypoxia and need nasal oxygen support.He had D-Dimer 12506,COVID-19 RTPCR positive and was treated with Remdesivir,ceftriaxone ,dexamethasone after which he had improvement in sensorium.At day 6 of illness he had generalized rigidity,bradykinesia with slow hypophonic speech and was needing support to sit and walk . A provisional diagnosis of infection related parkinsonism was considered and Cerebrospinal fluid study,MRI Brain and spine ,Blood culture were done .His Cerebrospinal fluid study has normal protein , glucose,cells, stains and culture and negative autoimmune and paraneoplastic plane . His urine culture,blood culture was positive for salmonella typhi and serum widal titre was 1:640.MRI Brain and spine does not show any new abnormalities except old trauma sequalae. He was treated with Levo-dopa carbidopa and titrated to a dose of 675 mg/day and had sustained improvement with levo-dopa carbidopa .There are 6 other case of COVID-19 associated parkinsonism in literature .There are also few case of typhoid associated case of parkinsonism described in literature . Our patient had combined infection of both COVID-19 and typhoid associated parkinsonism. Result(s): We report a case of Infection related parkinsonism secondary to combined COVID-19 plus typhoid infection Conclusion(s): Exploring the potential relationship of co-infection SARS-CoV-2 and Salmonella typhi infection with development of parkinsonism is essential because of the epidemiological implications,as well as to gain a better understanding of the pathophysiological aspects of these disorders.
ABSTRACT
A 5-month-old, intact male, yellow Labrador retriever was presented with a 24-hour history of anorexia and vomiting. Abdominal imaging revealed the presence of a mechanical obstruction in the jejunum and peritoneal effusion. Cytologic evaluation and culture of the effusion prior to surgery identified a suppurative exudate with bacteria consistent with septic peritonitis and suspected to be related to the intestinal lesion. An exploratory laparotomy was performed, and a segment of jejunum was circumferentially severely constricted by an off-white, fibrous band of tissue. Resection and anastomosis of the strangulated segment of jejunum and excision of the constricting band provided resolution of the clinical signs. The dog made a complete recovery. Histologic evaluation revealed the band to be composed of fibrovascular and smooth muscle tissue, consistent with an idiopathic anomalous congenital band. No other gastrointestinal lesions were observed, either grossly at surgery or histologically in the resected segment of intestine. To our knowledge, a similar structure has not been reported in the veterinary literature.Copyright © 2022 Canadian Veterinary Medical Association. All rights reserved.
ABSTRACT
Background: Neurological autoimmune disorders are often triggered by bacterial and viral infections, with growing evidence supporting coronavirus disease 2019 (COVID-19) infection precipitation of these disorders. COVID-19 is already implicated in causing discrete para-infectious neurological syndromes: acute disseminated encephalomyelitis (ADEM), transverse myelitis, neuromyelitis optica spectrum disorders (NMOSD), Guillain-Barre syndrome (GBS), and is also associated with encephalopathy, acute cerebrovascular disease, neuromuscular disorders, and seizures. Case Presentation: We describe a case of a 43-year-old Asian woman with chronic Hepatitis B (HBV) co-infected acutely with COVID-19, presenting with urinary retention, bilateral blindness, thoracic sensory level, and quadriparesis. Extensive workup narrowed down her diagnosis as seronegative NMOSD. She had complete resolution of symptoms after treatment with concurrent plasma exchange (PLEX), high dose corticosteroids, and emtricitabine-tenofovir. Follow-up visit showed no seroconversion at 6 months and no relapses. Conclusion(s): Our literature review highlights the likely link between COVID-19 infection and the development of neurologic autoimmune diseases. Our literature review supports a virus-triggered immune-mediated process rather than neuro-invasion. Many viral illnesses have been linked to the development of NMOSD and anti-AQP4 antibody-related myelitis. Additionally, there is limited literature linking chronic HBV infection with the development of optic neuritis and speculation thatcross-reactivity between HBsAg and myelin antigens may lead to the development of demyelinating diseases in the CNS and PNS. We observed remarkable clinical improvement after treatment with alternating days of IV methylprednisolone and therapeutic PLEX.Copyright © 2022
ABSTRACT
Background: Treprostinil is a prostacyclin analogue which has been approved in the EU for intravenous (i.v.) and subcutaneous (SC) administration in patients with PAH. LIQ861 is a dry powder formulation of treprostinil which can be used for inhalation via a handheld device. Objectives and methods: LTI-201 was a multicentre, Phase 2, open-label, dose-escalation study to evaluate the HD dose-response and safety of LIQ861, followed by an open-label extension period. In "Part A" HD response was measured by right heart catheterization for 120 minutes after a single 26.5 or 53 mug dose of LIQ861. In "Part B" patients were titrated to symptomatic relief (<=159 mug QID) and were reassessed after 16 weeks using right heart catheterization and clinical assessments. Result(s): Fifteen PAH Patients (60 % female, mean age 56 +/- 14.3 years, mean pulmonary vascular resistance (PVR) 605+/-246 dynes/sec/cm-5) were included. In Part A HD measures (PVR and mean pulmonary arterial pressure) improved with a peak response after 15 minutes for both doses. The study was stopped early due to the COVID19 pandemic with only 6 patients completing Part B. At Week 16, these HD responses also improved and clinical assessments improved or remained stable for these patients. All doses of LIQ861 were generally well-tolerated with only one serious adverse event (short episode of hypoxia after inhalation). The most frequently reported adverse events were cough and throat irritation and most were assessed as mild in severity. Conclusion(s): LIQ861 was overall safe and well tolerated. An expected improvement in HD measures was seen with acute and chronic dosing.
ABSTRACT
Background: Fatigue is a common symptom after a COVID-19 infection. There is evidence to support COVID-19 rehabilitation (CoR) improving symptoms. However, there is concern that exercise therapies may increase postexertional symptom exacerbation (PESE). Aim(s): To determine the effect of 6 weeks of CoR on fatigue and symptoms of PESE. Method(s): 148 patients (55 +/- 13 y;56 [38%] male) completed 6 weeks of CoR including symptom-titrated exercise and education. Fatigue was assessed pre- and post-CoR using the Functional Assessment Chronic Illness TherapyFatigue questionnaire (FACIT). Patients with a FACIT score <30 were defined as having severe fatigue. PESE symptoms were assessed in a sub-group of patients (n=44) using a subscale of the DePaul Symptom Questionnaire (DSQ). A mean composite score was calculated for DSQ symptom questions. Result(s): FACIT score reduced pre- to post-CoR with a mean change of -5 +/- 9;p<0.01. The DSQ composite score improved by 20 +/- 21 (p<0.01, n=44). The magnitude of change in the DSQ composite score pre- to post-CoR was not different in those with (26 +/- 22) and without (19 +/- 21) severe fatigue (p=0.44). Conclusion(s): CoR has demonstrated improvements in fatigue and symptoms associated with PESE. The improvement in PESE symptoms pre- to post-CoR was similar in patients with and without severe fatigue, advocating the use of CoR in both cohorts.
ABSTRACT
INTRODUCTION: Fentanyl and midazolam are highly lipophilic agents commonly used as continuous infusions for sedation. Based on the pharmacokinetics, a bolus dose could shorten the time to achieve steady state concentrations before being maintained with an increase in the continuous infusion. Upfront bolus dosing may avoid excessive uptitration to a maximum rate leading to drug accumulation, adverse reactions, and addition of other sedatives. The purpose of this study is to compare the efficacy and safety of bolus doses versus no bolus doses prior to up-titration of fentanyl and midazolam continuous infusions for sedation in mechanically ventilated adult patients in the medical intensive care unit (MICU). METHOD(S): This retrospective cohort study looked at adults receiving fentanyl or midazolam infusions for sedation for at least 24 hours admitted to the MICU at North Shore University Hospital from October 2021 to April 2022. The 2 cohorts are patients pre- and post-implementation of education on fentanyl and midazolam bolus doses. Patients were excluded if they were receiving concurrent neuromuscular blocking agents, had concurrent diagnosis of uncontrolled seizures, catastrophic stroke, intracranial hemorrhage, or COVID-19 as the primary diagnosis. The primary outcome of the study is duration of mechanical ventilation (MV). RESULT(S): Thirty-six patients were analyzed with 25 in the control group and 11 in the study group. More patients in the study group had history of leukemia (8% vs 45%, p=0.018) and a higher number of sedatives prior to study drug infusion (p=0.0383). There was no difference in the median duration of MV (6 vs 9 days, p=0.1179). The control group had a statistically significant lower sedation intensity score on days 1 and 2 of sedation that on average was 9.6 and 8.5 units lower, respectively. Outcomes including number of concomitant sedatives, in-hospital mortality and time to Richmond Agitation Sedation Scale (RASS) goal were not statistically significant. Adverse events were similar between groups. CONCLUSION(S): Low protocol adherence and small sample size limit the interpretation of results. Thus, larger studies would be required to assess if there is a difference in MV using the bolus vs no bolus dose titration. Next steps include further data collection and protocol reinforcement.
ABSTRACT
Introduction: COVID-19 pandemic has affected everyone's life, especially children with Type 1 DM with a poor economic background. Monitoring of blood glucose and their follow up with the health care professionals were badly affected during these times. Objective(s): To assess the effectiveness of continuous blood glucose monitoring and SMBG on HbA1c level in children with Type 1 diabetes mellitus in COVID-19 pandemic. Method(s): All children diagnosed with Type 1 Diabetes mellitus with poor economic background aged between 3 and 18 years attending the diabetic OPD in a tertiary care Government hospital in south India were included in this study. Participants were randomized to study arm (CGMS+SMBG) and control arm (SMBG alone). Subjects in study group were placed on ProCGM for 14 days along with regular SMBG and control group were asked to use SMBG and data were analyzed and used to titrate the insulin dose. Result(s): There were 62 children in both the groups. In the intervention group, 30 were boys and 32 were girls. In the control group, 20 were boys and 42 were girls. In the intervention group, baseline and follow-up values of HbA1c were 11.232 +/- 1.53 and 10.14 +/- 1.99;hyperglycemia were 61.42 +/- 24.35 and 55.12 +/- 22.14;and hypoglycemia were 3.12 +/- 0.215 and 3.10 +/- 0.96 respectively. In the control group, baseline and follow-up values of HbA1c were 11.62 +/- 1.62 and 11.78 +/- 1.57;hyperglycemia were 49.92 +/- 24.64 and 53.34 +/- 17.23;and hypoglycemia were 3.09 +/- 5.01 and 3.45 +/- 7.97 respectively. There was a reduction in HbA1C levels (1.09 +/- 0.31) and in incidences of hyperglycemia and hypoglycemia in the intervention group. Conclusion(s): In resource limited settings, use of ProCGMS once in 2 or 3 months will help in understanding the factors affecting glycemic variability. It can reduce school absenteeism for hospital visits and also can be used as an educational tool for families in the management of diabetes.
ABSTRACT
SESSION TITLE: Close Critical Care Calls SESSION TYPE: Case Reports PRESENTED ON: 10/18/2022 11:15 am - 12:15 pm INTRODUCTION: Heparin is the preferred anticoagulant for use in pregnancy while on extracorporeal membrane oxygenation (ECMO) (1). Alternatives to heparin in this patient population are not well studied as heparin-induced thrombocytopenia is rare in pregnancy. Parenteral non-heparin anticoagulants available in the United States include the direct thrombin inhibitors argatroban and bivalirudin, both of which are utilized in ECMO. Guidelines recommend avoidance of these agents in pregnancy if at all possible (2). Whereas case reports support the safe use of argatroban in pregnancy, to our knowledge, there are no known documented reports of bivalirudin use in this patient population (3). Here we describe the successful use of bivalirudin during pregnancy. CASE PRESENTATION: A 25 year old G2P1 was transferred to our institution at 28 weeks gestation for further management of acute hypoxic respiratory failure secondary to COVID-19. On hospital day 2 the patient was urgently placed on venovenous (VV) ECMO for refractory hypoxemia, high dead space with acidosis, and the inability to provide adequate gas exchange and lung protection with mechanical ventilation alone. Following ECMO cannulation with a 25f cannula in the right femoral vein and a 21f cannula in the right internal jugular vein, she was anticoagulated with heparin at a rate of 12 units/kg/hr. This was titrated to target a PTT goal of 60-80 seconds. On ECMO day 2, the TEG demonstrated a markedly hypocoagulable state, and the heparin nomogram called for increasing heparin dosing based on PTT. Given the already high dose of heparin that the patient was on (32.9 units/kg/hr), the decision was made to switch from heparin to bivalirudin to prevent over anticoagulation and reduce bleeding risk. Bivalirudin was titrated to a goal PTT of 50-60 seconds, with an initial rate of 0.15 mg/kg/hr (dose range 0.15-0.22 mg/kg/hr). Therapy was continued and on ECMO day 11, at 29w6d the patient delivered via cesarean section. Bivalirudin was discontinued 2.5 hours prior to the surgical procedure which resulted with no fetal bleeding complications. The patient was decannulated from ECMO on day 20 and was later discharged from the hospital. The newborn is developing well and meeting age adjusted milestones. DISCUSSION: Bivalirudin was selected based on institutional experience and the pharmacokinetic properties of the drug (half-life of 25 minutes) as we considered a situation where an emergent delivery may be indicated. Bivalirudin successfully prevented clotting of the circuit with no maternal or fetal bleeding complications during its use. CONCLUSIONS: Our case report describes a multidisciplinary approach to managing a pregnant patient on ECMO requiring anticoagulation using an alternative medication to heparin. This is the first documented use of bivalirudin in pregnancy. Reference #1: ELSO Guidelines for Cardiopulmonary Extracorporeal Life Support Extracorporeal Life Support Organization, Version 1.4 August 2017. Ann Arbor, MI, USA www.elso.org. Reference #2: Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(Suppl): e691S–736S Reference #3: Young SK, Al-Mondhiry HA, Vaida SJ, et al. Successful use of argatroban during the third trimester of pregnancy: case report and review of the literature. Pharmacotherapy 2008;28: 1531–6. DISCLOSURES: No relevant relationships by Jacqueline Finger No relevant relationships by Caitlin Gluck No relevant relationships by Cameron Hypes No relevant relationships by John Rathbun
ABSTRACT
Case series: Extracorporeal membrane oxygenation (ECMO) use for severe acute respiratory distress syndrome due to coronavirus disease 2019 (COVID-19) patients has increased during the second wave of the pandemic. However, there are many complications associated with the management of ECMO in critically ill COVID- 19 patients. We report a case series of challenges and strategies for managing critically ill COVID-19 patients on ECMO support for severe ARDS. Seven COVID-19 patients required VV ECMO of which three were women and four were men of median age of 43 years. Among seven, three cases (42%) recovered. We experienced multiple challenges and complications in the management of the patients, being a non-ECMO centre with limited resources, in heavy workload during the second wave of the pandemic. All the patients required multiple invasive procedures like placement of invasive lines, frequent bronchoscopies for bronchial toileting. Displacement of both ECMO cannulas required repositioning under ultrasound guidance, four patients underwent percutaneous tracheostomy on ECMO. Three patients had ECMO-oxygenator failure that required the exchange of a new ECMO circuit. ACT was monitored for the management of anticoagulation. A challenging task is to achieve a balance between bleeding and thrombotic events, for which anticoagulation had to be stopped for the acceptable ACT, required transfusion of multiple blood products for correcting coagulopathy. One patient developed HIT antibodies and managed with bivalirudin for the management of anticoagulation which was challenging in titrating the drug dose and ACT. Two patients had an intracranial haemorrhage on ECMO support, managed conservatively despite anticoagulation. Pseudoaneurysm of femoral vein diagnosed and managed with ultrasound-guided thrombin injection. Four patients got decannulated from ECMO. One patient had unexplained severe haemolysis immediately after initiation of ECMO, unfortunately, he could not recover. Management of VV ECMO in resource-limited, non-ECMO centre in a pandemic is challenging. Mortality depends on various factors, despite expertise, advanced critical care management in COVID- 19 ARDS and ECMO. Increased use of VV ECMO during the second wave of pandemic reported significant changes in strategies for management of challenges, though further studies are still required for the best outcome.
ABSTRACT
Objectives: Reactivation of hepatitis B is defined as dramatic increase in hepatitis B virus (HBV) replication in a patient with inactive or resolved hepatitis B. Reactivation can occur spontaneously but typically is triggered by immunosuppressive therapy or discontinuation of antiviral treatment. Some cases with COVID-19 progress into severe or critical disease requiring immunosuppressive therapy. Materials and Methods: We report the case of hepatitis B virus reactivation in a young adult with COVID-19. Results: 40-year-old male presented on day 7 of disease with sustaining fever and weakness. Chest CT scan revealed ground glass opacity. Nasopharyngeal mucus sample showed positive for SARSCov-2 PCR. Oxygen saturation (SpO2) was over 93% on room air. 10 years ago patient was diagnosed with HBV infection HBeAg +and high viral concentration, thus tenofovir was initiated. After 3 year of AVT seroconversion of HBeAg was achieved, after 5 years of AVT HBV PCR was negative. As treatment for COVID-19 high doses of methylprednisolone was administered and titrated during a month. Patient refused AVT, and it was terminated. COVID-19 resolved but after 2 months blood analysis revealed following: ALT' 357 U/L, AST' 147 U/L, GGT' 110U/l, ALP' 67 U/L, PCR HBsAg' 11.000 U/L, HBeAg' positive, PCR HBV' positive. HBV reactivation was diagnosed and ATV was restarted. After 1 week of ATV HBsAg lowered to 9000, HBeAg became negative, ALT-1400 U/L, AST-375 U/L, GGT-191U/L, ALP-164U/L. 1 month later HBsAg was 76 U/L, HBeAg-negative and ALT-90 U/L, AST-46 U/L, GGT-116 U/L, ALP-72 U/L. After 2 months HBsAg became negative, without AntiHBsAg, ATV was continued. Conclusion: This case is a vivid example of the association of HBV reactivation and immunosuppressive treatment with discontinuation of AVT during COVID-19 and illustrates the importance of AVT maintenance and careful consideration of high doses of steroids in patients with HBV infection.
ABSTRACT
Background: The neurobiology of depression can be heterogeneous with multiple hypotheses proposed, including serotonin and neuroinflammatory pathways, each falling short of explaining the complete picture. Several reports describe the increased frequency of depression in the community following the COVID-19 pandemic and reports about neuropsychiatric sequela of the virus are emerging and the possible role of neuroinflammation. We present a patient who developed severe depression with psychotic features subsequent to his COVID-19 infection and was treated successfully with ECT following several failed medication trials. Case: A 49-year-old male with a past medical history of type II diabetes, hyperlipidemia, hypertension, chronic kidney disease, and gastroesophageal reflux disease was diagnosed with COVID-19 in January 2021. Upon initial diagnosis, neither admission nor treatment with steroids was required. He presented to the emergency department four days later with sepsis, pneumonia, and AKI secondary to COVID-19 along with the new onset of suicidal ideations with plans to cut himself and significant psychomotor features despite no previous history of mental illness or treatment. His EEG showed diffuse slow waves, consistent with encephalopathy, but no delirium was noted. He exhibited irritability, anger, anhedonia, negativism, and isolated himself in his room. He demonstrated delusional fear about his apartment exploding due to electricity disconnected for not paying his bills. He misinterpreted the blood draws as someone suspecting he has HIV. Treatment started on the medical floor and he was later transferred to the psychiatric floor. Several psychotropic medications were tried separately including citalopram 20mg, escitalopram 20mg, and bupropion (titrated to 300mg) with the addition of aripiprazole 5 mg without improvement. ECT was considered and his depression and psychosis improved following 6 treatments of bilateral ECT. He was discharged following completion of 10 ECT treatments on 300 mg of bupropion daily and 5mg olanzapine at night. Discussion: Viral infections such as HIV, Hepatitis C, and Influenza are associated with neuropsychiatric sequelae, including depression. COVID-19 infection is occasionally associated with ‘cytokine storm’ which may exacerbate neuroinflammation via increases in cytokines and possible activation of mast cells and microglia.[1] The role of elevated pro-inflammatory cytokines and glucocorticoid receptor resistance is widely studied. Interleukin-6 and CRP are the most strongly linked to depression with a high correlation for anhedonia and psychomotor retardation, prominent features of depression in our case, hinting at a possible role of neuroinflammation. [2] Psychotic features and psychomotor retardation are predictors of ECT response which matched the response to ECT in this case. References: 1. Kempuraj, Duraisamy, et al. COVID-19, mast cells, cytokine storm, psychological stress, and neuroinflammation. The Neuroscientist 2020: 402-414. 2. Tiemeier, Henning, et al. Inflammatory proteins and depression in the elderly. Epidemiology 2003: 103-107.
ABSTRACT
RATIONALE: Pulmonary arterial hypertension (PAH) is a rare, progressive disease leading to right ventricular failure and premature death. The functional limitation and survival of patients with PAH remains unsatisfactory. Ralinepag, an orally available, potent, and selective, nonprostanoid, prostacyclin receptor agonist, is a new chemical entity in development to treat PAH. METHODS: The ADVANCE OUTCOMES (NCT03626688) study is a randomized, double-blind, placebocontrolled, event-driven study evaluating the efficacy and safety of ralinepag in subjects with PAH. In this event-driven, Phase 3 study, approximately 700 subjects with PAH treated with standard of care are randomly assigned (1:1) to receive ralinepag or placebo. Dosing is individualized and titrated based on tolerability and clinical response. The primary objective is to assess the effect of ralinepag on the time to first adjudicated clinical worsening event;a composite endpoint including death, hospitalization due to worsening of PAH, initiation of inhaled or infused prostacyclins, disease progression, or unsatisfactory long-term response. Additional secondary assessments during the study include changes from Baseline to Week 28 in N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walk distance (6MWD), WHO/New York Heart Association (NYHA) Functional Class, and health-related quality of life measures. Exploratory assessments will evaluate biomarkers and pharmacogenetics. Subject safety is evaluated by capturing adverse events, hospitalizations, clinical laboratory, and ECG parameters. Subjects who experience a clinical worsening event or are participating at study closure are eligible to enter an open-label extension study (ROR-PH-303 [NCT03683186]). Long-term survival will be followed for all subjects until study closure. RESULTS: Enrollment is ongoing at approximately 200 sites in 33 countries following implementation of risk mitigation steps related to the Covid-19 pandemic. Enrollment will continue until 228 adjudicated clinical worsening events have occurred. The interim assessment includes 281 subjects randomized in 29 different countries;97% of participants have completed 28 weeks of treatment. The majority of subjects were female (79.4%) with a median age of 48.0 years, were receiving dual background therapy (82.9%), and were classified as Functional Class II (59.3%). Overall, 48 clinical worsening events have been reported at the time of the interim assessment. Of these, 34 subjects elected to continue treatment in the open-label extension study. An independent Data Monitoring Committee reviewed safety data after 50, 100, and 250 subjects were randomized and recommended study continuation without modification. CONCLUSIONS: ADVANCE OUTCOMES will assess whether ralinepag can improve function, delay disease progression, and prolong survival in subjects with PAH.
ABSTRACT
Introduction: Recognition of myositis-associated interstitial lung disease (ILD) has been increasing due to the recent identification of specific antibodies that are linked to a particular phenotype of myositis-ILD such as antisynthetase syndrome. The anti-Ro52 antibody has been found in multiple connective tissue diseases but its association with ILD is unclear. In fact, the literature on the phenotype of patients with an isolated anti-Ro52 antibody is very scarce. Case Presentation: A 57-year-old retired firefighter with history of gastroesophageal reflux presented to the hospital with a 4-week history of cough and progressive dyspnea with no other symptoms. He had presented to an urgent care facility where he tested negative for SARs-CoV-2 and was given antibiotics and inhalers without a clinical response. Patient required 2L/min of oxygen on admission. He had no other signs of autoimmune disease or other organ involvement. Chest CT showed peripheral ground glass opacities with basilar reticulations and bronchiectasis (Figure 1). WBC and CPK were normal and aldolase was mildly elevated. Initial serologies revealed an ANA 1:320 and a weakly positive p-ANCA with negative PR3/MPO antibodies. Patient was started on prednisone 60 mg and discharged five days later on mycophenolate mofetil (MMF) and 2L/min of oxygen. At 2-week follow-up, his extensive autoimmune panel showed a high titer of Anti-Ro52 antibody. An in depth ILD questionnaire revealed a family history of lupus and the remote use of a short course of steroids 20 years ago after a biceps biopsy showed polymyositis. On chart review, 10 years ago the patient had elevated CPK levels of 255 to 404, in the context of a nonspecific flank pain that resolved without intervention. At his 3-month follow-up, the patient still required 40mg of prednisone, reported dyspnea on exertion and required oxygen with ambulation. Rituximab was added to his regimen and his symptoms significantly improved;at 6-month follow-up, his FVC% improved from 53% to 70% and the patient was no longer on oxygen. Prednisone was titrated down to 10mg and he was continued on MMF 3g/day and Rituximab every 6 months. Discussion: We present a patient with Anti-Ro52 antibody myositisassociated ILD who required 3 immunosuppressive agents to control his disease. This case adds to the very scarce literature on ILD secondary to Anti-Ro52 antibody and highlights the importance of an extensive antibody testing for patients with ILD of unclear etiology, for diagnostic and therapeutic purposes. Further studies describing the phenotype of these patients are warranted. (Figure Presented).
ABSTRACT
Objective: Uncontrolled hyperglycaemia is associated with poor clinical outcomes among patients with COVID-19. Diabetes mellitus and hyperglycemia at presentation, are independent risk factors for disease severity and worse outcome of COVID-19 infection. Methods: We evaluated the association of biomarkers of COVID-19 (CRP, D-Dimer and Ferritin) with the random blood sugar (RBS) as reported through SMBG by the patients who were already under regular care, across two dedicated diabetes centres. We compared the levels of CRP, D-Dimer and Ferritin across the groups with RBS < 200 and with RBS ≥ 200, Normal values: CRP 0-5 mg/L, D-Dimer < 0.5 mg/dl, Ferritin 30-400 ng/mL Results: The mean age of the patients was 59 years (SD±13, 95% CI 58 to 60). 256 were male. In our cohort, 378 (87%) were mild cases and 56 (12.9%) were moderate cases. The mean RBS in mild cases at the first consultation was 198 mg/dL (SD±45, 95% CI 170 to 231). The mean CRP (mg/dl), D-Dimer (mg/L) and Ferritin (mg/L) in mild cases were 6.7 (SD±3, 95% CI 5.5 to 7.3), 0.62 (SD±2, 95% CI 0.57 to 6.6) and 485 (SD±34, 95% CI 455 to 516), respectively. The mean RBS in moderate cases at the first consultation was 225 mg/dL (SD±32, 95% CI 196 to 259). The mean CRP (mg/dl), D-Dimer (mg/L) and Ferritin (mg/L) in moderate cases cases were 12.1 (SD±4, 95% CI 6.2 to 13.9), 1.3 (SD±2, 95% CI 0.9 to 1.7) and 655 (SD±42, 95% CI 588 to 691), respectively. There were 92 patients (21.1%) who were initiated on Premixed Analog insulin regimen to achieve glycemic control. Mild cases were managed by standard care approach for diabetes care, including oral drugs. 58 patients (63%) needed uptitration of insulin regimen as the RBS was over 300mg/dL, as a predefined threshold. Discussion/Conclusion: We observed that the T2DM patients with higher grade of hyperglycemia had higher concentrations of prognostic biomarkers. This might have happened due to inflammatory reactions and related tissue destruction. COVID-19 vaccination program should also target those populations with higher RBS to improve their outcomes. We could not quantify the grade of insulin resistance and obesity that would have independently deteriorated the glycemic control with accelerated transition of mild to moderate COVID-19. Our study highlights the need to evaluate COVID-19 biomarkers guided by higher RBS and accordingly predict the progress of mild to moderate cases and timely intervene to manage these patients, while optimally utilising the resources for management of COVID-19.
ABSTRACT
Objective: Uncontrolled hyperglycaemia is associated with poor clinical outcomes in patients with COVID-19. Basal-bolus (BB) insulin regimen is recommended for intensification and is safe and effective. However, this is complex in COVID era, especially for initiation with challenges in deployment of healthcare personnel with gaps in required expertise. Hence, implementation of an effective insulin therapy is challenging. Methods: We evaluated the impact of initiating premix analog insulin regimen (PA) in T2D patients diagnosed with COVID-19 during the second wave of the pandemic (n=434), who consulted virtually. Insulin initiation was based on random blood sugar (RBS) as reported through SMBG by the patients who were already under regular care, across two dedicated diabetes management centres. Patients were advised to contact over Whatsapp in case self-reported RBS was above 300 mg/dL Results: The mean age of the patients was 59 years (SD±13, 95% CI 58 to 60). 256 were male. 48 patients (11%) were started with basal insulin (43 glargine, 5 degludec) and were optimally managed by dose uptitration. There were 92 patients (21.1%) who were initiated on PA twice daily to achieve glycemic control. Of these, 56 patients (12.9%) were diagnosed as moderate COVID-19 and required corticosteroids. Among these, 42 patients (75%), on PA regimen reported post lunch and dinner glycemic spikes which necessitated additional pre-lunch dose of premix analogue. 36 patients with mild COVID-19, were continued on PA twice daily and doses were uptitrated based on the SMBG reports. The rest 378 (87%) mild COVID-19 cases, were managed by standard care approach for diabetes care, including oral drugs. The mean RBS at the first consultation at insulin initiation was 211 mg/dL (SD±98, 95% CI 192 to 230). On first follow up teleconsultation;mean RBS in mild COVID-19 was 178 mg/dL (SD±50, 95% CI 138 to 195), while those who progressed to moderate COVID-19, RBS was 267 mg/dL (SD±101, 95% CI 210 to 298). On second follow up;mean RBS in mild COVID-19 was 168 mg/dL (SD±54, 95% CI 148 to 183) and in moderate COVID-19 was 203 mg/dL (SD±88, 95% CI 174 to 258). 138 patients (31.7%) needed uptitration of insulin regimen Discussion/Conclusion: Simplified insulin regimen based on premix analog insulin has the potential for timely initiation of insulin, titration and intensification to third dose of PA to optimise the management of T2D in COVID-19. Our study did not account for the compliance to beyond the second teleconsultation and the pandemic prevented the estimation of A1C and did not account for patients who transformed as severe COVID-19 patients who needed hospitalisation
ABSTRACT
INTRODUCTION: In patients with unreliable activated partial thromboplastin time (aPTT) measurements who require anticoagulation with a direct thrombin inhibitor (DTI), the only reliable alternative measurement at present is a dilute thrombin time (dTT). However, this assay is not always readily available, which limits accurate real-time dose adjustments necessary to maintain therapeutic anticoagulation. DESCRIPTION: A 57 year-old woman with a history of antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, and multiple prior deep venous thromboses and pulmonary emboli was admitted with COVID-19 pneumonia and intubated due to hypoxic respiratory failure. Argatroban was initiated in place of her home medication warfarin. This patient had a prolonged aPTT value at baseline and overnight dTT assay measurements were limited at our institution. To overcome this challenge, a multidisciplinary team of hematology and pharmacy clinicians created a modified aPTT algorithm. By measuring aPTT and dTT simultaneously from patient plasma samples, a patientspecific aPTT target range was derived and argatroban dosing was titrated accordingly. Subsequent aPTT values in the modified target range corresponded to therapeutic dTT values, indicating therapeutic anticoagulation was successfully achieved and maintained. Patient plasma samples were also evaluated retrospectively using a novel point-of-care (POC) coagulation test to detect and quantify the effect of argatroban. A Clotting Time Score (CTS) was derived for each sample tested. Comparison of CTS and dTT values demonstrated moderate positive correlation between test results. All CTS results accurately reflected if argatroban dosing achieved an appropriate level of anticoagulation. DISCUSSION: Therapeutic anticoagulation with a DTI in a patient with unreliable aPTT measurements is challenging but can be achieved with use of a modified aPTT scale, which in our case study was retrospectively confirmed by corresponding dTT measurements. Early validation of a novel test that could offer a rapid, POC alternative to dTT when dTT measurements are necessary but not readily available is promising. Such a technology could dramatically improve rapid accurate titration of DTIs to maintain therapeutic anticoagulation.
ABSTRACT
BACKGROUND: The pandemic that occurred at the end of 2019 was caused by the coronavirus 2 (Severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). Various speculations mention that the long-term effects of coronavirus disease 2019 (COVID-19) infection can cause pulmonary fibrosis. Acute respiratory distress syndrome (ARDS) is one that can cause pulmonary fibrosis due to injury to the lungs. CASE REPORT: This report discusses a case of pulmonary fibrosis caused by critical COVID-19 (Coronavirus disease) in 38-year-old male patient with hypertension and obesity comorbidities. The patient was treated for 51 days in intensive care unit with 60 L/min high flow nasal cannula assisted oxygenation;then his condition improved as evidenced by his negative Real Time-Polymerase Chain Reaction test result, and was subsequently transferred to a non-COVID-19 ward using non-rebreathing mask at 10–15 L/min, which was later titrated to 2–4 L/min nasal canulla. Patient was treated in the non-COVID ward for 16 days. The total number of days of hospitalization was 67 days. Patient had his thorax photo taken 3 times and non-contrast thorax computed tomography (CT) scan 3 times. Based on the evaluation of his thorax CT scan on day 23, we found a vast fibrosis in patient’s lungs. Many literatures state that lung fibrosis can be triggered by ARDS, a condition due to the infection from SARS-CoV-2. CONCLUSION: COVID-19 infection can progress overtime and may cause pulmonary fibrosis. The most serious phase of this virus infection is characterized by sudden and excessive release of proinflammatory mediators that lead to lung damage with large fibrosis and rapid onset of ARDS. To further our understanding of this issue, we present the case report of lung fibrosis caused by critical COVID-19 infection.
ABSTRACT
Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) due to an acquired deficiency in the enzyme ADAMTS13 leads to ultra-large von Willebrand multimers, thrombocytopenia and microangiopathic hemolytic anemia. Complications include microvascular and macrovascular thrombosis. We present an unusual case of a patient with a history of refractory aTTP who experienced relapsed aTTP following COVID-19 vaccine. Case Description: A 57-year-old African-American male with a history of refractory aTTP experienced a relapse following 3 years of remission after receiving COVID-19 vaccination. The patient was initially diagnosed with aTTP in 2016, after presenting with symptoms of dark urine, mild headaches and transient episodes of aphasia and paresthesia. Due to symptoms and persistently low ADAMTS13 levels, he required prolonged and extensive treatment including over 5 weeks of daily therapeutic plasma exchange (TPE), followed by gradual reduction in frequency of TPE sessions, as well as trials of rituximab, eculizumab, steroids, mycophenolate mofetil and bortezomib. Ultimately, he achieved remission after 9 months of intermittent TPE, 3 months of weekly bortezomib 1 mg/m 2, mycophenolate mofetil up-titrated to 1,750 mg twice daily, and then slowly tapered off over a 2-year period. The patient was doing well for 3 years without manifestations of aTTP (2 years off all therapeutics), until he developed a petechial rash 7 weeks after receiving the second dose of the Moderna COVID-19 vaccine. He was found to have acute thrombocytopenia with platelets of 38 x 10 9/L (normal range 135-317 x 109/L), from a baseline of 200-300 x 10 9/L. He was referred to the emergency department, where additional labs were notable for mildly elevated LDH of 508 U/L (normal range 122-222 U/L), hemoglobin of 12.4 g/dL (normal range 13.2-16.6 g/dL), creatinine at baseline, and peripheral blood smear showing 1-3 schistocytes per high-powered field. ADAMTS13 activity level was t <5% (normal >/= 70%), with positive ADAMTS13 inhibitor screen and titer of 1.5 (normal <0.4), consistent with relapsed aTTP. The patient was admitted to the hospital, and initiated on daily TPE, with steroids and diphenhydramine prior to each TPE session. He quickly improved with TPE alone, but given his history of refractory aTTP, he was discharged on weekly rituximab for 4 weeks and caplacizumab 11 mg daily for 30 days. His platelets remained stable within the upper limit of normal during his 30 day course of caplacizumab. However, 3 weeks after completion of caplacizumab, he had an acute drop in his platelets to 23 x 10 9/L. His ADAMTS13 level was again found to be <5%, and inhibitor level was the highest that it had ever been at 11.4. He was again hospitalized and underwent 8 sessions of daily TPE, as well as re-initiation of caplacizumab, mycophenolate mofetil 500 mg bid (with increasing taper), and a prednisone taper. Intravenous Cyclophosphamide 750 mg/m 2 was also added every 3 weeks. With this regimen, patient's platelet count normalized and remain stable, and his ADAMTS13 activity level has reached 52-59%. Discussion: Cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) have been described as a complication following vaccination with formulations containing replication-defective adenoviral vectors (AstraZeneca-Oxford and Johnson&Johnson COVID-19 vaccines)(Arepally and Ortel 2021, Simpson, Shi et al. 2021). VITT and aTTP are both immune-mediated, however, VITT is distinct and pathogenically linked to autoimmune heparin-induced thrombocytopenia (HIT), given the presence of anti-platelet factor 4 antibodies in these patients, whereas aTTP is due to reduction in ADAMTS13 level, secondary to an antibody inhibitor of ADAMTS13 (Arepally and Ortel 2021). Recently, cases have been reported of de novo aTTP developing shortly after COVID-19 vaccination with all available vaccines, except the Moderna (mRNA-1273) vaccine (Al-Ahmad, Al-Rasheed et al. 2021, de Bruijn, Maes et al. 2021, Maayan, Kirgner et al. 2021, Ruhe, Schnetzke et al. 2021, Waqar, Khan et a . 2021, Yocum and Simon 2021). Additionally, cases of relapsed aTTP have been described following only the BNT162B2 (Pfizer-BioNTech) vaccine (Maayan, Kirgner et al. 2021, Sissa, Al-Khaffaf et al. 2021). This is the first case, to our knowledge, reported in the literature of aTTP following vaccination with Moderna's mRNA-1273 vaccine. Disclosures: No relevant conflicts of interest to declare.