Direct bilirubin and the neutrophil-to-monocyte ratio timely predict intensive care unit admission in patients with severe acute respiratory syndrome coronavirus-2 infection (COVID-19)

Objective: Intensive care units (ICUs) collapsed under the global wave of coronavirus disease 2019 (COVID-19). Thus, we designed a clinical decision-making model that can help predict at hospital admission what patients with COVID-19 are at higher risk of requiring critical care. Method(s): This was a cross-sectional study in 119 patients that met hospitalization criteria for COVID-19 including less than 30 breaths per minute, peripheral oxygen saturation < 93%, and/or >= 50% lung involvement on imaging. Depending on the need for critical care, patients were retrospectively assigned to ICU and non-ICU groups. Demographic, clinical, and laboratory parameters were collected at admission and analyzed by classification and regression tree (CRT). Result(s): Forty-five patients were admitted to ICU and 80% of them were men older than 57.13 +/- 12.80 years on average. The leading comorbidity in ICU patients was hypertension. The CRT revealed that direct bilirubin (DB) > 0.315 mg/dl together with the neutrophil-to-monocyte ratio (NMR) > 15.90 predicted up to correctly in 92% of the patients the requirement of intensive care management, with sensitivity of 93.2%. Preexisting comorbidities did not influence on the tree growing. Conclusion(s): At hospital admission, DB and NMR can help identify nine in 10 patients with COVID-19 at higher risk of ICU admission.Copyright © 2022 Sociedad Medica del Hospital General de Mexico.

Persisting exertional dyspnea and perceived exercise intolerance after mild Covid-19: a critical role for breathing dysregulation?

Background: After mild Covid-19, a subgroup of patients reports post-acute sequelae of Covid-19 (PASC), in which exertional dyspnea and perceived exercise intolerance are common. Underlying pathophysiological mechanisms remain incompletely understood. We studied outcomes from cardiopulmonary exercise test (CPET) in these patients. Method(s): In this observational study, we included patients referred for the analysis of PASC after mild Covid-19 in whom CPET was performed after standard clinical work-up turned out unremarkable. Cardiocirculatory, ventilatory and metabolic response to, and breathing patterns during exercise at physiological limits were analyzed. Result(s): Twenty-one patients (76% female, mean age 40y) who reported severe fatigue (CIS-fatigue >= 35), dyspnea (mMRC 2 (IQR1-2)) and disability in physical role functioning (SF-36) underwent CPET at 32 weeks (IQR 22-52) after Covid-19. Mean peak oxygen uptake was 99% (SD13) of predicted with normal anaerobic thresholds at 62% (SD11) of predicted oxygen uptake. No cardiovascular or gas exchange abnormalities were detected. Twenty out of the 21 patients (95%) demonstrated breathing dysregulation, existing of ventilatory inefficiency (29%), abnormal course of breathing frequency and tidal volume (57%), and acute or chronic respiratory alkalosis in resting blood gases (67%). Conclusion(s): In the absence of deconditioning, breathing dysregulation may explain the experienced exertional dyspnea and exercise intolerance in patients with PASC after mild Covid-19.

Acid-base imbalance as a risk factor for mortality among COVID-19 hospitalized patients.

Severe coronavirus disease 2019 (COVID-19) infection can lead to extensive lung infiltrate, a significant increase in the respiratory rate, and respiratory failure, which can affect the acid-base balance. No research in the Middle East has previously examined acid-base imbalance in COVID-19 patients. The present study aimed to describe the acid-base imbalance in hospitalized COVID-19 patients, determine its causes, and assess its impact on mortality in a Jordanian hospital. The study divided patients into 11 groups based on arterial blood gas data. Patients in normal group were defined as having a pH of 7.35-7.45, PaCO2 of 35-45 mmHg, and HCO3- of 21-27 mEq/L. Other patients were divided into 10 additional groups: mixed acidosis and alkalosis, respiratory and metabolic acidosis with or without compensation, and respiratory and metabolic alkalosis with or without compensation. This is the first study to categorize patients in this way. The results showed that acid-base imbalance was a significant risk factor for mortality (P<0.0001). Mixed acidosis nearly quadruples the risk of death when compared with those with normal levels (OR = 3.61, P=0.05). Furthermore, the risk of death was twice as high (OR = 2) for metabolic acidosis with respiratory compensation (P=0.002), respiratory alkalosis with metabolic compensation (P=0.002), or respiratory acidosis with no compensation (P=0.002). In conclusion, acid-base abnormalities, particularly mixed metabolic and respiratory acidosis, were associated with increased mortality in hospitalized COVID-19 patients. Clinicians should be aware of the significance of these abnormalities and address their underlying causes.

Negative alactic base excess is reversed by hemoperfusion in septic patients

Introduction: Gattinoni et al. have recently introduced a new parameter: the "alactic base excess"(ABE). ABE is equivalent to the number of strong acids, other than lactate, which are present in the plasma in abnormal concentrations, negative ABE being associated with higher mortality in sepsis. Hemoperfusion (HPF) is an extracorporeal procedure that involves the passage of blood through an adsorption cartridge, where solutes are removed by direct binding to the sorbent material. Then, it was decided to explore the influence of HPF on negative ABE value in sepsis. Material(s) and Method(s): Basal values of ABE, standard base excess (SBE), and lactate (mean, standard deviation [SD]) were obtained. The difference between these parameter values before and after four sessions of HPF (HA330) (delta value) was evaluated. Student's t-test and Wilcoxon test were applied. Result(s): From 32 patients (age: 57+/-13) suffering from respiratory insufficiency secondary to COVID-19 who were treated with HPF in the critical care unit of Clinica de la Mujer, Bogota (Colombia), 6 patients presented with metabolic acidosis with negative ABE value (-2.7+/-1) with negative SBE (-4.7+/-1) and high lactate serum value (2+/-0.7 mmol/L). Delta ABE, SBE, and lactate were: 7.7 (p = 0.005), 6.1 (p = 0.003), and 1.6 (p = NS), respectively. Thus, negative ABE was significantly reversed by HPF, since SBE value turned positive without significant change in lactate. Conclusion(s): Negative alactic parameter was significantly reversed by HPF in septic patients. It is necessary to carry out evaluations in larger groups to estimate their impact on clinical outcomes. Copyright © 2022 The Authors.

SPONTANEOUS PNEUMOMEDIASTINUM: PROGNOSTIC MARKER IN PATIENTS WITH COVID-19 PNEUMONIA?

SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Pneumomediastinum is the presence of air or other gas in the mediastinum which can be due to trauma related to mechanical ventilation or spontaneous in preexisting lung diseases. Here, we present the case of Covid-19 pneumonia, who developed pneumomediastinum without any trauma or other risk factors. CASE PRESENTATION: A 56-year-old male COVID unvaccinated with a history of essential hypertension presented to the ED with shortness of breath and worsening cough for one week. He was living with his father, who was admitted to the ICU and receiving treatment for COVID pneumonia. The patient appeared to be in respiratory distress. His initial vital signs were temperature of 99.6 F, respiratory rate of 26 breaths per minute, blood pressure 125/71 mm Hg, heart rate 109 beats per minute with a regular rhythm, and oxygen saturation of 50% while he was breathing ambient air. Pulmonary examination revealed use of respiratory accessory muscle and widespread bilateral coarse rhonchi on auscultation. The rest of the physical examination was within normal limits. RT- PCR COVID -19 test was positive. The blood gas analysis reported respiratory alkalosis. Inflammatory markers were elevated: erythrocyte sedimentation rate (35.2 mg/L), C-Reactive Protein (17.70 mg/dL), Ferritin (1108.1 ng/mL), Lactate Dehydrogenase (813 U/L), Lactate (2.4 mg/dL), D-Dimer (35.20 mg/L) and Troponin High Sensitivity-236.6 ng/L. His CBC, electrolytes, and kidney function were normal. Chest X-ray showed Pneumomediastinum with dense basilar predominant consolidation. CT Angio Chest with contrast reported Pneumomediastinum likely from the left central airway source and bilateral dense ground glass consolidation. An echocardiogram showed an ejection fraction of 60-65%, no valvular abnormalities. He was placed on vapotherm(Oxygen 40L/min) with 100% FiO2. He was given Dexamethasone 6mg for ten days, Remdesivir, Barcitinib, and a 7-day course of Azithromycin and Ceftriaxone for community-acquired pneumonia. He was advised to practice prone positioning for 12 hours or more per day. Pulmonology, Infectious Disease, and Cardiology were consulted. Gradually, his oxygen requirement was weaned down and Pneumomediastinum resolved on serial chest x rays. He was discharged on home oxygen in a clinically stable condition. DISCUSSION: Pneumomediastinum in viral pneumonia is rare. The exact mechanism is unknown. Covid-19 pneumonia causes diffuse alveolar wall damage, which might cause air leakage into the mediastinum. The development of pneumomediastinum is an ominous sign in these patients. Fortunately, our patient did not worsen and was weaned off high flow oxygenation requirement. CONCLUSIONS: Few isolated reported cases of pneumomediastinum in a COVID-19 patient have been associated with life-threatening complications. It should be used as a prognostic marker, and close monitoring of these patients is advisable. Reference #1: Damous, S.H.B., dos Santos Junior, J.P., Pezzano, Á.V.A. et al. Pneumomediastinum complicating COVID-19: a case series. Eur J Med Res 26, 114 (2021) DISCLOSURES: No relevant relationships by Saad Ansari No relevant relationships by Akshit Chitkara No relevant relationships by Sudeshna Ghosh No relevant relationships by Femina Patel

PATHOPHYSIOLOGY OF LACTIC ACIDOSIS IN PATIENTS WITH ASTHMA

SESSION TITLE: Challenges in Asthma SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Asthma is a chronic illness affecting 334 million people worldwide[1]. Asthma affects the respiratory gas exchange, which plays a significant role in acid-base balance. Acid-base disorders in asthma involve respiratory alkalosis, respiratory acidosis, and AG acidosis[2]. CASE PRESENTATION: A 37 years old Hispanic male with a PMH of intermittent asthma presents with progressive dyspnea for three days, worse with activity and decreases with rest. He reported no [cough, fever, rhinorrhea, chest pain]. No orthopnea. He is vaccinated for COVID ( 2 Pfizer doses), has no sickness exposure, and works as a driver. The patient is not a smoker. Physical Exam: Blood pressure 124/72 mmHg. Heart Rate 100 PPM. Temperature 97.1 F.Respiratory Rate 21BPM.SPO2 90% General appearance: acute distress with nasal flaring. Heart: Normal S1, S2. RRR. Lung: Poor air entry with diffuse wheeze bilaterally. He was placed on a 6 LPM NC. CBC and differential were unremarkable. He was started on methylprednisone, Ceftriaxone, and azithromycin. The patient was started on inhaled Salbutamol and Budesonide. Chest X-ray was unremarkable, Chemistry was unremarkable except for elevated Lactic acid 4.7, There was no concern for reduced tissue perfusion or hypoxia, with no evidence of an infectious process because both viral and bacterial causes for pneumonia were excluded, and antibiotics were stopped. A serial lactic acid level trend was 4.5/4.3/ 4.1/ 4 on the first day, while on the next day, it was 3.1/ 2.9/ 2.7/ 2.5/ 3.5, we stopped trending his lactic acid level. He improved and was discharged on an oral taper steroid and inhaled steroids with a B2 agonist. DISCUSSION: There are two types of Lactic acidosis in patients with asthma: 1- Type-A results from impaired oxygen delivery to tissues and reduced tissue perfusion in severe acute asthma may be accompanied by reduced cardiac output. 2- Type B where oxygen delivery is normal, but the cellular function is impaired due to increased norepinephrine in plasma, increasing metabolic rate and lactate production, drugs like beta-agonists increase glycogenolysis leading to an increased pyruvate concentration;pyruvate is converted to lactic acid. B2 agonist increases lipolysis and increases Acetyl CoA, this increase in Acetyl CoA inhibits the conversion of pyruvate to Acetyl CoA, increasing pyruvate which will be converted to lactic acid[2], Theophylline is a non-selective 5'-phosphodiesterase inhibitor and potentiates the activity of ß-adrenergic agents by increasing the intracellular concentration of cAMP, Glucocorticoids are also known to increase the ß-receptor's sensitivity to ß-adrenergic agonists. CONCLUSIONS: Providers are increasingly challenged by hyperlactatemia,it is not harmful but elevated Lactic acid levels and clearance rate is used for prognostication,hyperlactatemia might be misleading,and all possible causes of elevated lactic acid levels must be explored. Reference #1: 10.5334/aogh.2412 Reference #2: https://doi.org/10.3390/jcm8040563 Reference #3: Edwin B. Liem, Stephen C. Mnookin, Michael E. Mahla;Albuterol-induced Lactic Acidosis. Anesthesiology 2003;99:505–506 doi: https://doi.org/10.1097/00000542-200308000-00036 DISCLOSURES: No relevant relationships by Vasudev Malik Daliparty No relevant relationships by Abdallah Khashan No relevant relationships by Samer Talib No relevant relationships by MATTHEW YOTSUYA

BELZUTIFAN-INDUCED HYPERSENSITIVITY PNEUMONITIS

SESSION TITLE: Using Imaging for Diagnosis Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Immunotherapy is now a standard of care in solid-tumor oncology following the approvals of CTLA-4 and PD-1 inhibitors. Belzutifan, a small-molecule HIF-2a inhibitor, has recently gained FDA-approval for the treatment of advanced von Hippel-Lindau (VHL) associated renal cell carcinomas. CASE PRESENTATION: A 63-year-old female presented to our hospital with a one-day history of progressive dyspnea. Medical history is significant for metastatic renal cell carcinoma with pulmonary metastasis. Family and social history were noncontributory. Her cancer diagnosis was established in 2019 and had undergone cytoreductive nephrectomy and treatment with axitinib/pembrolizumab. As she had little improvement with immunotherapy, she was enrolled in a clinical trial at Memorial Sloan Kettering. Due to further disease progression, she was transitioned to lenvatinib/everolimus, though the treatment was discontinued due to anorexia and worsening pulmonary symptoms. Further work up revealed that she had ERG, MPL, VHL gene mutations. Thus, she was started on belzutifan two weeks prior to her presentation. Initial vitals were significant for hypoxia on room air that recovered with high flow nasal cannula (40L/80%). Physical examination was remarkable for severe respiratory distress with coarse breath sounds bilaterally. Laboratory studies revealed an acute leukocytosis with a neutrophilic prominence and a chronic metabolic alkalosis. COVID, flu PCR were negative. Chest x-ray demonstrated diffuse bilateral reticulonodular opacities. CTA revealed innumerable pulmonary nodules with areas of mass-like consolidation and a loculated left-sided pleural effusion. She was covered with azithromycin/ceftriaxone along with high-dose steroids and was admitted to the stepdown unit for further management. While in stepdown, she had a left PleurX catheter placed given her large effusion which was complicated by bloody output that required one unit of blood. Despite high-dose steroids, she had persistent hypoxia. As she remained unstable, goals of care discussions were held, which ultimately led to a change in code status to comfort measures. All aggressive measures were discontinued. She was started on comfort medications and ultimately passed away. DISCUSSION: Currently, neoplasms associated with VHL mutations are managed surgically to minimize the risk of metastatic disease. Nearly 70% of all patients with VHL mutations will develop renal cell carcinomas which means most patients undergo numerous surgical procedures. HIF-2a inhibition therefore offers an effective alternative that could reduce surgical burden and offer a new approach to management of VHL-associated disease. However due to its new approval, several adverse effects have yet to be documented. CONCLUSIONS: We report the only known case of Belzutifan-induced hypersensitivity pneumonitis and hope this case will become a useful contribution to the literature. Reference #1: Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R;MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med. 2021 Nov 25;385(22):2036-2046. doi: 10.1056/NEJMoa2103425. PMID: 34818478. DISCLOSURES: No relevant relationships by Garrett Fiscus No relevant relationships by Niala Moallem No relevant relationships by Raj Parikh

"BUT I AM TOO YOUNG FOR THIS": EARLY PRESENTATION OF USUAL INTERSTITIAL PNEUMONIA

SESSION TITLE: Diagnosis of Lung Disease through Pathology Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Usual interstitial pneumonia (UIP) is a histological term used to describe a pattern of interstitial fibrosis with alternating areas of the normal lung with temporal fibrosis and architectural alteration due to chronic scarring or honeycomb change. It is a subset of idiopathic interstitial pneumonias (IPF) that usually presents in the sixth and seventh decades of life with progressive dyspnea on exertion and productive cough. CASE PRESENTATION: We present a 46 y/o man with a history of thyroid disease, hypertension and a former smoker of 20 pack-year smoking. Presented to ED complaining of low oxygen saturation with pulse oximetry at home with readings between 60-80%. Accompanied with progressive dyspnea on exertion and unintentional weight loss of 80 pounds in the last year. Also referred productive cough of white sputum that was worse in the morning. Home nebulized Albuterol therapy did not provide improvement. Denied recent viral respiratory infections, night sweats, environmental exposures nor family history of lung disease. DISCUSSION: Physical exam demonstrated bilateral expiratory dry crackles and pulse oximetry oxygen saturation at room air of 78%. RBBB evidenced on EKG. Bloodwork showed polycythemia with hemoglobin of 17.8;ABG's with pH: 7.40, Pco2: 42.2, PO2: 59.8, HCO3: 26, O2 sat: 90.8 and ideal PO2: 85.6 consistent with metabolic alkalosis with BMP CO2 of 30, A/a gradient: 43.0. Mycoplasma IgM, Influenza A & B and COVID-19 antigen test were negative. CXR with increased vascular markings, chest CT demonstrated small pericardial effusion, bilateral coarse interstitial pulmonary markings and bronchiectasis suggestive of chronic interstitial lung disease with no specific pattern. Left heart catheterization revealed right ventricular hypertrophy, normal EF >55%, and no evidence of coronary disease. Alpha-1 antitrypsin: 158, EPO: 6.5, HIV, and hepatitis panel were all negative. Rheumatology work up with only an ANA antibody positive, with titer 1:160. Patient underwent VATS procedure with wedge biopsy of the right upper and middle lobe that revealed usual interstitial pneumonia pattern. Patient improved and was discharged on home oxygen 3L. At follow-up, treatment was started with Nintedanib and Sildenafil Citrate. He had clinical improvement and oxygen requirements decreased to intermittent oxygen. CONCLUSIONS: Patients with interstitial pulmonary fibrosis experience slow progressive decline with typical clinical presentation over 60 years of age. This case remarks the importance of the need for stratification of interstitial lung disease classification, when pattern and history are non specific, with the use of VATS procedure for early start of treatment. Our patient with no environmental exposure or connective tissue disease had an uncommon early presentation of usual interstitial pneumonia. Reference #1: Tibana, R.C.C., Soares, M.R., Storrer, K.M. et al. Clinical diagnosis of patients subjected to surgical lung biopsy with a probable usual interstitial pneumonia pattern on high-resolution computed tomography. BMC Pulm Med 20, 299 (2020). https://doi.org/10.1186/s12890-020-01339-9 DISCLOSURES: No relevant relationships by Jesse Aleman No relevant relationships by Carlos Martinez Crespí no disclosure submitted for Jean Ramos;No relevant relationships by Alexandra Rodriguez Perez No relevant relationships by Paola Vazquez No relevant relationships by Nahomie Veguilla Rivera

Fast tracking and early on table extubation following living donor liver transplantation, can we expand the criteria?

Background: Traditionally, patients were kept intubated for 48 hours in the postoperative period. Living donor liver transplantation poses a different set of challenges. Most of the predictors mentioned in the literature were, low MELD, low BMI, and with stable comorbidities etc. for early extubation following living donor liver transplantation. We assessed the feasibility of fast tracking and early extubation in our patients, who were not fitting in those mentioned predictors in the literature. Methods: We present a case series of 6 patients who were fast tracked and extubated early, following living donor liver transplantation, out of 22 patients over the last 6 months. Results: All these patients were aged more than 45 yrs, with an average age of 55.8 yrs, average MELD score of 20.8, Child status C, some of our patients had cardio pulmonary comorbidities. patient 2, was COPD, post asymptomatic COVID, with CoRad score3 on HRCT, patient 5, was class 3 obese with no OSA, patient 6, had Hypertension, CAD- triple vessel disease, post CABG 7 yrs back, The intraoperative metabolic parameters like base excess and Lactates were showing good correction and all of them had very minimal inotropic support at the time of extubation, with Norepinephrine < 0.05mcg/kg/minutes. There was no post reperfusion hemodynamic instability or PRS in our patients, the average GRWR in our patients was 0.94, the mean anhepatic period, warm ischemia and cold ischemia times were pretty low. None of them had any significant postoperative complications. Conclusions: We propose, we can safely fast track and extubate early, following living donor liver transplantation with high MELD scores, and stable comorbidities. Further, large studies are needed to look for the feasibility of expanding the criteria for early extubation.

SPONTANEOUS PNEUMOTHORAX IN AN HIV/AIDS PATIENT WITH CONCURRENT COVID-19 AND PNEUMOCYSTIS PNEUMONITIS

CASE: A 25-year-old homeless male with nonadherent HIV presented with dyspnea on exertion for 4 days, productive cough for 1 week, fevers, chills and night sweats. He arrived hypoxic to 74% requiring 2L O2 and was cachectic on exam. WBC, lactate and procalcitonin were normal. C-reactive protein was 26.7 mg/L, LDH was 686 units/L and COVID-19 was positive. An arterial blood gas showed a primary respiratory alkalosis with a secondary metabolic alkalosis. Computed tomography of the chest, abdomen and pelvis with contrast showed multifocal large thin-walled cavitary lesions throughout the bilateral lungs with subpleural large cystic disease. Dexamethasone, remdesivir and empiric antibiotics were initiated. Absolute CD4 count was 7 cells/uL with HIV-1 RNA load of 139,000 copies/mL. Sputum was positive for Pneumocystis jirovecii (PCP) by DFA and PCR, but no evidence of mycobacterium. Trimethoprim-sulfamethoxazole (TMP-SMX) was added. On hospital day 13, he developed severe right-sided chest pain, dyspnea and required up to 15L O2. A chest x-ray revealed a large right-sided pneumothorax (PTX) and a chest tube was placed. Cardiothoracic Surgery was consulted for consideration of bullectomy with pleurodesis;this was not recommended as the cystic lesions were extensive with some intraparenchymal. His oxygen requirements improved and his chest tube was removed in 6 days. He was discharged on hospital day 21 to begin prophylactic dosing of TMP-SMX until his CD4 count was over 200 cells/uL and to attend his first appointment at an outpatient HIV clinic the following day. IMPACT/DISCUSSION: Secondary spontaneous pneumothorax (SSP) can be a complication of necrotizing pneumonia due to PCP. In one study, in a cohort of 599 patients with HIV infection, only 1.2% developed a PTX. Bilateral PTX is more common with PCP, unlike in our patient. In HIV, the degree of immunosuppression can influence the cause of PTX. Our patient had a PTX with a CD4 count under 200, which is more common with PCP. In addition, SSP as a complication of SARS-CoV-2 is more rare. There are case series that describe COVID-19 patients who develop PTX in the absence of barotrauma secondary to mechanical ventilation. However, this is uncommon as one retrospective study reports PTX occurring in 1% of patients with COVID-19 requiring hospital admission. In this case, it is unclear to what extent the patient's concomitant COVID-19 contributed to the development of a PTX. Our patient was ineligible for definitive intervention to prevent recurrence, thus underwent tube thoracostomy placement which is consistent with the majority of treated patients. While the prognosis of PTX secondary to COVID-19 is generally good, prognosis of cominant co-infection with PCP is an area of further research as the overall mortality of PCP-induced PTX alone can be 23%. CONCLUSION: This case represents a rare occurrence of spontaneous pneumothorax secondary to both PCP and COVID-19. We suggest the incidence to increase as the pandemic continues.

PNEUMOCYSTIS JIROVECI PNEUMONIA IN A PATIENT WITH SARCOIDOSIS ON CHRONIC STEROIDS

CASE: A 75-year-old male with history of sarcoidosis, heart failure, atrial fibrillation, hypertension, and mitral valve replacement presented to the emergency department with dyspnea and dry cough for one week. He endorsed fatigue and chills, but denied subjective fever, weight loss, edema, or congestion. Vitals were notable for a temperature of 100.3 F, respiratory rate of 25, and SpO2 of 82% on room air, which increased to 95% on 10 L of oxygen. Physical exam revealed clear lung sounds bilaterally without accessory muscle use. Labs showed a leukocytosis of 15.6, hemoglobin of 11.6, and pro-BNP of 631.2. ABG revealed compensated respiratory alkalosis. BMP, troponin, EKG, and COVID-19 PCR tests were all unremarkable. Of note, the patient had been on prednisone 10 mg daily for the past four years for sarcoidosis which was increased to 20 mg daily one month prior. After admission, further work-up revealed elevations in pro-calcitonin of 0.61, LDH of 396, and 1,3-beta-D-glucan of >500. Chest CT revealed bilateral scattered ground-glass opacities and underlying evidence of chronic interstitial disease. The patient was continued on a higher dose of prednisone 40 mg twice daily and started on atovaquone 750 mg twice daily for empiric Pneumocystis jiroveci pneumonia (PJP) therapy. Unfortunately, he continued to deteriorate and required intubation. His bronchoalveolar lavage fluid returned positive for Pneumocystis jiroveci by DFA. The patient was started on high- dose TMP-SMX. However, he developed DIC, bilateral upper extremity DVTs, and hyperkalemia thought to be secondary to TMP-SMX. The family decided to withdraw care and the patient passed. IMPACT/DISCUSSION: The role of Pneumocystis jiroveci pneumonia (PJP) prophylaxis in non-HIV patients on chronic steroids remains poorly elucidated and lacks evidence in literature. While some experts support prophylaxis for those on daily prednisone equivalents of greater than 20 mg for over 4 weeks, others suggest that daily prednisone equivalents of greater than 30 mg for over 12 weeks should warrant prophylaxis. We describe a patient with sarcoidosis who was on 20 mg of daily prednisone for over 4 weeks without PJP prophylaxis and subsequently died while battling PJP. Nearly 53% of PJP infections occur in nonHIV patients. Studies in patients with leukemia or organ transplant have shown that PJP prophylaxis with TMP-SMX decreases PJP occurrence by 85% and PJP-related mortality by 83%. The scarcity of literature on the use of PJP prophylaxis, particularly in those with chronic lung diseases such as sarcoidosis that require prolonged steroids, impedes timely consideration of PJP prophylaxis and poses a significant risk to these patients. CONCLUSION: We describe a patient with sarcoidosis on chronic steroids who subsequently developed a fatal case of PJP. Our case highlights the need to consider PJP as a differential diagnosis in non-HIV patients on steroids, and more importantly, to consider PJP prophylaxis in these individuals.

Study of Arterial Blood Gas Analysis in Moderate-to-Severe COVID-19 Patients.

Background The high prevalence of pneumonia and renal involvement in coronavirus disease 2019 (COVID-19) leads to frequent acid-base abnormalities in serious patients and affects prognosis. In this study, we aimed to assess the arterial blood gas (ABG) and acid-base patterns in COVID-19 patients admitted to a tertiary care hospital. Methodology A retrospective observational study was conducted in a designated COVID-19 hospital involving 267 reverse transcription-polymerasechain reaction-positive COVID-19 patients. Demographic and laboratory data including ABG data within the first day after admission and in patients with multiple ABG analyses, only the first measurement was collected and analyzed statistically, including its association with comorbidities. Results The most common age group of the patients was 51-60 years (30.8%), with a male predominance (male:female = 2.7:1). The most common comorbidities were hypertension, diabetes mellitus, and chronic obstructive pulmonary disease found in 147 (55%) COVID-19 patients. Alkalosis and acidosis were observed in 145 (54.3%) and 50 (18.7%) patients, respectively. The most common ABG abnormality observed was primary respiratory alkalosis with secondary metabolic acidosis in 67 (25.1%) patients, followed by primary respiratory alkalosis with secondary metabolic alkalosis in 54 (20.2%) patients. Statistically significant negative correlation was found with PaCO2 and pH (r = -0.530, p < 0.0001), statistically significant positive correlation was found between pH and base (r = 0.533, p < 0.0001), pH and TCO2 (r = 0.260, p < 0.0001), and pH and HCO3 (r = 0.354, p < 0.0001). Conclusions Acid-base abnormalities are commonly encountered in COVID-19 patients. Respiratory alkalosis as a part of a single or mixed pattern on ABG was the most common pattern found in critically ill COVID-19 patients. ABG on admission in moderate-to-severe COVID-19 patients can help in the early correction of metabolic abnormalities leading to improved patient outcomes.

IMPAIRED ACE2 GLYCOSYLATION AND PROTEASE ACTIVITY LOWERS SUSCEPTIBILITY TO SARS-COV-2 INFECTION IN GITELMAN/BARTTER SYNDROMES

Objective: ACE2, part of the counterregulatory arm of the ennin-angiotensin system, serves both as protective toward oxidative stress and cardiovascular ennin ling and as key entry for SARS-CoV-2. ACE2 has two isoforms, non-glycosylated and glycosylated, being this latter accountable for the binding with SARS-CoV-2. After the binding, viruses use proteases as cathepsin-L (Cat-L) to entry the cells. Both ACE2 glycosylation and Cat-L activity are pH-dependent. Gitelman and Bartter syndromes (GS/BS), rare genetic tubulopathies, are characterized by electrolytic alterations, activation of the ennin-angiotensin system, yet normo-hypotension, increased levels of ACE2 and metabolic alkalosis with likely increased intracellular pH. We reported that during the first wave of COVID-19 in early 2020 none of our cohort of 128 GS/BS patients from the major hotspots in Northern Italy had been infected or suffered any major COVID-19 symptoms and in a second survey on the same cohort in 2021 we reported only 8 positives, 4 asymptomatic and 4 with very light symptoms This study aims to investigate potential mechanisms as ACE2 glycosylation and Cat-L activity related to patients' metabolic alkalosis and viral entry/infection. Design and method: Mononuclear cells ACE2 glycosylation (Western blot) and blood Cat-L activity (ELISA) from 20 GS/BS patients have been compared to those from 15 heathy subjects. Results: Non-glycosylated ACE2 was higher in GS/BS (0.82 ± 0.19 d.u. vs 0.67 ± 0.13 p = 0.01);glycosylated ACE2 was not different (0.85 ± 0.28 in GS/BS vs 0.73 ± 0.23 p = 0.19). Cat-L activity was lower in GS/BS (3.90 ± 1.13 r.f.u. vs 5.31 ± 0.8 p < 0.001) and inversely correlated with blood bicarbonate (HCO3-), while a negative correlation between glycosylated ACE2 and HCO3- approaches statistical significance (p = 0.08). Conclusions: GS/BS's metabolic alkalosis, likely by increasing intracellular pH, influences the glycosylation of ACE2 and the activity of Cat-L, providing a mechanistic explanation for the near complete absence of COVID-19 or its symptoms reported in our cohort. These findings provide a rationale for pursuing the identification and/or synthesis of new drugs that specifically target ACE2 glycosylation and/or proteases involved in SARS-CoV-2 infection.

IMPAIRED ACE2 GLYCOSYLATION AND PROTEASE ACTIVITY LOWERS SUSCEPTIBILITY TO SARS-COV-2 INFECTION IN GITELMAN/BARTTER SYNDROMES

BACKGROUND AND AIMS: ACE2, part of the counter-regulatory arm of the renin-angiotensin system, serves both as protective toward oxidative stress and cardiovascular remodeling and as a key entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 has two isoforms, non-glycosylated and glycosylated, the latter being accountable for the binding with SARS-CoV-2. After the binding, viruses use proteases as cathepsin-L (Cat-L) to entry the cells. Both ACE2 glycosylation and Cat-L activity are pH-dependent. Gitelman and Bartter syndromes (GS/BS), rare genetic tubulopathies, are characterized by electrolytic alterations, activation of the renin-angiotensin system, yet normo-hypotension, increased levels of ACE2 and metabolic alkalosis with likely increased intracellular pH. We reported that during the first wave of COVID-19 in early 2020 none of our cohort of 128 GS/BS patients from the major hotspots in Northern Italy had been infected or suffered any major COVID-19 symptoms and in a second survey on the same cohort in 2021, we reported only eight positives, four asymptomatic and four with very light symptoms This study aims to investigate potential mechanisms as ACE2 glycosylation and Cat-L activity related to patients' metabolic alkalosis and viral entry/infection. METHOD: Mononuclear cells ACE2 glycosylation (Western blot) and blood Cat-L activity (ELISA) from 20 GS/BS patients have been compared with those from 15 healthy subjects. RESULTS: Non-glycosylated ACE2 was higher in GS/BS (0.82 ± 0.19 d.u. versus 0.67 ± 0.13, P = 0.01);glycosylated ACE2 was not different (0.85 ± 0.28 in GS/BS versus 0.73 ± 0.23, P = 0.19). Cat-L activity was lower in GS/BS (3.90 ± 1.13 r.f.u. versus 5.31 ± 0.8, P <0 0.001) and inversely correlated with blood bicarbonate (HCO3 -), while a negative correlation between glycosylated ACE2 and HCO3 - approaches statistical significance (P = 0.08). CONCLUSION: GS/BS's metabolic alkalosis, likely by increasing intracellular pH, influences the glycosylation of ACE2 and the activity of Cat-L, providing a mechanistic explanation for the near-complete absence of COVID-19 or its symptoms reported in our cohort. These findings provide a rationale for pursuing the identification and/or synthesis of new drugs that specifically target ACE2 glycosylation and/or proteases involved in SARS-CoV-2 infection.

A curious method to commit suicide

Objective: The COVID-19 pandemic has generated an increase in anxiety-depressive disorders throughout society, with an evident impact on children and adolescents, further precipitated by limitations in social activities during confinement. The increase in home isolation with abuse of new technologies, often far from parental control, involves risky situations such as the case we present. Case report: A 19-year-old man diagnosed with major depressive disorder, with psychiatric admissions since July 2019 for overdose with suicidal intent was home treated with methylphenidate 40mg, mirtazapine 15mg and vortioxetine 10mg. In August, the patient was searching for information on the Internet about euthanasia and suicide without pain in different pages and Internet forums. He bought two products online (by Amazon) that seemed effective for this purpose: a kilogram packet of sodium nitrate and a bottle of antifreeze. Finally, he decided on the first option due to the risk of suffering after ingesting antifreeze. On August 26 (4:00 pm), he ate a tablespoon (80 mg) of sodium nitrate. He developed dyspnea and feeling overwhelmed so he decided to informed his family of what he had done and an ambulance was called. He was transferred to hospital and given oxygen. At 7:00 pm in the emergency department he was noted to have a greyish coloration (“hot dead” appearance) with poor respiratory mechanics, tachycardic, tachypneic, with signs of peri-arrest: blood pressure 96/50mmHg, heart rate 145 bpm, respiratory rate 30/min, oxygen saturations 70%. He also had uncoordinated movements, and could not obey orders. The patient was sedated for intubation and mechanical ventilation. An arterial blood gas analysis performed after intubation showed: pH 7.35, pO2 165mmHg, pCO2 24mmHg, base excess -10.4, bicarbonate 14.5 mEq/L, potassium 3.1 mmol/L, methemoglobin 83%, carboxyhemoglobin 1.4%, lactate 13.3mmol/L. Methylene blue 1% (75mg intravenously) and activated charcoal by nasogastric tube were administered (after intubation). Later, he was admitted to the intensive care unit (9:20 pm). Physicians from this unit decided to administrate hydroxocobalamin (5 g intravenously at 00.39 am). The patient was extubated and discharged from the intensive care unit 36 hours after his admission to the department of Internal Medicine, without clinical complications;later he was transferred to Psychiatry Department. Conclusion: The toxic mechanism of sodium nitrate is related to the generation of methemoglobin. This patient survived a potentially lethal methemoglobin level following intentional ingestion of sodium nitrate with prompt administration of an antidote.

Endocrine disorders in COVID-19: a look from a different perspective

Background: COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, particularly known for its respiratory symptoms. Nevertheless, a wide variety of clinical manifestations has been associated with COVID-19, including Kawasaki disease, Guillain- Barré syndrome and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Clinical Case: A 55-years-old woman, affected by immune thrombocytopenia on prednisone therapy, presented with intense fatigue, hyporexia and vomit. She had no fever, no cough, nor other symptoms. She referred a quick prednisone decalage in previous days. ABG showed metabolic alkalosis, severe hyponatremia and hypokalemia. The patient tested positive for SARS-CoV-2. Further investigation showed euvolemic hyponatremia (102 mEq/L) with normal urine osmolality (275 mOsm/Kg), findings consistent with COVID-19-related SIADH. We set a corticosteroid therapy with Prednisone 37,5 mg/die for 5 days, then 25 mg/die for 2 days. After 7 days of hospitalization, the patient tested negative for SARS-CoV-2. In the meantime, kalemia and natremia were back in range. Conclusions: Despite COVID-19 being identified as severe respiratory viral infection, progressively many relevant endocrine manifestations have been reported greatly contributing to the severity of the clinical presentation. There is the urgent need to collect in international multicentric efforts data on all these aspects of the pituitary involvement in COVID-19 patients.

SARS-COV-2 AND TYPE 1 DIABETES IN CHILDREN: IS THERE A DIFFERENCE IN INCIDENCE OR PATIENT CHARACTERISTICS DURING THE PANDEMIC? PRELIMINARY RESULTS

Background and Aims: In 2020 the Sars-CoV-2 pandemic affected the whole world. Some centers reported changes in incidence of type 1 diabetes (T1D) in children and in the severity of the disease at presentation. In our center as well we had the impression that incidence and severity of illness at presentation of new onset T1D changed during the pandemic. The aim of this study is to provide data on incidence and severity of illness at presentation of new onset T1D in children in our center (covering the province of Antwerp (Belgium)). Methods: In this observational, (large) single center study including children (<16 years) with newly diagnosed T1D, patient characteristics, anamnestic data and biochemical values were evaluated. Data from children with diagnosis between January 2015 and February 2020 (n = 203) where compared to children with diagnosis from March 2020 to February 2021 (n = 51). Results: Non-parametric testing showed no significant difference in age, glycemia, HbA1c, C-peptides, ketone bodies, pH, bicarbonate and base-excess at diagnosis during the first year of the pandemic. Duration of complaints before presentation was not longer and the need for intensive care was not higher during the pandemic. The total daily insulin dose at discharge did not differ from to the five years prior to the pandemic. Conclusions: We conclude that Sars-Cov-2 pandemic did not change presentation of new onset T1D in children in our center: there was no increase in incidence, no delay in presentation, no change in patient characteristics or severity of illness. Efforts should be made to obtain nationwide data.

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

ObjectiveTo delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.DesignRetrospective case series.SettingTongji Hospital in Wuhan, China.ParticipantsAmong a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.Main outcome measuresClinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.ResultsThe median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83;73%) than in recovered patients (88;55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113;100%), type I respiratory failure (18/35;51%), sepsis (113;100%), acute cardiac injury (72/94;77%), heart failure (41/83;49%), alkalosis (14/35;40%), hyperkalaemia (42;37%), acute kidney injury (28;25%), and hypoxic encephalopathy (23;20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.ConclusionSevere acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.