High Serum Lactate Research Articles

Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for T lymphoblastic leukemia/lymphoma

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.

Distribution and clinical features of lymphomas involving skin in Taiwan.

A wide variety of primary and secondary lymphoma types involves the skin. However, reports with comparisons between both groups are limited in Taiwan. We retrospectively enrolled all cutaneous lymphomas and evaluated their clinicopathologic features. There were 221 cases of lymphoma: 182 (82.3%) primary and 39 (17.7%) secondary. Mycosis fungoides was the most common primary T-cell lymphoma, 92 (41.7%) cases, followed by CD30-positive T-cell lymphoproliferative disorders including lymphomatoid papulosis (n=33, 14.9%) and cutaneous anaplastic large cell lymphoma (n=12, 5.4%). The most frequent primary B-cell lymphomas were marginal zone lymphoma (n=8, 3.6%) and diffuse large B-cell lymphoma (DLBCL), leg type (n=8, 3.6%). DLBCL including variants was the most common secondary lymphoma involving skin. Most primary lymphomas presented at low-stage (T-cell, 86%; B-cell, 75%), whereas the majority of secondary lymphomas presented at high-stage (T-cell, 94%; B-cell, 100%). Patients with secondary lymphomas had an older mean age, more frequent B symptoms, lower serum albumin and hemoglobin, and a higher frequency of atypical lymphocytes in blood than those with primary lymphomas. In primary lymphomas, older age, lymphoma types, decreased lymphocyte counts and atypical lymphocytes in blood were poorer prognostic factors. In secondary lymphoma patients, lymphoma types, high serum lactate dehydrogenase and low hemoglobin levels predicted poorer survival. We found that the distribution of primary cutaneous lymphomas in Taiwan mirrors that of other Asian countries but shows some differences as compared with Western countries. Primary cutaneous lymphomas have a better prognosis than secondary lymphomas. Histologic classification of lymphomas highly correlated with disease presentation and prognosis.

Duration of Invasive Mechanical Ventilation Post-Liver Transplantation: Does One Size Fit All?

Duration of Invasive Mechanical Ventilation Post-Liver Transplantation: Does One Size Fit All?

Clinical characteristics and outcomes of critically ill coronavirus disease 2019 patients in Malaysia during the first wave: A multi-center observational study (COVIDICU-MY).

Coronavirus disease 2019 (COVID-19) emerged with a wide range of clinical presentations; Malaysia was not spared from its impact. This study describes the clinical characteristics of COVID-19 patients admitted to intensive care unit, their clinical course, management, and hospital outcomes. COVIDICU-MY is a retrospective analysis of COVID-19 patients from 19 intensive care units (ICU) across Malaysia from 1 March 2020 to 31 May 2020. We collected epidemiological history, demographics, clinical comorbidities, laboratory investigations, respiratory and hemodynamic values, management, length of stay and survival status. We compared these variables between survival and non-survival groups. A total of 170 critically ill patients were included, with 77% above 50 years of age [median age 60, IQR (51-66)] and 75.3% male. Hypertension, diabetes mellitus, hyperlipidemia, chronic cardiac disease, and chronic kidney disease were most common among patients. A high Simplified Acute Physiology Score (SAPS) II score [median 45, IQR (34-49)] and Sequential Organ Failure Assessment (SOFA) score [median 8, IQR (6-11)] were associated with mortality. Patients were profoundly hypoxic with a median lowest PaO2/FiO2 ratio of 150 (IQR 99-220) at admission. 91 patients (53.5%) required intubation on their first day of admission, out of which 38 died (73.1% of the hospital non-survivors). Our sample had more patients with moderate Acute Respiratory Distress Syndrome (ARDS), 58 patients (43.9%), compared to severe ARDS, 33 patients (25%); with both ARDS classification groups contributing to 25 patients (54.4%) and 11 patients (23.9%) of the non-survival group, respectively. Cumulative fluid balance over 24 h was higher in the non-survival group with significant differences on Day 3 (1,953 vs. 622 ml, p < 0.05) and Day 7 of ICU (3,485 vs. 830 ml, p < 0.05). Patients with high serum creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and low lymphocyte count throughout the stay also had a higher risk of mortality. The hospital mortality rate was 30.6% in our sample. We report high mortality amongst critically ill patients in intensive care units in Malaysia, at 30.6%, during the March to May 2020 period. High admission SAPS II and SOFA, and severe hypoxemia and high cumulative fluid balance were associated with mortality. Higher creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and lymphopenia were observed in the non-survival group.

Assessment of diagnostic procedures and tools of COVID-19 among Iraqi patients: A systematic review

Background: The pandemic SARS – CoV2 is a novel virus disease that first appeared in China in December 2019. On February 24, 2020, the disease spread throughout Iraq, and many different studies were conducted on it. This study highlights the procedures for diagnosing COVID-19 and evaluating tools among Iraqi patients through a systematic review of research conducted in Iraq during the past two years (2020–2021). Methods: From March 2020 to December 31, 2021, articles on relevant themes were carefully searched in the main databases: Science Direct, PubMed, Embase, and Iraqi Academic Scientific Journals. Using keywords related to COVID-19 and Iraq yielded a total of 2743 articles. Articles were chosen for this systematic review based on inclusion and exclusion criteria, according to the PRISMA 2020 statement for reporting systematic review. Only Iraqi studies that reported data on diagnostic procedure outcomes were included, with a total of 21 articles chosen. Results: A total of 21 articles were found to be relevant, which reviewed the biochemical and hematological parameters as diagnostic procedures and tools in Iraqi patients. The biochemical parameters are as follows: triglycerides, cholesterol, APRs, liver functions tests, kidney functions tests, antibodies, cytokines, and minerals. The hematological parameters are as follows: ABO group, red blood cell (RBC) indices, white blood cell (WBC) indices, and platelet indices. Conclusion: Diagnostic procedures and tools for COVID-19 among Iraqi patients were in agreement with the majority of other global studies. High serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin, d-dimer, lactate dehydrogenase (LDH), and cytokines were associated with severe COVID-19 pneumonia and also hypoalbuminemia, lymphocytopenia, and neutrophilia. Biochemical and hematological parameters might be significant indicators for COVID-19 evaluation.

Gene signature for the prediction of the trajectories of sepsis-induced acute kidney injury

BackgroundAcute kidney injury (AKI) is a common complication in sepsis. However, the trajectories of sepsis-induced AKI and their transcriptional profiles are not well characterized.MethodsSepsis patients admitted to centres participating in Chinese Multi-omics Advances In Sepsis (CMAISE) from November 2020 to December 2021 were enrolled, and gene expression in peripheral blood mononuclear cells was measured on Day 1. The renal function trajectory was measured by the renal component of the SOFA score (SOFArenal) on Days 1 and 3. Transcriptional profiles on Day 1 were compared between these renal function trajectories, and a support vector machine (SVM) was developed to distinguish transient from persistent AKI.ResultsA total of 172 sepsis patients were enrolled during the study period. The renal function trajectory was classified into four types: non-AKI (SOFArenal = 0 on Days 1 and 3, n = 50), persistent AKI (SOFArenal > 0 on Days 1 and 3, n = 62), transient AKI (SOFArenal > 0 on Day 1 and SOFArenal = 0 on Day 3, n = 50) and worsening AKI (SOFArenal = 0 on Days 1 and SOFArenal > 0 on Day 3, n = 10). The persistent AKI group showed severe organ dysfunction and prolonged requirements for organ support. The worsening AKI group showed the least organ dysfunction on day 1 but had higher serum lactate and prolonged use of vasopressors than the non-AKI and transient AKI groups. There were 2091 upregulated and 1,902 downregulated genes (adjusted p < 0.05) between the persistent and transient AKI groups, with enrichment in the plasma membrane complex, receptor complex, and T-cell receptor complex. A 43-gene SVM model was developed using the genetic algorithm, which showed significantly greater performance predicting persistent AKI than the model based on clinical variables in a holdout subset (AUC: 0.948 [0.912, 0.984] vs. 0.739 [0.648, 0.830]; p < 0.01 for Delong’s test).ConclusionsOur study identified four subtypes of sepsis-induced AKI based on kidney injury trajectories. The landscape of host response aberrations across these subtypes was characterized. An SVM model based on a gene signature was developed to predict renal function trajectories, and showed better performance than the clinical variable-based model. Future studies are warranted to validate the gene model in distinguishing persistent from transient AKI.

Cerebrospinal fluid soluble programmed death-ligand 1 is a useful prognostic biomarker in primary central nervous system lymphoma.

The increased expression of programmed death-ligands 1 and 2 (PD-L1 and PD-L2, respectively) on tumour cells contributes to immune evasion, suggesting that these proteins are attractive therapeutic targets. This study aimed to evaluate the validity of cerebrospinal fluid (CSF) soluble PD-L1 (sPD-L1) and soluble PD-L2 (sPD-L2) as biomarkers for primary central nervous system lymphoma (PCNSL). We determined the CSF concentrations of sPD-L1 and sPD-L2 in 46 patients with PCNSL using enzyme-linked immunosorbent assays (ELISAs). A control group comprised 153 patients with other brain tumours, inflammatory/infectious status, or neurodegenerative diseases. Only CSF sPD-L1 levels were significantly higher in patients with PCNSL relative to the controls. CSF sPD-L1 also exhibited superior overall discrimination performance compared to CSF sPD-L2 in diagnosing PCNSL. Compared with patients with PCNSL with low CSF sPD-L1 levels, more patients with high levels had high serum lactate dehydrogenase levels, leptomeningeal involvement, and deep-brain involvement. Furthermore, CSF sPD-L1 could predict poor survival in PCNSL but CSF sPD-L2 could not. Intriguingly, CSF sPD-L1 levels were correlated with disease status and their dynamic changes post treatment could predict time to relapse. In conclusion, this study identified CSF sPD-L1 as a promising prognostic biomarker, indicating a therapeutic potential of PD-L1 blockade in PCNSL.

DETERMINANTS INFLUENCING LENGTH OF ICU STAY IN RENAL TRANSPLANT RECIPIENTS UNDERGOING GENERAL ANAESTHESIA

Background: In this study, we wantedto evaluate the duration of intensive care unit (ICU) stay in renal transplant recipients and identify the perioperative factors affecting the duration of ICU stay. Materials And Methods: This was a hospital basedprospective cohort study conducted among 76 patients who presented with renal transplantationto the Department ofAnaesthesiology and Intensive Care Unit, Max Super Speciality Hospital, Mohali of Punjab State, from May 2018 toApril 2019after obtaining clearance from Institutional Ethics Committee and written informed consent from the study participants. Results: Longer ICU stay was associated with pleural effusion and left ventricular hypokinesia(p value &lt;0.05). No significant association was found between other clinical conditions and duration of ICU stay.Longer ICU stay was associated if duration of dialysis is longer and thrice a week dialysis. This was statistically significant (p value &lt;0.05).Higher mean serum lactate levels were associated with longer ICU stay (p value &lt;0.05).Longer ICU stay was found in those who had lower mean arterial pressure, higher systolic blood pressure and lower urine output. This was found to be statistically significant. Longer ICU stay was associated with low blood pH, higher serum lactate and lower urine output during post-operative period. This was found to be significant Conclusion:There were certain factors which affected the duration of ICU stay – Older age, higher ASA grades, longer duration of dialysis, and higher frequency of dialysis.Among the perioperative parameters- preoperative mean serum lactate levels, intraoperative lower mean arterial pressure, lower systolic blood pressure and lower urine output, post-operative low blood pH, higher serum lactate and lower urine output were associated with longer duration of ICU stay.

Improving Prognosis of Aggressive Natural Killer Cell Leukemia in Japan

Introduction Aggressive natural killer cell leukemia (ANKL) is a rare leukemic form of mature NK cell neoplasm that is closely associated with the Epstein-Barr virus (EBV). Patients with ANKL show a fulminant clinical course and poor prognosis with a median overall survival (OS) of a few months after diagnosis. L-asparaginase (L-asp)-containing chemotherapies and allogeneic hematopoietic stem cell transplantation (HSCT) are considered as effective therapeutic strategies. However, owing to the rarity of this disease, the characteristics and outcomes of ANKL remain unclear. Methods Data of 103 patients diagnosed with ANKL between 2002 and 2021 from 64 hospitals were retrospectively analyzed. Diagnosis was based on the World Health Organization classification and was verified by two co-authors (AF and RS). Patients registered in our previous ANKL studies were excluded. Results Patient's median age was 50 years (range, 17-90 years), and males accounted for 58%. Twelve patients (12%) had a medical history of chronic active EBV infection (9%), severe mosquito bite allergy (5%), and chronic lymphoproliferative disorder of NK cells (1%). B symptoms were commonly observed at the time of diagnosis (89%). Performance status (PS) was poor (2-4) in more than half of patients (53%). The median percentage of ANKL cells was 20.0% (range, 0-93.4) in bone marrow (BM) and 10.3% (range, 0-89) in peripheral blood (PB). ANKL cells express CD2 (95%), CD7 (53%), CD16 (41%), CD56 (95%), and EBER (86%). Fifty-two patients analyzed (58%) had chromosomal abnormalities by G-banding method, including chromosome 17 abnormalities in 19, deletion of 6q in 11, and isochromosome 7 in 5. Blood tests at diagnosis typically showed pancytopenia with a median white blood cell count of 2,900/μl, hemoglobin level of 10.3g/dl, and platelets 4.3×104/μl. High serum lactate dehydrogenase and soluble interleukin-2 receptor level were also observed (median, 882U/l and 8,475U/dl, respectively). The most common extra-nodal site of involvement was the BM (100%), followed by the spleen (84%), liver (70%), and PB (59%). Median OS of the present cohort was 5.3 months, and 1-year OS was 25.7%. Prognosis was significantly better in patients who underwent HSCT than in those who did not undergo HSCT (P < 0.001). The median OS and 1-year OS were 12.0 months and 52.3% in the former group and 1.7 months and 3.8% in the latter. Eighty-three patients received multi-agents-containing chemotherapy, while the others received single agent or did not receive any anti-lymphoma chemotherapy owing to poor general condition. The most common first-line chemotherapy was the SMILE regimen (39%), followed by anthracycline-based regimens, mainly CHOP (24%), DeVIC (15%) and other L-asp-containing regimens (8%). The response rate was highest in patients treated with SMILE (66%), followed by those who received other L-asp-containing regimens (57%), DeVIC (36%) and anthracycline-based regimens (32%). OS was significantly better in patients who received SMILE than in those who did not receive SMILE (1-year OS 39.3% vs. 12.1%, P < 0.001, Figure). Furthermore, the HSCT rate was significantly higher in patients who received SMILE (68% vs. 26%, P < 0.001). Multivariate analysis using the Cox proportional hazards model showed good PS (0-1) (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23-0.91, P = 0.03), administration of SMILE (HR 0.43, 95% CI 0.23-0.80, P = 0.009), and HSCT (HR 0.26, 95% CI 0.12-0.58, P = 0.001) were independent factors associated with favorable OS. Conclusion The present study showed better OS as compared with our previous study. The SMILE chemotherapy and HSCT were suggested to be key components of the therapeutic strategy for ANKL. Further studies are warranted to validate these findings. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Serum Lactate Dehydrogenase Is a Sensitive Predictor of Systemic Complications of Acute Pancreatitis.

Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory disease that can cause various complications, including systemic inflammatory response syndrome (SIRS), pleural effusion, ascitic fluid, myocardial infarction, and acute kidney injury (AKI). However, there is still a lack of rapid and effective indicators to assess the disease. The aim of this study was to investigate the associations of high serum lactate dehydrogenase (LDH) levels with AP severity and systemic complications. AP patients treated from July 2014 to December 2020 were retrospectively enrolled. They were divided into elevated (n = 93) and normal (n = 143) LDH groups. Their demographic data, clinical data, hospital duration, and hospital expenses were analyzed. Linear and binary logistic regression analyses were used to determine whether elevated LDH is a risk factor for AP severity and complications after adjusting for confounders. There were significant differences in AP severity scores (Ranson, MODS, BISAP, APACHE II, and CTSI), hospital duration, hospital expenses, and the incidences of complications (SIRS, pleural effusion, ascitic fluid, myocardial infarction, and AKI) between the elevated and normal LDH groups. After adjusting for confounders, elevated LDH was associated with AP severity scores and hospital duration and expenses (based on linear regression analyses) and was a risk factor for the occurrence of AP complications and interventions, that is, diuretic and vasoactive agent use (based on binary logistic regression analyses). Elevated LDH is associated with high AP severity scores and high incidences of complications (SIRS, pleural effusion, ascitic fluid, myocardial infarction, and AKI).

Outcomes of high‑dose methotrexate for CNS prophylaxis in diffuse large B‑cell lymphoma with an intermediate or high CNS‑International Prognostic Index: A single‑center retrospective cohort study.

Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) is rare (2-5% of cases), but is a devastating complication with a poor survival rate. The administration of high-dose methotrexate (HDMTX) for CNS prophylaxis in patients with DLBCL is controversial and variable in the literature. The present study aimed to evaluate the clinical outcomes of HDMTX CNS prophylaxis in patients with intermediate and high CNS-International Prognostic Index (IPI) DLBCL using real-world data. An observational retrospective cohort study was conducted of all patients with intermediate and high CNS-IPI DLBCL treated at Princess Noorah Oncology Center (King Abdulaziz Medical City, Jeddah, Saudi Arabia) between January 2010 and December 2020. Patients were treated with HDMTX either intravenously or intrathecally, according to the physician's evaluation of the patient. Data on patient clinical characteristics, CNS relapses, risk factors and survival rates were obtained from hospital records. Data were analyzed using Student's unpaired t-test and the χ2 test to compare the two subgroups, the Kaplan-Meier survival method with log-rank test to calculate and compare the survival rates, and regression analysis to determine the risk factors for CNS relapse and death. The study included 358 patients (n=32 with HDMTX CNS prophylaxis and n=326 without CNS prophylaxis). Patients in the CNS prophylaxis group had a significantly higher CNS relapse rate than those in the non-CNS prophylaxis group (12.5% vs. 1.8%; P=0.008). Patients who received CNS prophylaxis were younger and had an advanced stage of disease, with extranodal involvement and a high serum lactate dehydrogenase level at presentation. CNS prophylaxis was significantly associated with CNS relapse, while relapsed disease was associated with the risk of death (all P<0.05). In conclusion, the present study found that patients with intermediate and high CNS-IPI who received HDMTX CNS prophylaxis did not have fewer CNS relapses; however, those without CNS relapse had higher survival rates. In addition to CNS prophylaxis, Stage of DLBCL and IPI were significantly associated with CNS relapse. Future randomized control trials are needed to evaluate the efficacy of HDMTX CNS prophylaxis in patients with DLBCL.

The multiple roles of LDH in cancer.

High serum lactate dehydrogenase (LDH) levels are typically associated with a poor prognosis in many cancer types. Even the most effective drugs, which have radically improved outcomes in patients with melanoma over the past decade, provide only marginal benefit to those with high serum LDH levels. When viewed separately from the oncological, biochemical, biological and immunological perspectives, serum LDH is often interpreted in very different ways. Oncologists usually see high serum LDH only as a robust biomarker of a poor prognosis, and biochemists are aware of the complexity of the various LDH isoforms and of their key roles in cancer metabolism, whereas LDH is typically considered to be oncogenic and/or immunosuppressive by cancer biologists and immunologists. Integrating these various viewpoints shows that the regulation of the five LDH isoforms, and their enzymatic and non-enzymatic functions is closely related to key oncological processes. In this Review, we highlight that serum LDH is far more than a simple indicator of tumour burden; it is a complex biomarker associated with the activation of several oncogenic signalling pathways as well as with the metabolic activity, invasiveness and immunogenicity of many tumours, and constitutes an extremely attractive target for cancer therapy.

Predicting factors and outcomes of acute myocarditis in children - a 5-year experience in a teaching hospital from the Eastern province of Saudi Arabia.

Myocarditis in children is not very common, but the state of the disease is similar to viral influenza, making it challenging for a clinician to make an early diagnosis and treatment plan. Elevated levels of inflammatory biomarkers like C-reactive protein, serum lactate, troponin, and abnormal ECG may be helpful for high-index suspicion of myocarditis. This study aimed to determine the predicting factors and outcomes of acute myocarditis in children admitted to a teaching hospital in the Eastern province of Saudi Arabia. Complete medical records of 80 pediatric patients with acute myocarditis over 5 years (from 2015 to 2019) were retrieved, including demographic characteristics, laboratory investigations including cardiac enzymes (serum lactate, CPR, and troponin), and ECG findings for the diagnosis of myocarditis based on tachycardia and bradycardia. There were 22 (27.5%) mortalities that took place during the hospital stay. Low WBC (mmol/dl) levels were associated with in-hospital mortality (p 0.001), whereas high serum lactate levels (>2 mmol) were not. Association of troponin level (0.15ng/mL) was not significantly associated with mortality (p=0.496). The area under the ROC=0.947 (95% C.I: 0.88-1.0) revealed highly significant predictive validity at the 2.3 best cutoff point, having 90.9% and 87.9% sensitivity and specificity, respectively. Clinical factors and elevated biomarkers were associated with poor prognosis and in-hospital mortality in pediatric myocarditis. Serum lactate and troponin levels demonstrated high predictive validity for early diagnosis.

Metformin toxicity: A meta-summary of case reports.

BACKGROUNDMetformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes. Due to the lack of randomized control trials, most of the data pertaining to the clinical course, therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series. AIMTo analyse the symptomology, clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.METHODSWe performed a systematic search from PubMed, Science Direct, Reference Citation Analysis (https://www.referencecitationanalysis.com/) and Google Scholar databases using the terms “metformin” AND “toxicity” OR “overdose” OR “lactic acidosis” OR “hyperlactatemia”. The inclusion criteria were: (1) Case reports or case series with individual patient details; and (2) Reported toxicity or overdose of metformin in adults, published in the English language. Data regarding baseline demographics, clinical presentation, therapeutic interventions, intensive care unit course and overall outcome were collected. RESULTSTwo hundred forty-two individual cases were analysed, from 158 case reports and 26 case series, with a cumulative mortality of 19.8%. 214 (88.4%) patients were diabetics on metformin. 57 (23.6%) had acute ingestion, but a great majority (76.4%) were on metformin in therapeutic doses when they developed toxicity. Metformin associated lactic acidosis (MALA) was the most commonly reported adverse effect present in 224 (92.6%) patients. Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia. The organ support used was renal replacement therapy (RRT) (68.6%), vaso-pressors (58.7%) and invasive mechanical ventilation (52.9%). A majority of patients (68.6%) received RRT for toxin removal, renal dysfunction and correction of MALA. Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT.CONCLUSIONMost of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions. These patients may develop severe lactic acidosis, leading to significant morbidity and need for organ support. Despite severe MALA and the need for multiple organ support, they may have good outcomes, especially when RRT is used. The dose of metformin, serum pH, lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.

Indications, outcomes and complications after ECMO implantation in the cath lab - a single-center retrospective study

Abstract Funding Acknowledgements Type of funding sources: None. Background Despite the increase of extracorporeal membrane oxygenation (ECMO) employment around the globe over the last decades, studies describing the emergency use of venoarterial (VA)-ECMO in the cardiac catheterization laboratory (CCL) are scarce. Purpose The aim of this study was to describe the patient population that received ECMO in the CCL of a tertiary care center and the associated complications and outcomes. Methods In this single-center retrospective study we reviewed the baseline clinical and laboratory characteristics, indications and outcomes of adult patients, who received VA-ECMO between 2011 and 2019. Results In the given time period, ECMO use in the CCL increased drastically. Mean age of the 83 patients was 58.3 ± 12.5 years, 78.3% were male. From 2011 to 2018 ECMO-use in the CCL increased drastically. The most common indication for ECMO implantation was cardiac arrest (66%), followed by cardiogenic shock (12%), high-risk PCI (11%), and procedure-related complications (10%). While 30-day mortality in the total study population was 69%, it varied greatly depending on the underlying indication for ECMO therapy (cardiac arrest 78%, cardiogenic shock 20%, high-risk PCI 44%, procedure-related complications 88%). The most commonly occurring complications were acute kidney injury (20%) and cannula site bleeding (20%), followed by extremity complications (19%), sepsis (18%), major bleeding (10%) and stroke (8%). Of interest, patients receiving ECMO therapy after in-hospital cardiac arrest showed greater survival rates (28.2%) as compared to patients after out of hospital cardiac arrest (18.2%; p=0.045). High serum lactate levels (p=0.018) and low baseline pH values (p=0.001) at baseline were associated with a significantly increased 30-day mortality after ECMO implantation. Conclusion The emergency use of VA-ECMO in the CCL increased over the last years and was associated with a high 30-day mortality in our study population. Still, a &amp;gt;20% survival rate in the group of patients with refractory cardiac arrest, an otherwise futile situation, suggests that VA-ECMO implantation is reasonable in selected patients. As high admission serum lactate levels and the baseline pH are strong predictors of outcome, such parameters may be used to guide decision making.

Bedside intra-aortic balloon pump implant in cardiac intensive care unit

Abstract Funding Acknowledgements Type of funding sources: None. Background Intra-aortic balloon pumping (IABP) support has been progressively reappraised, especially for the acute decompensated heart failure (ADHF) cardiogenic shock (CS) scenario(1). IABP features an easy implantation technique and can rapidly be deployed bedside. This avoids the need of patient transfer to the catheterization laboratory (CathLab) and the inherent risk of destabilization and makes it an attractive approach in case of unstable hemodynamics. However, despite decades of IABP utilization, no data is available on the safety and feasibility of the IABP bedside implant. Aim Aim of this study was to assess the safety and feasibility of bedside IABP implant and to characterize the phenotype of patients who receive this support. Methods We retrospectively reviewed all consecutive patients who received bedside IABP in the last 12 months. For comparison purposes we also selected all consecutive patients who underwent IABP implant in the CathLab in the same timespan. Major vascular complication was defined as thoracic aortic dissection, access-related vascular injury leading to either death, unplanned percutaneous/surgical intervention, need for ≥4 blood unit transfusions, amputation for distal embolization, or irreversible end-organ damage. All analyses were performed with R. Results A total of 77 patients were included: 22 (28.6%) received bedside, and 55 (71.4%) CathLab IABP implant. A total of 62 (81.6%) patients were male, age was 73 (64-79) years, and invasive mechanical ventilation was required in 54 (70.1%): no differences were observed between groups. Bedside IABP implant was guided by trans-esophageal echocardiography in 10 (45.5%) and trans-thoracic echocardiography in 12 (54.5%) patients. Patients in the bedside IABP cohort had more often pre-existing heart failure (HF, 72.7 vs 32.7%; p=0.001), presented with ADHF (45.5 vs 12.7%; p=0.002) and in overt CS (77.3 vs 34.5%; p&amp;lt;0.001). They also demonstrated lower systolic arterial pressure [90.0 (86.2-102.5) vs 123.0 (104.5-140.0) mmHg; p=0.007], lower left ventricular ejection fraction [LVEF, 20 (15-25) vs 25 (20-35)%; p&amp;lt;0.001] and higher serum lactate [5.4 (3.6-8.5) vs 2.0 (1.3-3.7) mmol/L; p=0.001]. Despite worse baseline conditions than the CathLab group, bedside IABP cohort experienced a similar in-hospital mortality (22.7 vs 18.2%; p=0.649), similar major bleeding events (27.3 vs 12.7%; p=0.124), and similar major vascular complications (4.5 vs 5.5%; p=0.871). No patient experienced cerebrovascular events. Conclusion In this single-center experience, bedside IABP implant appeared safe and feasible. No difference was observed in terms of in-hospital mortality or major vascular complications between the bedside and CathLab groups, despite worse clinical conditions in the bedside IABP group. This strategy was often employed in critically-ill patients with ADHF with CS, were IABP use is increasing.

Serum albumin at resection predicts in-hospital death, while serum lactate and aPTT on the first postoperative day anticipate anastomotic leakage after Ivor-Lewis-esophagectomy

BackgroundAnastomotic leakage (AL) is a major complication after esophagectomy, potentiating morbidity and mortality. There are several patient risk factors associated with AL, but high-fidelity postoperative predictors are still under debate. The aim was to identify novel reliable predictors for AL after esophagectomy.MethodsA high-volume single-center database study, including 138 patients receiving Ivor-Lewis-esophagectomy between 2017 and 2019, was performed. Serum levels of albumin, aPTT, and lactate before and after surgery were extracted to assess their impact on AL and in-hospital mortality.ResultsHigh serum lactate on postoperative day 1 (POD1) could be shown to predict AL after esophagectomy [AL vs. no AL: 1.2 (0.38) vs. 1.0 (0.37); p < 0.001]. Accordingly, also differences of serum lactate level between end (POD0-2) and start of surgery (POD0-1) (p < 0.001) as well as between POD1 and POD0-1 (p < 0.001) were associated with AL. Accordingly, logistic regression identified serum lactate on POD 1 as an independent predictor of AL [HR: 4.37 (95% CI: 1.28–14.86); p = 0.018]. Further, low serum albumin on POD0 [2.6 (0.53) vs. 3.1 (0.56); p = 0.001] and high serum lactate on POD 0–1 [1.1 (0.29) vs. 0.9 (0.30); p = 0.043] were associated with in-hospital death. Strikingly, logistic-regression (HR: 0.111; p = 0.008) and cox-regression analysis (HR: 0.118; p = 0.003) showed low serum albumin as an independently predictor for in-hospital death after esophagectomy.ConclusionsThis study identified high serum lactate as an independent predictor of AL and low serum albumin as a high-fidelity predictor of in-hospital death after esophagectomy. These parameters can facilitate improved postoperative treatment leading to better short-term as well as long-term outcomes.

A rare case of type 1 citrullinemia in newborn

Citrullinemia type I (CTLN1) is a rare and lethal autosomal recessive genetic disorder. CTLN1 is caused by deficiency or absence of the enzyme arginino succinate synthetase (ASS). We reported a rare case of CTLN1 in a male full-term neonate. This report related to a full-term male child, born out of 3rd degree consanguineous marriage, admitted at our unit on DOL-3 with severe dehydration. ABG showed persistent severe metabolic acidosis despite of adequate treatment. So, suspecting an inborn error of metabolism (IEM) investigations were done in which we found high serum ammonia, serum lactate and urinary sodium. TMS and GCMS were done which observed a profile which can be seen in case of citrullinemia. CTLN1 is a rare and lethal genetic disorder. High index of suspicion is needed when patients present with such complex symptoms. Diagnosing and timely intervention helps in reducing the morbidity and mortality and with treatment, people with citrullinemia type 1 can have normal growth and development.

Contemporary Care and Outcomes of Critically Ill Children with Myocarditis

<h3>Purpose</h3> To describe contemporary management and outcomes in children with myocarditis admitted to the cardiac intensive care unit (ICU) and to identify characteristics associated with mortality. <h3>Methods</h3> All patients diagnosed with myocarditis by the treating clinician in the Pediatric Cardiac Critical Care Consortium (PC4) registry from 8/2014-6/2020 were included. Descriptive statistics summarized cohort characteristics and outcomes. Univariable analyses and multivariable logistic regression evaluated factors associated with in-hospital mortality. <h3>Results</h3> There were 847 ICU admissions for myocarditis in 51 centers. Median age was 12y (IQR 2.7-16). In-hospital mortality occurred in 53 patients (6.3%), 60 (7.1%) had cardiac arrest, and 17 (2%) underwent heart transplant during the admission. Mechanical ventilation was required in 339 patients (40%) and MCS in 177 (21%): ECMO-only in 142 (16.7%), ECMO-to-VAD in 20 (2.4%), E-CPR in 43 (5%), VAD-only in 15 (1.8%) patients. MCS was associated with in-hospital mortality; 20.3% receiving MCS died compared to 2.5% without MCS (p<0.001). Mortality was not different between ECMO-only, ECMO-to-VAD, and VAD-only groups. Median time from ICU admission to ECMO was 2.0hr (IQR 0-9.4) and to VAD was 9.9d (IQR 6.3-16.8). Time to MCS was not associated with mortality. Patient characteristics associated with unadjusted in-hospital mortality were younger age, smaller BSA, higher serum lactate, higher BNP, and lower eGFR on ICU admission (Table). In multivariable modeling, smaller BSA and low eGFR remained associated with mortality. <h3>Conclusion</h3> This contemporary cohort of critically ill children with myocarditis frequently required high-resource therapies such as mechanical ventilation and ECMO. However, the vast majority of patients survived to hospital discharge and rarely received VAD and/or heart transplant. Smaller patient size and renal dysfunction were independently associated with mortality.

Factors Associated with Development of Acute Kidney Injury After Liver Transplantation.

Early post-liver transplant (LT) acute kidney injury (AKI) has been associated with worse short-term and long-term outcomes, but the incidence and risk factors in our population are unknown. We designed a prospective, singlecenter, longitudinal cohort study to determine the incidence of AKI during the immediate postoperative period of LT, and to identify the risk factors associated with AKI after LT. Pre-operative and intraoperative variables were analyzed to determine if there was any correlation with the development of post-operative AKI. Eighty-six patients were included in the final analysis; from them, 45 (52%) developed AKI in the following 30 days after LT. The presence of hepatic encephalopathy prior to LT was the factor most strongly associated with the development of AKI (Relative Risk 3.67, 95% Confidence Interval 1.08-8.95). Other factors associated with AKI development were male gender and a higher serum lactate during surgery. AKI was a frequent complication that significantly worsened the prognosis of LT recipients and was associated with an increased 30-day mortality rate. The presence of hepatic encephalopathy strongly predicted the development of severe AKI.