Effect of the Immunoglobulin G-A-M Treatment on Hepatic Functions and Mortality rates in Patients with Septic Shock

Sepsis is defined as life-threatening organ dysfunction caused by the disorder of the body′s response to infection.Sepsis is the focus of critical illness medicine and difficult problems nowadays.At present, the incidence of sepsis in children is still high around the world.If the treatment is not timely, sepsis can develop into septic shock, multiple organ dysfunction syndrome, which is a serious threat to human health.Therefore, the early identification, diagnosis and treatment of sepsis is important for reducing mortality.And the biomarkers play an important role in the early diagnosis of sepsis, pathogenetic condition and prognosis as well as efficacy evaluation.This article summarized the biomarkers of sepsis in recent years. Key words: Children; Sepsis; Biomarkers,

Background: Sepsis has a poor prognosis for critically ill patients, even with intensive management. Early diagnosis of sepsis and detection of patients with worsening prognosis are important for immediate intervention to improve the clinical outcome. Objective: To investigate serum presepsin (PS) and procalcitonin (PCT) as early diagnostic and prognostic biomarkers for sepsis in critically ill patients. Methods: 60 critically ill patients with sepsis were subdivided into three groups of sepsis, severe sepsis and septic shock according to Acute Physiology and Chronic Health Evaluation II (APACHEII) and quick Sequential Organ Failure Assessment (qSOFA) scores. Patients were compared with 20 age and sex matched controls. Serum PS and PCT were measured by enzyme linked immunosorbent assay (ELISA). Results: Serum PS and PCT levels were significantly increased in septic patients than controls, and their increase was positively correlated with progression of sepsis severity till reached the highest levels in septic shock. Receiver operating characteristic (ROC) curve for predicting sepsis revealed that PS has the highest area under curve (AUC) (0.967) with 97.5% sensitivity, 85% specificity and cut-off of >635.5 pg/mL, followed by PCT that has AUC (0.946), 97.5% sensitivity, 95% specificity and cut-off of >319.7 pg/mL. C-reactive protein (CRP) showed the lowest AUC (0.902) with 75% sensitivity, 100% specificity and cut-off of >7 mg/L. ROC curve for predicting septic shock showed that PS has the highest AUC (0.969) with 90% sensitivity, 97.5% specificity and cut-off of >5500.6 pg/mL, followed by CRP that has AUC (0.945), 90% sensitivity, 87.5% specificity and cut-off of >63 mg/L. PCT showed the lowest AUC (0.889) with 90% sensitivity, 97.5% specificity and cut-off of >822.1 pg/mL. Conclusions: Serum PS and PCT were promising biomarkers for early diagnosis and prognosis of sepsis in critically ill patients, but PS was superior to PCT.

Early diagnosis and treatment of sepsis and septic shock in children results in improved outcomes. However, diagnosis is hampered by lack of specific diagnostic tests and relies on the recognition of the alterations of vital signs and protean systemic manifestations associated with infections, signs that mimic many critical illnesses. As a result, the early diagnosis of sepsis is usually presumptive and is based on the suspicion or presence of an infection in combination with the systemic changes. Suspicion should be heightened in vulnerable risk groups such as those with immune compromise due to underlying disease or medication use. Thus, on many occasions, treatment of sepsis is initiated on clinical suspicion pending the outcomes of ongoing evaluations and laboratory findings.What is of relevance to the emergency clinicians is the initial recognition, resuscitation, and treatment in the first few hours of presentation. To best accomplish these tasks, contemporary guidelines suggest that the use of a "recognition bundle" containing a trigger tool for rapid identification, a "resuscitation and stabilization bundle" to enable adherence to best practice, and a "performance bundle" to identify and overcome barriers to best practice be used.Although there are no universally acceptable tools to accomplish these tasks, the various iterations used in quality improvement initiatives have consistently demonstrated better care processes and outcomes. In this article, we outline the contemporary approach to sepsis in the first hours after presentation.

Objective To assess the clinical utility of measurement of plasma heparin-binding protein (HBP) in diagnosis and prognosis of sepsis. Methods This is a retrospective study on the performance of plasma heparin-binding protein, procalcitonin and C-reaction protein in the early diagnosis of sepsis. Thirty-one patients with sepsis, 16 patients with severe sepsis, 12 patients with septic shock and 37 control patients without confirmed sepsis, all admitted to the Intensive Care Units (ICU) of the Third Hospital Affiliated to Wenzhou Medical University and Wenzhou Central Hospital from August 2014 to November 2016, were enrolled in the study. The plasma level of HBP, procalcitonin (PCT) and C-reactive protein (CRP) were measured, and the detailed clinical data were retrieved from the patient chart records for all patients described above. Comparison of each laboratory and clinical parameters between groups was carried out by Non-parameter Test. The efficiency of each parameter was calculated by receiver operating characteristics curves (ROC) analysis. The correlation between HBP, PCT or CRP and clinical or other laboratory parameters was explored using Spearman correlation analysis. Results HBP was significantly elevated in patients with severe sepsis[(100.65±58.82)ng/ml and(31.86±36.87)ng/ml, Z=-3.856, P<0.05; (100.65±58.82)ng/ml and(24.96±17.49)ng/ml, Z=-3.556, P<0.05]and in patients with septic shock[(148.28±99.73)ng/ml and(31.86±36.87)ng/ml, Z=-4.432, P<0.05; (148.28±99.73)ng/ml and(24.96±17.49)ng/ml, Z=-4.157, P<0.05], respectively, while CRP[(154.64±62.90)mg/L and(92.56±67.49)mg/L, Z=-2.749, P<0.05; (154.64±62.90)mg/L and (79.21±51.80)mg/L, Z=-3.218, P<0.05]and PCT[(32.86±39.93)ng/ml and(2.70±6.24)ng/ml, Z=-3.395, P<0.05; (32.86±39.93)ng/ml and(4.21±14.94)ng/ml, Z=-4.092, P<0.05]were increased only in patients with septic shock (P<0.05). For HBP, the area of under the ROC curves (AUC) was the biggest (AUC=0.687), indicating the clinical significance(P<0.05) with excellent sensitivity(0.729) at the optimal cut-off value(18.58 ng/ml). In addition, HBP(APTT: r=0.244, P=0.016; PT: r=0.351, P<0.001; INR: r=0.314, P=0.002; D-Dimer: r=0.334, P=0.001; lactic acid: r=0.394, P<0.001), CRP(APTT: r=0.271, P=0.008; PT: r=0.348, P=0.001; INR: r=0.264, P=0.009; D-Dimer: r=0.257, P=0.012; lactic acid: r=0.329, P=0.001) and PCT(APTT: r=0.375, P<0.001; PT: r=0.523, P<0.001; INR: r=0.535, P<0.001; D-Dimer: r=0.254, P=0.013; lactic acid: r=0.422, P<0.001)were positively correlated to coagulation function and to lactate. Conclusion HBP could probably be acted as an important biomarker for diagnosis and prognosis for patients with sepsis, esp., for patients with severe sepsis and septic shock.(Chin J Lab Med, 2017, 40: 451-455) Key words: Blood proteins; Carrier proteins; Antimicrobial cationic peptides; Sepsis; C-reactive protein; Calcitonin

To evaluate the clinical value and specificity of atrial natriuretic peptide (ANP) in early diagnosis of sepsis. A prospective study was performed. Data of patients with sepsis were consecutively collected from September 2007 to December 2012 according to the international criteria for the diagnosis of sepsis, and that of 114 patients admitted to intensive care unit (ICU) and the cadre health care ward were divided into three groups: systemic inflammatory response syndrome (SIRS) group (n=37), sepsis group (n=41) and severe sepsis group (including severe sepsis and septic shock, n=36). Venous blood of each patient was drawn instantly when admitted to ICU. The concentration of plasma ANP in each group was determined on the 1st day using a new type of sandwich immunofluorescence assay, and other biomarkers, such as procalcitonin (PCT, detected with double antibody immunochemi luminometry), blood lactic acid (detected with electrode meter), and C-reactive protein (CRP, detected with immunonephelometric analysis), and the acute physiology and chronic health evaluation II (APACHEII) score was recorded. APACHEII score and biomarkers were compared among three groups. The risk factor for severity was confirmed with stepwise regression, and the value of each index in early diagnosis of sepsis was analyzed with receiver operating characteristic (ROC) curve. The plasma concentration of ANP exhibited a gradual increase with the aggravation of the disease, and the median ANP value was found to be highest in the severe sepsis group compared with SIRS group and sepsis group [μg/L: 0.26 (0.22) vs. 0.19 (0.05), 0.21 (0.08), P<0.01 and P<0.05]. The regression equation was established at y=0.69 + 0.66APACHEIIscore + 1.285 ANP value, with group as independent variable, and APACHEII score, ANP, PCT, CRP and blood lactic acid value as dependent variables. It could be concluded that APACHEII score and ANP value were correlated with severity of sepsis, and accordingly they were regarded as the independent predictors of severity of sepsis. It was found through the ROC curve analysis of ANP in the sepsis patients, that the area under the ROC curve for ANP [0.805, P=0.000, 95% confidence interval (95%CI) 0.726-0.883, sensitivity 75.8%, specificity 78.4%] was similar with the area under the APACHEII score (0.820, P=0.000, 95%CI 0.742-0.897, sensitivity 68.4%, specificity 78.4%), and it was apparently higher than AUCs of PCT (0.716, P=0.000, 95%CI 0.622-0.810, sensitivity 67.1%, specificity 62.2%), CRP (0.569, P=0.236, 95%CI 0.463-0.675, sensitivity 76.3%, specificity 41.5%), or blood lactic acid (0.566, P=0.254, 95%CI 0.453-0.679, sensitivity 75.0%, specificity 48.6%). Plasma ANP concentration is clinically valuable in early diagnosis and severity assessment of sepsis, and it is more specific and sensitive than biomarkers PCT and CRP.

The disappointing results of new adjunctive therapies for sepsis in large clinical studies prompted the late Roger Bone to suggest that “we should spend more time to achieve an accurate diagnosis and less time for searching a magic bullet” [1]. However, not only important for valid clinical investigation, accurate and early diagnosis of sepsis may also help improve patient outcome. Because of the importance of the subject matter, we asked experts in the ~eld to discuss some new aspects and recent ~ndings that might be helpful in improving the diagnosis of sepsis. Sepsis is nowadays de~ned as a systemic response to severe infections [2]. Sepsis is diagnosed when clinical evidence of infection is accompanied by signs of systemic in_ammation. These statements have been translated to a set of clinical and laboratory criteria for the diagnosis of sepsis. For clinical purposes, the diagnostic criteria of sepsis should identify patients at an early stage of the syndrome, prompting clinicians to search for and treat infection, apply appropriate supportive therapy, and monitor for organ failure and other complications. For study purposes, the diagnostic criteria of sepsis should identify patients who would potentially bene~t from new (immunomodulatory) therapeutic approaches. Multicenter immunomodulatory trials of sepsis conducted 10 years ago started using uniform clinical diagnostic criteria for identifying septic patients [3]. These studies helped de~ne what sepsis means when certain clinical and laboratory criteria are used. Based on the characteristics of the patients included in these trials, Roger Bone published important clinical data regarding the epidemiology of sepsis (as de~ned by those criteria) and proposed using a set of criteria for “early detection and treatment of a group of very high-risk patients with sepsis” [4]. The term “sepsis syndrome” was coined for this group of patients. The “sepsis syndrome” was diagnosed when clinical evidence of infection was accompanied by evidence of in_ammation and poor organ perfusion or of organ dysfunction. Clinical evidence of infection meant that there was no longer a need to have bacteriological evidence such as positive blood cultures and that clinical criteria suf~ced [4,5]. To further clarify inadequacies arising from the de~nition of the sepsis syndrome, members of the American College of Chest Physicians and the American Society of Critical Care Medicine (ACCP/SCCM) provided a new set of de~nitions for both clinical and experimental applications [2]. The “systemic in_ammatory response syndrome” (SIRS) was de~ned as the presence of two or more of the following diagnostic criteria: changes in body temperature (fever or hypothermia), changes in white blood cell counts (leukocytosis or leukopenia or increases in immature neutrophils), tachycardia, and tachypnea. Sepsis was then de~ned as the systemic in_ammatory response to an infection, severe sepsis as sepsis associated with organ dysfunction, hypoperfusion, or hypotension, and septic shock as persistence of hypoperfusion or hypotension despite _uid resuscitation. The diagnostic criteria thus comprises signs of in_ammation and evidence of infection to diagnose sepsis and signs of remote organ failure to address the severity of the in_ammatory response. Some points are of importance: First, common signs of in_ammation such as changes in body temperature, changes in leukocyte count, changes in neutrophil granulation, tachycardia etc. may have an infectious or non-infectious etiology and are neither speci~c nor sensitive for sepsis. Of note, only two signs, namely changes in leukocyte counts and changes in body temperature can be directly related to in_ammation whereas tachycardia and tachypnea cannot. Second, the disappointing results of immunomodulatory trials in septic patients have raised doubts as to whether clinical and laboratory criteria alone may suf~ce in identifying groups of patients who would most likely bene~t from such therapies. We note that the diagnosis of sepsis, an important ~rst step for both clinicians and clinical investigator, still has many pitfalls. These shortcomings of the de~nitions and diagnostic criteria call for new diagnostic tools and parameters. Some parameters may be needed in early clinical identi~cation of such patients, others may be important in gauging the in_ammatory response and monitoring the immune status of the patient, still others may help identify subgroups of septic patients who may bene~t from proor anti-in_ammatory therapies. In this issue of the journal, parameters and markers of the septic response and their scienti~c and clinical

Objective To investigate the value of multiple inflammatory cells and clinical score in early diagnosis and prognosis assessment of trauma sepsis risks. Methods This retrospective control study enrolled 209 severe trauma patients admitted from January 2010 and May 2016. White blood cell count, lymphocyte count and percentage, monocyte count and percentage, neutrophil count and percentage, ratio of neutrophil to lymphocyte count (N/L), acute physiology and chronic health evaluation (APACHE) Ⅱ score, sequential organ failure assessment (SOFA), improved early warning score (MEWS), Glasgow coma score (GCS), multiple organ dysfunction syndrome (MODS) score and lactic acid (LAC) were collected on the day of admission and 3, 5, 7 days after trauma. These data were applied to construct weighted and biological score models for early diagnosis and prognosis of traumatic sepsis. Receiver operating characteristic curve (ROC) was performed and area under the curve (AUC) was calculated to measure the value of the two models in early diagnosis and prognosis of sepsis. Results AUC of the weighted model combined by APACHE Ⅱ score, SOFA score and MEWS was 0.729 on the day of admission. AUC of the weighted model combined by inflammatory cells was 0.680 and AUC of the biological score model was 0.800 3 days after trauma (P 0.05). AUC of the biological score model had significant difference 3 days and 5 days after trauma (P<0.05). Of the weighted model combined by APACHE Ⅱ score, MODS score, GCS and LAC to evaluate the prognosis of sepsis, the AUC showed significant difference on the day of admission (0.838), 3 days after trauma (0.878), 5 days after trauma (0.947) and 7 days after trauma (0.936) (P<0.05). Conclusions Biological score possesses better effect on early diagnosis of sepsis 3 days after trauma. Weighted model combined by APACHE Ⅱ score, MODS score, GCS and LAC can effectively predict the prognosis of sepsis 5 days after trauma. Key words: Sepsis; Diagnosis, differential; Prognosis

Severe sepsis (systemic inflammation secondary to infection combined with acute organ dysfunction) and septic shock (severe sepsis combined with hypotension not rectified by fluid resuscitation) are complex multifactorial medical conditions with significant associated morbidity and mortality, and are among the leading causes of death in the intensive care unit (ICU). Even with aggressive treatment, the mortality has been shown to be around 40 percent (Bernard et al., 1997) and in some studies has been reported to be as high as 71.9 percent (Sasse et al., 1995). In 2001, Angus et al conducted a study of the incidence, cost, and outcome of severe sepsis in the United States of America; the results showed an incidence of 3 cases per 1,000 population, a mortality rate of 28.6 percent, and a cost of $22,100 per case, giving an annual cost of $16.7 billion (Angus et al., 2001). The same study showed that the number of deaths per year associated with severe sepsis is equal to that of acute myocardial infarction, yet myocardial infarction has attracted far more attention and funding in terms of treatment and management research, leaving sepsis a relatively unacknowledged problem. With severe sepsis having such a high incidence, high and increasing mortality rate, and high annual cost, it is becoming a prime target for research into improving diagnosis, management, and survival. Reducing morbidity and mortality in severe sepsis and septic shock has been the primary goal of the Surviving Sepsis Campaign (SSC) – a global initiative developed by the European Society of Intensive Care Medicine (ESICM), the International Sepsis Forum (ISF), and the Society of Critical Care Medicine (SCCM) to raise awareness of sepsis among healthcare professionals and to improve and standardize the early diagnosis and treatment of sepsis (Welcome To The Surviving Sepsis Campaign Website,n.d.). Containing a number of the world’s experts on sepsis, this campaign attempts to tackle various challenges in the diagnosis and management of sepsis. Some of the challenges lie in the complexity of the condition and the variability in the presentation and course of sepsis, with many of the symptoms being of a general nature and easily attributable to a number of other conditions and etiologies. This makes it quite difficult to create a standard clinical definition of sepsis. This lack of definitive criteria for a diagnosis of sepsis makes it easily misdiagnosed, and consequently improperly treated. If, however, a diagnosis of sepsis is made, it is often still made late and treatment is less effective if delayed. As is discussed later in this chapter,

OBJECTIVES:Source control is important in management of septic shock. We studied differences in outcomes of patients with sepsis and septic shock who required source control intervention compared with those who did not need such intervention and the effect of the timing of source control on various clinical outcomes.DESIGN:Prospective observational study from February 28, 2020, to March 31, 2021.SETTING:Medical ICU of academic quaternary medical center.PATIENTS:Two hundred five adult (≥18 yr) ICU patients.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Patients were divided into a medical treatment group and a source control group. Patients requiring source control were further divided into early (intervention performed < 24 hr) and late (≥ 24 hr) source control groups. The primary outcomes were 30-day and ICU mortality. Secondary outcomes were ICU and hospital length of stay (LOS), days on mechanical ventilation, and need for renal replacement therapy. A total of 45.9% patients underwent source control. Of these, early source control was performed in 44.7% and late source control in 55.3% of patients. There was no significant difference in 30-day mortality or ICU mortality in the medical versus source control groups or in early versus late source control groups. Compared with the medical group, mean hospital LOS (11.5 vs 17.4 d; p < 0.01) and ICU LOS (5.2 vs 7.7 d; p < 0.01) were longer in the source control group. The hospital LOS (12.5 vs 21.4 d; p < 0.01) and ICU LOS (5.2 vs 9.7 d; p < 0.01) were also longer in patients who had delayed source control than in patients who had early source control. There were no significant differences in other outcomes.CONCLUSIONS:Although mortality was similar, patients who had delayed source control had a longer ICU and hospital LOS. Early source control may improve health care utilization in septic shock patients.

Background Sepsis and its complications are one of the leading causes of mortality. Timely diagnosis and treatment are highly important in reducing morbidity and mortality. Serum biomarkers may aid in the early diagnosis of sepsis and therapeutic intervention. Procalcitonin (PCT) is a peptide precursor of the hormone calcitonin, and its primary trigger is infection. Increased serum PCT is associated with bacterial endotoxin and inflammatory cytokines. Therefore, PCT is widely used as a biomarker for bacterial infection and sepsis. Clinically, PCT greater than 2 ng/mL is associated with high risk of sepsis, and PCT less than 0.5 ng/mL is associated with low risk. We aimed to investigate the correlation between PCT and blood culture in the early diagnosis of sepsis in an unselected population with suspected bloodstream infections and evaluated the interpretative criteria helpful in diagnosis of systemic bacterial infection or sepsis. Methods We retrospectively analyzed medical records of 127 patients (72 (56.7%) males and 55 (43.3%) females) aged (X±SD(69.2±20.4) range (4-100 years) from different hospital departments who visited Dr. Sulaiman Alhabib Group of Hospitals (HMG) in Riyadh from January 2021 to December 2022. with suspected bloodstream infections who had PCT data and blood culture results. PCT was quantitatively determined by the BRAHMS PCT assay on the Abbott Allinity I System, which is a two-step chemiluminescent microparticle immunoassay (CMIA). Blood culture was done using BactAlert system (bioMérieux). Results Among study group blood culture was positive in 75 cases (59.1%) and negative in 52 cases (40.9), PCT was positive in 107 cases (84.3%) and negative in 20 cases (15.7%). Both tests were correlated (either positive or negative) in 71 cases (56%). PCT results were correlated to culture results (applying cutoff value 0.1 ng/ml) using Pearson Chi-Square test and results were insignificant (P value &amp;gt; 0.5). PCT found to have sensitivity of 84% (73.7% to 91.5%, 95% CI) and specificity of 15.4% (6.9 to 28.1%, 95% CI) To assess the significance of interpretative criteria, PCT results were classified into 3 groups (moderate risk for progression to sever sepsis (0.5-1.99 ng/ml), sever systematic response (2-9.99 ng/ml) and high likelihood of sever sepsis or septic shock (= 10ng/ml). One way ANOVA studies show Significant difference among the 3 subgroups of culture negative cases (F value =3.48, P= 0.38) and among culture positive cases (F value= 4.56, P= 0.14). However, the student T test shows insignificant results when each risk category was compared among culture positive and negative cases (p value of 0.73, 0.83, 0.75 respectively). Conclusion PCT elevated levels in study population may indicate sepsis (good screening assay with accepted sensitivity) but should be interpreted cautiously alongside with blood culture results. Further research is needed to establish the specificity of PCT. Test interpretative criteria may work as good predictor of inflammatory status rather than septic status

Objective To investigate the value of pro-adrenomedullin (pro-ADM) in the early diagnosis of sepsis. Methods Seventy-five patients admitted to ICU, who fulfilled the diagnostic criteria for sepsis, were divided into the sepsis group (n=54) and the non-sepsis group (n=21) . Blood samples were collected at the day of ICU admission, and the concentrations of serum pro-ADM and PCT were measured. The sensitivity and specificity of the diagnostic biomarkers were analyzed by using receiver operating characteristic curve, and the critical values were established. Results Compared with the non-sepsis group, the concentrations of proADM, PCT, CRP, and WBC significantly increased in the sepsis group, and there were statistical significance in the increasing concentrations of proADM, PCT, and CRP. The area under the curve of proADM was larger than that of PCT and CRP. The sensitivity of proADM was not significantly different from that of PCT (84% vs 86%) , which was significantly better than that of CRP and WBC. The specificity, positive predictive value and negative predictive value of proADM were all 100%, respectively, which were better than those of PCT, CRP and WBC. Conclusion Plasma pro-ADM level is significantly elevated in the early stage of sepsis, which may be used in the early diagnosis of sepsis. As a biomarker for the diagnosis of sepsis, Pro-ADM shows higher diagnostic accuracy than the conventional biomarkers PCT, WBC and CRP. It favors the early detection and early diagnosis of sepsis. Key words: Sepsis; Pro-ADM; Early diagnosis

Since the outcome in septic patients can significantly be improved if the appropriate therapy is introduced timely early, the early diagnosis of sepsis and its complications is essential. The aim of this study was to compare mean values of the initial blood concentrations of lactate, C-reactive protein and creatinine and the severity of illness and the outcome of sepsis. A total of 30 septic patients were included in the study. The diagnosis of sepsis and its complications was made according to consensus criteria. The severity of illness was scored by an acute physiology, age and chronic health evaluation septic score. The patients were subdivided into different groups, those with sepsis, severe sepsis or septic shock, those with or without multiple organ dysfunction syndrome, and survivors and nonsurvivors. The differences in mean values of lactate levels among all studied groups were significantly high, whereas the level of C-reactive protein were significantly higher only in the non-survivors compared to the survivors (p < 0.05). The concentrations of creatinine were significantly higher in the patients with septic shock compared to the patients with sepsis, and in the patients with multiple organ dysfunction syndrome and the non-survivors compared to the corresponding groups (p < 0.05). The septic score clearly discriminated patients with different severity of sepsis, development of multiple organ dysfunction syndrome and survival and positively correlated with the concentrations of lactate, C-reactive protein and creatinine (the best correlation ranks were with lactate levels, p < 0.001). Our results suggest that lactate level is a better parameter of illness severity and outcome of sepsis than levels of C-reactive protein and creatinine. When compared to the above parameters, the septic score determined on the day of admission to hospital is a much better criterion to classify patients into groups with different severity of sepsis, with and without multiple organ dysfunction syndrome and into survivors and non-survivors.

Rebuttal From Dr Jones

INTRODUCTION: Recent studies from China reported have reported various rates of abnormal liver function tests in patients hospitalized with COVID-19 infection. However, data from the United States is limited. We sought to evaluate abnormalities in liver function tests (LFTs) in patients presenting with COVID-19 in the United States and compared them to a control group of hospitalized patients tested negative for COVID-19. METHODS: Patients with confirmed COVID-19 infection at our institution between January and March of 2020 were included. Patients who were suspected to have COVID-19 but tested negative served as controls. Information regarding patient demographics and laboratory values was recorded. RESULTS: A total of 139 patients with COVID-19 and 131 were controls were included. There was no difference between COVID-19 patients and controls in age (67.4 years versus 67.8 years, P = 0.8) or gender (female: 46% versus 59.4%, P = 0.5). Upon presentation, LFTs were abnormal in 44.9% of COVID patients compared to 35.8% controls (P = 0.12) There was no difference in the proportion of patients with elevated total bilirubin and international normalized ratio (INR) among COVID patients and controls. A higher proportion of COVID patients than controls had abnormal serum Alanine Aminotransferase (ALT) (27.9% versus 16.5%, P = 0.02) and serum Aspartate Aminotransferase (AST) levels (41.8% versus 22.1%, P < 0.001). A lower proportion of COVID patients had abnormal serum alkaline phosphatase (ALP) levels (10% versus 22.7%, P = 0.005) as compared to controls [Table 1]. Elevation in ALT and AST greater than 3 times the upper limit of normal was only seen in 5 COVID-19 patients. CONCLUSION: Abnormal LFTs are common on presentation in COVID-19 patients. However, the liver injury is predominantly mild and hepatocellular. Synthetic liver dysfunction is uncommon in COVID-19 patients.Table 1.: Proportion with elevated liver function tests in COVID patients and controls

Objective To study the clinical manifestations, risk factors, treatment and prognosis of carbapenem-resistant klebsiella pneumoniae (CRKP) sepsis in premature infants. Method A retrospective analysis was done for the premature infants diagnosed with klebsiella pneumoniae sepsis and admitted to the neonatal wards of the Hospital from April 2015 to March 2018. According to the results of drug sensitive test, the infants was assigned to CRKP group and non-CRKP group. The perinatal factors, clinical manifestations, treatment, and prognosis of the two groups were analyzed. Furthermore, high risk factors for CRKP group were analyzed. Result A total of 39 premature infants with KP sepsis were included in our study. There were 23 cases in the CRKP group and 16 cases in the non-CPAP group. In CPKP group, the gestational age was (29.5±0.6) weeks, the birth weight was (1 177±272) g. In non-CRKP group, the gestational age was (30.0±0.5) weeks, the birth weight was (1 387±220) g. Univariate Logistic regression analysis showed that low birth weight was a risk factor for CRKP sepsis in premature infants (OR=1.203, 95%CI 1.068~1.355, P=0.002). The proportion of that required combination treatment with antibiotics and the incidence of intracranial hemorrhage after infection in the CPKP group were both higher than that in the non-CRKP group (P<0.05). The proportion and duration of antibiotics used in the first week before the onset of infection in infants with CRKP sepsis and combined antibiotic treatment were significantly higher than those in infants with CPKP sepsis and single antibiotic treatment. The use of antibiotics in the first week before the onset of infection was an independent risk factor for the combined drug treatment of premature infants with CRKP sepsis (OR=10.500, 95%CI 1.015~108.577, P=0.049). In the CRKP group, the improvement rate was 87.0% (20/23), 2 cases were withdrew, and 1 case deceased. In the non-CPKP group, the improvement rate was 87.5% (14/16), and 2 deceased. Conclusion The lower the birth weight, the greater the risk of infection with CRKP sepsis. The proportion of need combination treatment with antibiotics is high in infants with CRKP sepsis. The use of antibiotics in the first week before the onset of infection is a risk factor for combined antibiotic treatment in premature infants with CRKP sepsis. Key words: Klebsiella, pneumoniae; Drug resistance, bacterial; Carbapenems; Sepsis; Infant, premature