Rapid Resolution of Life-Threatening Hypertriglyceridemia after Evinacumab Administration in a Pediatric HSCT Recipient: A Case Report.

Evinacumab, a human monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3), has recently been approved by the U.S. Food and Drug Administration as an add-on therapy for homozygous familial hypercholesterolemia (HoFH) in patients of 12 years and older. Its role as a triglyceride-lowering drug is also emerging in the literature. However, it has not been approved for this indication yet, neither in the adult nor in the pediatric population. We describe the case of a 10-year-old boy who underwent an allogeneic hematopoietic stem cell transplant for acute lymphoblastic leukemia complicated by chronic graft-versus-host disease (GVHD) and presented life-threatening refractory hypertriglyceridemia due to the concomitant use of ruxolitinib and sirolimus. After the failure of the insulin treatment and due to the technical impossibility of performing lipid apheresis, the child underwent evinacumab treatment, obtaining a dramatic rapid reduction in triglyceride and cholesterol levels. This is the first report of a pediatric patient younger than 12 years in Europe receiving evinacumab to treat severe hypertriglyceridemia. The therapy with angiopoietin-like proteins inhibitors has been effective, safe, and well-tolerated in our patient, suggesting that evinacumab may be used in the pediatric population when other therapeutic strategies are ineffective or contraindicated.

The impact of body composition on mortality of COVID-19 hospitalized patients: A prospective study on abdominal fat, obesity paradox and sarcopenia.

BACKGROUND & AIMS: Obesity has been described as a predisposing risk factor to severe forms of COVID-19, but conflicting results are emerging on its real impact on the mortality of COVID-19. We aimed to compare clinical outcomes and mortality among COVID-19 patients according to obesity, metabolic syndrome and adiposity distribution. METHODS: We conducted a prospective observational study of all consecutive adult patients with a confirmed diagnosis of SARS-CoV-2 infection admitted to the Infectious Diseases Clinic at Udine Hospital, Italy, from January 2021 to February 2021. At admission, the study population was submitted to specific anthropometric, laboratory and bioimpedance analysis (BIA) measurements and divided into five groups according to: 1) BMI < or >30 kg/m2; 2) waist circumference (WC) < or >98 cm for women, < or >102 cm for men; 3) presence or absence of metabolic syndrome (MS); 4) visceral adipose tissue (VAT) distribution; and 5) presence or absence of sarcopenia (SP) both based on BIA. We then compared clinical outcomes (ventilatory support, intensive care unit (ICU) admission, ICU length of stay, total hospital length of stay and mortality), immune and inflammatory makers and infectious and non-infectious acute complications within the five groups. RESULTS: A total of 195 patients were enrolled in the study. The mean age of patients was 71 years (IQR 61-80) and 64.6% (126) were male. The most common comorbidities were hypertension (55.9%) and MS (55.4%). Overall mortality was 19.5%. Abdominal adiposity, measured both with WC and with BIA, and SP were significantly associated with need for increased ventilator support (p = 0.013 for WC; p = 0.037, 0.027 and 0.009 for VAT; p = 0.004 and 0.036 for FMI; and p = 0.051 for SP), but not with ICU admission (WC p = 0.627, VAT p = 0.153, FMI p = 0.519 and SP p = 0.938), length of stay (WC p = 0.345, VAT p = 0.650, FMI p = 0.159 and SP p = 0.992) and mortality (WC p = 0.277, VAT p = 0.533, FMI p = 0.957 and SP p = 0.211). Obesity and MS did not discriminate for the intensity of ventilatory outcome (p = 0.142 and p = 0.198, respectively), ICU admission (p = 0.802 and p = 0.947, respectively), length of stay (p = 0.471 and p = 0.768, respectively) and mortality (p = 0.495 and p = 0.268, respectively). We did not find significant differences in inflammatory markers and secondary complications within the five groups. CONCLUSIONS: In patients admitted with COVID-19, increased WC, visceral abdominal fat and SP are associated with higher need for ventilatory support. However, obesity, MS, SP and abdominal adiposity are not sensitive predictive factors for mortality.

Relationship between cytokine release and stress hyperglycemia in patients hospitalized with COVID-19 infection.

Introduction: Stress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19. Methods: In a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission. Results: Patients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078-6.012) and death (OR 2.281; CI 1.049-7.369) independently of diabetes and other major confounders. Conclusions: In patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis.

Validation of a Saliva-Based Test for the Molecular Diagnosis of SARS-CoV-2 Infection.

BACKGROUND: Since the beginning of the pandemic, clinicians and researchers have been searching for alternative tests to improve the screening and diagnosis of the SARS-CoV-2 infection. Currently, the gold standard for virus identification is the nasopharyngeal (NP) swab. Saliva samples, however, offer clear, practical, and logistical advantages but due to a lack of collection, transport, and storage solutions, high-throughput saliva-based laboratory tests are difficult to scale up as a screening or diagnostic tool. With this study, we aimed to validate an intralaboratory molecular detection method for SARS-CoV-2 on saliva samples collected in a new storage saline solution, comparing the results to NP swabs to determine the difference in sensitivity between the two tests. METHODS: In this study, 156 patients (cases) and 1005 asymptomatic subjects (controls) were enrolled and tested simultaneously for the detection of the SARS-CoV-2 viral genome by RT-PCR on both NP swab and saliva samples. Saliva samples were collected in a preservative and inhibiting saline solution (Biofarma Srl). Internal method validation was performed to standardize the entire workflow for saliva samples. RESULTS: The identification of SARS-CoV-2 conducted on saliva samples showed a clinical sensitivity of 95.1% and specificity of 97.8% compared to NP swabs. The positive predictive value (PPV) was 81% while the negative predictive value (NPV) was 99.5%. Test concordance was 97.6% (Cohen's Kappa = 0.86; 95% CI 0.81-0.91). The LoD of the test was 5 viral copies for both samples. CONCLUSIONS: RT-PCR assays conducted on a stored saliva sample achieved similar performance to those on NP swabs, and this may provide a very effective tool for population screening and diagnosis. Collection of saliva in a stabilizing solution makes the test more convenient and widely available; furthermore, the denaturing properties of the solution reduce the infective risks belonging to sample manipulation.

Prognostic Role of Malnutrition Diagnosed by Bioelectrical Impedance Vector Analysis in Older Adults Hospitalized with COVID-19 Pneumonia: A Prospective Study.

BACKGROUND: Little is known on the clinical relevance of the nutritional status and body composition of patients hospitalized with SARS-CoV-2 infection. The aim of our study was to assess the prevalence of malnutrition in patients with COVID-19 pneumonia using bioelectrical impedance vector analysis (BIVA), and to evaluate the relationship of their nutritional status with the severity and outcome of disease. METHODS: Among 150 consecutive patients who were hospitalized with COVID-19 pneumonia, 37 (24.3%) were classified as malnourished by BIVA, and were followed-up for 60 days from admission. Outcome measures were differences in the need for invasive mechanical ventilation, in-hospital mortality, and the duration of hospital stay in survivors. RESULTS: During 60 days of follow-up, 10 (27%) malnourished patients and 13 (12%) non-malnourished patients required invasive mechanical ventilation (p = 0.023), and 13 (35%) malnourished patients and 9 (8%) non-malnourished patients died (p < 0.001). The average duration of the hospital stay in survivors was longer in patients with malnutrition (18.2 ± 15.7 vs. 13.2 ± 14.8 days, p < 0.001). In survival analyses, mechanical ventilation free (log-rank 7.887, p = 0.050) and overall (log-rank 17.886, p < 0.001) survival were significantly longer in non-malnourished than malnourished patients. The Cox proportional ratio showed that malnutrition was associated with an increased risk of mechanical ventilation (HR 4.375, p = 0.004) and death (HR 4.478, p = 0.004) after adjusting for major confounders such as age, sex, and BMI. CONCLUSIONS: Malnutrition diagnosed with BIVA was associated with worse outcomes in hospitalized patients with COVID-19 pneumonia.

Postoperative Streptococcus constellatus Bacteremia in a 75-Year-Old Patient with Pyometra: A Case Report.

BACKGROUND Pyometra is an accumulation of pus in the uterine cavity. It is rare in the general population but more common in elderly women. If diagnosed in the early stage, life-threating conditions may be avoided. The most common etiological microorganisms of pyometra are Escherichia coli, Bacteroides species, Staphylococci (eg, epidermidis) and Streptococci. Occasionally, atypical bacteria may be the cause. CASE REPORT We present the case of a 75-year-old woman, with multiple risk factors, admitted to the Gynecology Department with a 15-day history of yellowish-brown vaginal discharge. Because of rapid enlargement of the uterine cavity, the patient underwent to endometrial curettage. Three hours after surgery, she developed a high-grade fever, and Streptococcus constellatus was isolated in her blood cultures. A specific antibiotic therapy was administered for a total of 14 days, resulting in complete resolution of the infection. CONCLUSIONS This case report describes a rare case of bacteremia caused by Streptococcus constellatus, that resulted from a pyometra. The classic triad of symptoms (postmenopausal bleeding, vaginal discharge, and lower abdominal pain) may be helpful for diagnosis; however, 50% of patients are asymptomatic. An early recognition of the condition is important to avoid rare but risky consequences, such as perforation of the uterus itself. Nevertheless, surgery can cause dangerous complications such as bacteremia. A different spectrum of bacteria may be involved in the development of pyometra, even in atypical cases, mostly when multiple comorbidities are present. A correct evaluation and management of the patient is essential to guarantee a good prognosis in this rare infection.

Hyposmia and Dysgeusia in COVID-19: Indication to Swab Test and Clue of CNS Involvement.

OBJECTIVE: To evaluate the prevalence of hyposmia and dysgeusia in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their temporal relationship with the onset of other symptoms. METHODS: We performed a retrospective analysis of patients admitted during the month of March 2020 to the nonintensive COVID unit of Udine University Hospital on the basis of a positive swab test and/or of clinical-radiologic signs of SARS-CoV-2 infection. Patients were interviewed with a standardized questionnaire. Clinical and laboratory data were collected. Data were analyzed with descriptive statistics, and results expressed as point estimates and 95% confidence intervals (CIs). RESULTS: Of 141 patients admitted, 93 were interviewed. Hyposmia and dysgeusia were present in 58 cases (62.4%). In 22.4% of them, olfactory and gustatory impairment clearly preceded systemic symptoms. The presence of active smoking was very limited in both groups: 8.6% in hyposmic vs 2.9% in normosmic patients (odds ratio 3.2; 95% CI 0.3-28.6). Moreover, total leukocytes and neutrophils count were respectively 23% (effect estimate 1.23; 95% CI 1.06-1.42) and 29% (effect estimate 1.29; 95% CI 1.07-1.54) lower in the hyposmic cohort. No difference was found for other inflammatory biomarkers. CONCLUSIONS: Hyposmia and dysgeusia are common in SARS-CoV-2 infection and can precede systemic symptoms. They should be actively searched and prompt close monitoring and isolation until infection is confirmed or disproven. The lower number of total leukocytes and neutrophils in hyposmic patients might indicate an early-phase virus-induced cytopenia.

MR-proADM as prognostic factor of outcome in COVID-19 patients.

Mid Regional pro-ADM (MR-proADM) is a promising novel biomarker in the evaluation of deteriorating patients and an emergent prognosis factor in patients with sepsis, septic shock and organ failure. It can be induced by bacteria, fungi or viruses. We hypothesized that the assessment of MR-proADM, with or without other inflammatory cytokines, as part of a clinical assessment of COVID-19 patients at hospital admission, may assist in identifying those likely to develop severe disease. A pragmatic retrospective analysis was performed on a complete data set from 111 patients admitted to Udine University Hospital, in northern Italy, from 25th March to 15th May 2020, affected by SARS-CoV-2 pneumonia. Clinical scoring systems (SOFA score, WHO disease severity class, SIMEU clinical phenotype), cytokines (IL-6, IL-1b, IL-8, TNF-α), and MR-proADM were measured. Demographic, clinical and outcome data were collected for analysis. At multivariate analysis, high MR-proADM levels were significantly associated with negative outcome (death or orotracheal intubation, IOT), with an odds ratio of 4.284 [1.893-11.413], together with increased neutrophil count (OR = 1.029 [1.011-1.049]) and WHO disease severity class (OR = 7.632 [5.871-19.496]). AUROC analysis showed a good discriminative performance of MR-proADM (AUROC: 0.849 [95% Cl 0.771-0.730]; p < 0.0001). The optimal value of MR-proADM to discriminate combined event of death or IOT is 0.895 nmol/l, with a sensitivity of 0.857 [95% Cl 0.728-0.987] and a specificity of 0.687 [95% Cl 0.587-0.787]. This study shows an association between MR-proADM levels and the severity of COVID-19. The assessment of MR-proADM combined with clinical scoring systems could be of great value in triaging, evaluating possible escalation of therapies, and admission avoidance or inclusion into trials. Larger prospective and controlled studies are needed to confirm these findings.

Blood ozonization in patients with mild to moderate COVID-19 pneumonia: a single centre experience.

The emerging outbreak of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. We prescribed some promising medication to our patients with mild to moderate pneumonia due to SARS-CoV-2, however such drugs as chloroquine, hydrossichloroquine, azithromycin, antivirals (lopinavir/ritonavir, darunavir/cobicistat) and immunomodulating agents (steroids, tocilizumab) were not confirmed as effective against SARS-CoV2. We, therefore, started to use auto-hemotherapy treated with an oxygen/ozone (O2/O3) gaseous mixture as adjuvant therapy. In Udine University Hospital (Italy) we performed a case-control study involving hospitalized adult patients with confirmed COVID-19 with mild to moderate pneumonia. Clinical presentations are based upon clinical phenotypes identified by the Italian Society of Emergency and Urgency Medicine (SIMEU-Società Italiana di Medicina di Emergenza-Urgenza) and patients that met criteria of phenotypes 2 to 4 were treated with best available therapy (BAT), with or without O3-autohemotherapy. 60 patients were enrolled in the study: 30 patients treated with BAT and O2/O3 mixture, as adjuvant therapy and 30 controls treated with BAT only. In the group treated with O3-autohemotherapy plus BAT, patients were younger but with more severe clinical phenotypes. A decrease of SIMEU clinical phenotypes was observed (2.70 ± 0.67 vs. 2.35 ± 0.88, p = 0.002) in all patients during hospitalization but this clinical improvement was statistically significant only in O3-treated patients (2.87 ± 0.78 vs. 2.27 ± 0.83, p < 0.001), differently to the control group (2.53 ± 0.51 vs. 2.43 ± 0.93, p = 0.522). No adverse events were observed associated with the application of O2/O3 gaseous mixture. O2/O3 therapy as adjuvant therapy could be useful in mild to moderate pneumonia due to SARS-CoV-2. Randomized prospective study is ongoing [Clinical Trials.gov ID: Z7C2CA5837].

Parental Psychological Factors and Quality of Life of Children With Inflammatory Bowel Disease.

OBJECTIVES: Parents have a central role in the management of children with inflammatory bowel disease (IBD). Alterations in parental psychological well-being may affect the patient's health-related quality of life (HRQoL). This study aimed to evaluate the correlation between maternal and paternal distress, anxiety, depression and pain catastrophizing and the HRQoL of patients with IBD. METHODS: Children with IBD ages 8 to 18 years and their parents were prospectively recruited. Children answered questionnaires on HRQoL while parents completed an assessment of distress, anxiety, depression, and pain catastrophizing. Univariate and multivariate regression models analysis were used to evaluate correlations between parental measures and patient's HRQoL and between the factors related to children health and parental psychological suffering. RESULTS: One hundred patients (45 Crohn disease, 55 ulcerative colitis), 90 mothers and 62 fathers were enrolled. Parents had high levels of distress while anxiety, depression, and pain catastrophizing levels were relatively low. Parental distress had the most substantial correlation with children's HRQoL and was associated with patients' disease activity and recent flares. On multivariate regression analysis, parental factors explained less than 20% of the variance in the children's HRQoL scores. Mothers suffered from psychological alterations more frequently than fathers, but the parental inter-rater agreement was strong in regards to distress and anxiety. CONCLUSIONS: Parental distress is high and correlates with the HRQoL of children with IBD. Interventions aimed at evaluating and managing parental distress should be considered during the management of children with IBD.

The Role of Distress and Pain Catastrophizing on the Health-related Quality of Life of Children With Inflammatory Bowel Disease.

OBJECTIVES: Inflammatory bowel disease (IBD) can be particularly challenging during the pediatric age with a relevant impact on patient's health-related quality of life (HRQoL). Disease activity accounts for only a small part of the variability in HRQoL, and psychological factors can play a significant role. We aimed to evaluate the impact of patient's distress and pain catastrophizing on children and adolescents with IBD. METHODS: We prospectively recruited children aged 8 to 18 with IBD and recorded demographic and disease characteristics. Patients answered questionnaires on HRQoL (IMPACT III), distress (distress thermometer [DT]), and pain catastrophizing (Pain Catastrophizing Scale-Children [PCS-C]). Univariate and multivariate regression models analysis were used to evaluate correlations between patients' characteristics, disease activity, distress, pain catastrophizing, and HRQoL. RESULTS: Seventy-one patients were enrolled (median age 13.6, 49.3% Crohn disease, 50.7% ulcerative colitis). Median HRQoL, DT, and PCS-C scores were 78.6 (interquartile range 68.0-87.1), 3.0 (1.0-5.0), and 12.0 (4.0-23.0), respectively. Patient's distress and pain catastrophizing levels significantly correlated with HRQoL. Pain catastrophizing had the strongest impact on HRQoL (Spearman correlation coefficient, ρ = 0.73), followed by distress (ρ = 0.67), and ulcerative colitis severity (ρ = 0.67). The DT and the PCS-C scores were significantly associated (ρ = 0.46). CONCLUSIONS: Distress and pain catastrophizing have a significative impact on HRQoL in young patients with IBD. Physicians should recognize the role of these psychological factors and consider cognitive-behavioral therapy to optimize the patient's health.