Distinct clinical parameters were associated with shorter spontaneous resolution in children with non-tuberculous mycobacterial lymphadenitis.

AIM: Non-tuberculous mycobacteria (NTM) lymphadenitis typically resolves spontaneously, yet factors influencing the duration remain explored. We aimed to identify clinical parameters associated with shorter spontaneous resolution. METHODS: This cohort study included children with NTM lymphadenitis from 1 January 2015 to 1 March 2021 at Copenhagen University Hospital. Time-to-event analysis assessed clinical parameters associated with the duration of NTM lymphadenitis. RESULTS: Sixty children (57% boys) with a median age of 24 months (range 11-84) were included; 13 (22%) received primary surgery, 13 (22%) underwent surgery after a wait-and-see period and 34 (57%) received no intervention. In children without intervention, the median duration was 10 months (range 2-25). Faster resolution was associated with parental-reported lymph node enlargement within 2 weeks (HR 2.3, 95% CI 1.0-5.0; p = 0.044), abscess on ultrasound examination (HR 3.3, 95% CI 1.5-7.3; p = 0.003) and skin discoloration and/or perforation within 3 months of onset (HR 4.3, 95% CI 1.3-14.4; p = 0.017 and HR 3.7, 95% CI 1.5-9.1; p = 0.005). CONCLUSION: Knowledge of predictors for shorter spontaneous resolution of NTM lymphadenitis, such as rapid initial lymph node enlargement, abscess on ultrasound examination, and skin discoloration and/or perforation within 3 months of disease onset, may guide clinical management decisions concerning surgery versus a conservative approach.

Invasive group A streptococcal infections in children and adolescents in Denmark during 2022-23 compared with 2016-17 to 2021-22: a nationwide, multicentre, population-based cohort study.

BACKGROUND: A historic increase in paediatric invasive group A streptococcal (iGAS) infections was reported globally in 2022. iGAS infections can lead to severe manifestations (eg, pleural empyema, necrotising fasciitis, toxic shock syndrome, osteomyelitis, septic arthritis, and meningitis). We aimed to compare the incidence and severity of iGAS infections overall, for distinct clinical phenotypes, and for GAS emm variants in Denmark in 2022-23 with reference to the previous six seasons (ie, 2016-17, 2017-18, 2018-19, 2019-20, 2020-21, and 2021-22). METHODS: In this nationwide, multicentre, population-based cohort study, we included all children and adolescents in Denmark aged 0-17 years with a positive culture of GAS or GAS confirmed through PCR-based methods from otherwise sterile sites in 2022-23 and the previous six seasons from 2016-17 to 2021-22. For all seven seasons, data were obtained from week 21 to week 20 of the next year. Patients at all 18 paediatric hospital departments in Denmark were identified through the Danish Microbiology Database, in which iGAS isolates from sterile sites are prospectively registered, including emm typing. We obtained electronic medical health records for each patient admitted with a diagnosis of iGAS. We calculated the incidence of iGAS per 1 000 000 inhabitants aged 0-17 years in each season from week 21 to week 20 of the next year and the risk ratios (RRs) for incidence of iGAS, distinct disease manifestations, and emm variants in 2022-23 versus the three pre-COVID-19 seasons in 2016-17, 2017-18, and 2018-19 using Fisher's exact test and Pearson's χ2 test. FINDINGS: Among the Danish population of 1 152 000 children and adolescents aged 0-17 years, 174 with iGAS disease were included. 76 children and adolescents with iGAS during 2022-23 were identified; 31 (41%) of 76 were female and 45 (59%) were male. 98 children and adolescents with iGAS during 2016-17 to 2021-22 were identified; 41 (42%) of 98 were female and 57 (58%) were male. There was an increase in incidence of iGAS from mean 22·6 (95% CI 14·7-33·1) per 1 000 000 children and adolescents during 2016-17 to 2018-19 to 66·0 (52·0-82·6) per 1 000 000 during 2023-23 (RR 2·9, 95% CI 1·9-4·6; p<0·0001). During the COVID-19 pandemic in 2019-20, 2020-21, and 2021-22, the mean incidence of iGAS was 6·1 (95% CI 2·4-12·5) per 1 000 000 children and adolescents. In 2022-23, there was a 9·5-fold increase in emm-12 (95% CI 2·2-40·8; p=0·0002) and a 2·7-fold increase in emm-1 (1·3-5·5; p=0·0037). The most common clinical manifestations of iGAS in 2022-23 were soft-tissue infections, which increased by 4·5-fold (1·9-10·9; p=0·0003), and complicated pneumonia with parapneumonic effusion, which increased by 4·0-fold (1·4-11·4; p=0·0059), both compared with the three pre-COVID-19 seasons. Overall, there was no increased severity of iGAS in 2022-23 compared with the previous six seasons as measured by median duration of hospital stay (8 days, IQR 4-14 vs 9 days, 5-15; p=0·39), paediatric intensive care unit (PICU) admission (17 [22%] of 76 vs 17 [17%] of 98; p=0·53), duration of stay in PICU (4 days, IQR 2-10 vs 4 days, 2-11; p=0·84), or mortality (three [4%] of 76 vs three [3%] of 98; p=1·00). In 2022-23, there was a 3·6-fold (95% CI 1·8-7·3; p=0·0001) increase in children with a preceding upper respiratory tract infection and a 4·6-fold (1·5-14·1; p=0·0034) increase in children with a preceding varicella-zoster infection, both compared with the three pre-COVID-19 seasons. INTERPRETATION: In Denmark, the incidence of paediatric iGAS increased in 2022-23 compared with the three pre-COVID-19 seasons of 2016-17, 2017-18, and 2018-19. However, the course of iGAS disease in children and adolescents in 2022-23 was not more severe than in previous seasons. The high morbidity across all seasons highlights iGAS as a major invasive bacterial infection in children and adolescents. FUNDING: Innovation Fund Denmark.

Proteomic profiling reveals diagnostic signatures and pathogenic insights in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that emerged during the COVID-19 pandemic. Although recognized as an immune-mediated condition, the pathogenesis remains unresolved. Furthermore, the absence of a diagnostic test can lead to delayed immunotherapy. Using state-of-the-art mass-spectrometry proteomics, assisted by artificial intelligence (AI), we aimed to identify a diagnostic signature for MIS-C and to gain insights into disease mechanisms. We identified a highly specific 4-protein diagnostic signature in children with MIS-C. Furthermore, we identified seven clusters that differed between MIS-C and controls, indicating an interplay between apolipoproteins, immune response proteins, coagulation factors, platelet function, and the complement cascade. These intricate protein patterns indicated MIS-C as an immunometabolic condition with global hypercoagulability. Our findings emphasize the potential of AI-assisted proteomics as a powerful and unbiased tool for assessing disease pathogenesis and suggesting avenues for future interventions and impact on pediatric disease trajectories through early diagnosis.

Fatal SARS-CoV-2-Associated Panton-Valentine Leukocidin-producing Staphylococcal Bacteremia: A Nationwide Multicenter Cohort Study.

We reviewed all cases of Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) bacteremia in Danish children between 2016 and 2021. We found 2 fatal cases with preceding viral prodrome due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the usual benign course of SARS-CoV-2 infection in children, awareness of possible superinfection with PVL-SA in a child with rapid deterioration is crucial to ensure adequate treatment, including antimicrobial drugs with antitoxin effect.

Platelet hyperreactivity in response to on- and off-pump coronary artery bypass grafting.

Hypercoagulability has been reported after off-pump coronary artery bypass grafting (OPCAB) compared with patients undergoing standard coronary artery bypass grafting (CABG) with cardiopulmonary bypass. The aim of this study was to evaluate the changes in platelet reactivity in response to cardiac surgery, both OPCAB and CABG. Platelet reactivity was monitored pre- and postoperatively (days 1 and 4) in elective OPCAB (n = 29) and CABG (n = 24) patients using the maximal amplitude (MA) parameter obtained with thrombelastography. Platelet reactivity was also examined at 1 month in 30 of the 53 patients. Twenty-three percent of the patients (12/53) had a preoperative MA value above normal reference value (MA > 69 mm). By postoperative day 4, 88% of the patients presented with an MA > 69 mm, and significant increases in MA were shown in both groups (p < .0001). Of the 30 patients examined at 1 month after surgery, 75% of the patients with high preoperative MA (6/8) remained at this level. In contrast, only 4.5% of patients with normal preoperative MA (1/22) presented with high MA at day 30. MA has previously been shown to correlate with the incidence of thrombotic and ischemic complications and this study identified 23% of patients needing coronary bypass surgery to be at high risk for recurrent ischemic events at 1 month after surgery, based on the MA. These results suggest that a more aggressive antithrombotic treatment might be warranted for patients undergoing coronary artery bypass grafting, both OPCAB and CABG, presenting with a high MA pre- and postsurgery.

[Neonatal suppurative parotitis in a six-day-old, mature boy].

Neonatal suppurative parotitis is a rare condition with approximately 50 cases reported in the literature in English since 1970. It is characterized by parotid swelling along with other local inflammatory sign, and some neonates present with fever and irritability. Pus secretion from the ipsilateral parotid duct is pathognomonic. The most common pathogen is Staphylococcus aureus, but other microorganisms are reported. We describe a case of a six-day-old, mature boy, previously healthy, who presented with fever, tender swelling of the right parotid and pus secretion from the parotid duct.

Immune response after one or two doses of pandemic influenza A (H1N1) monovalent, AS03-adjuvanted vaccine in HIV infected adults.

INTRODUCTION: Continued research is needed to evaluate and improve the immunogenicity of influenza vaccines in HIV infected patients. We aimed to determine the antibody responses after one or two doses of the AS03-adjuvanted pandemic influenza A (H1N1) vaccine in HIV infected patients. METHOD: Following the influenza season 2009/2010, 219 HIV infected patients were included and divided into three groups depending on whether they received none (n=60), one (n=31) or two (n=128) doses of pandemic influenza A (H1N1) vaccine. At inclusion, antibody titers for all patients were analyzed and compared to pre-pandemic antibody titers analyzed from serum samples in a local storage facility. RESULTS: 4-9 months after a single immunization, we found a seroprotection rate of 77.4% and seroconversion rate of 67.7%. After two immunizations the rates increased significantly to seroprotection rate of 97.7% and seroconversion rate of 86.7%. CONCLUSION: A single dose of AS03-adjuvanted pandemic influenza A (H1N1) vaccine created an adequate immune response in HIV infected patients lasting as long as 4-9 months. Two doses improved the immunogenicity further.

[Botulism in an infant]. / Botulisme hos et spaedbarn.

We describe a case of botulism in a 4.5 month-old girl with complete recovery after intravenous administration of botulism immune globulin. The girl was admitted for 19 days during which supplementary nasogastric feeding was necessary. Mechanical ventilation was not needed. Despite thorough investigation, contaminated food was not found. One particular batch of canned baby food was suspected and recalled from the market, but no contamination was found. The girl had not ingested honey. The condition is rare, but can be very serious and should be kept in mind in cases presenting with the well-defined symptoms of the condition.

Hypercoagulability and platelet inhibition after OPCAB. Randomized intervention with clopidogrel.

OBJECTIVE: Data on graft patency after Off-Pump Coronary Artery Bypass (OPCAB) suggest that the incidence of early graft closure is not increased compared to conventional coronary artery bypass surgery. However, hypercoagulability following OPCAB is still of concern, and acetylsalicylic acid as thromboembolic prophylaxis might be insufficient in the first weeks following OPCAB surgery. DESIGN: Twenty nine patients were randomly assigned to+/- 75 mg of clopidogrel until 30 days after OPCAB surgery. The follow-up time was 2 months including standard blood samples and thrombelastography (TEG) with a specific platelet inhibition assay, which was evaluated as a part of the study. RESULTS: In both groups a significant increase in TEG maximum amplitude was found 5 days after surgery. Platelet inhibition showed great variations but was significantly increased in the clopidogrel group (34.1%) vs. control group (11.0%) after 1 month. CONCLUSION: Hypercoagulability was seen 5 days after OPCAB and could not be demonstrated after 1 month. No clinical effects of the hypercoagulability were observed, and further research is needed to determine if clopidogrel should be recommended after OPCAB.

Higher Thrombelastograph platelet reactivity in cardiac surgery patients than in blood donors.

OBJECTIVES: Platelet reactivity, evaluated by Thrombelastograph (TEG) predicts the recurrence of ischemic events in patients undergoing percutaneous coronary intervention (PCI). The aim of this study was to investigate the platelet hyperreactivity and the variability in platelet reactivity due to ADP in cardiac surgery patients and donors. METHODS: Preoperative blood samples from 22 patients undergoing CABG surgery and 43 blood donors were analysed by the TEG Platelet Mapping assay. Maximal platelet reactivity and platelet reactivity response to ADP stimulation (MAADP) were evaluated. RESULTS: Maximal platelet reactivity (MAThrombin) and MAADP was higher in the CABG patients than in the blood donors, p=0.001 for MAThrombin and p<0.0001 for MAADP. Six patients (27.2%) had a MAThrombin above the normal reference range compared to only one (2.3%) of the healthy donors (p=0.005). CONCLUSIONS: The identification of a higher subpopulation of CABG patients compared to donors presenting with platelet reactivity above the normal range together with increased platelet responsiveness to ADP may reflect the higher risk for ischemic events in this cohort.