scholarly journals Treatment of COVID-19 pneumonia and acute respiratory distress with ramatroban, a thromboxane A2 and prostaglandin D2 receptor antagonist: A 4-Patient Case Series Report

Author(s):  
Martin L. Ogletree ◽  
Kate Chander Chiang ◽  
Rashmi Kulshreshta ◽  
Aditya Agarwal ◽  
Ashutosh Agarwal ◽  
...  

Abstract Importance Hypoxemia in COVID-19 pneumonia is dispositive for hospitalization and mechanical ventilation and contributes to mortality. Other than oxygen supplementation, there is no treatment that resolves hypoxemia in COVID-19 pneumonia. Objective COVID-19 pneumonia sustains a massive increase in lipid mediators, especially thromboxane A2 >> PGE2 > PGD2. Thromboxane A2 induces pulmonary venoconstriction, increases pulmonary capillary pressure and contributes to pulmonary edema. High thromboxane A2 metabolite levels are strongly associated with respiratory failure and mortality in hospitalized COVID-19 patients. Ramatroban (Baynas®, Bayer Yakuhin Ltd., Japan) is an inexpensive, orally bioavailable, thromboxane A2 receptor antagonist. Ramatroban was administered to patients with COVID-19 pneumonia and hypoxemia to explore the effect of thromboxane A2 antagonism on clinical symptoms and outcomes. Design, Setting, and Participants A retrospective case series comprising 4 consecutive outpatients, 22 to 87 years of age, with COVID-19 pneumonia and hypoxemia treated with ramatroban between April and July 2021 in India. Main Outcomes and Measures The primary outcome measure was blood oxygen saturation using pulse oximetry (SpO2). Secondary outcome measures were respiratory distress and need for hospitalization. Results Four COVID-19 outpatients had developed progressive respiratory distress and hypoxemia. Within 12-36 hours of the first dose of ramatroban, all four patients experienced increase in SpO2 and decrease in respiratory distress, which obviated hospitalization. Continued treatment for 5 days was associated with complete resolution of respiratory distress and hypoxemia. Conclusions and Relevance There is an unmet medical need for drugs that target the hemodynamic, prothrombotic, and maladaptive immune responses that lead to pneumonia and respiratory failure following SARS-CoV-2 infection. As an anti-vasospastic, broncho-relaxant, anti-thrombotic and immunomodulatory agent, ramatroban addresses the fundamental host response mechanisms underlying respiratory and critical organ failure in COVID-19. Ramatroban merits study in randomized clinical trials that might offer hope for a cost-effective pandemic treatment.

2022 ◽  
Author(s):  
Martin L. Ogletree ◽  
Kate Chander Chiang ◽  
Rashmi Kulshreshta ◽  
Aditya Agarwal ◽  
Ashutosh Agarwal ◽  
...  

Abstract Importance Hypoxemia in COVID-19 pneumonia is dispositive for hospitalization and mechanical ventilation and contributes to mortality. Other than oxygen supplementation, there is no treatment that resolves hypoxemia in COVID-19 pneumonia. Objective COVID-19 pneumonia sustains a massive increase in lipid mediators, especially thromboxane A2 >> PGE2 > PGD2. Thromboxane A2 induces pulmonary venoconstriction, increases pulmonary capillary pressure and contributes to pulmonary edema. High thromboxane A2 metabolite levels are strongly associated with respiratory failure and mortality in hospitalized COVID-19 patients. Ramatroban (Baynas®, Bayer Yakuhin Ltd., Japan) is an inexpensive, orally bioavailable, thromboxane A2 receptor antagonist. Ramatroban was administered to patients with COVID-19 pneumonia and hypoxemia to explore the effect of thromboxane A2 antagonism on clinical symptoms and outcomes. Design, Setting, and Participants A retrospective case series comprising 4 consecutive outpatients, 22 to 87 years of age, with COVID-19 pneumonia and hypoxemia treated with ramatroban between April and July 2021 in India. Main Outcomes and Measures The primary outcome measure was blood oxygen saturation using pulse oximetry (SpO2). Secondary outcome measures were respiratory distress and need for hospitalization. Results Four COVID-19 outpatients had developed progressive respiratory distress and hypoxemia. Within 12-36 hours of the first dose of ramatroban, all four patients experienced increase in SpO2 and decrease in respiratory distress, which obviated hospitalization. Continued treatment for 5 days was associated with complete resolution of respiratory distress and hypoxemia. Conclusions and Relevance There is an unmet medical need for drugs that target the hemodynamic, prothrombotic, and maladaptive immune responses that lead to pneumonia and respiratory failure following SARS-CoV-2 infection. As an anti-vasospastic, broncho-relaxant, anti-thrombotic and immunomodulatory agent, ramatroban addresses the fundamental host response mechanisms underlying respiratory and critical organ failure in COVID-19. Ramatroban merits study in randomized clinical trials that might offer hope for a cost-effective pandemic treatment.


2021 ◽  
pp. 112067212110000
Author(s):  
Annabel LW Groot ◽  
Jelmer S Remmers ◽  
Roel JHM Kloos ◽  
Peerooz Saeed ◽  
Dyonne T Hartong

Purpose: Recurrent contracted sockets are complex situations where previous surgeries have failed, disabling the wear of an ocular prosthesis. A combined method of surgery and long-term fixation using custom-made, three-dimensional (3D) printed conformers is evaluated. Methods: Retrospective case series of nine patients with recurrent excessive socket contraction and inability to wear a prosthesis, caused by chemical burns ( n = 3), fireworks ( n = 3), trauma ( n = 2) and enucleation and radiotherapy at childhood due to optic nerve glioma ( n = 1) with three average previous socket surgeries (range 2–6). Treatment consisted of a buccal mucosal graft and personalized 3D-printed conformer designed to be fixated to the periosteum and tarsal plates for minimal 2 months. Primary outcome was the retention of an ocular prosthesis. Secondary outcome was the need for additional surgeries. Results: Outcomes were measured at final follow-up between 7 and 36 months postoperatively (mean 20 months). Eight cases were able to wear an ocular prosthesis after 2 months. Three cases initially treated for only the upper or only the lower fornix needed subsequent surgery for the opposite fornix for functional reasons. Two cases had later surgery for cosmetic improvement of upper eyelid position. Despite pre-existing lid abnormalities (scar, entropion, lash deficiency), cosmetic outcome was judged highly acceptable in six cases because of symmetric contour and volume, and reasonably acceptable in the remaining two. Conclusions: Buccal mucosal transplant fixated with a personalized 3D-designed conformer enables retention of a well-fitted ocular prosthesis in previously failed socket surgeries. Initial treatment of both upper and lower fornices is recommended to avoid subsequent surgeries for functional reasons.


2021 ◽  
Author(s):  
Martin L. Ogletree ◽  
Kate Chander Chiang ◽  
Rashmi Kulshreshta ◽  
Aditya Agarwal ◽  
Ashutosh Agarwal ◽  
...  

Abstract COVID-19 associated pneumonia and acute respiratory distress syndrome are characterized by a lipid mediator storm with massive increases in lung and systemic thromboxane A2 >> prostaglandin D2. Thromboxane A2 is a potent vasoconstrictor of pulmonary veins >> arteries, and thereby promotes an increase in pulmonary capillary pressures, transudation of fluid into the alveolar space, pulmonary edema and ARDS. Thromboxane A2 also increases vascular permeability, contracts bronchial smooth muscle, triggers and amplifies platelet activation, and promotes a prothrombotic state. PGD2 promotes a Th2 immune response that is atypical for viral infections and inhibits antiviral defense by suppressing interferon λ expression. D-dimers, urinary 11-dehydro-TxB2, and IL-13, a Th2 cytokine, have emerged as key biomarkers of severity and organ failure in COVID-19. Ramatroban is an orally bioavailable, potent, dual antagonist of the thromboxane A2 (TPr) and PGD2 (DPr2) receptors. We report use of ramatroban in 4 COVID-19 outpatients, 22 to 87 years of age, with acute onset / worsening of respiratory distress and hypoxemia. All four patients experienced decrease in respiratory distress and increase in SpO2, within hours of the first dose and thereby avoided hospitalization. By the 5th day all 4 patients had complete resolution of respiratory distress and hypoxemia. Ramatroban (Baynas®, Bayer Yakuhin Ltd., Japan) has an established safety profile, having been indicated in Japan for the treatment of allergic rhinitis for over 20 years. As a broncho-relaxant, anti-vasospastic, anti-thrombotic and immunomodulator, ramatroban addresses the fundamental pathophysiologic mechanisms underlying respiratory and critical organ failure in COVID-19, and therefore merits urgent clinical trials that might impact the ongoing pandemic.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatme Seval Ismail ◽  
Johannes van de Nes ◽  
Ilka Kleffner

Abstract Background Posterior reversible encephalopathy syndrome (PRES) is clinical-neuroradiologically defined and potentially reversible, so there are limited data about histopathological findings. We aimed to describe the clinical and paraclinical features of patients with PRES with regard to its reversibility. Methods This retrospective case series encompasses 15 PRES cases out of 1300 evaluated patients from a single German center between January 1, 2010, and June 15, 2020. PRES was established according to the diagnostic criteria as proposed by the Berlin PRES Study 2012. One of the cases studied was subject to brain autopsy. Results From the 15 patients studied (median age 53 years, range 17–73; 11 female), 67 % presented with epileptic seizures, 40 % suffered from encephalopathy with reduced consciousness and 53 % developed delirium, while 47 % had headache and visual disturbances. Subcortical brain MRI abnormalities related to PRES were observed in all patients. One patient developed spinal ischemia and another Guillain-Barré syndrome in addition to PRES. Hypertensive blood pressure was the main underlying/trigger condition in all patients. Clinical symptoms and MRI changes were not reversible in 42 %, even progressive in 3 out of these 5 patients. Median time from symptom onset to diagnosis in these non-reversible cases was 7 days (range 0–13), while the median delay in diagnosis in the reversible group was 1 day (range 0–3). Cerebellar/brain stem involvement and status epilepticus were more frequently in patients with non-reversible disease course. Mortality due to PRES occurred in 13 % of these patients. Neuropathological examination of the brain of a 57-year-old female patient revealed major leukencephalopathic changes, fibrinoid necrosis of endothelial cells and fresh petechial hemorrhages in accordance with PRES. Conclusions Our case series demonstrates that PRES was not reversible in 42 % of the studied patients. Delay in diagnosis seems to contribute to limited reversibility and poor outcome.


2021 ◽  
Author(s):  
Fumihiro Ogawa ◽  
Yasufumi Oi ◽  
Kento Nakajima ◽  
Reo Matsumura ◽  
Tomoki Nakagawa ◽  
...  

Abstract Background: Coronavirus disease (COVID-19) pneumonitis associated with severe respiratory failure has a high mortality rate. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently observed. Coagulopathy has emerged as a significant contributor to thrombotic complications. Although recommendations have been made for anticoagulant use for COVID-19, no guidelines have been specified.Case presentation: We describe four cases of critical COVID-19 with thrombosis detected by enhanced CT scan. The CT findings of all cases demonstrated typical findings of COVID-19 and pulmonary embolism or deep venous thrombus without critical exacerbation. Two patients died of respiratory failure due to COVID-19.Discussion: Previous reports have suggested coagulopathy with thrombotic signs as the main pathological feature of COVID-19, but no previous reports have focused on coagulopathy evaluated by whole-body enhanced CT scan. Changes in hemostatic biomarkers, represented by an increase in D-dimer and fibrin/fibrinogen degradation products, indicated that the essence of coagulopathy was massive fibrin formation. Although there were no clinical symptoms related to their prognosis, critical COVID-19-induced systemic thrombus formation was observed. Conclusions: Therapeutic dose anticoagulants should be considered for critical COVID-19 because of induced coagulopathy, and aggressive follow-up by whole body enhanced CT scan for systemic venous thromboembolism (VTE) is necessary.


2021 ◽  
pp. 42-43
Author(s):  
Rohan J Desai ◽  
Prasad Ugargol

Background: Amitraz is a pharmaceutical, veterinary, and agricultural product which is used worldwide to control ectoparasites in animals. Its widespread use has led to increased cases of poisoning in rural parts of India. Aim: To study the clinical features, complications, laboratory abnormalities and outcome of the patients with acute amitraz intoxication. Methodology: The study is a retrospective case series study conducted in HSK hospital between the period of Feb 2019 and May 2020. Results: A total of 11 patients were analysed and results revealed CNS depression and vomiting in 8 of those patients with 1 patient with respiratory failure requiring mechanical ventilation. Conclusion: Amitraz poisoning appears to be severe with CNS depression being the most common symptom. But most patients stabilise and recover quickly. Patients should be monitored for respiratory failure as it is a dreadful complication. Treatment is symptomatic as no antidote is available.


2020 ◽  
pp. 000348942097323
Author(s):  
Mohammad Al-Alawneh ◽  
Ladd Caballero ◽  
Elijah DeBroux ◽  
Michael J. Herr ◽  
Amy Claire Petro ◽  
...  

Objective: Standards for treatment of laryngeal clefts remain poorly defined. There are no large case series that report the efficacy of injection laryngoplasty (IL) in the treatment of pediatric Type 1 laryngeal clefts (LC-1). The objective of this study is to measure the effect of IL in young children with LC-1. Methods: A retrospective case series of 130 patients was completed over 3 years at a at a single institution included patients aged 1 month to 8 years, diagnosed with aspiration and penetration issues during swallowing based on a Videofluoroscopic Swallow Study (VFSS). Patients underwent surgical evaluation and intervention using carboxymethylcellulose gel injection. Collected data points included age in months at time of first injection, gender, race, pre- and post-operation VFSS scores, number of injections, co-morbidities and post-operative complications. VFSS scores were evaluated pre- and post-operatively to assess efficacy of intervention. A secondary outcome was efficacy in patients with aspiration compared to those with penetration alone. Results: This study included 77 male and 53 female patients. Sixty-two patients (48%) demonstrated a significant post-operative improvement in their swallowing function ( P < .05). There were no statistical differences in age, number of injections, or the volume of the first injection. Patients that showed a post-operative improvement in swallowing function were on average 5 months older and had more severe aspiration and penetration compared to those who did not demonstrate a post-operative benefit and underwent less injections. The volume of injection did not appear to play a role in the success rate. Conclusion: Injecting the inter-arytenoid area in patients with LC-1 appears to confer some benefit to close to half of our patient population. Successful procedures seemed to occur in patients with more severe aspiration and penetration and older age.


2020 ◽  
Vol 14 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Cezara Danilov ◽  
Christoph Ihle ◽  
Francisco F. Fernandez ◽  
Gunnar Blumenstock ◽  
Thomas Wirth ◽  
...  

Purpose The aim of the study was to evaluate predictable parameters with the highest sensitivity used in the diagnosis of children septic shoulder arthritis. Methods All children treated in our paediatric orthopaedic hospital between 2000 and 2017 with intraoperative verified septic arthritis of the shoulder were included in this retrospective study. Diagnostic procedures e.g. ultrasound, MRI, radiograph or blood samples as well as typical clinical symptoms were evaluated as predictable parameters for septic shoulder arthritis in paediatric patients. Descriptive statistics as well as sensitivity analysis were performed. Results In all, 25 children, 20 boys and five girls, aged from eight days to 15 years, were included for further statistical analysis. All parameters included were tested for sensitivity with binomial confidence intervals (Cis) of 95%. Predictive parameters with highest sensitivity were pseudo paralysis (100%, CI 0.86 to 1.00) and C-reactive protein (CRP) (96%, CI 0.79 to 0.99) superior to temperature (52%, CI 0.3 to 0.73), white blood count (11%, CI 0.01 to 0.34), radiograph (21%, CI 0.04 to 0.50), ultrasound (71%, CI 0.47 to 0.88) or MRI (100%, CI 0.78 to 1.00). Conclusion The diagnosis of a septic arthritis of the shoulder in children can be challenging for the clinician and especially for the resident doctor. Clinical symptoms such as pseudo paralysis and increased CRP level must be considered as predictive markers not to delay further diagnostics and treatment. Level of Evidence IV


Children ◽  
2020 ◽  
Vol 7 (12) ◽  
pp. 303
Author(s):  
Daniel T. Cater ◽  
Aimee R. Ealy ◽  
Erin Kramer ◽  
Samer Abu-Sultaneh ◽  
Courtney M. Rowan

Patients with acute respiratory distress syndrome (ARDS) commonly have dependent atelectasis and heterogeneous lung disease. Due to the heterogenous lung volumes seen, the application of positive end expiratory pressure (PEEP) can have both beneficial and deleterious effects. Alternating supine and prone positioning may be beneficial in ARDS by providing more homogenous distribution of PEEP and decreasing intrapulmonary shunt. In pediatrics, the pediatric acute lung injury and consensus conference (PALICC) recommended to consider it in severe pediatric ARDS (PARDS). Manually prone positioning patients can be burdensome in larger patients. In adults, the use of rotational beds has eased care of these patients. There is little published data about rotational bed therapy in children. Therefore, we sought to describe the use of a rotational bed in children with PARDS. We performed a retrospective case series of children who utilized a rotational bed as an adjunctive therapy for their PARDS. Patient data were collected and analyzed. Descriptive statistical analyses were performed and reported. Oxygenation indices (OI) pre- and post-prone positioning were analyzed. Twelve patients with PARDS were treated with a rotational bed with minimal adverse events. There were no complications noted. Three patients had malfunctioning of their arterial line while on the rotational bed. Oxygenation indices improved over time in 11 of the 12 patients included in the study while on the rotational bed. Rotational beds can be safely utilized in pediatric patients. In larger children with PARDS, where it may be more difficult to perform a manual prone position, use of a rotational bed can be considered a safe alternative.


2020 ◽  
Vol 9 (5) ◽  
pp. 523-529 ◽  
Author(s):  
William R Otto ◽  
Sarah Geoghegan ◽  
Leila C Posch ◽  
Louis M Bell ◽  
Susan E Coffin ◽  
...  

Abstract Background Understanding the prevalence and clinical presentation of coronavirus disease 2019 in pediatric patients can help healthcare providers and systems prepare and respond to this emerging pandemic. Methods This was a retrospective case series of patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across a pediatric healthcare network, including clinical features and outcomes of those with positive test results. Results Of 7256 unique children tested for SARS-CoV-2, 424 (5.8%) tested positive. Patients aged 18–21 years had the highest test positive rate (11.2%), while those aged 1–5 years had the lowest (3.9%). By race, 10.6% (226/2132) of black children tested positive vs 3.3% (117/3592) of white children. By indication for testing, 21.1% (371/1756) of patients with reported exposures or clinical symptoms tested positive vs 3.8% (53/1410) of those undergoing preprocedural or preadmission testing. Of 424 patients who tested positive for SARS-CoV-2, 182 (42.9%) had no comorbidities, 87 (20.5%) had asthma, and 55 (13.0%) were obese. Overall, 52.1% had cough, 51.2% fever, and 14.6% shortness of breath. Seventy-seven (18.2%) SARS-CoV-2–positive patients were hospitalized, of whom 24 (31.2%) required respiratory support. SARS-CoV-2-targeted antiviral therapy was given to 9 patients, and immunomodulatory therapy to 18 patients. Twelve (2.8%) SARS-CoV-2-positive patients required mechanical ventilation, and 2 patients required extracorporeal membrane oxygenation. Two patients died. Conclusions In this large cohort of pediatric patients tested for SARS-CoV-2, the rate of infection was low but varied by testing indication. The majority of cases were mild and few children had critical illness.


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