Are corticosteroids safe in adolescent and adult patients with infectious mononucleosis? A retrospective cohort study.

BACKGROUND AND AIM: The use of systemic corticosteroids during Epstein-Barr virus (EBV)-induced infectious mononucleosis is a controversial but widespread practice. We aimed to investigate the frequency of complications in adolescents and adults with infectious mononucleosis in relation to the use of corticosteroids. METHODS: We reviewed the clinical records of 396 patients admitted to the hospital with infectious mononucleosis (52.0% male; median age, 19 years; range, 15-87 years), with a focus on both short-term (infectious and non-infectious) and long-term (hematological malignancies) complications in relation to corticosteroid use. RESULTS: A total of 155 (38.6%) patients received corticosteroids at some point during infectious mononucleosis. Corticosteroid use was significantly (P≤0.002) associated with sore throat, lymphadenopathy, leukocytosis, and with antibiotics use (mainly indicated after suspicion of tonsillar bacterial superinfection). Overall, 139/155 (89.7%) patients who were treated with corticosteroids also received antibiotics either before or during hospitalization, compared with 168/241 (69.7%) patients who did not. The frequency of short-term severe complications, either infectious (peritonsillar-parapharyngeal abscess or bacteremia) or non-infectious (splenic rupture, severe thrombocytopenia, myopericarditis, or lymphocytic meningitis) were similar in patients receiving and not receiving corticosteroids. After a median of 15 years of follow-up, only one Hodgkin's lymphoma was diagnosed, in a patient who was not treated with corticosteroids during infectious mononucleosis. CONCLUSIONS: The use of systemic corticosteroids during EBV-induced infectious mononucleosis is generally safe, at least with concomitant antibiotic therapy. However, this should not encourage the use of corticosteroids in this context, given that their efficacy has yet to be demonstrated.

Frank's Sign and Cardiovascular Risk: An Observational Descriptive Study.

PURPOSE: This study was undertaken to analyze the relationship between the diagonal earlobe crease and the main indices of cardiovascular risk, considering the crease's anatomical variations. METHODS: The study group consisted of 1050 adults residing in Spain. Participants underwent the following determinations: age, sex, body mass index, smoking habit, blood pressure, glycemia, glycated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and cardiovascular events. Cardiovascular risk was calculated applying the Framingham-Anderson equation, the Systematic Coronary Risk Evaluation equation, and the Atherosclerotic Cardiovascular Disease Risk Score calculator. Both earlobes were examined, recording diagonal earlobe crease presence, length and depth, and presence of accessory creases. Results were analyzed by using chi-square test, Student's t test, analysis of variance, and Mann-Whitney or Kruskal-Wallis tests. To extract the functions of cardiovascular risk, a script in R was created (https://cran.r-project.org/). RESULTS: The estimated cardiovascular mortality risk was significantly higher in individuals who presented diagonal earlobe crease (P < .001). The number of individuals with moderate, high, or very high cardiovascular risk increased significantly as the presence of the crease increased (23.8% had no crease, 35.6% had unilateral creases, and 58% had bilateral creases; P < .001). The mean cardiovascular risk estimated was significantly higher for individuals with longest and deepest diagonal earlobe crease (P < .001 and P < .001, respectively), and with accessory creases (P < .001). CONCLUSIONS: The diagonal earlobe crease is independently associated with higher cardiovascular risk scores, especially when the crease is complete, bilateral, deep, and has accessory creases.

Reproducibility of continuous glucose monitoring results under real-life conditions in an adult population: a functional data analysis.

Continuous glucose monitoring systems (CGM) are a very useful tool to understand the behaviour of glucose in different situations and populations. Despite the widespread use of CGM systems in both clinical practice and research, our understanding of the reproducibility of CGM data remains limited. The present work examines the reproducibility of the results provided by a CGM system in a random sample of a free-living adult population, from a functional data analysis approach. Functional intraclass correlation coefficients (ICCs) and their 95% confidence intervals (CI) were calculated to assess the reproducibility of CGM results in 581 individuals. 62% were females 581 participants (62% women) mean age 48 years (range 18-87) were included, 12% had previously been diagnosed with diabetes. The inter-day reproducibility of the CGM results was greater for subjects with diabetes (ICC 0.46 [CI 0.39-0.55]) than for normoglycaemic subjects (ICC 0.30 [CI 0.27-0.33]); the value for prediabetic subjects was intermediate (ICC 0.37 [CI 0.31-0.42]). For normoglycaemic subjects, inter-day reproducibility was poorer among the younger (ICC 0.26 [CI 0.21-0.30]) than the older subjects (ICC 0.39 [CI 0.32-0.45]). Inter-day reproducibility was poorest among normoglycaemic subjects, especially younger normoglycaemic subjects, suggesting the need to monitor some patient groups more often than others.

Association of a Novel Homozygous Variant in ABCA1 Gene with Tangier Disease.

Tangier disease (TD) is a rare autosomal recessive disorder caused by a variant in the ABCA1 gene, characterized by significantly reduced levels of plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-I). TD typically leads to accumulation of cholesterol in the peripheral tissues and early coronary disease but with highly variable clinical expression. Herein, we describe a case study of a 59-year-old male patient with features typical of TD, in whom a likely pathogenic variant in the ABCA1 gene was identified by whole-exome sequencing (WES), identified for the first time as homozygous (NM_005502.4: c.4799A>G (p. His1600Arg)). In silico analysis including MutationTaster and DANN score were used to predict the pathogenicity of the variant and a protein model generated by SWISS-MODEL was built to determine how the homozygous variant detected in our patient may change the protein structure and impact on its function. This case study describes a homozygous variant of the ABCA1 gene, which is responsible for a severe form of TD and underlines the importance of using bioinformatics and genomics for linking genotype to phenotype and better understanding and accounting for the functional impact of genetic variations.

Hematological Abnormalities Beyond Lymphocytosis During Infectious Mononucleosis: Epstein-Barr Virus-Induced Thrombocytopenia.

Background: Thrombocytopenia during Epstein-Barr virus mononucleosis is well-known; however, no recent series have investigated its frequency, associated factors, and evolution. The present study aimed to investigate platelet count characteristics in adult patients with infectious mononucleosis. Methods: We reviewed the clinical records of 400 patients admitted to the hospital with infectious mononucleosis (52.0% male; median age, 19 years [range, 15-87 years]), focusing on blood platelet counts, thrombocytopenia prevalence and outcomes. Results: Thrombocytopenia (platelet count ≤150 ×109/L) was present in 119 (29.7%) patients. Thirty-two (8.0%) patients showed platelet counts lower than 100 ×109/L. Thrombocytopenia was severe (platelets <50 ×109/L) in 6 (1.5%) patients. Thrombocytopenia was associated with a lower frequency of typical mononucleosis symptoms such as sore throat and lymphadenopathy, lower frequency of positive heterophil antibodies, higher serum bilirubin concentration and prothrombin time, lower blood leukocyte and lymphocyte count, lower concentration of serum immunoglobulin G and immunoglobulin A concentrations, and larger spleen size. Thrombocytopenia normalized quickly during follow-up. Only 2 cases required specific therapy. Platelet counts significantly increased during follow-up, even in cases without baseline thrombocytopenia. There were no significant hemorrhagic complications. Conclusions: Transient thrombocytopenia is common during infectious mononucleosis in adult patients. Patients with thrombocytopenia have distinct clinical and biological features; it is typically mild during infectious mononucleosis. Cases of severe thrombocytopenia are rare and were not associated with hemorrhagic complications in this series.

Implications of Inflammatory and Oxidative Stress Markers in the Attenuation of Nocturnal Blood Pressure Dipping.

To date, no model has jointly encompassed clinical, inflammatory, and redox markers with the risk of a non-dipper blood pressure (BP) profile. We aimed to evaluate the correlation between these features and the main twenty-four-hour ambulatory blood pressure monitoring (24-h ABPM) indices, as well as to establish a multivariate model including inflammatory, redox, and clinical markers for the prediction of a non-dipper BP profile. This was an observational study that included hypertensive patients older than 18 years. We enrolled 247 hypertensive patients (56% women) with a median age of 56 years. The results showed that higher levels of fibrinogen, tissue polypeptide-specific antigen, beta-2-microglobulin, thiobarbituric acid reactive substances, and copper/zinc ratio were associated with a higher risk of a non-dipper BP profile. Nocturnal systolic BP dipping showed a negative correlation with beta-globulin, beta-2-microglobulin, and gamma-globulin levels, whereas nocturnal diastolic BP dipping was positively correlated with alpha-2-globulin levels, and negatively correlated with gamma-globulin and copper levels. We found a correlation between nocturnal pulse pressure and beta-2-microglobulin and vitamin E levels, whereas the day-to-night pulse pressure gradient was correlated with zinc levels. Twenty-four-hour ABPM indices could exhibit singular inflammatory and redox patterns with implications that are still poorly understood. Some inflammatory and redox markers could be associated with the risk of a non-dipper BP profile.

Jaundice in relation to immune activation during Epstein-Barr virus-induced infectious mononucleosis.

BACKGROUND: Liver involvement during infectious mononucleosis is common, but jaundice is considered rare. This study aimed to investigate serum bilirubin concentrations in patients with infectious mononucleosis and immune abnormalities associated with jaundice. METHODS: We report on an adult patient with monoclonal B lymphocytosis and IgM-lambda gammopathy who developed a severe icteric hepatitis during infectious mononucleosis. We then reviewed the clinical records of 389 patients admitted to the hospital with infectious mononucleosis between 1995 and 2018 (51.7% male patients; median age, 19 years; range, 15-87 years) with focus on liver abnormalities and associated factors. RESULTS: Fifty-nine patients (15.1%) had serum bilirubin concentrations between 1.5 and 3 mg/dL, and 47 patients (12.0%) had serum bilirubin >3 mg/dL. Patients with increased bilirubin concentrations had a distinct clinical presentation, with more frequent abdominal pain, nausea and vomiting, and less frequent sore throat than patients with normal bilirubin. Age and sex were not significantly different for the patients with increased and normal serum bilirubin concentrations. The patients with increased serum bilirubin concentrations showed higher levels of immune activation markers than the patients with normal bilirubin, including blood lymphocyte counts, serum IgM, and ß2-microglobulin concentrations. Heterophile antibody-positive patients (88.6%) showed similar bilirubin concentrations but higher aspartate aminotransferase and alkaline phosphatase levels than their heterophile-negative counterparts. Serum bilirubin elevations normalized quickly during follow-up. CONCLUSIONS: Transient hyperbilirubinemia is common during severe (in-hospital) infectious mononucleosis in adult patients. Patients with hyperbilirubinemia have less frequent pharyngitis symptoms and more frequent abdominal symptoms. Hyperbilirubinemia during infectious mononucleosis is associated with immune activation markers.

Age-Related Changes in Serum N-Glycome in Men and Women-Clusters Associated with Comorbidity.

(1) Aim: To describe, in a general adult population, the serum N-glycome in relation to age in men and women, and investigate the association of N-glycome patterns with age-related comorbidity; (2) Methods: The serum N-glycome was studied by hydrophilic interaction chromatography with ultra-performance liquid chromatography in 1516 randomly selected adults (55.3% women; age range 18-91 years). Covariates included lifestyle factors, metabolic disorders, inflammatory markers, and an index of comorbidity. Principal component analysis was used to define clusters of individuals based on the 46 glycan peaks obtained in chromatograms; (3) Results: The serum N-glycome changed with ageing, with significant differences between men and women, both in individual N-glycan peaks and in groups defined by common features (branching, galactosylation, sialylation, fucosylation, and oligomannose). Through K-means clustering algorithm, the individuals were grouped into a cluster characterized by abundance of simpler N-glycans and a cluster characterized by abundance of higher-order N-glycans. The individuals of the first cluster were older, showed higher concentrations of glucose and glycation markers, higher levels of some inflammatory markers, lower glomerular filtration rate, and greater comorbidity index; (4) Conclusions: The serum N-glycome changes with ageing with sex dimorphism. The N-glycome could be, in line with the inflammaging hypothesis, a marker of unhealthy aging.

Time above range for predicting the development of type 2 diabetes.

Aim: To investigate the prognostic value of time range metrics, as measured by continuous glucose monitoring, with respect to the development of type 2 diabetes (T2D). Research design and methods: A total of 499 persons without diabetes from the general population were followed-up for 5 years. Time range metrics were measured at the start and medical records were checked over the period study. Results: Twenty-two subjects (8.3 per 1,000 person-years) developed T2D. After adjusting for age, gender, family history of diabetes, body mass index and glycated hemoglobin concentration, multivariate analysis revealed 'time above range' (TAR, i.e., with a plasma glucose concentration of >140 mg/dL) to be significantly associated with a greater risk (OR = 1.06, CI 1.01-1.11) of developing diabetes (AUC = 0.94, Brier = 0.035). Conclusions: Time above range provides additional information to that offered by glycated hemoglobin to identify patients at a higher risk of developing type 2 diabetes in a population-based study.

Longitudinal relationship of liver injury with inflammation biomarkers in COVID-19 hospitalized patients using a joint modeling approach.

The mechanisms underlying liver disease in patients with COVID-19 are not entirely known. The aim is to investigate, by means of novel statistical techniques, the changes over time in the relationship between inflammation markers and liver damage markers in relation to survival in COVID-19. The study included 221 consecutive patients admitted to the hospital during the first COVID-19 wave in Spain. Generalized additive mixed models were used to investigate the influence of time and inflammation markers on liver damage markers in relation to survival. Joint modeling regression was used to evaluate the temporal correlations between inflammation markers (serum C-reactive protein [CRP], interleukin-6, plasma D-dimer, and blood lymphocyte count) and liver damage markers, after adjusting for age, sex, and therapy. The patients who died showed a significant elevation in serum aspartate transaminase (AST) and alkaline phosphatase levels over time. Conversely, a decrease in serum AST levels was observed in the survivors, who showed a negative correlation between inflammation markers and liver damage markers (CRP with serum AST, alanine transaminase [ALT], and gamma-glutamyl transferase [GGT]; and D-dimer with AST and ALT) after a week of hospitalization. Conversely, most correlations were positive in the patients who died, except lymphocyte count, which was negatively correlated with AST, GGT, and alkaline phosphatase. These correlations were attenuated with age. The patients who died during COVID-19 infection displayed a significant elevation of liver damage markers, which is correlated with inflammation markers over time. These results are consistent with the role of systemic inflammation in liver damage during COVID-19.

Changes in Serum N-Glycome for Risk Drinkers: A Comparison with Standard Markers for Alcohol Abuse in Men and Women.

Background and aim: Glycomic alterations serve as biomarker tools for different diseases. The present study aims to evaluate the diagnostic capability of serum N-glycosylation to identify alcohol risk drinking in comparison with standard markers. Methods: We included 1516 adult individuals (age range 18-91 years; 55.3% women), randomly selected from a general population. A total of 143 (21.0%) men and 50 (5.9%) women were classified as risk drinkers after quantification of daily alcohol consumption and the Alcohol Use Disorders Identification Test (AUDIT). Hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) was used for the quantification of 46 serum N-glycan peaks. Serum gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and red blood cell mean corpuscular volume (MCV) were measured by standard clinical laboratory methods. Results: Variations in serum N-glycome associated risk drinking were more prominent in men compared to women. A unique combination of N-glycan peaks selected by the selbal algorithm shows good discrimination between risk-drinkers and non-risk drinkers for men and women. Receiver operating characteristics (ROC) curves show accuracy for the diagnosis of risk drinking, which is comparable to that of the golden standards, GGT, MCV and CDT markers for men and women. Additionally, the inclusion of N-glycan peaks improves the diagnostic accuracy of the standard markers, although it remains relatively low, due to low sensitivity. For men, the area under the ROC curve using N-glycome data is 0.75, 0.76, and 0.77 when combined with GGT, MCV, and CDT, respectively. In women, the areas were 0.76, 0.73, and 0.73, respectively. Conclusion: Risk drinking is associated with significant variations in the serum N-glycome, which highlights its potential diagnostic utility.

Transient hypertriglyceridemia: a common finding during Epstein-Barr virus-induced infectious mononucleosis.

BACKGROUND: Hypertriglyceridemia can occur in lymphoproliferative disorders. Infectious mononucleosis is a self-limiting, benign lymphoproliferative disorder. This study aimed to investigate the serum triglyceride concentrations and their change over time in patients with infectious mononucleosis. METHODS: We evaluated an adult patient with severe hypertriglyceridemia (>1000 mg/dL) during infectious mononucleosis and reviewed the records of 360 patients admitted to our hospital because of infectious mononucleosis (median age, 19 years; range, 15-87 years; 51.4% male). We compared the serum triglyceride concentrations with those of a control sample from the general population (n=75). A second triglyceride measurement, obtained during convalescence (median of 30 days after the initial determination), was available for 160 patients. RESULTS: The triglyceride concentrations in the acute phase (median: 156 mg/dL) were significantly higher than those of the controls (median, 76 mg/dL; P<0.001). A total of 194 (53.9%) patients presented with hypertriglyceridemia (>150 mg/dL), which was more common in the patients older than 30 years than in the younger patients (78.6% vs. 50.6%; P<0.001). A significant correlation (P<0.005) was observed between the triglyceride levels and white blood cell counts, total cholesterol levels, and liver damage markers. The triglyceride concentrations decreased during convalescence (P<0.001) and were lower than the initial measurement in 83.7% of the cases. Conversely, the total cholesterol concentrations during the acute phase were lower than those of the controls and increased during convalescence (P<0.001). CONCLUSIONS: Patients with severe infectious mononucleosis frequently show mild, transient hypertriglyceridemia. Further studies are needed to elucidate the mechanisms underlying this finding.

C-Reactive Protein versus Erythrocyte Sedimentation Rate: Implications Among Patients with No Known Inflammatory Conditions.

BACKGROUND: Measurements of C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) are frequently ordered jointly in clinical practice. AIM: To investigate the factors associated with discordances between CRP concentration and ESR in adults. METHODS: We conducted a cross-sectional study of 1472 adults with no known inflammatory disorders (44.5% male; median age, 52 years; range, 18-91 years), randomly selected from a municipality in Spain. The participants underwent simultaneous measurements of ESR, serum CRP, and interleukin-6 concentrations. Alcohol consumption, smoking, and physical activity were evaluated by questionnaire. Body mass index (BMI) measurement and metabolic syndrome criteria were available for all participants. RESULTS: Most (n = 1123, 74.9%) of the participants showed normal CRP and ESR values. Sixty-nine (4.6%) participants showed high CRP and ESR values. Seventy-two (4.8%) participants showed a discordant pattern of high ESR and normal CRP values, which was associated with age after adjusting for sex, alcohol consumption, physical activity, BMI, and the presence of metabolic syndrome (odds ratio [OR], 1.052; 95% CI, 1.034-1.071; P < .001). A total of 208 (13.8%) participants showed a discordant pattern of high CRP and normal ESR values, which was associated with BMI after adjusting for covariates (OR, 1.099; 95% CI, 1.064-1.136; P < .001). BMI appeared to be the main determinant of serum CRP concentrations in this population. Serum interleukin-6 concentrations were positively associated with the discordant pattern of high CRP and normal ESR values. CONCLUSION: In this general adult population with no overt inflammatory disease, the discordant pattern of high ESR and normal CRP was associated with greater age, whereas the pattern of high CRP and normal ESR was associated with higher BMI.

Trombocitosis extrema durante una pielonefritis aguda. Consecuencia colateral de la pandemia por Coronavirus (COVID-19) / Extreme thrombocytosis during acute pyelonephritis. Collateral consequence of the Coronavirus (COVID-19) pandemic

A young woman with extreme (>1,000x109/L) thrombocytosis during Escherichia coli pyelonephritis is presented. Diagnosis of pyelonephritis was delayed after several teleconsultations for atypical symptoms during the COVID-19 pandemic. Virtual clinic models can lead to protracted courses and bizarre manifestations of infectious disease. (AU)

Factors associated with serum IgM concentrations: a general adult population study.

BACKGROUND AND AIM: To investigate the influence of common factors on serum immunoglobulin M (IgM) concentrations in adults, and clinical associations with high and low values. METHODS: We measured serum IgM levels using immunonephelometry in a random sample of 1510 individuals (aged 18-91 years, 44.7% male). We obtained data defining metabolic syndrome from all participants, defined atopy by skin prick tests to aeroallergens, and assessed lifestyle factors by questionnaire. RESULTS: Women showed higher IgM concentrations than men; 95 (6.3%, mostly male) individuals showed low (<0.40 g/L) IgM values, and 64 (4.2%, mostly female) showed high (>2.30 g/L) IgM values. Individuals with abnormal IgM concentrations had no history of opportunistic infections nor a different atopy prevalence. Serum IgM concentrations decreased with age, and obesity was negatively associated with IgM concentrations. Alcohol consumption, smoking, physical activity, and metabolic syndrome had no significant influence in the multivariate analyses. CONCLUSIONS: Many adults in the general population show abnormally high or low IgM concentrations with no evidence of immunodeficiency-associated diseases. Sex and age should be considered when defining reference IgM concentrations.

Clinical and capillaroscopic findings in patients with liver disease and proximal apparent leukonychia (Terry nails and its variants).

ABSTRACT: Terry nails and Lindsay nails are similar forms of proximal apparent leukonychia (PAL). A change in nail bed vascularity is thought to be responsible for PAL. The study was aimed at investigating the frequency of PAL in patients attending a liver disease clinic, the factors associated with its presence, its value for detecting cirrhosis, its prognostic value for mortality, and associated capillaroscopic findings.A total of 521 patients were included (age range, 18-94 years; 69% men). Systematic nail photographs were evaluated by 2 independent investigators. Disease-related data were obtained from the medical records. Mortality was evaluated after 7 years of follow-up. Nailfold capillaroscopy was performed on a subset of 80 patients.PAL was present in 228 patients (43.8%; Terry nails in 205, Lindsay nails in 20, and both in 3). The kappa-coefficient of interobserver agreement was 0.82. The presence of PAL was associated with cirrhosis and, accordingly, with portal hypertension and hepatocellular dysfunction. The positive likelihood ratio of PAL for the diagnosis of cirrhosis was 1.6 (95% CI 1.3-1.92). PAL was independently associated with chronic alcohol abuse and was not a significant predictor of mortality. Venous loop dilatation and prominence of the venous plexus were observed on capillaroscopy in patients with cirrhosis but were not significantly associated with PAL.In summary, PAL is a common finding in patients from a liver clinic; it is associated with liver cirrhosis and with alcohol abuse. PAL is not associated with specific capillaroscopic findings. We propose the generic term proximal apparent leukonychia instead of classic eponymous titles to avoid confusion in the literature.