SARS-CoV-2 RNA monitoring in wastewater as a potential early warning system for COVID-19 transmission in the community: A temporal case study.

MDSCs in sepsis-induced immunosuppression and its potential therapeutic targets.

Diseases caused by pathogenic bacteria in animals (e.g., bacterial pneumonia, meningitis and sepsis) and plants (e.g., bacterial wilt, angular spot and canker) lead to high prevalence and mortality, and decomposition of plant leaves, respectively. Melatonin, an endogenous molecule, is highly pleiotropic, and accumulating evidence supports the notion that melatonin's actions in bacterial infection deserve particular attention. Here, we summarize the antibacterial effects of melatonin in vitro, in animals as well as plants, and discuss the potential mechanisms. Melatonin exerts antibacterial activities not only on classic gram-negative and -positive bacteria, but also on members of other bacterial groups, such as Mycobacterium tuberculosis. Protective actions against bacterial infections can occur at different levels. Direct actions of melatonin may occur only at very high concentrations, which is at the borderline of practical applicability. However, various indirect functions comprise activation of hosts' defense mechanisms or, in sepsis, attenuation of bacterially induced inflammation. In plants, its antibacterial functions involve the mitogen-activated protein kinase (MAPK) pathway; in animals, protection by melatonin against bacterially induced damage is associated with inhibition or activation of various signaling pathways, including key regulators such as NF-κB, STAT-1, Nrf2, NLRP3 inflammasome, MAPK and TLR-2/4. Moreover, melatonin can reduce formation of reactive oxygen and nitrogen species (ROS, RNS), promote detoxification and protect mitochondrial damage. Altogether, we propose that melatonin could be an effective approach against various pathogenic bacterial infections.

Bacteriostatic Potential of Melatonin: Therapeutic Standing and Mechanistic Insights.

Introduction: Human adenovirus (HAdV) is a common pathogen in children with acute respiratory infections (ARIs). However, limited information is available regarding the association of HAdV types and outcomes in children with severe adenovirus pneumonia. Thus, this study aimed to describe the epidemiological, molecular, and clinical features of HAdV among hospitalized children with ARIs in Wenzhou, southeastern China. Methodology: Nasopharyngeal swab or sputum specimens were prospectively collected from hospitalized children with ARIs from January 2018 to December 2019. HAdV was detected using direct immunofluorescence. We performed multiplex polymerase chain reaction (PCR) combined with capillary electrophoresis to target the hypervariable region of the hexon gene to identify HAdV types 1, 2, 3, 4, 5, 7, 14, 21, 37, 40, 41, and 55. We analyzed epidemiological, molecular, and clinical data according to the HAdV types. Results: HAdVs were detected in 1,059 (3.5%) of 30,543 children tested. We included 947 children cases with monotype HAdV identified using PCR in the analysis. Phylogenetic analysis revealed that HAdV-3 (43.8%), HAdV-7 (33.6%), HAdV-2 (11.4%), and HAdV-1 (7.4%) were the predominant types. Among 550 (58.1%) children with HAdVs from December 2018 to August 2019, HAdV-3 and HAdV-7 were the main types. The main diagnoses included 358, 232, 198, and 159 cases of pneumonia, tonsillitis, bronchitis, and upper respiratory tract infection (URTI), respectively. HAdV-7 (51.1%), HAdV-3 (36.9%), and HAdV-1 (2.2%) were mainly found in children with pneumonia, while HAdV-3 (48.0%), HAdV-7 (28.3%), and HAdV-2 (10.6%) were mainly found in children with bronchitis. Among children with URTIs, the main types were HAdV-3 (49.7%), HAdV-7 (22.6%), and HAdV-2 (13.2%), and among children with tonsillitis, the main types were HAdV-3 (47.4%), HAdV-2 (22.4%), and HAdV-7 (18.5%). Overall, 101 (55.2%) children required supplemental oxygen, 15 (8.2%) required critical care, and one (0.5%) with HAdV-7 pneumonia died. Conclusion: HAdV-3, HAdV-7, HAdV-2, and HAdV-1 were the predominant types identified among hospitalized children with ARIs in Wenzhou. From December 2018 to August 2019, there were outbreaks caused by HAdV-3 and HAdV-7. There were significant differences in HAdV types among children with pneumonia, tonsillitis, bronchitis, and URTI. HAdV-7 can cause more severe pneumonia in children than HAdV-3.

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The Epidemiology, Molecular, and Clinical of Human Adenoviruses in Children Hospitalized With Acute Respiratory Infections.

To assess the impact of plasma and platelet ratios and deficits in injured children with life-threatening bleeding.Secondary analysis of the MAssive Transfusion epidemiology and outcomes In Children study dataset, a prospective observational study of children with life-threatening bleeding events.Twenty-four childrens hospitals in the United States, Canada, and Italy.Injured children 0-17 years old who received greater than 40 mL/kg total blood products over 6 hours or were transfused under activation of massive transfusion protocol.Weight-adjusted blood product volumes received during the bleeding event were recorded. Plasma:RBC ratio (plasma/RBC weight-adjusted volume in mL/kg) and platelet:RBC ratio (platelet/RBC weight-adjusted volume in mL/kg) were analyzed. Plasma deficit was calculated as RBC mL/kg - plasma mL/kg; platelet deficit was calculated as RBC mL/kg - platelet mL/kg.Of 191 patients analyzed, median (interquartile range) age was 10 years (5-15 yr), 61% were male, 61% blunt mechanism, and median (interquartile range) Injury Severity Score was 29 (24-38). After adjusting for Pediatric Risk of Mortality score, cardiac arrest, use of vasoactive medications, and blunt mechanism, a high plasma:RBC ratio (> 1:2) was associated with improved 6-hour survival compared with a low plasma:RBC ratio (odds ratio [95% CI] = 0.12 [0.03-0.52]; p = 0.004). Platelet:RBC ratio was not associated with survival. After adjusting for age, Pediatric Risk of Mortality score, cardiac arrest, and mechanism of injury, 6-hour and 24-hour mortality were increased in children with greater plasma deficits (10% and 20% increased odds of mortality for every 10 mL/kg plasma deficit at 6 hr [p = 0.04] and 24 hr [p = 0.01], respectively); 24-hour mortality was increased in children with greater platelet deficits (10% increased odds of 24-hr mortality for every 10 mL/kg platelet deficit [p = 0.02)]).In injured children, balanced resuscitation may improve early survival according to this hypothesis generating study. Multicenter clinical trials are needed to assess whether clinicians should target ratios and deficits as optimal pediatric hemostatic resuscitation practice. 

Transfusion Ratios and Deficits in Injured Children With Life-Threatening Bleeding*

Multidrug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors and overall mortality for MDR/XDR Acinetobacter baumannii infected pediatric patients. This retrospective study included 102 pediatric patients who developed MDR/XDR Acinetobacter baumannii infection in the pediatric intensive care unit (PICU) of Shanghai Children’s Hospital in China from December 2014 to May 2018. Acinetobacter baumannii clinical isolates were recovered from different specimens including blood, sputum, bronchoalveolar lavage fluid, cerebrospinal fluid, ascites, hydrothorax, and urine. Antibiotic susceptibility test was determined according to the Clinical and Laboratory Standards Institute interpretive criteria. Clinical and biological data were obtained from the patients’ medical records. 102 patients with Acinetobacter baumannii infection were enrolled. The median age was 36 (9.6, 98.8) months, and there were 63 male in the case group. The overall mortality rate was 29.4%, while the Acinetobacter baumannii-associated mortality rate was 16.7% (17/102, 12 bloodstream infections, 4 meningitis and 1 intra-abdominal infection). Bloodstream infections occurred in 28 patients (27.5%), and 10 patients (9.8%) among them had central line-associated bloodstream infections (6 central venous catheters, 2 PICCs, 1 venous infusion port and 1 arterial catheter). Cerebrospinal fluid (CSF) cultures were positive in 4(3.9%) patients. 14(13.7%) patients got positive cultures in ascites and hydrothorax. Lower respiratory isolates (56/102) accounted for 54.9% of all patients. Non-survival patients appeared to have a lower NK cell activity (6.2% ± 3.61% vs. 9.15% ± 6.21%, P = 0.029), higher CD4+ T cell ratio (39.67% ± 12.18% vs. 32.66% ± 11.44%, P = 0.039),and a higher serum level of interlukin-8 (IL-8, 15.25 (1.62, 47.22)pg/mL vs. 0.1 (0.1, 22.99)pg/mL, P = 0.01) when Acinetobacter baumannii infection developed. Multivariate logistic analysis indicated that high serum level of Cr (RR, 0.934, 95%CI, 0.890–0.981; P = 0.007) and high BUN/ALB level (RR, 107.893, 95%CI, 1.425–870.574; p = 0.005) were associated with high risk of mortality in MDR/XDR Acinetobacter baumannii infected patients. MDR/XDR Acinetobacter baumannii infection is a serious concern in pediatric patients with high mortality. Bloodstream and central nervous system infection accounted for high risk of death. Acute kidney injury is associated with high risk of mortality.

/pdf/multidrug-resistant-and-extensively-drug-resistant-27uur1gvrs.pdf

Multidrug resistant and extensively drug resistant Acinetobacter baumannii hospital infection associated with high mortality: a retrospective study in the pediatric intensive care unit.

Background Extracorporeal therapy that included therapeutic plasma exchange (TPE) or continuous hemofiltration (CHF) for toxic epidermal necrolysis (TEN) syndrome was used in small number of patients. We aimed to describe the sequential mode of combined application of CHF and TPE in 3 TEN patients with multiple organ dysfunction (MODS) in pediatric intensive care unit. Methods Three patients with fatal TEN received sequential CHF and TPE due to unsatisfactorily conventional treatments. CHF was initiated and performed on a daily basis with 35-50 mL/kg.h replacement fluid at the rate of 3-5 mL/kg.min blood flow. CHF was temporarily interrupted for TPE, which was performed with exchange 1-1.5-fold of one body calculated plasma volume in each section. Results All 3 fatal TEN (with >30% involvement of body surface and MODS) following unsuccessful treatment with corticosteroids and intravenous immunoglobulin. Antibiotics were suspected in the TEN-triggered drugs. The range number of TPE sessions was 3-5 and the duration of CHF was from 120 h to 202 h. After initiation of TPE and CHF, blistering with extensive epidermal necrosis halted and the skin re-epithelialized within 2 weeks. Serum C-reactive protein, procalcitonin, tumor necrosis factor-α , and interlukin-6 decreased and percentage of natural killer cells increased in surviving children. Two patients survived to discharge and one case died due to nosocomial infection with multidrug-resistant Acinetobacter baumannii. Conclusion After sequential TPE and CHF, skin lesions and inflammatory response improved in TEN. Our result indicates extracorporeal therapy could be used as an alternative modality for fatal pediatric TEN.

Sequential Blood Purification for Pediatric Fatal Toxic Epidermal Necrolysis: A Case Series.

Objective: To investigate the risk factors of central nervous system (CNS) complications in children undergoing extracorporeal membrane oxygenation (ECMO) support. Methods: The clinical data, ECMO parameters, laboratory examination and outcome (follow-up to 90 d after discharge) of 82 children treated with ECMO in the pediatric intensive care unit (PICU) of Shanghai Children's Hospital from December 2015 to December 2021 were analyzed retrospectively in this study. The patients were divided into CNS complication group and non-CNS complication group. The ECMO mode, ECMO catheterization mode, clinical and laboratory indicators pre-ECMO and 24 h after ECMO initiation, in-hospital mortality and 90-day mortality were compared with Chi-square test, t test and nonparametric rank sum test. Kaplan-Meier method was used to draw survival curve, and Log-rank test was used to compare the difference in survival rate. The receiver operating characteristic (ROC) curve was used to evaluate the power of variables to predict CNS complications. Results: A total of 82 children were treated with ECMO, including 49 males and 33 females, aged 34 (8, 80) months. There were 18 cases suffering CNS complications, including cerebral hemorrhage in 8 cases, epilepsy in 6 cases, simple cerebral infarction in 3 cases, and cerebral hemorrhage combined with cerebral infarction in 1 case. Veno-arterial ECMO accounted for a greater proportion in CNS complication group (17/18 vs. 67% (43/64), χ2=4.02, P=0.045). A higher percentage of children with CNS complications underwent surgical cannulation compared to those in non-CNS complication group (16/18 vs. 53% (34/64), χ2=7.55, P=0.006). The laboratory results indicated that lower pre-ECMO pH value (7.24 (7.15, 7.28) vs. 7.35 (7.26, 7.45), Z=-3.65, P<0.001) and platelet count 24 h after ECMO initiation (66 (27, 135) ×109/L vs. 107 (61, 157) ×109/L, Z=-2.04, P=0.041) were associated with CNS complications. In the CNS complication group, 7 children died during hospitalization and 7 died during 90-day after admission, and there was no significant difference compared with those in the non-CNS complication group (7/18 vs. 31% (20/64), 7/18 vs. 34% (22/64), both P>0.05). The ROC curve analysis indicated that the area under the ROC curve for pre-ECMO pH value was 0.738 (95%CI 0.598-0.877), and the optimal cut-off value was 7.325. Conclusions: CNS complications in children undergoing ECMO support are common. Pre-ECMO pH value <7.325 is a risk factor for CNS complications. Reducing the veno-arterial ECMO and surgical cannulation can help reduce the occurrence of CNS complications.

[Analysis of risk factors of central nervous system complications supported on extracorporeal membrane oxygenation].

Objective The cancer patients with severe acute respiratory distress syndrome (ARDS) benefit from extracorporeal membrane oxygenation (ECMO) remains unanswered. We analyzed clinical characteristics and outcomes of pediatric patients with leukemia/lymphoma who developed ARDS and treated with ECMO. Methods Pediatric leukemia or lymphoma patients with ARDS who underwent ECMO between August 2017 and December 2021 were retrospectively analyzed in a tertiary pediatric intensive care unit (PICU). Results Seven patients with median age 53 (IQR 42–117) months and 4 males were included. Six cases of leukemia [5 of acute lymphocytic leukemia (ALL) and 1 of acute myelogenous leukemia (AML, M5)] and 1 of non-Hodgkin lymphoma with severe ARDS received ECMO on chemotherapy period. The etiology of ARDS is community or chemotherapy-associated bacterial or/and fungal or viral infection. All the patients received chemotherapy in the 2 weeks prior to ECMO and five were neutropenic at initial ECMO. Six cases underwent veno-arterial ECMO (VA ECMO) and 1 for veno-venous ECMO (VV-ECMO). The median duration of ECMO support was 122 (IQR 56–166) hours. Overall, 42.9% (three of seven) survived to hospital discharge and 6 months survival rate was 28.6% (two of seven). Bleeding was the main ECMO-associated complication occurring in 7 patients, followed by nosocomial infection in 4 cases. All the patients required vasopressor support, and 6 received continuous renal replacement therapy (CRRT). Conclusion Our experiences suggest that rescue ECMO provides a selective treatment strategy in childhood hematologic malignancies with severe ARDS.

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Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in children with leukemia/lymphoma: A retrospective case series

Miao, H.1; Cui, Y.1; Lu, Y.1; Sun, T.1; Dou, J.1; Ren, Y.1; Wang, C.2; Zhang, Y.3 Author Information 

OP003 [Infections » Sepsis]: SERUM VIMENTIN PREDICTS MORTALITY IN PEDIATRIC SEVERE SEPSIS: A PROSPECTIVE OBSERVATIONAL STUDY

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