Osman Oguz Demir

: Tularemia is a rare zoonotic infection with marked geographic clustering and long interepidemic periods. Pediatric data, particularly those on host immune responses during active disease and treatment, remain scarce. The authors aimed to evaluate clinical characteristics and treatment-associated cytokine dynamics in children with tularemia. In the present multicenter prospective study conducted in Türkiye, 40 pediatric patients with laboratory-confirmed tularemia and nine age- and sex-matched healthy controls were enrolled between April 2023 and November 2024. Clinical features, exposure history, and treatment outcomes were recorded. Serum cytokine levels, including interleukin (IL)-6, IL-2, IL-9, IL-5, IL-13, tumor necrosis factor-α, IL-10, interferon (IFN)-γ, IL-4, and IL-22, were measured using a multiplex bead-based assay and compared between patients and controls, between good and poor outcome groups, and longitudinally before and after therapy. A good outcome was defined as complete clinical resolution without suppuration, the need for surgical intervention, or relapse, whereas a poor outcome was defined as clinical nonresolution or progression. A total of 24 (60%) participants had a good outcome, and 16 (40%) had a poor outcome. Although baseline cytokine levels did not differ between groups, paired analyses revealed significant posttreatment reductions in IFN-γ ( P = 0.018), IL-6 ( P = 0.018), and IL-10 ( P = 0.032), consistent with resolution of infection-associated immune activation. A poor outcome was associated with increased exposure to natural water sources and a higher frequency of suppurative lymphadenopathy requiring surgical drainage. Baseline cytokine profiles did not predict treatment response; however, dynamic changes in IFN-γ, IL-6, and IL-10 were associated with clinical recovery. These findings highlight the importance of longitudinal immune monitoring and provide insight into immune dynamics in pediatric tularemia.

Human adenoviruses (HAdVs) may cause and are responsible for a broad range of pediatric illnesses. Although several cases are self-limiting, certain children may develop complications requiring pediatric intensive care (PICU). To address the role of HAdVs in children, we aimed to characterize the 10-year clinical spectrum of pediatric HAdVs infections and to identify factors associated with hospitalization and severe disease. This retrospective observational cohort study analyzed the clinical course of children (< 18 years) with laboratory-confirmed HAdV infection episodes treated at a tertiary pediatric center between 2014 and 2024. Demographic features, comorbidities, laboratory results, respiratory support requirements, PICU, and clinical outcomes were collected. The severe outcome was defined as a composite endpoint including PICU admission, invasive mechanical ventilation, and/or 30-day mortality. A total of 877 HAdV infection episodes were included, whereas 276 (31.5%) of the patients were hospitalized. Among hospitalized patients, 32.2% required respiratory support, 18.8% required PICU care, and the 30-day mortality was 2.5%. Overall, 104 children (11.9%) developed severe disease. Underlying medical conditions were significantly more frequent among children with severe disease, while those without underlying disease were more common in the non-severe group (69.8% vs. 22.1%; p < 0.001). Viral coinfections were detected in 35.8% of patients but were not associated with increased hospitalization or severity. In multivariable analysis, male sex (OR 2.30, 95% CI 1.23–4.29; p = 0.009), neurologic disease (OR 2.12, 95% CI 1.01–4.42; p = 0.045), cardiac disease (OR 3.27, 95% CI 1.49–7.17; p = 0.003), and hematopoietic stem cell transplantation (HSCT) (OR 4.32, 95% CI 1.36–13.7; p = 0.013) were independently associated with severe outcome. Conclusion : Human adenovirus infection represents a notable clinical burden in children, with a considerable proportion requiring hospitalization and developing severe disease. Underlying neurologic and cardiac diseases, as well as HSCT, were key risk factors for severe outcome, whereas viral coinfections were common but not associated with worse clinical outcome. What is Known? • Human adenovirus (HAdV) infections are common in children and usually self-limiting but may lead to severe disease. • Underlying medical conditions and immunosuppression have been associated with worse clinical outcomes in pediatric HAdV infections. What is New? • Underlying neurologic disease, cardiac disease, and HSCT were identified as independent predictors of severe outcome. • The findings highlight that host-related factors rather than viral coinfection are the main aspects of disease severity.

The definition of septic shock (SS) has been updated in 2020 by Surviving Sepsis Campaign (SCC) International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children as severe infection leading to cardiovascular dysfunction and “sepsis associated organ dysfunction” in children as severe infection leading to cardiovascular and/or non-cardiovascular organ dysfunction (Weiss SL et al., Pediatr Crit Care Med 2020; 21(2): p. e52-e106). SS is one of the most common causes of death in pediatric intensive care units with a mortality rate of 40–60%. About 90% of patients with severe sepsis are presented with high fever. In critically ill pediatric patients fever control is crucial because the increase in oxygen consumption caused by high fever worsens the catabolic process and results in cardiopulmonary collapse. External cooling is an option to manage fever in sepsis which alleviate risk of drug side effect and might be insufficient (Honore PM et al. Ann Intensive Care 2019; 9:56). SCCM guidelines recommend emergent source control after resuscitation and initial stabilization. Hypercytokinemia characterized with increased pro-inflammatory and anti-inflammatory cytokine levels is related with mortality in sepsis. Therefore, recently multiple studies about immunomodulation, immunosuppression and cytokine removal (immunoadsorption) have been reported as alternative implications (Honore PM, 2019). However, there is no strong evidence for routine use of these techniques. We, herein, present a case of SS which developed due to peritonitis as a complication of gastrostomy. In the management of this case, we demonstrated the efficacy of percutaneous peritoneal washing and internal cooling in the control of refractory fever which was resistant despite antibiotic and antipyretic treatments. An 8-year-old female patient, who was followed with the diagnosis of cerebral palsy and familial epilepsy syndrome due to SLC 13A5 deletion and SLC18A2 frameshift mutation, was hospitalized for aspiration pneumonia. During the inpatient period, anti-reflux surgery (Nissen fundoplication) and Stumm gastrostomy was performed because of recurrent aspiration pneumonia, swallowing disorder and massive gastroesophageal reflux. On 22^nd post-operative day, the patient developed respiratory distress, abdominal distension and tenderness on physical examination. A leakage of enteral feeding solution from the gastrostomy suggesting gastrostomy tube displacement was observed. As no improvement was seen under non-invasive mechanical ventilation, the patient was intubated. Abdominal X-ray enhanced with a water-soluble contrast medium revealed leakage of the contrast medium into the peritoneum ([Fig. 1]). Abdominal ultrasonography revealed echogenic intra-abdominal free fluid with a 6 cm thickness, and then 650 ml enteral nutrition solution was drained out from the abdominal cavity through the peritoneal catheter instead of laparotomy since the patient’s clinical status was not stable to underwent general anesthesia. Empiric antimicrobial therapy was extended with vancomycin, meropenem, ornidazole, fluconazole. She also had hypotension which required inotropic supports, including adrenaline, noradrenaline, and dopamine; her vasoactive-inotropic score (VIS) reached to 30 gradually ([Fig. 2]). Despite three days broad spectrum antibiotic treatment and first line source control with drain, there was no improvement in patient’s clinical status and the patient's fever persisted around 40°C under antipyretic therapy and aggressive external cooling. To cope with fever and the source of hyperinflammation, intraperitoneal sterile washing was applied through percutaneous peritoneal drainage catheter for effective source control and cold (+4°C) isotonic saline solution was used to provide internal cooling. 10 cc/kg of cold isotonic saline was filled into the peritoneum with two-hour cycles. After filling, the catheter was left for free drainage without keeping the liquid inside. The patient's fever dropped below 37.5°C after the third washing session. With the decrease of fever, the patient became hemodynamically stable and inotropic treatments were started to be tapered off (VIS:25) within first hours and the need for inotropic therapy was significantly reduced in the first 24 hours (VIS:10) ([Fig. 2]). After continuing the administration for 48 hours, the body temperature remained stable within normal ranges. We did not observe electrolyte imbalance, dehydration, and fluid overload with this intervention during three days of the procedure ([Table 1]). Once the patient’s situation became stabilized in Day 8, gastrostomy displacement was confirmed with the surgical exploration and gastrostomy was surgically revised and Jackson-Prett type peritoneal drain was inserted, and she was extubated on the second postoperative day. The feeding through gastrostomy, was reinstituted with a gradual increase up to 8×200 cc/day. The physical examination findings of the patient improved, and the drain was removed. Article published online: 10 December 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany