Off-label use of dalbavancin in children: a case series.

INTRODUCTION: Dalbavancin is an antibiotic active against most Gram-positive bacteria approved for acute bacterial skin and skin structure infections (ABSSSI). Owing to its long half-life, it is being increasingly used for other indications. PATIENTS AND METHODS: We present a case series of children and adolescents treated with dalbavancin for osteoarticular, catheter-related and other non-ABSSSI infections. RESULTS: Dalbavancin was prescribed to 15 patients. Six (40%) were female and median age at prescription was 11.9 (IQR 1.3-18.0) years. Most of them (12/15) had significant comorbidities. Patients presented mainly with deep surgical site infections, osteoarticular infections and central-line-associated bloodstream infections. The most common isolate was Staphylococcus aureus followed by Staphylococcus epidermidis. Major reasons to prescribe dalbavancin were to ensure compliance and patients' convenience. Two patients discontinued the drug due to adverse events possibly related to it. The rest of the patients completed the treatment with dalbavancin, with a median duration of 56 days (IQR 17.5, 115.5). All achieved complete resolution and present no relapse after a median follow-up of 9.9 months (IQR 4.8, 16.6). CONCLUSIONS: Dalbavancin was a safe, effective and convenient alternative in selected paediatric patients with complicated non-ABSSSI infections caused by Gram-positive bacteria.

T-Cell Immune Responses in Newborns and Long-Term Sequelae in Congenital Cytomegalovirus Infection (CYTRIC Study).

OBJECTIVE: The objective of this study was to assess the role of T-lymphocyte immune responses in newborns with congenital cytomegalovirus (CMV) infection (cCMV) and their potential association with the development of long-term sequelae. STUDY DESIGN: A multicenter, prospective study from 2017 to 2022 was conducted across 8 hospitals in Spain. Blood samples were collected within the first month of life from neonates diagnosed with cCMV. Intracellular cytokine staining was employed to evaluate the presence of CMV-specific interferon-gamma (IFN-γ)-producing CD8+ and CD4+ T lymphocytes (CMV-IFN-γ-CD8+/CD4+) using flow cytometry. The development of sequelae, including hearing loss and neurologic impairment, was assessed during follow-up. RESULTS: In total, 64 newborns were included; 42 infants (65.6%) had symptomatic cCMV. The median age at the last follow-up visit was 25.3 months (IQR 20.1-34.4). Eighteen infants had long-term sequelae (28.1%), predominantly hearing loss (20.3%) and neurologic disorders (15.6%). No relationship was observed between total count or percentage of CMV-specific IFN-γ-CD8+ or CD4+ lymphocytes and long-term sequelae. Multivariable analysis demonstrated an association between lower total lymphocyte count and long-term sequelae (aOR 0.549, 95% CI: 0.323-0.833), which requires further study. CONCLUSIONS: CMV-specific IFN-γ-CD4+ and CD8+ T-lymphocyte responses in neonates with cCMV were not predictive of long-term sequelae.

Exploring the causal role of intimate partner violence and abuse on depressive symptoms in young adults: a population-based cohort study.

BACKGROUND: Previous studies have shown an association between experience of intimate partner violence and abuse (IPVA) and depression. Whether this is a causal relationship or explained by prior vulnerability that influences the risk of both IPVA and depression is not known. METHODS: We analysed data from the Avon Longitudinal Study of Parents and Children prospective cohort (N = 1764 women, 1028 men). To assess the causal association between IPVA at 18-21 years old and logged depressive symptom scores at age 23, we used (i) multivariable linear regression, (ii) inverse probability of treatment weighting (IPTW), and (iii) difference-in-difference (DiD) analysis, which compared the mean change in logged depressive symptom scores between ages 16 and 23 between those who experienced IPVA and those who did not. RESULTS: Women who experienced IPVA had on average 26% higher depressive symptom scores after adjustment for measured confounders (ratio of geometric means 1.26, 95% CI 1.13 to 1.40). In men, the difference was 5% (ratio of geometric means 1.05, 95% CI 0.92 to 1.21). Results from IPTW analysis were similar. In the DiD analysis, there was no evidence that being exposed to IPVA affected the change in depressive symptom scores over time compared to being in the non-exposed group for either women (difference-in-differences 1%, -12 to 16%) or men (-1%, -19 to 20%). CONCLUSIONS: Multivariable linear regression and IPTW suggested an association between IPVA and higher depressive symptom score in women but not men, but DiD analysis indicated a null effect in both women and men. This suggests the causal origins of higher depressive symptoms in this young adult population are likely to reflect prior vulnerability that leads to both higher depressive symptoms and increased risk of IPVA exposure.

Being silenced, loneliness and being heard: understanding pathways to intimate partner violence & abuse in young adults. a mixed-methods study.

BACKGROUND: International research shows the significance and impact of intimate partner violence and abuse (IPVA) as a public health issue for young adults. There is a lack of qualitative research exploring pathways to IPVA. METHODS: The current mixed-methods study used qualitative interviews and analysis of longitudinal cohort data, to explore experiences of pathways to IPVA. Semi-structured Interviews alongside Life History Calendars were undertaken to explore 17 young women's (19-25 years) experiences and perceptions of pathways to IPVA in their relationships. Thematic analysis was undertaken. Based on themes identified in the qualitative analysis, quantitative analysis was conducted in data from 2127 female and 1145 male participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort study. We fitted regression models to assess the association of child maltreatment, parental domestic violence, and peer-to-peer victimisation, by age 12, with loneliness during adolescence (ages 13-14), and the association of loneliness during adolescence with IPVA (age 18-21). Mediation analysis estimated the direct effects of maltreatment on IPVA, and indirect effects through loneliness. FINDINGS: All women interviewed experienced at least one type of maltreatment, parental domestic violence, or bullying during childhood. Nearly all experienced IPVA and most had been multi-victimised. Findings indicated a circular pathway: early trauma led to isolation and loneliness, negative labelling and being silenced through negative responses to help seeking, leading to increased experiences of loneliness and intensifying vulnerability to further violence and abuse in young adulthood. The pathway was compounded by intersectionality. Potential ways to break this cycle of loneliness included being heard and supported, especially by teachers. Quantitative analysis confirmed an association between child maltreatment and loneliness in adolescence, and an association between loneliness in adolescence and experience of IPVA in young adult relationships. CONCLUSION: It is likely that negative labelling and loneliness mediate pathways to IPVA, especially among more disadvantaged young women. The impact of early maltreatment on young people's wellbeing and own relationships is compounded by disadvantage, disability and ethnicity. Participants' resilience was enabled by support in the community.

Benefits of a Pediatric Antimicrobial Stewardship Program in Antimicrobial Use and Quality of Prescriptions in a Referral Children's Hospital.

OBJECTIVES: To evaluate the results of the first 24 months of a postprescription review with feedback-based antimicrobial stewardship program in a European referral children's hospital. STUDY DESIGN: We performed a pre-post study comparing antimicrobial use between the control (2015-2016) and the intervention periods (2017-2018) expressed in days of therapy/100 days present. Quality of prescriptions was evaluated by quarterly cross-sectional point-prevalence surveys. Length of stay, readmission rates, in-hospital mortality rates, cost of systemic antimicrobial agents, and antimicrobial resistance rates were included as complementary outcomes. RESULTS: Total antimicrobial use and antibacterial use significantly decreased during the intervention period (P = .002 and P = .001 respectively), and total antifungal use remained stable. A significant decline in parenteral antimicrobial use was also observed (P < .001). In 8 quarterly point-prevalence surveys (938 prescriptions evaluated), the mean prevalence of use of any antimicrobial among inpatients was 39%. An increasing trend in the rate of optimal prescriptions was observed after the first point-prevalence survey (P = .0898). Nonoptimal prescriptions were more common in surgical than in medical departments, in antibacterial prescriptions with prophylactic intention, and in empirical more than in targeted treatments. No significant differences were observed in terms of mortality or readmission rates. Only minor changes in antimicrobial resistance rates were noted. CONCLUSIONS: Our antimicrobial stewardship program safely decreased antimicrobial use and expenditure, and a trend toward improvement in quality of prescription was also observed.

Renal Function Impairment in Children With Congenital Cytomegalovirus Infection: A Cross-sectional Study.

BACKGROUND: We aimed to determine the prevalence and severity of glomerular and tubular renal dysfunction by means of urinalysis in infants and toddlers with congenital cytomegalovirus infection (cCMV) and their association with cCMV disease, viruria and antiviral treatment. METHODS: This cross-sectional study was done using the Spanish Registry of Congenital Cytomegalovirus Infection. First-morning urine samples were collected from January 2016 to December 2018 from patients <5 years old enrolled in Spanish Registry of Congenital Cytomegalovirus Infection. Samples were excluded in case of fever or other signs or symptoms consistent with acute infection, bacteriuria or bacterial growth in urine culture. Urinary protein/creatinine and albumin/creatinine ratios, urinary beta-2-microglobulin levels, hematuria and CMV viruria were determined. A 0.4 cutoff in the urinary albumin/protein ratio was used to define tubular (<0.4) or glomerular (>0.4) proteinuria. Signs and symptoms of cCMV at birth, the use of antivirals and cCMV-associated sequelae at last available follow-up were obtained from Spanish Registry of Congenital Cytomegalovirus Infection. RESULTS: Seventy-seven patients (37 females, 48.1%; median [interquartile range] age: 14.0 [4.4-36.2] months) were included. Symptom-free elevated urinary protein/creatinine and albumin/creatinine ratios were observed in 37.5% and 41.9% of patients, respectively, with tubular proteinuria prevailing (88.3%) over glomerular proteinuria (11.6%). Proteinuria in the nephrotic range was not observed in any patients. In multivariate analysis, female gender was the only risk factor for tubular proteinuria (adjusted odds ratio = 3.339, 95% confidence interval: 1.086-10.268; P = 0.035). cCMV disease at birth, long-term sequelae, viruria or the use of antivirals were not associated with urinalysis findings. CONCLUSIONS: Mild nonsymptomatic tubular proteinuria affects approximately 40% of infants and toddlers with mostly symptomatic cCMV in the first 5 years of life.

Neuroimaging in infants with congenital cytomegalovirus infection and its correlation with outcome: emphasis on white matter abnormalities.

OBJECTIVE: To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of white matter abnormalities (WMAs). METHODS: Multicentre retrospective cohort study of 160 infants with cCMV (103 symptomatic). A four-grade neuroimaging scoring system was applied to cranial ultrasonography and MRI acquired at ≤3 months. WMAs were categorised as multifocal or diffuse. Temporal-pole WMAs (TPWMAs) consisted of swollen or cystic appearance. Apparent diffusion coefficient (ADC) values were obtained from frontal, parieto-occipital and temporal white matter regions. Available follow-up MRI at ≥6 months (N=14) was additionally reviewed. Neurodevelopmental assessment included motor function, cognition, behaviour, hearing, vision and epilepsy. Adverse outcome was defined as death or moderate/severe disability. RESULTS: Neuroimaging scoring was associated with outcome (p<0.001, area under the curve 0.89±0.03). Isolated WMAs (IWMAs) were present in 61 infants, and WMAs associated with other lesions in 30. Although TPWMAs and diffuse pattern often coexisted in infants with IWMAs (p<0.001), only TPWMAs were associated with adverse outcomes (OR 7.8; 95% CI 1.4 to 42.8), including severe hearing loss in 20% and hearing loss combined with other moderate/severe disabilities in 15%. Increased ADC values were associated with higher neuroimaging scores, WMAs based on visual assessment and IWMAs with TPWMAs. ADC values were not associated with outcome in infants with IWMAs. Findings suggestive of progression of WMAs on follow-up MRI included gliosis and malacia. CONCLUSIONS: Categorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis.

No pain, no gain: depressed clients' experiences of cognitive behavioural therapy.

OBJECTIVES: Cognitive behavioural therapy (CBT) is an effective treatment for depression, but many clients do not complete therapy. What clients find difficult about CBT is poorly understood. This study explored clients' views and experiences of face-to-face CBT. DESIGN: A mixed methods design was used to collect data as part of the CoBalT trial. METHOD: Participants randomized to CBT indicated their reasons for never starting or stopping therapy on the follow-up questionnaires. In-depth qualitative interviews took place with a purposive sample (n = 26) of those randomized to CBT. Framework analysis was used to analyse across the data. RESULTS: Seventy-four participants withdrew from therapy or were discharged for non-adherence. A total of 54 (73%) gave reasons for not starting or stopping CBT; mostly the time/location was inconvenient or they had other commitments. Interviews identified that clients could struggle in, and between, CBT sessions. This was true for those who did and did not complete therapy. CBT homework was the biggest challenge and was often associated with negative school homework experiences. Although clients may have disliked aspects of CBT, those who attended more than one session felt that they had gained insight into managing their depression. CONCLUSION: Highlighting the possible barriers to adherence in CBT can help clinicians to better prepare clients in making an informed choice about therapy. Exploring these issues during therapy may also help with engagement. Despite the challenges, clients can still benefit from CBT by learning strategies that enable them to effectively deal with their depression.

Young People and Intimate Partner Violence: Experiences of Institutional Support and Services in England.

Purpose: Young people (YP) are at greater risk of experiencing intimate partner violence and abuse (IPVA), with high prevalence rates at 18-25 years and potentially severe short and long-term health and social impacts. YP often view adult support services as not for them and more research is needed to understand effective responses to IPVA among different groups. Methods: Semi-structured interviews alongside Life History Calendars were undertaken to explore 18 young peoples' (18-25 years) experiences of community and service level responses to their IPVA between 2019-2020. Thematic analysis and case studies were carried out. Results: Participant accounts commonly described what did or did not help within: education; primary care physicians and maternity services; third sector or non-government support organisations; and counselling and support workers. YP wanted clearer information on identifying abuse from a younger age in schools and better access and signposting to specialist services. They benefited the most from equal power dynamics in relationships with professionals where they were supported to make their own decisions. Conclusions: Professionals in all sectors (including schools) need IPVA trauma-informed training that encourages equal power dynamics, with a clear understanding of and access to referral pathways, to be able to respond to the needs of YP experiencing IPVA.

Categories of Intimate Partner Violence and Abuse Among Young Women and Men: Latent Class Analysis of Psychological, Physical, and Sexual Victimization and Perpetration in a UK Birth Cohort.

BACKGROUND: In the UK, around one-third of young people are exposed to Intimate Partner Violence and Abuse (IPVA) by 21 years old. However, types of IPVA victimization in this population (psychological, physical, sexual), and their relationship with impact and perpetration are poorly understood. METHODS: Participants in a UK birth cohort reported IPVA victimization and perpetration by age 21. We carried out a latent class analysis, where we categorized IPVA by types/frequency of victimization, and then assigned individuals to their most probable class. Within these classes, we then estimated rates of reported: 1) types of negative impacts (sad, upset/unhappy, anxious, depressed, affected work/studies, angry/annoyed, drank/took drugs more); 2) types/frequency of perpetration. RESULTS: Among 2130 women and 1149 men, 32% and 24% reported IPVA victimization (of which 89% and 73% reported negative impact); 21% and 16% perpetration. Victimization responses were well represented by five classes, including three apparent in both sexes: No-low victimization (characterized by low probabilities of all types of victimization; average probabilities of women and men belonging to this class were 82% and 70%); Mainly psychological (15% and 12%); Psychological and physical victimization (4% and 7%), and two classes that were specific to women: Psychological and sexual (7%); Multi-victimization (frequent victimization for all three types; 4%). In women, all types of negative impact were most common in the Psychological and sexual and Multi-victimization classes; for men, the Psychological and physical class. In women, all types of perpetration were most common for the Mainly psychological, Psychological and physical and Multi-victimization classes; in men, the Mainly psychological and Psychological and physical classes. DISCUSSION: In this study of young people, we found categories of co-occurrence of types and frequency of IPVA victimization associated with differential rates of negative impact and perpetrating IPVA. This is consistent with emerging evidence of IPVA differentiation and its variable impact in other populations.

Incremental cholecalciferol supplementation up to 15 µg/d throughout winter at 51-55° N has no effect on biomarkers of cardiovascular risk in healthy young and older adults.

Two separate, identical, double-blind, randomized, placebo-controlled intervention studies were carried out in the south and north of Ireland (51-55°N). Men and women aged 20-40 y (n = 202) and ≥64 y (n = 192) received cholecalciferol at doses of 0 (P), 5 (D3-5), 10 (D3-10), or 15 (D3-15) µg/d (0-600 IU) during wintertime. Serum 25-hydroxyvitamin D [s25(OH)D], intact parathyroid hormone, systolic and diastolic blood pressure, fasting lipids, glucose and insulin, HOMA-IR, high-sensitivity CRP, matrix metalloproteinase-9, and its inhibitor (tissue inhibitor metalloproteinase-1) were measured at baseline (October) and 22 wk later at endpoint (March). Vitamin D receptor Fok I and Taq I genotypes were analyzed and dietary intakes of vitamin D and calcium were assessed. In young adults, s25(OH)D decreased from baseline to endpoint (P < 0.001), except in the D3-15 group, who maintained the baseline concentration of ~70 nmol/L. Older adults had lower s25(OH)D at baseline (median, 54.2 nmol/L) and concentrations increased in the D3-10 and D3-15 groups (P < 0.001). There were no significant effects of supplementation on cardiovascular disease (CVD) risk biomarkers in either age group. Fasting glucose and total and HDL cholesterol were lower (P < 0.05) in older adults with the Fok 1 ff genotype than in those with FF or Ff. Putative effects of vitamin D on cardio-metabolic health will only be evident at higher intakes than the current RDA and possibly in individuals at particular risk of low s25(OH)D and/or CVD risk.

Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol response to supplementation in healthy young and older Irish adults.

There is increasing epidemiological evidence linking sub-optimal vitamin D status with overweight and obesity. Although increasing BMI and adiposity have also been negatively associated with the change in vitamin D status following supplementation, results have been equivocal. The aim of this randomised, placebo-controlled study was to investigate the associations between anthropometric measures of adiposity and the wintertime serum 25-hydroxycholecalciferol (25(OH)D) response to 15 µg cholecalciferol per d in healthy young and older Irish adults. A total of 110 young adults (20-40 years) and 102 older adults ( ≥ 64 years) completed the 22-week intervention with >85 % compliance. The change in 25(OH)D from baseline was calculated. Anthropometric measures of adiposity taken at baseline included height, weight and waist circumference (WC), along with skinfold thickness measurements to estimate fat mass (FM). FM was subsequently expressed as FM (kg), FM (%), FM index (FMI (FM kg/height m2)) and as a percentage ratio to fat-free mass (FFM). In older adults, vitamin D status was inversely associated with BMI (kg/m2), WC (cm), FM (kg and %), FMI (kg/m2) and FM:FFM (%) at baseline (r - 0·33, - 0·36, - 0·33, - 0·30, - 0·33 and - 0·27, respectively, all P values < 0·01). BMI in older adults was also negatively associated with the change in 25(OH)D following supplementation (ß - 1·27, CI - 2·37, - 0·16, P = 0·026); however, no such associations were apparent in younger adults. Results suggest that adiposity may need to be taken into account when determining an adequate wintertime dietary vitamin D intake for healthy older adults residing at higher latitudes.

Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells.

We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

Host, technical, and environmental factors affecting QuantiFERON-TB Gold In-Tube performance in children below 5 years of age.

Interferon-gamma release assays performance can be impaired by host-related, technical and environmental factors, but data in young children are limited. We performed a cross-sectional study of children < 5 years-of-age at risk of tuberculosis (TB), using QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. The impact of the following was evaluated: (i) host-related [age; hematological parameters; erythrocyte sedimentation rate (ESR); C-reactive protein (CRP); and tobacco smoke exposure (TSE) based on serum cotinine concentrations], (ii) technical (pre-analytical delay) and (iii) environmental factors (annual season; monthly temperatures). Of 204 children, 35 (17.2%) were diagnosed with latent TB infection or TB disease. QFT-GIT results were indeterminate in 14 (6.9%) patients. In multivariate analysis, younger age and higher ESR were associated with lower positive control responses (beta: 0.247, p = 0.002 and - 0.204, p = 0.007, respectively), and increasing age was associated with lower rates of indeterminate QFT-GIT results [OR (95% CI) 0.948 (0.903-0.996) per month, p = 0.035]. In children with positive QFT-GIT results, average monthly temperatures correlated with antigen responses (r = 0.453, p = 0.020); also, antigen responses were lower in winter than in other seasons (p = 0.027). Serum cotinine concentrations determined in a subgroup of patients (n = 41) indicated TSE in 36 (88%), positive control responses being lower in children with TSE (p = 0.034). In children < 5 years-of-age, young age, elevated ESR, temperature, annual season and TSE can affect the performance of QFT-GIT assays.

Maintenance of wintertime vitamin D status with cholecalciferol supplementation is not associated with alterations in serum cytokine concentrations among apparently healthy younger or older adults.

Epidemiological studies have shown that low vitamin D status results in impaired immune function and is associated with the prevalence of autoimmune and inflammatory conditions. Vitamin D supplementation has been shown to reduce circulating concentrations of inflammatory markers in such conditions. However, the possible beneficial effect of vitamin D supplementation in the general population, particularly for those individuals living at high latitudes where hypovitaminosis D is common during wintertime, remains unclear. The aim of this study was to assess the effect of vitamin D supplementation using doses of 5, 10, and 15 µg/d cholecalciferol (D3) compared with placebo on cytokine concentrations throughout winter in apparently healthy younger (aged 20-40 y) and older (aged ≥64 y) adults. A total of 211 younger and 202 older adults completed the 22-wk intervention (from October to March) with >85% compliance. Serum concentrations of 25-hydroxycholecalciferol [25(OH)D3], high sensitivity C-reactive protein, IL-6, IL-10, soluble CD40 ligand, TGFß, TNFα, and fibrinogen were measured using ELISA. 25(OH)D3 concentrations significantly decreased in the placebo and 5 and 10/d µg D3 groups in the younger cohort and in the placebo group in the older cohort. Whereas 15 µg/d D3 supplementation maintained 25(OH)D3 concentrations in the younger cohort (baseline, 75.9 nmol/L; postintervention, 69.0 nmol/L) and significantly increased concentrations in the older cohort (baseline, 55.1 nmol/L; postintervention, 73.9 nmol/L), it had no significant effect on cytokine concentrations (ANCOVA, P > 0.05). The long-term effects of low vitamin D status remain to be elucidated and optimization of vitamin D status in otherwise healthy individuals may potentially have lasting beneficial effects on the immune system.

Renal Involvement in Congenital Cytomegalovirus Infection: A Systematic Review.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most frequent mother-to-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term morbidity. The kidney is a target organ for CMV, which replicates in renal tubules and is excreted in large quantities in urine for years in children with cCMV infection. Nonetheless, kidney disease has rarely been reported in cCMV-infected patients. OBJECTIVE: We aimed to describe the available data on renal involvement in patients with cCMV infection at the pathologic, functional, anatomical, and/or clinical levels. METHODS: A systematic search was performed in the MEDLINE/PubMed, SCOPUS, and Cochrane databases. Studies describing any renal involvement in fetuses or neonates aged ≤3 weeks at diagnosis of microbiologically confirmed cCMV infection were eligible. RESULTS: Twenty-four articles were included, with a very low level of evidence. Pathologic findings in autopsy studies universally described CMV typical inclusion bodies in tubular cells. No functional studies were identified. cCMV infection was not associated with an increased risk of kidney malformations. Congenital nephrotic syndrome was the most common clinical condition associated with cCMV, but a causal relationship cannot be established. CONCLUSIONS: Typical pathological features of cCMV infection are very common in renal tissue, but they do not seem to entail significant consequences at the anatomical or clinical levels.

Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease.

Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that (a) MIS-C and prepandemic KD cytokine profiles may be unique and justify the clinical differences observed, and (b) SARS-CoV-2-specific immune complexes (ICs) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 with MIS-C, 9 patients positive for SARS-CoV-2 by PCR without MIS-C (COVID), 14 with prepandemic KD, and 37 healthy controls (HCs). Thirty-four circulating cytokines were quantified in pretreatment serum or plasma samples and the presence of circulating SARS-CoV-2 ICs was evaluated in MIS-C patients. Compared with HCs, the MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ-induced response markers (including IFN-γ, IL-18, and IP-10) and inflammatory monocyte activation markers (including MCP-1, IL-1α, and IL-1RA) being the main triggers of inflammation. In linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-Cplus) differentiated from the remaining MIS-C patients in IFN-γ, IL-18, GM-CSF, RANTES, IP-10, IL-1α, and SDF-1 and incipient signs of macrophage activation syndrome. Circulating SARS-CoV-2 ICs were not detected in MIS-C patients. Our findings suggest a major role for IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.

Cholecalciferol supplementation throughout winter does not affect markers of bone turnover in healthy young and elderly adults.

Although there have been several studies of the effect of vitamin D status on bone turnover in the elderly, the findings are unclear, and, furthermore, to date very few have investigated this in young adults. The objective of these randomized, placebo-controlled, double-blind, 2-center intervention studies was to investigate the effect of cholecalciferol supplementation (0, 5, 10, and 15 microg cholecalciferol/d) throughout winter time on indices of vitamin D status and bone turnover in young (aged 20-40 y; n = 215) and elderly (aged > or = 64 y; n = 204) adults, with relatively high mean calcium intakes of 976 and 874 mg/d, respectively. Fasting serum concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, bone-specific alkaline phosphatase, and carboxyterminal collagen crosslinks were measured by enzyme immunoassays at baseline and endpoint. Fok I and Taq I vitamin D receptor (VDR) genotypes were determined by real-time PCR. Endpoint serum 25(OH)D increased (P < 0.0001) in a dose-related manner with increasing supplemental cholecalciferol (up to 15 microg/d) in 20-40-y olds and up to 10 microg/d in > or = 64-y olds. Endpoint serum PTH was lower (P < 0.05) in the 3 cholecalciferol-supplemented groups compared with that in the placebo group in > or = 64-y olds, but cholecalciferol supplementation did not affect other markers in either cohort and there was no significant interaction with VDR genotype. In conclusion, cholecalciferol supplementation alone throughout winter did not affect bone turnover markers in apparently healthy young and elderly adults, even when stratified by VDR genotype.