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BACKGROUND Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of .antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants. METHODS We used a case-control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than 6 months of age. Between July 1 2021 and March 8,2022 we enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 states. We estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.6172 (delta) variant (July 1 2021 to December 18 2021) and the B.1.1.259 (omicron) variant (December 19, 2021, to March 8, 2022). RESULTS A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age 2 months) and512 control infants were enrolled and included in the analyses; 16°/0 of the case infants and 29 of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants 113 (21%) received intensive care (64 [1296] received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant's mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95 confidence interval ICI] 33 to 65) overall 80% (95% CI 60 to 90) during the delta period and 38% (95% CI 8 to 58) during the omicron period. Effectiveness was 6996 (95% CI,50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI 3 to 60) during the first 20 weeks of pregnancy. CONCLUSIONS Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19 including for critical illness among infants young- er than 6 months of age. (Funded by the Centers for Disease Control and Prevention.) [ABSTRACT FROM AUTHOR]

BACKGROUND The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 US. hospitals between March 15 and October 31, 2020. The effectiveness ofinitial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use ofvasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75°6 had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probabilityweighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.) [ABSTRACT FROM AUTHOR]

BACKGROUND Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores =2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. [ABSTRACT FROM AUTHOR]

The objective of our study was to determine the role of ibuprofen in protecting neutropenic rats from cardiopulmonary injury due to endotoxemia. We hypothesized that ibuprofen would offer pulmonary protection by altering cytokine production. Neutropenic rats received E. coli lipopolysaccharide (LPS) alone or ibuprofen and LPS. After 4 h, arterial blood gases, heart rate and blood pressure were measured. Blood and bronchoalveolar lavage fluid (BALF) were collected for TNF- alpha and MIP-2 concentrations. Lung tissue for iNOS mRNA and myeloperoxidase were obtained. The ibuprofen group had decreased heart rate and better oxygenation. Ibuprofen suppressed TNF- alpha and MIP-2 production in blood and MIP-2 concentrations in BALF. Lung mRNA for iNOS was higher in the ibuprofen group. Neutrophil infiltration in the lung was similar in both groups. Ibuprofen attenuated cardiopulmonary dysfunction by decreasing the early cytokine response. The balance of vasodilator to vasoconstrictor production in the lung may favor vasodilation as shown by increased iNOS mRNA and suppression of thromboxane., (Copyright 2001 Harcourt Publishers Ltd.)

Background: Elevated plasma lactate has been shown to correlate with mortality in patients with septic shock. Heat stress prior to sepsis has resulted in reduction in acute lung injury and mortality. We investigated whether heat stress resulted in decreased plasma lactate concentration and protected the lung by decreasing the inflammatory response to sepsis., Results: Plasma lactate concentration was elevated in septic rats without prior heat stress. Lactic acid levels were significantly lower in heat-treated septic rats (P < 0.05) and were not significantly different when compared with control rats. Septic rats with or without heat pretreatment had significantly higher myeloperoxidase activity in the lung than did control groups. Heat pretreatment did not prevent neutrophil infiltration or inflammatory mediator production in the lung., Conclusion: Prior heat stress ameliorates lactic acidemia in rat sepsis. Heat stress did not attenuate the pulmonary inflammatory process. The mechanism of heat-induced protection from lactic acidemia in sepsis needs to be further explored.

Ibuprofen, a cyclooxygenase inhibitor, improves pulmonary and cardiovascular injury in endotoxemia. We studied the mechanism of the beneficial effects of ibuprofen in relation to production of inflammatory mediators which influence vascular tone in endotoxemia. Rats were randomly assigned to one of three groups: (1) control, (2) endotoxemia alone; and (3) ibuprofen pretreatment and endotoxemia. Plasma and lung lavage concentrations of tumor necrosis factor, thromboxane B2 (TXB2), leukotriene (LT) C4,D4,E4 and nitric oxide (NO) were determined over a 2 h period. Pretreatment with ibuprofen resulted in increased survival, and attenuation of pulmonary and cardiovascular dysfunction when compared to the rats receiving endotoxin alone. The marked elevation in plasma TXB2 concentration in endotoxemic rats was prevented by pretreatment with ibuprofen. Similarly, pretreatment with ibuprofen prevented the decrease in lung lavage NO levels in endotoxemic rats. The improved survival and cardiopulmonary protection in endotoxemic rats pretreated with ibuprofen appears to be related to decreased thromboxane production and preservation of endothelial production of nitric oxide.

Purpose: Signs and symptoms of delayed hemolytic transfusion reaction (DHTR) may resemble those of vaso-occlusive crises in patients with sickle cell anemia (SCA). The diagnosis of DHTR therefore presents a challenge to the clinician when treating such patients. The current study describes a patient with SCA and DHTR secondary to red cell anti-s antibody, manifesting as painful extremeties, severe hemolytic anemia, and acute oliguric renal failure., Patients and Methods: A 17-year-old patient with homozygous hemoglobin S presented 8 days after partial exchange transfusions with severe anemia and signs and symptoms resembling vaso-occlusive crisis. Clinical course was complicated by intravascular hemolysis and acute renal failure., Results: Anti-s antibody was detected in the eluate. Diagnosis of DHTR was made. Treatment included single volume whole blood exchange transfusion and continuous veno-venous hemofiltration with dialysis., Conclusions: The possibility of DHTR should be considered in a patient with SCA with hemolytic anemia. Acute renal failure is a rare complication of anti-s antibody-associated DHTR. Such reactions can be successfully managed with exchange transfusion and continuous hemofiltration with dialysis.

Background: Proinflammatory mediators that include tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) and anti-inflammatory mediators such as interleukin-10 (IL-10) modulate the immune response to endotoxemia. IL-10 downregulates the production of TNF-alpha and MIP-2. Acute lung injury may occur secondary to neutrophil chemotaxis mediated by chemokine MIP-2. We studied the temporal relationship of TNF-alpha, MIP-2, and IL-10 in rat endotoxemia and correlation of MIP-2 concentrations with acute lung injury., Methods: Ten ventilated rats were randomized to receive an intravenous infusion of 2 mg/kg Escherichia coli lipopolysaccharide (n = 6) or saline placebo (n = 4). Blood pressure was continuously monitored and arterial blood was obtained for lactate, blood gas, TNF-alpha, IL-10, and MIP-2 measurements at baseline, 2, 4, and 5.5 hours after LPS or saline infusion., Results: Endotoxemia resulted in hypotension, lactic acidemia, and increased alveolar-arterial oxygen gradient (A-a O2 gradient) compared with the placebo group. TNF-alpha, MIP-2, and IL-10 levels were increased 2 hours after endotoxemia. Subsequently, TNF-alpha levels declined while IL-10 and MIP-2 levels remained elevated. Control rats had no significant increase in cytokine production at any time point. MIP-2 concentrations correlated with A-a O2 gradient, an indicator of lung injury (r = 0.56, p < 0.001)., Conclusions: MIP-2, possibly released by TNF-alpha stimulation of macrophages, is associated with acute lung injury possibly by inducing neutrophil chemotaxis. IL-10 may exert its counter-inflammatory response by inhibiting the release of TNF-alpha in endotoxemia.

Objective: To evaluate the clinical characteristics and neurologic outcome of children with carbon monoxide poisoning treated with normobaric oxygen therapy., Methods: We reviewed the medical records of all children with a diagnosis of carbon monoxide exposure admitted during a 10-year period. Exposures were categorized as (1) severely toxic, carboxyhemoglobin level >25%; (2) toxic, carboxyhemoglobin level 10.1 to 25%; (3) suspected toxic, carboxyhemoglobin level < or = 10% with acute neurologic manifestations; or (4) nontoxic, carboxyhemoglobin < or = 10% without acute neurologic manifestations., Results: One hundred six patients (median age, 3.5 years; range, 0.1-14.9 years) were identified, 37 with severe toxic, 37 with toxic, 13 with suspected toxic, and 19 with nontoxic exposures. The most common presenting signs or symptoms included altered level of consciousness, metabolic acidosis, tachycardia, and hypertension. All patients received normobaric oxygen for 5.5 hours (range, 0.6-44 hours). Carboxyhemoglobin levels decreased to less than 3% in 3.6 hours (range, 0-15.5 hours). Fifteen patients died, three from massive burn injury, eight from hypoxic-ischemic encephalopathy after cardiopulmonary arrest at presentation, and four from late complications of burn injury. Seven survivors did not recover their premorbid neurologic state, four of whom had respiratory arrest when rescued. Two patients had initial neurologic recovery followed by transient deterioration at 4 and 14 days after exposure. One patient developed seizures and was found to have bilateral occipital lobe infarctions 51 days after exposure., Conclusion: Acute neurologic manifestations after carbon monoxide exposure are common in children. These resolve rapidly with normobaric oxygen, however. Persistent sequelae are primarily related to asphyxia. Delayed neurologic syndromes are uncommon in children treated with normobaric oxygen.

Objective: To determine the diagnostic value of cerebrospinal fluid tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 released into the cerebrospinal fluid of patients with ventriculoperitoneal shunt infection., Design: Prospective, observational study., Setting: University teaching hospital., Patients: Sixty-four patients requiring cerebrospinal fluid aspiration for suspected ventriculoperitoneal shunt malfunction., Interventions: Cerebrospinal fluid samples were obtained by shunt aspiration at the time of patient presentation., Measurements and Main Results: TNF-alpha and IL-1 beta concentrations were measured by enzyme-linked immunosorbent assay, and IL-6 activity by bioassay. The sensitivity, specificity, predictive values, and overall efficiency for each cytokine were determined based on the cerebrospinal fluid culture results. Ten patients had positive cerebrospinal fluid cultures, eight of which yielded Staphylococcus species, and one each Acinetobacter and Pseudomonas. Cerebrospinal fluid TNF-alpha, IL-1 beta, IL-6, protein, and leukocyte concentrations were significantly increased in patients with shunt infection. Cerebrospinal fluid IL-6 activity had the highest diagnostic accuracy of the cytokines evaluated, with sensitivity of 80% and specificity of 98%., Conclusions: The presence of cerebrospinal fluid inflammatory cytokines strongly suggests ventriculoperitoneal shunt infection. Detection of these cytokines in the cerebrospinal fluid could be used for earlier diagnosis of bacterial infection.

We determined the efficacy of continuous arteriovenous hemofiltration (CAVH) and a thromboxane synthetase inhibitor (TSI) on survival and their effect on TXA2, PGI2, TNF alpha, and IL-1beta production in rat endotoxemia. Thirty-six endotoxemic rats were randomized to one of 4 groups: (A) no TSI, sham CAVH; (B) no TSI, CAVH; (C) TSI, sham CAVH; and (D) TSI, CAVH. Either CAVH (Group B) or pretreatment with TSI (Group C) resulted in increased survival time. CAVH did not prevent the rise in TX (Group B). TNF alpha levels at 2 h after LPS infusion were higher in Group D compared to Group B (26.1 +/- 3.7 vs 13.2 +/- 4.3 ng/mL, P < 0.05) respectively. IL-1beta was detected earlier in Groups C,D when compared to Groups A,B (P < 0.02). TNF alpha and IL-1beta were not ultrafiltered. CAVH and the inhibition of TX synthesis independently improved survival in endotoxemia, however, their beneficial effects were not additive. While TSI may improve survival by blocking TXA2 production, the salutary effects of CAVH appear to be from removal of an undetermined TXA2 dependent mediator. TNF alpha and IL-1beta concentrations do not appear to influence survival times in this model.

Objectives: a) To demonstrate the effect of high-frequency ventilation on gas exchange in children with severe acute respiratory failure unresponsive to conventional ventilation; b) to identify patients at high risk of death early after institution of high-frequency ventilation., Setting: Tertiary care pediatric intensive care unit in a university hospital., Design: A cross-sectional, observational study with factorial design., Patients: Thirty-one patients with severe acute respiratory failure defined as a Pao2/F1o2 of < 150 torr (< 20 kPa) with a positive end-expiratory pressure of > or = 8 cm H2O and/or Paco2 of > 60 torr (> 8 kPa) with an arterial pH < 7.25., Interventions: Patients received either high-frequency oscillation or jet ventilation if respiratory failure was unresponsive to conventional ventilation and if the underlying disease process was deemed reversible., Measurements and Main Results: Thirty-one children were managed with high-frequency ventilation, 11 children with jet and 20 children with oscillator. Arterial blood gases and level of ventilatory support were recorded before and at 6, 24, 48, 72, and 96 hrs after institution of high-frequency ventilation. There was an improvement in an arterial pH, Paco2, Pao2, and Pao2/FID2 6 hrs after institution of high-frequency ventilation (p < .01). This improvement, along with decreased need for oxygen, was sustained through the subsequent course. Twenty-three (74%) of 31 children treated with high-frequency ventilation survived. Survivors showed an increase in an arterial pH, Pao2, Pao2/FIO2, and a decrease in Paco2 within 6 hrs, whereas nonsurvivors did not. Oxygenation index was the best predictor of outcome. A combination of an initial oxygenation index of > 20 and failure to decrease the oxygenation index by > 20% by 6 hrs after initiation of high-frequency ventilation predicted death with 88% (7/8) sensitivity and 83% (19/23) specificity, with an odds ratio of 33 (p = .0036, 95% confidence interval 3-365)., Conclusions: In patients with potentially reversible underlying diseases resulting in severe acute respiratory failure that is unresponsive to conventional ventilation, high-frequency ventilation improves gas exchange in a rapid and sustained fashion. The magnitude of impaired oxygenation and its improvement after high-frequency ventilation can predict outcome within 6 hrs.

Tumor necrosis factor (TNF) has been implicated in hemodynamic changes of endotoxic shock. The temporal relationship of hypotension and TNF release in endotoxemia was studied. Carotid arteries of five intubated rats were cannulated and Escherichia coli 0127:B8 lipopolysaccharide (LPS) was infused over 10 seconds. Arterial blood pressure (ABP), heart rate, and plasma TNF concentrations were measured at 0, 5, 15, 30, and 60 mins. Five to 15 mins after LPS, there was a marked decline in ABP (146 +/- 23 vs 57 +/- 5 mm Hg, p < 0.005), without a significant rise in TNF. The heart rate did not change. From 15 to 60 mins, there was a rise in TNF concentrations (523 +/- 333 vs 5783 +/- 629 pg/ml, p < 0.005) while the same degree of hypotension persisted. It is concluded that early hypotension after acute endotoxemia is not dependent on TNF alone. However, TNF may play a role in sustaining hypotension after endotoxemia.

We determined the efficacy of continuous arteriovenous hemofiltration (CAVH) in removing tumor necrosis factor (TNF), thromboxane A2, and prostacyclin, and in improving survival in endotoxemia. Twelve rats were given 10 mg/kg of E. coli 0:127:B8 lipopolysaccharide. Fifteen min later, the rats were randomized to ultrafiltered or non-ultrafiltered groups. Blood and ultrafiltrate were collected for TNF, thromboxane B2 (TxB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). After 4 hr, surviving rats were sacrificed. Five of 6 ultrafiltered and none of 6 non-ultrafiltered rats survived 4 hr. Plasma TxB2 > 1,000 pcg/ml and its rate of increase within the first 2 hr predicted death (P < 0.03). Ultrafiltration decreased the rate of rise in TxB2 (P < 0.04). Plasma TxB2 inversely correlated with TxB2 clearance by ultrafiltration. The concentration and rate of increase in TNF and 6-keto-PGF1 alpha did not predict survival. We conclude that CAVH improves short term survival in endotoxemia. Salutary effects appear to be due to thromboxane A2 removal.

Severity of illness and clinical characteristics of parainfluenza virus (PIV) infection were evaluated in 81 hospitalized children over a 4 year period. Fifty three patients were previously healthy and 28 had preexisting pulmonary abnormalities associated with bronchopulmonary dysplasia (BPD), congenital heart disease (CHD), asthma, or prematurity. When compared with formerly healthy children, the patients with preexisting pulmonary abnormalities were more likely to develop lower than upper respiratory tract illness (P less than 0.0001). In the lower respiratory tract infection group, patients with preexisting pulmonary abnormalities were sicker (P = 0.047), were hospitalized longer (P = 0.016), required more supplemental oxygen (P = 0.004), and were older (8.8 vs. 5.1 months) than previously healthy patients. Nosocomial infection occurred only in BPD patients. All these patients developed pneumonia. They were sicker (P = 0.0018), requiring more therapy (P = 0.0038) than other patients with preexisting pulmonary abnormalities and lower respiratory tract disease. Patients with BPD should be placed in protective isolation during PIV epidemics.

Fourteen cases of severe clonidine poisoning occurring in children over a 5-yr period were reviewed. The typical patient was a previously healthy toddler who ingested clonidine while visiting a relative. All patients were lethargic on admission and most were admitted with bradycardia or miosis. Hypotension was more likely to develop after admission. Recovery occurred within 48 h with only symptomatic treatment. Significant morbidity from clonidine ingestion occurred in terms of hospitalization, invasive monitoring, and mechanical ventilation.

Cocaine abuse has increased greatly in recent years, creating important medical, legal, and social problems. Urine drug testing is used to diagnose cocaine ingestion. The presence of the cocaine metabolite benzoylecgonine (BZ) is commonly believed to be proof of recent cocaine intoxication. However, oral ingestion of even a minute quantity of cocaine can result in a positive test result. BZ was detected in the urine of four nonbreast-fed infants aged 6 weeks to 14 months who were admitted with diagnoses unrelated to cocaine poisoning. These infants were exposed to cocaine by passive inhalation of vapors generated by adult caretakers smoking "crack" cocaine. Two of the infants were retested 12 hours later and had no detectable BZ, strongly suggesting ingestion of a subpharmacologic amount of cocaine. Because passive inhalation of cocaine can produce measurable urine BZ concentrations, a positive urine screen does not necessarily indicate poisoning or intentional administration of the substance and therefore is not proof of child abuse or neglect.

A 10-year-old patient with severe autoimmune hemolytic anemia (AIHA) presented with heart failure. Hemoglobin levels remained dangerously low despite multiple blood transfusions and corticosteroid therapy. A two-volume exchange transfusion promptly restored and maintained satisfactory hemoglobin levels. An exchange transfusion should be considered in selected patients with AIHA when severe hemolysis results in life-threatening anemia, and repeated blood transfusions are unsuccessful in maintaining safe hemoglobin levels. Such an approach may be especially applicable in children in whom plasma-pheresis may not be suitable because of technical limitations.