The risk of venous thromboembolism and blood hyperlactatemia is associated with increased mortality among critically ill patients with Covid-19.

INTRODUCTION: Coronavirus disease 2019 (Covid-19) following venous thromboembolism (VTE) and blood hyperlactatemia are associated with higher mortality. However, reliable biomarkers for this association remain to be elucidated. This study investigated the associations of VTE risk and blood hyperlactatemia with mortality among critically ill Covid-19 patients admitted to the intensive care unit (ICU). METHODS: In this single-centre retrospective study, we included 171 patients aged ≥18 years with confirmed Covid-19 admitted to the ICU at a tertiary healthcare clinic in the Eastern region of Saudi Arabia between 1 March 2020 and 31 January 2021. Patients were divided into two groups: survivor and non-survivor. The survivors have been identified as the patients discharged from the ICU alive. The VTE risk was defined using a Padua prediction score (PPS) >4. The blood lactate concentration (BLC) cut-off value >2 mmol/L was used to determine the blood hyperlactatemia. RESULTS: Multi-factor Cox analysis showed that PPS >4 and BLC >2 mmol/L were more likely to be significantly associated with higher odds of ICU mortality in critically ill Covid-19 patients (hazard ratio [HR] = 2.80, 95% confidence interval [CI] = 1.00-8.08, p = 0.050; HR = 3.87, 95% CI = 1.12-13.45, p = 0.033, respectively). The Area under the Curve for VTE and blood hyperlactatemia were 0.62 and 0.85, respectively. CONCLUSION: VTE risk and blood hyperlactatemia have been associated with a higher mortality risk in critically ill Covid-19 patients who are hospitalized in the ICU in Saudi Arabia. According to our findings, these people needed more effective VTE prevention strategies based on a personalized assessment of their risk of bleeding. Moreover, persons without diabetes and other groups with a high risk of dying from COVID-19 may be recognized by measuring glucose as having elevated glucose and lactate jointly.

Idiopathic anomalous congenital band causing small intestinal obstruction in a 5-month-old dog

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.

Exercise precision medicine for type 2 diabetes: Targeted benefit or risk?

Concurrent exercise and metformin administration may reduce the acute and chronic effects of exercise on glucose metabolism in the patients with type 2 diabetes (T2D). However, several studies suggest that combing metformin and exercise treatment may have neither additive effect nor even cause adverse effects in T2D patients. This case report aimed to highlight the challenges associated with prescribing exercise to type 2 diabetes patients undergoing metformin treatment. A 67-years old woman was followed-up for five months, including assessment of the acute and chronic glucose and lactate metabolism induced by concomitant exercise and metformin. The findings were four-fold: 1) During a high-intensity interval training bout, blood glucose systematically decreased, while blood lactate concentrations fluctuated randomly; 2) Basal blood lactate levels were well above 2 mmol/L on days with medication only; 3) Combined exercise and metformin administration induced additive effects on the normalization of glucose and 4) high levels of physical activity had a positive impact on the continuous glucose fluctuations, while decreased levels of physical activity induced a large fluctuation of glucose due to home confinement of an infectious disease caused by the SARS-CoV-2 virus. Our findings showed that when combined with exercise and metformin treatment for T2D patients, exercise may contribute to improving glycemic control while metformin may elevate lactate levels in the long term. The observed results underline the need to prescribe exercise and monitor lactate levels for reducing possible risks associated with metformin treatment and reinforce the importance of tailoring exercise therapy.

Critical Progression, Risk Factors and Survival in Mis-C: Amazon Experience

BACKGROUND AND AIM: Highlighting the importance of risk factors for mortality in critical Multisystem Inflammatory Syndrome in children (MIS-C). To identify risk factors and survival time in children with critical MIS-C. METHOD(S): A multicenter prospective cohort in metropolitan Belem city, involving 65 children with critical MIS-C. We determined short-term (all-cause) mortality in MIS-C group compared with a cohort of 326 critical ill subjects followed up for a median of 5.4 months. The study outcome included the follows: death, need of invasive ventilation or more than 3 organs dysfunctions. Risk factors were tested using univariate regression models, followed by multivariable Cox regression models. RESULT(S): The main featuring were lymphopenia (day one median 1249, IQR: 960-1773 vs. 2393, IQR: 1108-4280.75, p=0.033, HR:1.0, CI: 0.99-1.1), hyperlactatemia (day three median 1.93, IQR:1.2-4.0 vs.1.6, IQR:1.0-2.5, p=0,020, HR: 1.17, CI:1.1-1.23), CK-MB (day one median 28.1, IQR: 24-84.1 vs. 13.3, HR:8.1-26.4, p=0.01, HR: 1.2, CI:1.0- 1.3), high troponin I (day one 0.28, IQR: 0.02-1.8 vs. 0.11, IQR:0.04-0.18, p<0.0001, HR:1.1, CI:1.0-1.2 and day three 0.2, IQR:0.012-13.4 vs. 0.06, IQR:0.02-0.10, p=0.002, HR: 1.09, CI: 1.07-1.2) and shock [26 (51%) vs.34 (22.4%), p<0.0001, HR: 6.7, CI: 3.9-11.7]. Comorbidities (HR:8.8, CI: 1.65-47.14, p=0.011) and high drive pressure (HR:5.9, CI:2.23-15.51, p<0.0001) were associated with mortality. Survival time in patients with MIS-C was shorter (mean 89.5;SD 8.4 vs. 134.8;SD 4.7 days, log-rank 29.7, p<0.0001). CONCLUSION(S): The main factors associated with critical MIS-C were comorbidities, high drive pressure and pneumonia at admission, with shorter survival times. (Figure Presented).

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

LIVER ABSCESS DEVELOPMENT IN THE POSTACUTE COVID-19 PHASE

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

SARS-2 related HUPRA syndrome presenting with neonatal lactic acidosis

Introduction: Mitochondria are organelles that fulfill the energy requirements for cells, which is essential for their survival and function. Mitochondria function is dependent on both mitochondrial (mtDNA) and nuclear genes (Tucker, 2010). SARS2 is a nuclear gene that encodes the mitochondria seryl-tRNA synthetase precursor. It catalyzes the attachment of serine to tRNA and in the biosynthesis of selenocysteinyl-tRNA in the mitochondria. Pathogenic variation in the gene is associated with HUPRA syndrome, which is characterized by hyperuricemia, pulmonary hypertension, renal failure, and metabolic alkalosis (Rivera, 2013). It is important to recognize this autosomal recessive condition as it presents in infancy, can lead to death, and has recurrence implications for carrier couples. Case Description: We present a term neonate male who experienced tachypnea at birth requiring respiratory support;echocardiogram concerning for pulmonary hypertension and right ventricular hypertrophy requiring ionized nitric oxide. During his hospitalization, he developed lactic acidosis (consistently 10–12 mmol/L, reaching 26 mmol/L), seizures, and his newborn screen results flagged as abnormal for severe combined immunodeficiency (SCID) due to low Tcell count. He was transferred to a tertiary medical center due to continued elevated lactate levels. During admission to the tertiary medical center, he was found to have hyperkalemia, elevated BUN/Cr, and elevated lactate levels. Additionally, pre-prandial and postprandial lactate and pyruvate levels were obtained. It was found that hyperlactatemia was persistent and not related to feedings. The patient developed a presumed pulmonary hypertensive crisis at 8 weeks of age, and in the setting of chronic intrinsic renal dysfunction and chronic lactic acidosis, the family elected to transfer him to the home hospital for compassionate extubation where he died. Notable genetics evaluation findings included urine organic acid results showing markedly and persistently elevated levels of fumaric acid and lactic acid concerning for fumarase deficiency or a mitochondrial oxidative phosphorylation disorder and plasma amino acids showing elevated alanine and proline indicative of lactic acidosis. An array CGH showed 2% areas of homozygosity, consistent with known shared parental ancestry. The results of combined mitochondrial genome and Mitochondrial Nuclear Gene Panel was ordered. The results revealed two SARS2 variants: (c.988C>T,p.R330W and c.173T>A, p.L58Q). Both variants were classified as variants of uncertain significance (VUS) based on ACMG-AMP criteria (Richards, 2015) and parental testing to determine phase is ongoing. Discussion: Pathogenic variants in SARS2 lead to dysfunction of seryltRNA synthetase and is associated with HUPRA syndrome. Our patient harbors two variants in SARS2 classified as VUSes but based on clinical presentation the phenotype is consistent with HUPRA syndrome. The condition was first described in 2011 (Belostotsky, 2011) with 6 reported patients from 3 families (Belostotsky, 2011 and Rivera, 2013). Further study into pathogenic mechanism is important as no treatment exists, and the disease leads to death of the infants affected. Although the disease is very rare, it must be considered in infants with who present with symptoms of failure to thrive, hyperuricemia, pulmonary hypertension, renal failure, and metabolic alkalosis.

Septic shock 3.0 in severe COVID19 patients: Are we missing something clinically important?

Introduction/Purpose: COVID19 can be associated with life-threatening organ dysfunction due to septic shock, frequently requiring ICU admission, respiratory and vasopressor support. Therefore, clear clinical criteria are pivotal to early recognition of patients more likely to have poor outcomes, needing prompt organ support. Although most patients with severe COVID19 meet the Sepsis-3.0 criteria for septic shock, it has been increasingly recognized that, in this population, hyperlactatemia is frequently absent, possibly leading to an underestimation of illness severity and mortality risk. Purpose: This study aimed to identify the proportion of patients with COVID19 with hypotension despite adequate volume resuscitation, needing vasopressors to have a MAP>65mmHg, with and without hyperlactatemia, in ICU, and describe its clinical outcomes and mortality rate. Methods: We performed a single-center retrospective cohort study. All adult patients admitted to ICU with COVID19 were eligible and were further divided in 3 groups according to hyperlactatemia (lactate >2mmol/L) and persistent hypotension with vasopressor therapy requirement: (1) sepsis group (without both criteria), (2) vasoplegic shock (with persistent hypotension with vasopressor therapy requirement without hyperlactatemia) and (3) septic shock 3.0 (with both criteria). COVID19 was diagnosed using clinical and radiologic criteria with a SARS-CoV-2 positive RT-PCR test. Qui-square test was used for categorical variables and Kruskal-Wallis and logistic regression were used on continuous variables for statistical assessment of outcomes between groups. Kaplan-Meier survival curve and logrank test were also obtained. Results: 103 patients (mean age 62 years, 71% males) were included in the analysis (N=45 sepsis, N=25 vasoplegic shock;N=33 septic shock 3.0). SOFA score at ICU admission and ICU length of stay were different between groups (p<0.001). Ventilator-free days and vasopressor-free days were also different between sepsis vs vasoplegic shock and septic shock 3.0 groups (both p<0.001 and p<0.001, respectively), and similar in vasoplegic vs septic shock 3.0 groups (p=0.387 and p=0.193, respectively). Mortality was significantly higher in vasoplegic shock and septic shock 3.0 when compared with sepsis group (p<0.001) without difference between the former two groups (p=0.595). Log rank test of Kaplan-Meier survival curves were also different (p=0.07). Logistic regression identified the maximum dose of vasopressor therapy used (OR 1.065;CI 95%: 1.023-1.108, p=0.02) and serum lactate level (OR 1.543;CI 95%: 1.069-2.23, p=0.02) as the major explanatory variables of mortality rates. Conclusions: In severe COVID19 patients, the Sepsis 3 criteria of septic shock may exclude patients with a similarly high risk of poor outcomes and mortality rate, that should be equally approached. (Table Presented).

Association between thiamine deficiency and hyperlactatemia among critically ill patients with diabetes infected by SARS-CoV-2.

BACKGROUND: The present study aims to verify the association between diabetes and thiamine deficiency in critically ill patients infected by severe acute respiratory syndrome coronavirus 2. METHODS: This is a descriptive cross-sectional study, whose demographic, anthropometric, and laboratory data (arterial lactate, bicarbonate, and plasma thiamine) were obtained in the first hours of admission to the intensive care unit. Patients with diabetes were compared with individuals without diabetes, and the correlation was performed between thiamine and lactate levels. Thiamine levels <28 µg/L were considered as thiamine deficiency. RESULTS: Overall, 270 patients met the inclusion criteria; 51.1% were men, and the median age was 74 years (66.8-81). The median value of thiamine was 54.0 µg/L (38-72.3), and 15.6% had thiamine deficiency. Among patients with diabetes, 26.3% had thiamine deficiency, and 69.3% had hyperlactatemia. There was an association between thiamine deficiency and diabetes (odds ratio 4.28; 95% CI, 2.08-8.81; P < .001). There was a strong negative correlation between thiamine and arterial lactate in patients with diabetes (r = -0.711, P < .001) and a moderate negative correlation in critically ill patients without diabetes (r = -0.489, P < .001). CONCLUSIONS: The prevalence of thiamine deficiency in critically ill patients due to coronavirus disease 2019 is higher in patients with diabetes. There is a negative correlation between thiamine and arterial lactate levels, which is higher in people with diabetes.