Coronavirus disease 2019 (COVID-19) in solid organ transplant recipients: A case-control study

Background: Material/Methods: Results: Conclusions: It is unclear whether solid organ transplant (SOT) patients have more severe coronavirus disease 2019 (COVID-19) and worse outcome than the general population. We conducted a case-control study on 32 SOT recipients and 84 non-SOT controls matched for age and sex admitted for confirmed COVID-19. The primary endpoint was in-hospital all-cause mortality rate. Secondary endpoints included severe acute respiratory distress syndrome (ARDS), use of high-flow oxygen therapy, and length of hospital stay. The median (IQR) Charlson comorbidity index (CCI) at admission was significantly higher in SOT recipients (6 (3-8) vs 3 (2-4); P<0.01). Fever was less frequent in SOT recipients (78% vs 94%, P=0.01). SOT recipients had a higher median SaO2/FiO2 at admission (452 [443-462] vs 443 [419-452], P<0.01) and reached the worst SaO2/FiO2 value later during hospitalization 15 (10-21) vs 11 (9-14) days, P=0.01). Both groups had a similar severe ARDS rate during hospitalization (33% vs 28%) (p=0.59). There were no significant differences during hospitalization in terms of highest level of respiratory support needed, or length of hospital stay: 8.5 (5.5-21) vs 11.5 (6.5-16.5) days; P=0.34) in SOT recipients when compared to controls. In-hospital all-cause mortality rates were significantly higher in SOT recipients (21.9% vs 4.7%, P<0.01; OR 1.08; 95% CI 0.10-10.98), but among patients who died, median CCI was similar between groups (8 [6-8] vs 7 [6-8]). In our experience, hospitalized SOT recipients for COVID-19 had higher in-hospital mortality compared to nonSOT patients, probably due to the greater number of underlying comorbidities, and not directly related to chronic immunosuppression

Mast cell-mediated splanchnic cholestatic inflammation

Introduction Splanchnic mast cells increase in chronic liver and in acute-on-chronic liver diseases. We administered Ketotifen, a mast cell stabilizer, and measured the mast cells in the splanchnic organs of cholestatic rats. Material and Methods These groups were studied: sham-operated rats (S; n = 15), untreated microsurgical cholestasic rats (C; n = 20) and rats treated with Ketotifen: early (SK-e; n = 20 and CKe; n = 18), and late (SK-l; n = 15 and CK-l; n = 14). Results The cholestatic rats showed systemic and splanchnic impairments, such as ascites, portal hypertension, and biliary proliferation and fibrosis. The rats also showed a splanchnic increase of TNF-α, IL-1β and MCP-1, and a reduction of IL-4, IL-10 and antioxidants. An increase of VEGF in the ileum and mesenteric lymphatic complex was associated with a liver reduction of TGF-β1. Ketotifen reduces the degree of hepatic insufficiency and the splanchnic inflammatory mediators, as well as VEGF and TGF-ß1 levels. Ketotifen also reduces the connective tissue mast cells in the mesenteric lymphatic complex of cholestatic rats, while increases the hepatic mucosal mast cells. Conclusions In cholestatic rats, Ketotifen improves liver function and ascites, and also reduces pro-inflammatory mediators in the splanchnic area. The decrease in connective tissue mast cells in the mesenteric lymphatic complex due to the administration of Ketotifen would lead to the improvement of the inflammatory splanchnic response, and consequently the abovementioned complications

High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4

[Abstract] Background and Aims. Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real‐world clinical practice, showed high rates of sustained virological response (SVR) in non‐cirrhotic genotype (GT)‐1 and GT‐4 patients. These results were slightly lower in cirrhotic patients. We investigated real‐life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. Methods. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV‐GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January‐2014 and December‐2015. Demographic, clinical, virological and safety data were analysed. Results. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109/L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%‐91.9%) than patients with less advanced liver disease (93.8%‐95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE‐associated discontinuation events occurred in 5.9% and 2.6%. Conclusions. In this large cohort of cirrhotic patients managed in the real‐world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations.Instituto de Salud Carlos III; PI15/0015

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case-control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p <.001) and at 6 months (63.4% vs. 90.1%, p <.001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p =.001) and 6 months (p <.001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17-83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03-1.36), and therapy with renin-angiotensin-aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47-34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline

Safety and Efficacy of Sofosbuvir plus Simeprevir in a Spanish Cohort of 622 Cirrhotic Patients Infected with Genotypes 1 or 4

Presentation Poste

Usefulness of Systemic Venous Ultrasound Protocols in the Prognosis of Heart Failure Patients: Results from a Prospective Multicentric Study

Mortality and re-admission rates for decompensated acute heart failure (AHF) is increasing overall and risk stratification might be challenging. We sought to evaluate the prognostic role of systemic venous ultrasonography in patients hospitalized for AHF. We prospectively recruited 74 AHF patients with a NT-proBNP level above 500 pg/mL. Then, multi-organ ultrasound assessments (lung, inferior vena cava (IVC), pulsed-wave Doppler (PW-Doppler) of hepatic, portal, intra-renal and femoral veins) were performed at admission, discharge, and follow-up (for 90 days). We also calculated the Venous Excess Ultrasound System (VExUS), a new score of systemic congestion based on IVC dilatation and pulsed-wave Doppler morphology of hepatic, portal and intra-renal veins. An intra-renal monophasic pattern (area under the curve (AUC) 0.923, sensitivity (Sn) 90%, specificity (Sp) 81%, positive predictive value (PPV) 43%, and negative predictive value (NPV) 98%), a portal pulsatility > 50% (AUC 0.749, Sn 80%, Sp 69%, PPV 30%, NPV 96%) and a VExUS score of 3 corresponding to severe congestion (AUC 0.885, Sn 80%, Sp 75%, PPV 33%, and NPV 96%) predicted death during hospitalization. An IVC above 2 cm (AUC 0.758, Sn 93.l% and Sp 58.3) and the presence of an intra-renal monophasic pattern (AUC 0. 834, sensitivity 0.917, specificity 67.4%) in the follow-up visit predicted AHF-related re-admission. Additional scans during hospitalization or the calculation of a VExUS score probably adds unnecessary complexity to the assessment of AHF patients. In conclusion, VExUS score does not contribute to the guidance of therapy or the prediction of complications, compared with the presence of an IVC greater than 2 cm, a venous monophasic intra-renal pattern or a pulsatility > 50% of the portal vein in AHF patients. Early and multidisciplinary follow-up visits remain necessary for the improvement of the prognosis of this highly prevalent disease

Prevalence and outcome of portal thrombosis in a cohort of cirrhotic patients undergoing liver transplantation

Introduction: The prevalence of portal vein thrombosis (PVT) in patients that have undergone liver transplantation (LT) is 9.7% (SD 4.5). The aim of our study was to determine the prevalence, assess the factors that are associated with PVT and clarify their association with prognosis in patients with liver cirrhosis (LC) and LT. Aims and methods: From 2005 to 2014, laboratory, radiological and surgical data were collected from patients with LC in our center who had undergone LT for the first time. Results: One hundred and ninety-one patients were included. The mean age was 55 (SD 9), 75.4% of patients were male and 48.7% had HCV. The Child-Pugh scores were A/B/C 41.9%/35.9%/25.5% and the MELD score was 15 (SD 6). Previous decompensations were: ascites (61.4%), hepatic encephalopathy (34.4%), variceal bleeding (25.4%), hepatocellular carcinoma (48.9%) and spontaneous bacterial peritonitis (SPB) (14.3%). The mean post-transplant follow-up was 42 months (0-113). PVT was diagnosed at LT in 18 patients (9.4%). Six patients were previously diagnosed using imaging tests (33.3%): 2 patients (11.1%) by DU and 4 patients (22.2%) by CT scan. All patients with PVT had DU in a mean time of 6 months before LT (0-44) and 90 patients (47.1%) had a CT scan in a median time of 6 months before LT (0-45). PVT was significantly related to the presence of SBP (33.3% vs 12.6%; p = 0.02) and lower levels of albumin (3.1g/dl vs 3.4g/dl; p = 0.05). MELD was higher in patients with PVT (16.6 vs 14.9; p = 0.3). There were no significant differences with regard to the need for transfusion of blood components. Moreover, the surgery time was similar in both groups. PVT correlated with a higher mortality in the first 30 days (8.8% vs 16.7%; p = 0.2). Conclusion: Prior history of SBP and lower levels of albumin were identified as factors associated with PVT. The pre-transplant diagnosis rate is very low and the presence of PVT may have implications for short-term mortality

COVID-19 in hospitalized solid organ transplant recipients in a nationwide registry study

ABSTRACT: Objectives: Underlying immunodeficiency has been associated with worse clinical presentation and increased mortality in patients with COVID-19. We evaluated the mortality of solid organ transplant (SOT) recipients (SOTR) hospitalized in Spain due to COVID-19. Methods: Nationwide, retrospective, observational analysis of all adults hospitalized because of COVID-19 in Spain during 2020. Stratification was made according to SOT status. The National Registry of Hospital Discharges was used, using the International Classification of Diseases, 10th revision coding list. Results: Of the 117,694 adults hospitalized during this period, 491 were SOTR: kidney 390 (79.4%), liver 59 (12%), lung 27 (5.5%), and heart 19 (3.9%). Overall, the mortality of SOTR was 13.8%. After adjustment for baseline characteristics, SOTR was not associated with higher mortality risk (odds ratio [OR] = 0.79, 95% confidence interval [CI] 0.60-1.03). However, lung transplantation was an independent factor related to mortality (OR = 3.26, 95% CI 1.33-7.43), while kidney, liver, and heart transplantation were not. Being a lung transplant recipient was the strongest prognostic factor in SOT patients (OR = 5.12, 95% CI 1.88-13.98). Conclusion: This nationwide study supports that the COVID-19 mortality rate in SOTR in Spain during 2020 did not differ from the general population, except for lung transplant recipients, who presented worse outcomes. Efforts should be focused on the optimal management of lung transplant recipients with COVID-19

Mortality by COVID-19 Before Vaccination - One Year Experience of Hospitalized Patients in Madrid

The aim of the study was to analyze the mortality and characteristics of deceased patients with COVID-19 during the first year of the pandemic. Methods, All admissions owing to COVID-19 at a tertiary hospital in Madrid were analyzed. Three waves were considered: March 2020 to June 2020, July 2020 to November 2020, and December 2020 to April 2021. Results, A total of 3,676 patients were identified. Among inpatients, no differences regarding age, sex, length of admission, or mortality were found between the 3 waves (p >0.05). The overall mortality rate was 12.9%. Among deceased patients, the median age was 82 years and the median Charlson Comorbidity Index was 6. Considering the main predictors for mortality by COVID-19 (age, sex, and concomitant comorbidities), only patients with previous lung disease were more prevalent in the third period (p <0.01). Finally, higher intensive care unit admission rates, a lower rate of patients coming from nursing homes, and a lower rate of patients with dementia were noted in the third period (p <0.05) among deceased patients. Conclusion One year after the onset of the pandemic, the mortality rate of hospitalized patients and the profile of non-survivors have not changed significantly. In the absence of vaccine benefits, advanced age and multiple pathologies are uniform characteristics of non-survivorsThis work has been supported by a grant from Instituto de Salud Carlos III (Expedient number CM19/00223

Pneumonia treated in the internal medicine department: Focus on healthcare-associated pneumonia

Patients with pneumonia treated in the internal medicine department (IMD) are often at risk of healthcare-associated pneumonia (HCAP). The importance of HCAP is controversial. We invited physicians from 72 IMDs to report on all patients with pneumonia hospitalized in their department during 2weeks (one each in January and June 2010) to compare HCAP with community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). We analysed 1002 episodes of pneumonia: 58.9% were CAP, 30.6% were HCAP and 10.4% were HAP. A comparison between CAP, HCAP and HAP showed that HCAP patients were older (77, 83 and 80.5years; p<0.001), had poorer functional status (Barthel 100, 30 and 65; p<0.001) and had more risk factors for aspiration pneumonia (18, 50 and 34%; p<0.001). The frequency of testing to establish an aetiological diagnosis was lower among HCAP patients (87, 72 and 79; p<0.001), as was adherence to the therapeutic recommendations of guidelines (70, 23 and 56%; p<0.001). In-hospital mortality increased progressively between CAP, HCAP and HAP (8, 19 and 27%; p<0.001). Streptococcus pneumoniae was the main pathogen in CAP and HCAP. Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) caused 17 and 12.3% of HCAP. In patients with a confirmed aetiological diagnosis, the independent risk factors for pneumonia due do difficult-to-treat microorganisms (Enterobacteriaceae, P. aeruginosa or MRSA) were HCAP, chronic obstructive pulmonary diseases and higher Port Severity Index. Our data confirm the importance of maintaining high awareness of HCAP among patients treated in IMDs, because of the different aetiologies, therapy requirements and prognosis of this population. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases