Long-Term Follow-Up of Kidney Function after Acute Liver Failure or Acute Liver Injury: A Cohort Study.

Introduction: Acute liver failure (ALF) is a rare disease with high mortality. Acute kidney injury (AKI) following ALF is frequent. We assessed AKI impact on long-term kidney function among ALF survivors. Methods: Observational cohort study including consecutive adult (age ≥16 years) patients with ALF or acute liver injury (ALI) admitted to a Portuguese tertiary center intensive care unit (ICU) between October 2013 and February 2020. KDIGO criteria were used to define AKI and chronic kidney disease (CKD). Primary outcome was the estimated glomerular filtration rate (eGFR), defined by the Chronic Kidney Disease Epidemiology Collaboration formula, at least 1 year after index ICU admission. Results: Among 104 patients with ALF (n = 74) or ALI (n = 30), mean (SD) age was 43.7 (18.0) years, and 44 were male. Among all patients (n = 104), following adjustment for age and SOFA score, AKI during the first 7 ICU days (n AKI = 57 and n renal replacement therapy [RRT] = 32) was independently associated with all-cause mortality (adjusted HR [95% CI] 11.61 [1.49-90.34]; p = 0.019). Among hospital survivors with long-term kidney function available (n = 56), median (interquartile range) >1 year eGFR was 95.3 (75.0-107.7) mL/min/1.73 m2 (mean [SD] follow-up of 3.1 [1.6] years). Among these hospital survivors, following adjustment for baseline eGFR, AKI during the first 7 ICU days (n AKI = 19 and n RRT = 10) was not associated with >1 year eGFR (p = 0.15). At least 1 year after index ICU admission, 5 patients developed CKD, none RRT-dependent. Conclusions: Among ALF or ALI survivors, AKI was not associated with significant long-term loss of kidney function.

Introdução: A falência hepática aguda (ALF) é uma doença rara com alta mortalidade. A lesão renal aguda (AKI) após ALF é frequente. Avaliamos o impacto da AKI na função renal de longo prazo entre os sobreviventes de ALF. Métodos: Estudo observacional de coorte incluindo adultos consecutivos (idade ≥16 anos) com FHA ou lesão hepática aguda (ALI) internados numa unidade de cuidados intensivos (UCI) num centro terciário português entre Outubro de 2013 e Fevereiro de 2020. Os critérios KDIGO foram usados para definir AKI e doença renal crónica (CKD). O endpoint primário foi a taxa de filtração glomerular estimada (eGFR), definida pela fórmula da Chronic Kidney Disease Epidemiology Collaboration, pelo menos um ano após a admissão na UCI. Resultados: Entre 104 pacientes com ALF (n = 74) ou ALI (n = 30), a idade média (DP) foi de 43.7 (18.0) anos e 44 eram do sexo masculino. Entre todos os pacientes (n = 104), após ajuste para idade e score SOFA, AKI durante os primeiros 7 dias de UCI (n AKI = 57 e n terapia de substituição renal (RRT) = 32) foi independentemente associada à mortalidade por todas as causas (HR ajustado [IC 95%] 11.61 [1.49­90.34]; p = 0.019). Entre os sobreviventes no hospital com função renal de longo prazo disponível (n = 56), a eGFR mediana (IQR) >1 ano foi de 95.3 (75.0­107.7) mL/min/1.73 m2 (média [DP] de acompanhamento de 3.1 [1.6] anos). Entre esses sobreviventes, após ajuste para eGFR basal, AKI durante os primeiros 7 dias de UCI (n AKI = 19 e n RRT = 10) não se associou com a eGFR >1 ano (p = 0.15). Pelo menos 1 ano após admissão na UCI, 5 pacientes desenvolveram DRC, nenhum dependente de RRT. Conclusões: Entre os sobreviventes de ALF ou ALI, AKI não se associou com perda significativa da função renal a longo prazo.

Ammonia and urea metabolism in acute liver failure: A multicentre cohort study.

BACKGROUND & AIMS: Ammonia is metabolized into urea in the liver. In acute liver failure (ALF), ammonia has been associated with survival. However, urea variation has been poorly studied. METHODS: Observational cohort including ALF patients from Curry Cabral Hospital (Lisbon, Portugal) and Clinic Hospital (Barcelona, Spain) between 10/2010 and 01/2023. The United States ALF Study Group cohort was used for external validation. Primary exposures were serum ammonia and urea on ICU admission. Primary endpoint was 30-day transplant-free survival (TFS). Secondary endpoint was explanted liver weight. RESULTS: Among 191 ALF patients, median (IQR) age was 46 (32; 57) years and 85 (44.5%) were males. Overall, 86 (45.0%) patients were transplanted and 75 (39.3%) died. Among all ALF patients, following adjustment for age, sex, body weight, and aetiology, higher ammonia or lower urea was independently associated with higher INR on ICU admission (p < .009). Among all ALF patients, following adjustment for sex, aetiology, and lactate, higher ammonia was independently associated with lower TFS (adjusted odds ratio (95% confidence interval [CI]) = 0.991 (0.985; 0.997); p = .004). This model predicted TFS with good discrimination (area under receiver operating curve [95% CI] = 0.78 [0.75; 0.82]) and reasonable calibration (R2 of 0.43 and Brier score of 0.20) after external validation. Among transplanted patients, following adjustment for age, sex, actual body weight, and aetiology, higher ammonia (p = .024) or lower (p < .001) urea was independently associated with lower explanted liver weight. CONCLUSIONS: Among ALF patients, serum ammonia and urea were associated with ALF severity. A score incorporating serum ammonia predicted TFS reasonably well.

Sequential Use of High-Volume Plasma Exchange and Continuous Renal Replacement Therapy in Hepatitis B Virus-Related Acute Liver Failure: A Case Report.

Background: Acute liver failure (ALF) may represent an indication for liver transplantation (LT). However, in patients who do not meet the criteria or who have contraindications for LT, support measures remain indicated since they may improve survival. Continuous renal replacement therapy (CRRT) can be considered in the presence of hyperammonemia, 3 times above the upper normal limit, and hepatic encephalopathy (HE), even in the absence of the classic indications. High-volume plasma exchange (HVPE) is an artificial liver support system with proven benefits in ALF, allowing ammonia and inflammatory mediator clearance. Both techniques, HVPE and CRRT, are associated with an increase in transplant-free survival. Case Summary: We share a case of a 51-year-old male, without relevant personal history, diagnosed with severe acute hepatitis B which progressed to ALF, with grade IV HE (West-Haven criteria) and hyperammonemia (423 µg/dL). Due to the simultaneously diagnosed malignant neoplasm, he was not a candidate for LT. After refractory to medical therapy, HVPE was started, followed by CRRT. There was a significant improvement in liver tests, allowing surgical treatment of malignancy. After recovery, the patient returned to his everyday life. Conclusion: The authors present a successful case in which an early and invasive approach to ALF was revealed to be a game changer. The lack of response to the measures instituted, as well as the contraindication for LT, motivated the institution of HVPE and CRRT. Both techniques proved to be an asset, allowing complete clinical recovery, reaffirming their role in ALF.

Background: A insuficiência hepática aguda (IHA) pode constituir uma indicação para transplante hepático (TH). Contudo, nos doentes que não cumprem os critérios ou que apresentam contraindicação para TH, as medidas de suporte continuam indicadas dado que podem ter benefício na sobrevivência. A terapêutica de substituição da função renal (TSFR) pode ser considerada na presença de hiperamonémia, superior a três vezes do limite superior do normal, e encefalopatia hepática (EH), mesmo na ausência das indicações clássicas. A plasmaferese de alto volume (PFAV) é um sistema de suporte artificial ao fígado (SSAF) com benefícios comprovados na IHA, permitindo a clearance de amónia bem como de mediadores inflamatórios. Ambas as técnicas, PFAV e TSFR, estão associadas ao aumento da sobrevivência livre de transplante. Resumo do caso: Apresentamos o caso de um homem de 51 anos, sem antecedentes pessoais de relevo, com o diagnóstico de hepatite B aguda grave que progrediu para IHA, com EH grau IV (critérios de West-Haven) e hiperamonémia (423 µg/dL). Devido ao diagnóstico simultâneo de neoplasia maligna, o doente não foi candidato a TH. Após refratariedade ao tratamento médico instituído, iniciou-se PFAV, seguida de TSFR. Verificou-se melhoria significativa das provas hepáticas, permitindo o tratamento cirúrgico da neoplasia. Após recuperação, o doente regressou ao seu quotidiano. Conclusão: Os autores apresentam um caso de sucesso em que uma abordagem precoce e invasiva revelou-se game-changer. A refratariedade às medidas instituídas, bem como a contraindicação ao TH, motivaram a instituição de HVPE e CRRT. Ambas as técnicas revelaram-se uma mais-valia permitindo a recuperação clínica total, reafirmando o seu papel na IHA.

The Impact of Donor Risk Index, Recipients' and Operative Characteristics on Post Liver Transplant One-Year Graft Failure: A Cohort Analysis.

Background and Aims: The donor risk index (DRI) quantifies donor-related characteristics potentially associated with increased risk of early graft failure. We aimed to assess the impact of the DRI, recipient and perioperative factors on post liver transplant (LT) outcomes. Methods: This was a single-center retrospective cohort study including all adult (≥18 years) patients who underwent LT from 01/2019 to 12/2019 at Curry Cabral Hospital, Lisbon, Portugal. Primary endpoint was 1-year graft failure post LT. Associations were studied with logistic regression. Results: A total of 131 cadaveric donor LT procedures were performed in 116 recipients. Recipients' median (IQR) age was 57 (47-64) years and 101/131 (77.1%) were males. Cirrhosis was the underlying etiology in 95/131 (81.2%) transplants. Based on 8 predefined donors' characteristics, median (IQR) DRI was 1.96 (1.67-2.16). Following adjustment for MELDNa score pre LT and SOFA score (adjusted odds ratio [aOR], 95% confidence interval [CI] = 0.91 [0.56-1.47]) or lactate (aOR [95% CI] = 2.76 [0.71-10.7]) upon intensive care unit (ICU) admission post LT, DRI was not associated with 1-year graft failure. However, higher SOFA score (aOR [95% CI] = 1.20 [1.05-1.37]) or lactate (aOR [95% CI] = 1.27 [1.10-1.46]) upon ICU admission post LT were independently associated with higher odds of 1-year graft failure. Conclusions: In a recent cohort of patients who underwent LT, DRI, despite being high, was not associated with 1-year graft failure, but SOFA score or lactate upon ICU admission post LT were.

Introdução: O índice de risco do dador (DRI) quantifica as características relacionadas com o dador potencialmente associadas com risco acrescido de falência precoce do enxerto. Procurou-se avaliar o impacto do DRI e factores relacionados com os receptores e cirurgia nos resultados clínicos após transplante hepático (LT). Materiais e Métodos: Estudo coorte retrospectivo de centro único incluindo todos os doentes adultos (≥18 anos) que receberam LT entre 01/2019 e 12/2019 no Hospital Curry Cabral, Lisboa, Portugal. O endpoint primário foi a falência do enxerto após um ano do LT. As associações foram estudadas com regressão logística. Resultados: Um total de 131 transplantes de dadores cadavéricos foram realizados em 116 receptores. A idade mediana (IQR) destes foi 57 (47­64) anos e 101/131 (77.1%) eram homens. A cirrose foi a etiologia subjacente em 95/131 (81.2%) transplantes. Com base nas 8 características dos dadores predefinidas, o DRI mediano (IQR) foi 1.96 (1.67­2.16). Após ajuste para o score MELDNa pre LT e o score SOFA (odds ratio ajustado [aOR], intervalo de confiança 95% [CI] = 0.91 [0.56­1.47]) ou o lactato (aOR [95% CI] = 2.76 [0.71­10.7]) após admissão na unidade de cuidados intensivos (ICU) pós LT, o DRI não se associou com a falência do enxerto um ano depois do LT. Contudo, um maior score SOFA (aOR [95% CI] = 1.20 [1.05­1.37]) ou lactato (aOR [95% CI] = 1.27 [1.10­1.46]) após admissão na ICU depois do LT associaram-se independentemente com a falência do enxerto um ano depois do LT. Conclusões: Num coorte recente de doentes submetidos a LT, o DRI, apesar de alto, não se associou com a falência precoce do enxerto precoce. Contudo, o score SOFA ou lactato após admissão na ICU depois do LT associaram-se com a falência precoce do enxerto.

Continuous passive paracentesis versus large-volume paracentesis in the prevention and treatment of intra-abdominal hypertension in the critically ill cirrhotic patient with ascites (COPPTRIAHL): study protocol for a randomized controlled trial.

BACKGROUND: Critically ill patients with cirrhosis and ascites are at high risk for intra-abdominal hypertension (IAH) which increases mortality. Clinical guidelines recommend maintaining intra-abdominal pressure (IAP) below 16 mmHg; nonetheless, more than three quarters of critically ill patients with cirrhosis develop IAH during their first week of ICU stay. Standard-of-care intermittent large-volume paracentesis (LVP) relieves abdominal wall tension, reduces IAP, optimizes abdominal perfusion pressure, and is associated with short-term improvement in renal and pulmonary dysfunction. However, there is no evidence of the superiority of different paracentesis strategies in the prevention and treatment of IAH in critically ill patients with cirrhosis. This trial aims to compare the outcomes of continuous passive paracentesis versus LVP in the prevention and treatment of IAH in patients with cirrhosis and ascites. METHODS: An investigator-initiated, open label, randomized controlled trial, set in a general ICU specialized in liver disease, was initiated in August 2022, with an expected duration of 36 months. Seventy patients with cirrhosis and ascites will be randomly assigned, in a 1:1 ratio, to receive one of two methods of therapeutic paracentesis. A stratified randomization method, with maximum creatinine and IAP values as strata, will homogenize patient baseline characteristics before trial group allocation, within 24 h of admission. In the control group, LVP will be performed intermittently according to clinical practice, with a maximum duration of 8 h, while, in the intervention group, continuous passive paracentesis will drain ascitic fluid for up to 7 days. The primary endpoint is serum creatinine concentration, and secondary endpoints include IAP, measured creatinine clearance, daily urine output, stage 3 acute kidney injury and multiorgan dysfunction assessed at day 7 after enrollment, as well as 28-day mortality rate and renal replacement therapy-free days, and length-of-stay. Prespecified values will be used in case of renal replacement therapy or, beforehand ICU discharge, liver transplant and death. Safety analysis will include paracentesis-related complication rate and harm. Data will be analyzed with an intention-to-treat approach. DISCUSSION: This is the first trial to compare the impact of different therapeutic paracentesis strategies on organ dysfunction and outcomes in the prevention and treatment of IAH in critically ill patients with cirrhosis and ascites. TRIAL REGISTRATION: ClinicalTrials.gov NCT04322201 . Registered on 20 December 2019.

Candida auris in Intensive Care Setting: The First Case Reported in Portugal.

Candida auris is an opportunistic human pathogen that has rapidly spread to multiple countries and continents and has been associated with a high number of nosocomial outbreaks. Herein, we report the first case of C. auris in Portugal, which was associated with a patient transferred from Angola to an ICU in Portugal for liver transplantation after a SARS-CoV-2 infection. C. auris was isolated during the course of bronchoalveolar lavage, and it was subjected to antifungal susceptibility testing and whole-genome sequence analysis. This isolate presents low susceptibility to azoles and belongs to the genetic clade III with a phylogenetic placement close to African isolates. Although clade III has already been reported in Europe, taking into account the patient's clinical history, we cannot discard the possibility that the patient's colonization/infection occurred in Angola, prior to admission in the Portuguese hospital. Considering that C. auris is a fungal pathogen referenced by WHO as a critical priority, this case reinforces the need for continuous surveillance in a hospital setting.

Early serum ammonia variation in critically ill patients with cirrhosis: A multicentre cohort study.

BACKGROUND: Serum ammonia variation in critically ill patients with cirrhosis has been poorly studied. AIM: To describe and assess the impact of serum ammonia variation in these patients' outcomes. METHODS: We studied patients ≥18 years old admitted to the intensive care units (ICUs) at University of Alberta Hospital (Edmonton, Canada) and Curry Cabral Hospital (Lisbon, Portugal; derivation cohort, n = 492) and Northwestern University Hospital (Chicago, USA; validation cohort, n = 600) between January 2010 and December 2021. Primary exposure was ICU days 1-3 serum ammonia. Primary endpoint was all-cause hospital mortality. RESULTS: In the derivation cohort, 330 (67.1%) patients were male and median (IQR) age was 57 (50-63) years. On ICU day 1, median ammonia was higher in patients with grade 3/4 hepatic encephalopathy (HE) than those with grade 2 HE or grade 0/1 HE (112 vs. 88 vs. 77 µmoL/L, respectively; p < 0.001). Furthermore, medium ammonia was higher in hospital non-survivors than survivors (99 vs. 86 µmol/L; p < 0.030). Following adjustment for significant confounders (age, HE, vasopressor use and renal replacement therapy delivery), higher ICU day 2 ammonia was independently associated with higher hospital mortality (adjusted OR per each 10 µmoL/L increment [95% CI] = 1.11 [1.01-1.21]; p = 0.024). In the validation cohort, this model with serial ammonia (ICU days 1 and 3) predicted hospital mortality with reasonably good discrimination (c-statistic = 0.73) and calibration (R2 = 0.19 and Brier score = 0.17). CONCLUSIONS: Among patients with cirrhosis in the ICU, early serum ammonia variation was independently associated with hospital mortality. In this context, serial serum ammonia may have prognostic value.

Fatal Case of Progressive Mpox in a Patient with AIDS-Viral Enteropathy and Malabsorption Demanding the Use of Full Parenteral ARV and Endovenous Cidofovir.

We report a fatal case of disseminated mpox infection that progressed over more than three months in an HIV-infected patient with acquired immunodeficiency syndrome (AIDS). Mucocutaneous, pleuropulmonary, central nervous system, and gastrointestinal involvement was documented. This course of disease resembles progressive vaccinia, a formerly reported disease caused by uncontrolled replication of smallpox vaccination orthopoxviruses in immunosuppressed patients. Severe small bowel involvement jeopardized normal oral tecovirimat and antiretroviral therapy absorption. This problem prompted the use of full parenteral antiretrovirals and endovenous cidofovir. Although a remarkable decrease in HIV viral load occurred in six days, mpox infection continued to progress, and the patient died of septic shock. This case offers new clinical insights on the presentation of severe disease in AIDS patients. Moreover, this case alerts for the need for prompt therapy initiation in patients at risk of ominous clinical progression.

Variation in the Care of Acute Liver Failure: A Survey of Intensive Care Professionals.

INTRODUCTION: Acute liver failure (ALF) is a rare disease with potentially high mortality. We sought to assess the individual approach to ALF by intensive care unit (ICU) professionals. METHODS: Cross-sectional survey of ICU professionals. Web-based survey capturing data on respondents' demographics, characteristics of patients with ALF admitted to ICU, and their management. RESULTS: Among 204 participants from 50 countries, 140 (68.6%) worked in Europe, 146 (71.6%) were intensivists, 142 (69.6%) admitted <25 patients with ALF per year, and 166 (81.8%) reported <25% of patients had paracetamol-related ALF. On patients' outcomes, 126 (75.0%) reported an emergency liver transplantation (ELT) rate <25% and 140 (73.3%) a hospital mortality rate <50%. The approach to ALF in the ICU varied with age, region, level of training, type of hospital, and etiology (prescribing N-acetylcysteine for paracetamol toxicity, triggers for endotracheal intubation, measurement of and strategies for lowering serum ammonia, extracorporeal device deployment, and prophylactic antibiotics). CONCLUSIONS: The management of patients with ALF by ICU professionals differed substantially concerning the relevant clinical measures taken. Further education and high-quality research are warranted.

INTRODUÇÃO: A falência hepatica aguda (ALF) é uma doença rara potencialmente letal. Pretendeu-se avaliar a abordagem individual à ALF por profissionais da Unidade de Cuidados Intensivos (UCI). MÉTODOS: Inquérito transversal de profissionais da UCI. Inquérito online capturando informação da demografia dos respondedores, características dos doentes com ALF admitidos na UCI e sua abordagem. RESULTADOS: Entre 204 participantes de 50 países, 140 (68.6%) trabalhavam na Europa, 146 (71.6%) eram inten-sivistas, 142 (62.9%) admitiam <25 doentes com ALF por ano, e 166 (81.8%) reportaram <25% dos doentes com ALF relacionada com paracetamol. Quanto aos resultados dos doentes, 126 (75.0%) reportaram uma taxa de transplantação hepatica emergente (ELT) <25% e 140 (73.3%) uma taxa de mortalidade hospitalar <50%. A abordagem da ALF variou com a idade, região, nível de treino, tipo de hospital, ou etiologia nos seguintes tópicos: prescrição de N-acetil-cisteína, critérios de intubação orotraqueal, medição e estratégias de control da amoniémia, uso de técnicas extracorporais, e a prescrição de antibióticos profilácticos. CONCLUSÕES: A abordagem de doentes com ALF por profissionais da UCI diferiu substancialmente em aspectos clínicos importantes. Educação e investigação de qualidade adicionais serão necessárias.

Hemodialysis catheter heparin lock related bleeding: Hemorrhagic shock every other day.

Catheter dysfunction is an important cause of catheter loss. In order to prevent this, locking solutions with minimal risk of systemic anticoagulation are used to ensure catheter patency. At present the most commonly used solutions are either heparin or sodium citrate. According to the literature use of sodium citrate may be advantageous in reducing bleeding events. We report a case of hemorrhagic shock following hemodialysis catheter lock with heparin, reversed after switching solution to sodium citrate.

Gut Microbiota Diversity and C-Reactive Protein Are Predictors of Disease Severity in COVID-19 Patients.

The risk factors for coronavirus disease 2019 (COVID-19) severity are still poorly understood. Considering the pivotal role of the gut microbiota on host immune and inflammatory functions, we investigated the association between changes in the gut microbiota composition and the clinical severity of COVID-19. We conducted a multicenter cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: (1) the WHO Clinical Progression Scale-mild, 19 (16.5%); moderate, 37 (32.2%); or severe, 59 (51.3%), and (2) the location of recovery from COVID-19-ambulatory, 14 (household isolation, 12.2%); hospitalized in ward, 40 (34.8%); or hospitalized in the intensive care unit, 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing, and the data obtained were further related to the clinical parameters of COVID-19 patients. The risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models. In comparison to mild COVID-19 patients, the gut microbiota of moderate and severe patients have: (a) lower Firmicutes/Bacteroidetes ratio; (b) higher abundance of Proteobacteria; and (c) lower abundance of beneficial butyrate-producing bacteria such as the genera Roseburia and Lachnospira. Multivariable regression analysis showed that the Shannon diversity index [odds ratio (OR) = 2.85, 95% CI = 1.09-7.41, p = 0.032) and C-reactive protein (OR = 3.45, 95% CI = 1.33-8.91, p = 0.011) are risk factors for severe COVID-19 (a score of 6 or higher in the WHO Clinical Progression Scale). In conclusion, our results demonstrated that hospitalized patients with moderate and severe COVID-19 have microbial signatures of gut dysbiosis; for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker of COVID-19 severity.

Optic Nerve Sheath Diameter in Acute Liver Failure: A Prospective Cohort Study.

INTRODUCTION: Acute liver failure (ALF) is a rare disease that may lead to cerebral edema and death. An increased optic nerve sheath diameter (ONSD) may reflect an early increase in intracranial pressure. We assessed the feasibility and safety of the ONSD measurement and its association with outcomes in patients with ALF. METHODS: This was an open-label prospective cohort study including adult patients with ALF admitted to a liver-specialized intensive care unit (ICU) in an academic center between October 2018 and February 2020 (among 24): 20 as intention-to-treat and 17 as per-protocol analyses. The ONSD measurement (primary exposure) used an ultrasound transducer (3 determinations on each eye per patient). The primary outcome was hospital mortality. RESULTS: Among the 20 patients, 11 (55.0%) were females and the mean age was 45 ± 16 years. On the day of ONSD measurement (median 32.4 h post-ICU admission; IQR 19.8-59.8): 8 patients (40.0%) were in a coma, the mean international normalized ratio (INR) was 3.3 ± 1.4, median bilirubin was 12.3 mg/dL (IQR 4.7-24.5), mean ammonia was 163 ± 101 µmol/L, and mean SOFA score was 11 ± 5. The mean bilateral ONSD was 5.6 ± 0.7 mm, with a very good correlation between right and left eyes (Pearson's r = 0.90). Ten (50.0%) patients were transplanted and 13 (65.0%) patients survived the hospital stay (all with a 2-month extended Glasgow Outcome Scale of 8). The mean ONSD was significantly higher for hospital non-survivors than survivors both in the intention-to-treat (6.2 vs. 5.3 mm; p = 0.004) and per-protocol (6.2 vs. 5.2 mm; p = 0.004) analyses. No adverse effects from ONSD measurements were reported. CONCLUSIONS: In patients with ALF, a higher ONSD was associated with higher hospital mortality. ONSD measurement is feasible and safe and may have prognostic value.

INTRODUÇÃO: A falência hepatica aguda (ALF) é uma doença rara que pode complicar com edema cerebral e morte. O aumento do diâmetro da bainha do nervo óptico (ONSD) pode reflectir um aumento precose da pressão intracraniana. Avaliámos a viabilidade e segurança da medição do ONSD e a sua associação com os resultados de doentes com ALF. MÉTODOS: Coorte prospectivo aberto incluindo doentes adultos com ALF admitidos numa unidade de cuidados intensivos (ICU) especializada em fígado entre 10/2018 e 02/2020 (em 24): 20 como análise intenção-de-tratar e 17 como análise por-protocolo. A medição do ONSD (exposição primária) foi realizada com um transdutor ultra-sónico (3 medições em cada olho por doente). O resultado primário foi a mortalidade hospitalar. RESULTADOS: Entre 20 doentes, 11 (55.0%) eram mulheres e a idade média (SD) foi 45 (16) anos. No dia da medição do ONSD (mediana (IQR) de 32.4 (19.8­59.8) horas pós admissão na ICU): coma em 8 (40.0%) doentes, INR médio (SD) de 3.3 (1.4), bilirrubina mediana (IQR) de 12.3 (4.7­24.5) mg/dL, amónia média (SD) de 163 (101) µmol/L, e SOFA médio (SD) de 11 (5). O ONSD bilateral médio (SD) foi de 5.6 (0.7) mm, com boa correlação entre os olhos (Pearson r = 0.90). Dez (50.0%) doentes foram transplantados e 13 (65.0%) sobreviveram à hospitalização (todos com escala de Glasgow Outcome aos 2 meses de 8). O ONSD médio foi significativamente maior nos não-sobreviventes do que nos sobreviventes quer na análise intenção-de-tratar (6.2 mm vs. 5.3 mm; p = 0.004) quer na análise por-protocolo (6.2 mm vs. 5.2 mm; p = 0.004). Não se registaram efeitos adversos. CONCLUSÕES: Em doentes com ALF, maior ONSD esteve associado com maior mortalidade hospitalar. A medição do ONSD é viável, segura, e poderá ter valor prognóstico.

Positive fluid balance was associated with mortality in patients with acute-on-chronic liver failure: A cohort study.

PURPOSE: We aimed to study the effect of FB in the outcomes of critically-ill patients with cirrhosis. MATERIALS: Retrospective analysis of all adult consecutive admissions of patients with cirrhosis and organ failures to the Intensive Care Unit (ICU) at Curry Cabral Hospital (Lisbon, Portugal) and University of Alberta Hospital (Edmonton, Canada) on 08/2013-08/2017. Primary exposure was FB at 3 and 7 days post ICU admission. Primary endpoint was hospital mortality. RESULTS: Amongst 333 patients, median age was 56 years and 67.6% were men. Median MELD, APACHEII, CLIF-SOFA, and CLIF-C-ACLF scores on ICU admission were 27, 28, 14, and 54, respectively. ICU and hospital mortality rates were 33.0% and 49.2%, respectively. While median FB at 3 days post ICU admission (+5.46 l vs. +6.62 l; P = 0.74) was not associated with hospital mortality, higher median FB at 7 days post ICU admission (+13.50 l vs. +6.90 l; P = 0.036) was associated with higher hospital mortality. This association remained significant (OR 95%CI = 1.04 [1.01;1.07] per each l) after adjustment for confounders (age, ascites, infection, lactate, and number of organ failures). CONCLUSIONS: FB may be a therapeutic target that helps to improve the outcomes of patients with acute-on-chronic liver failure. This data may inform future clinical trials.

Is the efficacy of remdesivir so different from that of lopinavir-ritonavir in severe COVID-19? The answer by real time-PCR: a narrative review.

This letter discusses the efficacy of current antiviral therapy used in severe COVID-19 infection. Since the first severe cases were documented, several antiviral options have been studied as adjuncts to standard supportive care [1, 2]. Firstly, the combination of lopinavir-ritonavir resurrected from SARS and MERS outbreaks and soon abandoned after the publication of several trials like the randomized controlled trial RECOVERY, which concluded that it was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progression to invasive mechanical ventilation or death [3]. Remdesivir is currently the only antiviral agent approved for the treatment of COVID-19. It is recommended for use in hospitalized patients who require supplemental oxygen. However, it is not routinely recommended for patients who require mechanical ventilation due to the lack of data showing any benefit at this advanced stage of the disease [4-6].

Kawasaki-like Syndrome as an Emerging Complication of SARS-CoV-2 Infection in Young Adults.

BACKGROUND: Kawasaki-like syndrome occurring in children during the COVID-19 pandemic has been labelled multisystem inflammatory syndrome in children (MIS-C) by the CDC and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS) by the ECDC. CASE REPORT: We report the case of an 18-year-old male patient presenting with a 72-hour history of abdominal pain, fever, erythematous skin rash, vomiting and diarrhoea. Examination showed he also had shock and he was first thought to have oedematous cholecystitis. SARS-CoV-2 infection was also diagnosed. He was admitted to the ICU, and echocardiography showed cardiac dysfunction, with a low ejection fraction and low cardiac index. High-sensitivity troponin serum levels were elevated. The patient received inotropic and vasopressor support. As he fulfilled several criteria for MIS-C/PIMS-TS, he was administered acetylsalicylic acid, corticosteroids and immunoglobulin, with a good clinical response. CONCLUSION: This case emphasizes how this severe presentation of COVID-19 can easily be misdiagnosed if the clinician is less aware of this syndrome in younger patients. LEARNING POINTS: SARS-CoV-2 infection is a diagnostic challenge in some patients with atypical clinical presentations, who may have MIS-C/PIMS-TS.Physicians should be aware of this condition when evaluating teenagers and young adults with COVID-19.