Influence of Tacrolimus Intrapatient Variability on Allograft Rejection Frequency and Survival Following Liver Transplantation.

BACKGROUND: Tacrolimus is the primary calcineurin inhibitor used in immunosuppressive regimens to prevent allograft rejection (AR) after organ transplantation. Recent studies have linked intrapatient variability (IPV) of tacrolimus with AR occurrence and reduced survival, especially in kidney transplant recipients. However, limited data are available on the impact of tacrolimus IPV on adverse outcomes after liver transplantation (LT). AIMS: The aim of this study was to assess the association between tacrolimus IPV using various methodologies with acute AR and long-term patient survival after LT. METHODS: All patients who underwent LT from January 2010 to July 2021 were retrospectively evaluated. Tacrolimus IPV was calculated for each patient using the mean and SD, mean absolute deviation (MAD), coefficient of variation (CV), and time in therapeutic range (TTR). These measures were then compared with AR within the first 24 months after LT and to long-term survival. RESULTS: Out of 234 patients, 32 (13.7%) developed AR and 183 (78.2%) survived, with a mean follow-up of 101 ± 43 months. Tacrolimus IPV, assessed by mean, SD, MAD, and CV, was 8.3 ± 2.1, 2.7 ± 1.3, 32.0% ± 11.7%, and 39.4% ± 15.4%, respectively. There was no statistically significant correlation between Tacrolimus IPV and AR or survival post-LT. CONCLUSIONS: In a large cohort of patients from diverse racial backgrounds, tacrolimus IPV was not associated with clinically relevant outcomes such as AR and survival after LT.

A new and simple score to predict adequate and deep response to ursodeoxycholic acid in patients with primary biliary cholangitis: the ALP-A score.

BACKGROUND: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), but a significant proportion of patients do not respond adequately, leading to increased risk of adverse outcomes. This study aims to develop a new and straightforward predictive score to identify PBC patients likely to achieve a complete response to UDCA. METHODS: A logistic regression analysis was conducted using a derivation cohort of PBC patients to identify pre-treatment variables associated with response to UDCA. This analysis led to the development of the ALP-A score, calculated as: Age at diagnosis divided by (alkaline phosphatase at diagnosis/upper limit of normal). ALP-A score accuracy was evaluated using the area under the ROC curve, validated with a large external cohort from Brazil. Additionally, the correlation between the ALP-A score and the previously validated UDCA response score (URS) was assessed. RESULTS: ALP-A score had good predictive power for adequate (AUC 0.794; 95% CI, 0.737-0.852) and deep (0.76; 95% CI, 0.69-0.83) UDCA response at 1 year of treatment. A cutoff score of 17 and 23 points was determined to be the optimal threshold for distinguishing adequate and deep responders, respectively, from non-responders. ALP-A score demonstrated a sensitivity of 73%, specificity of 71%, positive predictive value of 65%, negative predictive value of 78%, and overall accuracy of 72% for biochemical response. The URS displayed similar discriminative ability (AUC 0.798; 95% CI, 0.741-0.855). CONCLUSION: ALP-A score performs comparably to URS but offers the great advantage of simplicity for routine clinical use. It serves as a valuable tool to identify PBC patients less likely to respond to UDCA treatment, facilitating early consideration of alternative therapeutic approaches.

ACUTE ABDOMEN IN INTENSIVE CARE UNIT: ETIOLOGY, COMORBIDITY AND SEVERITY OF 1,523 PATIENTS.

BACKGROUND: Clinical features and outcomes of patients admitted to the intensive care unit due to acute abdomen are important to be investigated. AIMS: To evaluate the outcomes of critically ill subjects with acute abdomen according to etiology, comorbidity and severity. METHODS: Outcomes of 1,523 patients (878 women, mean age 66±18 years) consecutively admitted to a specialized gastrointestinal intensive care unit with different causes of acute abdomen from January 2012 to December 2019, were retrospectively evaluated according to etiology, comorbidity and severity. RESULTS: The most common causes of acute abdomen were obstructive and inflammatory, particularly large bowel obstruction (27%), small bowel obstruction (18%) and acute pancreatitis (17%). Overall mortality was 13%. Surgery was required in 34% of patients. Median length of stay in the hospital was 9 [1-101] days. On univariate analysis mortality was significantly associated with age, APACHE II, Charlson comorbidity index, requirement for surgery and malignancy (p<0.0001), but only APACHE II, Charlson comorbidity index and surgical interventional remained significant on multivariate analysis. CONCLUSIONS: Critically ill patients admitted to the intensive care unit with acute abdomen constitute a heterogeneous group of subjects with different prognosis. Mortality is more related to the severity of the disease, comorbidity and need for surgery than to the etiology of the acute abdomen.

Impact of tacrolimus intra-patient variability in adverse outcomes after organ transplantation.

Tacrolimus (Tac) is currently the most common calcineurin-inhibitor employed in solid organ transplantation. High intra-patient variability (IPV) of Tac (Tac IPV) has been associated with an increased risk of immune-mediated rejection and poor outcomes after kidney transplantation. Few data are available concerning the impact of high Tac IPV in non-kidney transplants. However, even in kidney transplantation, there is still a controversy whether high Tac IPV is indeed detrimental in respect to graft and/or patient survival. This may be due to different methods employed to evaluate IPV and distinct time frames adopted to assess graft and patient survival in those reports published up to now in the literature. Little is also known about the influence of high Tac IPV in the development of other untoward adverse events, update of the current knowledge regarding the impact of Tac IPV in different outcomes following kidney, liver, heart, lung, and pancreas tran splantation to better evaluate its use in clinical practice.

Retrieval of HCV patients lost to follow-up as a strategy for Hepatitis C Microelimination: results of a Brazilian multicentre study.

BACKGROUND: Several HCV patients in Brazil were lost to follow-up (LTFU) in the last two decades before achievement of sustained virological response (SVR). Strategies to recall those diagnosed but untreated patients have been used elsewhere with different success rates. AIM: To identify and retrieve LTFU patients in order to offer them the treatment with the current highly effective direct acting antiviral agents (DAAs). METHODS: Registries ofall HCV patients from three large reference centers in Brazil were retrospectively reviewed to identify those with no registry of SVR. Reasons for non-achievement of SVR were elicited in HCV-RNA + patients. All patients who were not treated or cured were contacted to offer the therapy with DAAs. RESULTS: 10,289 HCV patients (50% males, mean age 52 ± 11 years) were identified. Only 4,293 (41.7%) had been successfully treated previously. From the remaining 5,996 most were LTFU (59%), were not treated for other reasons (14.7%) or were non-responders (26.3%). After revision of the charts 3,559 were considered eligible to be retrieved. The callback success of phone calls was 18%, 13% to cellphone messages (SMS or WhatsApp) and 7% to regular mail. Five-hundred sixty patients had been already treatedor were on treatment and 234 were reported to be dead or transplanted. Finally, 201 had made an appointment and initiated antiviral treatment. CONCLUSION: Even considering the low callback rate, retrieval of LTFU patients was shown to be an important strategy forhepatitis C micro-elimination in Brazil.

Public knowledge and attitudes toward liver diseases and liver cancer in the Brazilian population: a cross sectional study.

Background: Little is known about the knowledge of the Brazilian population regarding prevention/screening/diagnosis of cirrhosis and hepatocellular carcinoma (HCC). We aimed to investigate the public knowledge/attitudes toward liver diseases in Brazil. Methods: A cross-sectional survey was conducted in which 1.995 adults were prospectively interviewed regarding knowledge about cirrhosis/HCC and attitudes toward vaccination and viral hepatitis (VH) testing. Findings: Most of the Brazilian subjects believe that alcohol abuse (63%-87%), NAFLD (29%-53%) and smoking (31%-47%) are the leading causes of cirrhosis/HCC. VH were less often linked to both diseases. Brazilians agreed that NAFLD is a risk factor for cirrhosis, cancer and cardiovascular diseases; 66%, 48% and 40% were submitted to hepatitis B vaccination and hepatitis B and C testing, particularly those with older age, higher level of education and income. Interpretation: VH was not considered by the majority of the Brazilians as an important cause liver disease, leading a large proportion of those subjects to neglect hepatitis B vaccination and hepatitis B and C testing. Funding: This work was supported by Brazilian Liver Institute.

Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. MATERIALS AND METHODS: The Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. RESULTS: Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5% of those subjects without cancer, p≤0.001), smoking (55% vs. 12.3%, p≤0.001), CREST syndrome (30% vs 7.6%, p=0.003) and prior azathioprine (30% vs 8%, p= 0.005) and prednisone (35% vs 14%, p= 0.018) use, whereas patients with EHM had a higher prevalence of smoking (42.3% vs 12.4% of those subjects without cancer, p= <0.001), AMA positivity (96.6% vs 80.1%, p≤0.001), azathioprine therapy (21% vs 7.9%, p= 0.01) and concurrent other autoimmune diseases. In multivariate analysis, cirrhosis, obesity and prior azathioprine therapy were independent risk factors for HCC, while Sjogren syndrome and psoriasis were associated with EHM. Fibrates reduced EHM risk. CONCLUSIONS: The prevalence of EHM is higher when compared to HCC in PBC patients. Cirrhosis, obesity, prior azathioprine use, and concurrent autoimmune diseases were significantly associated with cancer in PBC.

Telemonitoring of the Continuum of Care of Hepatitis C During the COVID-19 Pandemic in Brazil.

Introduction: To accomplish elimination of hepatitis C virus (HCV) by 2030, as proposed by the World Health Organization, the Brazilian Ministry of Health outlined the Hepatitis C Elimination Plan, which provides coverage of all critical steps in the continuum of care (CoC) of hepatitis C. As expected, the advent of COVID-19 pandemic has disrupted the CoC of hepatitis C worldwide. The Brazilian Liver Institute launched a remote patient monitoring (RPM) program to assist the general population at risk in HCV testing and to provide linkage and retention to care for HCV-positive subjects. The RPM program was also designed to relink HCV-positive patients lost to follow-up during the COVID-19 pandemic due to their limited access to the health care system. Methods: The HCV telemonitoring number was highly advertised in Brazilian media. The RPM program was conducted by dedicated health care personnel trained to follow a predefined script designed to provide awareness, ensure consistent information for educational purposes, and recruit eligible participants to be tested for HCV. Results: From August 2020 to December 2021, 3,738 subjects entered in contact with RPM. There were 26,884 interactions (mean 7.2 interactions per participant), mostly by WhatsApp (78%). Twenty out of those 221 subjects (9%) who tested were HCV positive. Those subjects altogether with 128 other patients with HCV, tested elsewhere, were followed in the HCV CoC. Up to now, 94% of them were linked to care, 24% are undergoing treatment and 8% achieved sustained virological response (SVR). Conclusions: Our preliminary results showed that HCV CoC telemonitoring was a feasible and useful strategy to follow HCV at-risk subjects through all cascade of care until SVR during the COVID-19 health care disruption. It could be used beyond the defervescence of SARS-CoV-2 pandemic to ensure linkage to care of those HCV-positive patients.

Impact of baseline abnormal liver enzymes in the outcome of COVID-19 infection.

Background: Little is known about the significance of liver function tests (LFT) abnormalities in COVID-19 and their impact on disease outcomes. The aims of the study were to evaluate abnormalities of LFT in patients with COVID-19 and their impact on disease severity, mortality, and correlation with leukocyte markers of inflammation. Methods: All patients with COVID-19 admitted to the emergency department (ED) of a single reference center were retrospectively evaluated. Data were collected using an electronic medical database covering the following variables: demographics, baseline complete blood count (CBC) and ratios, neutrophil-lymphocyte (NLR) and monocyte-lymphocyte ratios (MLR), systemic immune-inflammation index (SII), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Disease severity was defined by the presence of organ failure (OF) or requirement for intensive care unit (ICU) support. Mortality was considered as patient death during hospitalization. Results: A total of 1,539 subjects (799 women, mean age 57±18 years) with COVID-19 were evaluated. Abnormal AST and/or ALT were seen in 50% of them, with a frequency and magnitude that significantly correlated with leukocyte count and ratios. Both LFT were significantly associated with requirement for hospital and ICU admission and mortality. High AST levels were significantly associated with the presence, number, and types of OFs and in-hospital length of stay (LOS). Elevated ALT was also significantly associated with the aforementioned variables, with the exception of OFs presence, circulatory failure and LOS. Conclusions: LFT abnormalities are frequently seen in COVID-19 patients, reflect SARS-CoV-2 associated inflammation and may predict adverse outcomes. LFT may be useful to aid decision-making in the ED for hospital admission or scheduled outpatient reevaluation.

Response to Ursodeoxycholic Acid May Be Assessed Earlier to Allow Second-Line Therapy in Patients with Unresponsive Primary Biliary Cholangitis.

BACKGROUND: Response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has been traditionally assessed 1 to 2 years after treatment initiation. With the development of new drugs, some patients may benefit from an earlier introduction of second-line therapies. AIMS: This study aims to identify whether well-validated response criteria could correctly identify individuals likely to benefit from add-on second-line therapy at 6 months. METHODS: Analysis of a multicenter retrospective cohort which included only patients with clear-cut PBC. RESULTS: 206 patients with PBC (96.6% women; mean age 54 ± 12 years) were included. Kappa concordance was substantial for Toronto (0.67), Rotterdam (0.65), Paris 1 (0.63) and 2 (0.63) criteria at 6 and 12 months, whereas Barcelona (0.47) and POISE trial (0.59) criteria exhibited moderate agreement. Non-response rates to UDCA was not statistically different when assessed either at 6 or 12 months using Toronto, Rotterdam or Paris 2 criteria. Those differences were even smaller or absent in those subjects with advanced PBC. Mean baseline alkaline phosphatase was 2.73 ± 1.95 times the upper limit of normal (× ULN) among responders versus 5.05 ± 3.08 × ULN in non-responders (p < 0.001). CONCLUSIONS: After 6 months of treatment with UDCA, the absence of response by different criteria could properly identify patients who could benefit from early addition of second-line therapies, especially in patients with advanced disease or high baseline liver enzymes levels.

Acute abdomen in intensive care unit: etiology, comorbidity and severity of 1,523 patients / Abdome agudo em unidade de terapia intensiva: etiologia, comorbidades e severidade de 1.523 pacientes

ABSTRACT BACKGROUND: Clinical features and outcomes of patients admitted to the intensive care unit due to acute abdomen are important to be investigated. AIMS: To evaluate the outcomes of critically ill subjects with acute abdomen according to etiology, comorbidity and severity. METHODS: Outcomes of 1,523 patients (878 women, mean age 66±18 years) consecutively admitted to a specialized gastrointestinal intensive care unit with different causes of acute abdomen from January 2012 to December 2019, were retrospectively evaluated according to etiology, comorbidity and severity. RESULTS: The most common causes of acute abdomen were obstructive and inflammatory, particularly large bowel obstruction (27%), small bowel obstruction (18%) and acute pancreatitis (17%). Overall mortality was 13%. Surgery was required in 34% of patients. Median length of stay in the hospital was 9 [1-101] days. On univariate analysis mortality was significantly associated with age, APACHE II, Charlson comorbidity index, requirement for surgery and malignancy (p<0.0001), but only APACHE II, Charlson comorbidity index and surgical interventional remained significant on multivariate analysis. CONCLUSIONS: Critically ill patients admitted to the intensive care unit with acute abdomen constitute a heterogeneous group of subjects with different prognosis. Mortality is more related to the severity of the disease, comorbidity and need for surgery than to the etiology of the acute abdomen.

RESUMO RACIONAL: As características clínicas e os desfechos dos pacientes internados na unidade de terapia intensiva devido ao abdômen agudo são importantes serem investigados. OBJETIVOS: Avaliar os desfechos de indivíduos gravemente doentes com abdômen agudo de acordo com etiologia, gravidade e comorbidade. MÉTODOS: Os desfechos de 1.523 pacientes (878 mulheres, média de idade 66±18 anos) que foram previamente admitidos em uma unidade de terapia intensiva especializada em doenças gastrointestinais, com diferentes causas de abdômen agudo entre janeiro de 2012 e dezembro de 2019, foram avaliados retrospectivamente segundo etiologia, comorbidade e gravidade. RESULTADOS: As causas mais comuns de abdômen agudo foram obstrutivas e inflamatórias, com destaque para obstrução em colon (27%), em intestino delgado (18%) e pancreatite aguda (17%). A mortalidade geral foi de 13%. A cirurgia foi necessária em 34%. A média de permanência no hospital foi de 9 [1-101] dias. Na análise univariada a mortalidade foi significativamente associada à idade, APACHE II, índice de comorbidade de Charlson, necessidade de abordagem cirúrgica e presença de malignidade (p<0,0001), mas apenas APACHE II, índice de comorbidade de Charlson e intervenção cirúrgica permaneceram significativos na análise multivariada. CONCLUSÕES: Pacientes internados na unidade de terapia intensiva com abdômen agudo constituem um grupo heterogêneo de indivíduos com prognóstico diferente. A mortalidade está mais relacionada com a gravidade da doença, comorbidade e necessidade de cirurgia do que com a etiologia do abdome agudo.

MENTAL DISORDERS AND LIVER TRANSPLANTATION: A 2-YEAR COHORT STUDY.

BACKGROUND: Psychosocial assessment is a key component in evaluation for liver transplantation and may affect survival rates and outcomes. OBJECTIVE: The primary aim of this study was to investigate the impact of previous mental disorders and impulsivity on the 2-year surviving rate after liver transplantation. METHODS: We performed a prospective cohort study assessing end-stage liver disease individuals with and without psychiatric comorbidities for 2 years post-transplant. Psychiatric diagnosis was carried out through Mini-Plus 5.0.0 and impulsivity by using Barratt Impulsiveness Scale in the pre-transplant phase. We followed patient's status for 2 years after transplantation. The main outcome was death. We used a logistic regression to evaluate the association of psychiatric comorbidities with death and performed a survival analysis with Kaplan-Meier and Cox regression models. RESULTS: Between June 2010 and July 2014, 93 out of 191 transplant candidates received transplants. From the 93 transplant patients, 21 had psychiatric comorbidities and 72 had not. 25 patients died during the study. The presence of psychiatric comorbidities (P=0.353) and high impulsivity (P=0.272) were not associated to 2-year post transplant death. CONCLUSION: This study found no evidence that the presence of mental disorders and impulsivity worsened prognosis in post-liver transplantation.

Transtorno mental e transplante hepático: um estudo de coorte de 2 anos / Mental disorders and liver transplantation: a 2-year cohort study

ABSTRACT Background Psychosocial assessment is a key component in evaluation for liver transplantation and may affect survival rates and outcomes. Objective The primary aim of this study was to investigate the impact of previous mental disorders and impulsivity on the 2-year surviving rate after liver transplantation. Methods: We performed a prospective cohort study assessing end-stage liver disease individuals with and without psychiatric comorbidities for 2 years post-transplant. Psychiatric diagnosis was carried out through Mini-Plus 5.0.0 and impulsivity by using Barratt Impulsiveness Scale in the pre-transplant phase. We followed patient's status for 2 years after transplantation. The main outcome was death. We used a logistic regression to evaluate the association of psychiatric comorbidities with death and performed a survival analysis with Kaplan-Meier and Cox regression models. Results: Between June 2010 and July 2014, 93 out of 191 transplant candidates received transplants. From the 93 transplant patients, 21 had psychiatric comorbidities and 72 had not. 25 patients died during the study. The presence of psychiatric comorbidities (P=0.353) and high impulsivity (P=0.272) were not associated to 2-year post transplant death. Conclusion: This study found no evidence that the presence of mental disorders and impulsivity worsened prognosis in post-liver transplantation.

RESUMO Contexto: A avaliação psicossocial é essencial na avaliação para transplante hepático; ela pode afetar as taxas de sobrevida e outros desfechos. Objetivo: O objetivo principal deste estudo foi investigar o impacto de transtornos mentais prévios e impulsividade nos índices de sobrevivência após o transplante hepático. Métodos: Foi realizado um estudo prospectivo de coorte com indivíduos em estágio avançado da doença hepática com e sem comorbidades psiquiátricas no pré-transplante, acompanhados por 2 anos após o transplante. Na fase pré-transplante foi realizado o diagnóstico psiquiátrico através do Mini-Plus 5.0.0 e avaliada a impulsividade através da Escala de Impulsividade Barratt. Os pacientes foram acompanhados por 2 anos após o transplante. O desfecho principal foi óbito. Foi utilizada regressão logística para avaliar a associação entre comorbidades psiquiátricas e óbito. Também foi realizada análise de sobrevida com Kaplan-Meier e modelo de regressão Cox. Resultados: Entre junho de 2010 e julho de 2014 foram transplantados 93 pacientes entre os 191 candidatos. Dos 93 pacientes transplantados, 21 tinham comorbidade psiquiátrica e 72 não tinham. Durante o período de acompanhamento houve 25 óbitos. A presença de comorbidade psiquiátrica (P=0.353) e alta impulsividade (P=0.272) não foram associadas a óbito pós-transplante até segundo ano de cirurgia. Conclusão: Este estudo não encontrou evidências de que a presença de transtorno mental e impulsividade pioram o prognóstico pós-transplante hepático.

Perception of Brazilian medical students toward organ donation.

OBJECTIVE: Brazil ranks second in gross numbers of kidney and liver transplantations, but deceased organ donation is still far below the national demand for organs. Apart from a high family refusal rate, another significant barrier is healthcare workers' inappropriate knowledge concerning organ donation and transplantation. Since most of them have recently graduated from university, this study aimed to evaluate the awareness and attitudes of medical students concerning organ donation. METHODS: Between August and September 2021, a web-based survey with 10 overlapping questions was sent to medical students from several Brazilian universities after advertisements on social media. RESULTS: A total of 391 (60% female, mean age: 23 [17-41] years) students answered the survey. Most of them (91%) would like to donate organs in case of death, and 75% have already notified their family. The main reasons for not becoming a donor were fear of body manipulation (n=3) or family reaction (n=2) and religious reasons (n=2). When inquired, 54% were unaware of brain death criteria, and half of them claimed to have never discussed the topic in medical classes. Except for Glasgow coma scale (97%), pupillary (72%), and corneal (53%) reflexes, less than 25% knew other reflexes required for brain death diagnosis. CONCLUSION: Most medical students declared themselves as organ donors, and most informed their families. However, many students have never learned about crucial steps toward organ donation, which may impact their adequate recognition of potential organ donors later in life.

Leukocyte ratios are useful early predictors for adverse outcomes of COVID-19 infection.

Leukocyte biomarkers, including the neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte-(MLR), platelet-to-lymphocyte (PLR) ratios and systemic immune-inflammation index (SII) have been associated with severity and mortality of patients with COVID-19. The purpose of this study was to evaluate the association of baseline leukocyte biomarkers calculated in the emergency department (ED) with the disease severity and mortality. This was a retrospective cohort study that evaluated 1,535 (mean age 57+18 years) patients with SARS-CoV-2 infection in the ED of a single reference center. Outcomes were severity, defined as intensive care unit (ICU) admission requirement, and in-hospital mortality. All leukocyte biomarkers were calculated in the ED before the hospital admission. Their ability to predict the severity and mortality was measured using receiver operating characteristic (ROC) curves. Severity and mortality were observed in 30.9% and 12.6% of the patients, respectively, and were significantly correlated with NLR, MLR, PLR and SII, but only NLR was independently associated with both outcomes on multivariate analysis. Analysis of ROC curves revealed that NLR (0.78 for severity and 0.80 for mortality) and SII (0.77 for severity and 0.75 for mortality) had the best ability to predict mortality, when compared to other ratios. The highest AUC was observed for NLR, employing cut-off points of 5.4 for severity and 5.5 for mortality. Leukocyte biomarkers, particularly NLR, are capable of predicting the severity and mortality of patients with SARS-CoV-2 infection and could be important adjunct tools to identify patients in the ED that are more prone to develop adverse outcomes.

FREQUENCY AND SEVERITY OF LIVER INVOLVEMENT IN HYPERTENSIVE DISORDERS OF PREGNANCY.

BACKGROUND: Pre-eclampsia (PE) and eclampsia (E) are among the leading causes of maternal and fetal morbidity and mortality. Both are associated with an evolving spectrum of liver disorders. OBJECTIVE: The aim of this study was to evaluate the frequency and severity of liver involvement in pregnant women admitted to an intensive care unit with PE/E and to assess its influence on adverse maternal and fetal outcomes. METHODS: All subjects, hospitalized between January 2012 and March 2019, were retrospectively evaluated for clinical and biochemical liver-related abnormalities and their frequencies were subsequently correlated with maternal-fetal outcomes. RESULTS: A total of 210 women (mean age 31±6.4 years, mean gestational age 33.8±4.1 weeks) with PE/E were included in the study. Most of them had severe hypertension (n=184) and symptoms of abdominal pain (48%) and headache (40%). Liver enzymes abnormalities were seen in 49% of the subjects, usually less than five times the upper limit of normal. Subcapsular hemorrhage and spontaneous hepatic rupture were identified in one woman who died. No patient had definitive diagnosis for acute fatty liver of pregnancy, neither acute liver failure. A total of 62% of deliveries occurred before 37 weeks. Fetal mortality was observed in 6 (3%) cases. There was no correlation between mean levels of liver enzymes and maternal and fetal outcomes. CONCLUSION: Biochemical abnormalities of liver enzymes are frequently seen in women with PE/E, but outside the spectrum of HELLP syndrome, they are not associated with adverse maternal and fetal outcomes. Liver-related complications are rare but can be life-threatening.