The Significance of Serum Tumor Markers CEA, CA19-9, CA125, CA15-3 And AFP in Patients Scheduled for Orthotopic Liver Transplantation: Do Elevated Levels Really Mean Malignancy?

AIM AND BACKGROUND: Preparation of the patients for liver transplantation is a meticulous process and includes evaluation of tumor markers to rule out occult malignancy. Present study evaluated the significance of serum tumor markers in patients bound for liver transplantation due to viral and other etiologies of liver failure.PATIENTS AND METHODS: 381 patientswho underwent liver transplantation were included in the study. Demographic data, Model for End stage.Liver Disease (MELD) scores and serum tumor marker levels were prospectively collected.RESULTS: AFP levels were significantly higher in viral etiologies when compared to other etiologies (p<0.05).Ca 19-9 was significantly higher in viral etiologies (p<0.05). Among the viral etiologies HCV related liver failure had higher carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (Ca 19-9) levels (p<0.05). A correlation was found between increasing MELD scores and serum levels of tumor markers (p<0.05)CONCLUSIONS: Tumor markers such as AFP, CEA, Ca 125 and Ca 19-9 can be elevated in end stage liver disease. Their levels vary according to etiology and severity of disease. The diagnostic capabilities of these markers are reduced in end stage liver disease setting but they contribute to the evaluation of the pathophysiology of chronic liver disease. Transplantation can be performed safely in cases with high tumor marker levels provided that any occult malignancy is ruled out by means of imaging and endoscopic techniques. Tumor markers can guide the physician in determining the severity of liver cirrhosis and further studies are needed to validate such a relationship.

Comparison of pneumonia features in children caused by SARS-CoV-2 and other viral respiratory pathogens.

Pneumonia is a frequent manifestation of COVID-19 in hospitalized children. Methods The study involved 80 hospitals in the SARS-CoV-2 Spanish Pediatric National Cohort. Participants were children <18 years, hospitalized with SARS-CoV-2 community-acquired pneumonia (CAP). We compared the clinical characteristics of SARS-CoV-2-associated CAP with CAP due to other viral etiologies from 2012 to 2019. Results In total, 151 children with SARS-CoV-2-associated CAP and 138 with other viral CAP included. Main clinical features of SARS-CoV-2-associated CAP were cough 117/151(77%), fever 115/151(76%) and dyspnea 63/151(46%); 22/151(15%) patients were admitted to a pediatric intensive care unit (PICU), and 5/151(3%) patients died. Lymphopenia was found in 63/147(43%) patients. Chest X-ray revealed condensation (64/151[42%]) and other infiltrates (87/151[58%]). Compared with CAP from other viral pathogens, COVID-19 patients were older (8 vs.1 year; odds ratio [OR] 1.42 [95% confidence interval, CI 1.23;1.42]), with lower CRP levels (23 vs.48 mg/L; OR 1 [95%CI 0.99;1]), less wheezing (17 vs.53%; OR 0.18 [95%CI 0.11;0.31]) and greater need of mechanical ventilation, MV (7 vs.0.7%, OR 10.8 [95%CI 1.3;85). Patients with non-SARS-CoV-2-associated CAP had a greater need for oxygen therapy (77 vs.44%, OR 0.24 [95%CI 0.14;0.40]). There were no differences in the use of CPAP or HVF or PICU admission between groups. Conclusion SARS-CoV-2-associated CAP in children presents differently to other virus-associated CAP: children are older and rarely have wheezing or high CRP levels; they need less oxygen but more CPAP or MV. However, several features overlap, and differentiating the etiology may be difficult. The overall prognosis is good.

Clinical impact of serum exosomal microRNA in liver fibrosis

Background/aim We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Results NGS data revealed that exosomal miR-660-5p, miR-125a-5p, and miR-122 expression were changed significantly with the progression of liver fibrosis, of which miR-122 exhibited high read counts enough to be used as a biomarker. The level of exosomal miR-122 decreased as the pathologic fibrosis grade progressed and patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P < 0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis especially in combination with fibrosis-4 score and transient elastography. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker was greatly improved. Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of various fibrosis related proteins. Conclusion Exosomal miR-122 may serve as a useful non-invasive biomarker for liver fibrosis, especially in patients with non-viral etiologies of chronic liver disease.

Lung ultrasound may support internal medicine physicians in predicting the diagnosis, bacterial etiology and favorable outcome of community-acquired pneumonia

To assess the usefulness of lung ultrasound (LUS) for identifying community-acquired pneumonia (CAP) among adult patients with suspected lower respiratory tract infection (LRTI) and for discriminating between CAP with different cultural statuses, etiologies, and outcomes. LUS was performed at internal medicine ward admission. The performance of chest X-ray (CXR) and LUS in diagnosing CAP in 410 patients with suspected LRTI was determined. All possible positive results for pneumonia on LUS were condensed into pattern 1 (consolidation + / − alveolar-interstitial syndrome) and pattern 2 (alveolar-interstitial syndrome). The performance of LUS in predicting culture-positive status, bacterial etiology, and adverse outcomes of CAP was assessed in 315 patients. The area under the receiver operating characteristic curve for diagnosing CAP by LUS was significantly higher than for diagnosis CAP by CXR (0.93 and 0.71, respectively; p < 0.001). Pattern 1 predicted CAP with bacterial and mixed bacterial and viral etiologies with positive predictive values of 99% (95% CI, 94–100%) and 97% (95% CI, 81–99%), respectively. Pattern 2 ruled out mortality with a negative predictive value of 95% (95% CI, 86–98%), respectively. In this study, LUS was useful in predicting a diagnosis of CAP, the bacterial etiology of CAP, and favorable outcome in patients with CAP.

Burden of Cardiomyopathic Genetic Variation in Lethal Pediatric Myocarditis

Background - Acute myocarditis (AM) is a well-known cause of sudden death and heart failure, often caused by prevalent viruses. We previously showed that some pediatric AM correlates with putatively damaging variants in genes related to cardiomyocyte structure and function. We sought to evaluate whether deleterious cardiomyopathic variants were enriched among fatal pediatric AM cases in New York City compared to ancestry-matched controls. Methods - Twenty-four children (aged 3 weeks to 20 years) with death due to AM were identified through autopsy records; histologies were reviewed to confirm that all cases met Dallas criteria for AM and targeted panel sequencing of 57 cardiomyopathic genes was performed. Controls without cardiovascular disease were identified from a pediatric database and matched by genetic ancestry to cases using principal components from exome sequencing. Rates of putative deleterious genetic variation (DV) were compared between cases and controls. Where available, AM tissues underwent viral analysis by PCR. Results - DV were identified in 4 of 24 AM cases (16.7%), compared to 2 of 96 age and ancestry-matched controls (2.1%, P=0.014). Viral etiologies were proven for 6 of 8 AM cases (75%), including the one DV+ case where tissue was available for testing. DV+ cases were more likely to be female, have no evidence of chronic inflammation, and associate with sudden cardiac death than DV- cases. Conclusions - Deleterious variants in genes related to cardiomyocyte integrity are more common in children with fatal AM than controls, likely conferring susceptibility. Additionally, genetically-mediated AM may progress more rapidly and be more severe.

DEMOGRAPHIC PROFILE OF ACUTE FEBRILE ENCEPHALOPATHY CASES IN PEDIATRIC AGE GROUP PATIENTS: A STUDY FROM WESTERN RAJASTHAN

Acute Febrile Encephalopathy is a clinical term used to describe patients presenting with short febrile illnesses with altered mental states. Demographic distribution plays an essential role in the diagnosis of viral etiologies. One hundred ve suspected AFE cases were enrolled in the study. A detailed history by predesigned performa and laboratory investigations was obtained for data collection. Viral etiology was diagnosed in 32 (30.48%) cases. The male to female ratio was 1.39:1. Total 56.25% of positive cases were from the lower class, 28.13% from the middle class, and 15.63% from the upper class. 24 (75%) cases from rural, while only 8 (25%) of the urban population showed viral etiologies. In 19 (59.4%) cases were either history of incomplete vaccination or not vaccinated, 13 (40.6%) cases had a history of complete immunization among positive cases. The predominant clinical feature was fever (100%) followed by seizures 66(62.86%), vomiting 37(35.24%), headache 14(13.33%), paresis in 16(15.24%) and altered sensorium in 29(27.62%), respectively. To conclude, the etiologic panorama of AFE varies with several factors such as time and demographical location, age, and immunization status. There is an urgent need to conduct more studies to prole the viral etiologies according to their prevalence in geographical areas so the treatment can be tailored accordingly and prophylaxis treatment or immunization can be boosted in the population at risk of getting the disease.

#61: Antibiotic Use for Community-Acquired Pneumonia Among Hospitalized Children in Japan

Background Judicious use of antimicrobials is the cornerstone of action against antimicrobial resistance. Respiratory tract infections account for over 80% of pediatric antibiotic use in Japan. Antibiotics are generally used empirically for most hospitalized patients with pneumonia although it is becoming clearer that viral etiologies account for approximately 70% of these cases. Defining the characteristics of patients who are managed with a short course of antibiotics and subsequently do well, may lead to setting clinical criteria for early termination of antibiotics. Methods We performed a retrospective descriptive analysis. Medical charts of patients aged 3 months to 18 years, who were admitted with a diagnosis of pneumonia, bronchitis, bronchiolitis, or asthma to the Department of Interdisciplinary medicine at the National Center for Child Health and Development from March 2018 through February 2019 were reviewed. Those who had respiratory symptoms and were started on antibiotics within 48 hours of hospitalization were included. Those who had a focus of infection elsewhere or were immunocompromised were excluded. Results Of the 556 candidates, 80 patients met the criteria. The median age was 1.5 years which included 42.5% (34/80) with comorbidities. Underlying conditions included 9 with trisomy 21, and 8 with perinatal issues. Rapid antigen testing was performed and 7 patients with RSV, 5 patients with influenza, 1 patient with human metapneumovirus were identified. The average duration of antibiotic therapy was 7.2 days (range 2–14 days). There were no statistical differences in the characteristics of patients who received antibiotics for more or less than 5 days. The positivity of the rapid antigen test tended to be higher in those who received antibiotics for a shorter period (25% vs. 15%). There were no differences in the rate of readmission or complications between the two groups. Conclusion We were unable to identify a clear characteristic of patients who received short courses of antibiotics for pneumonia. The trend observed for those who had a point of care testing may suggest that the use of a multiplex PCR testing covering a greater number of pathogens would influence physician behavior in antibiotic use.

Spina bifida, diplomyelia and multiple malformations in a Texel lamb

ABSTRACT: This report described the clinical and pathological aspects of open spina bifida and diplomyelia along with multiple congenital malformations in a Texel lamb. Clinically, paresis of the thoracic limbs, paralysis of the pelvic limbs and a cutaneous opening in the lumbosacral region were observed. At necropsy, there was a focally extensive disruption of the skin associated with an absence of the dorsal portions of the lumbosacral vertebrae. Additionally, diplomyelia of the lumbar segment, mild hydromyelia of thoracic segment, and moderate communicating hydrocephalus of the lateral and third ventricles were noted. Possible viral etiologies (bovine viral diarrhea virus, bluetongue virus, and Schmallemberg virus) were not detected by RT-PCR, and toxic plants were not identified. Therefore, a possible genetic cause may not be discarded.