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The aim of this review is to discuss the rationale of and current evidence for prolonged beta-lactam infusion in the management of Gram-negative infections.
Pharmacokinetic/pharmacodynamic (PK/PD) data from various in-vitro and in-vivo experimental studies conclusively support prolonged infusion over intermittent infusion in terms of achieving effective beta-lactam exposure for maximal bacterial killing. Superior PK/PD target attainment has been demonstrated with prolonged beta-lactam infusion in patient populations that are more likely to have less susceptible Gram-negative infections. These populations include critically ill patients, cystic fibrosis patients and patients with malignant diseases. The clinical impact of prolonged beta-lactam infusion is likely to be the greatest in these patient groups critically ill patients with a high level of illness severity who are not receiving renal replacement therapy; patients with nonfermenting Gram-negative bacilli infection and patients with respiratory infection. Critically ill patients with augmented renal clearance may not achieve effective beta-lactam exposure even with the use of prolonged infusion. Maximizing the effectiveness of prolonged beta-lactam infusion via therapeutic drug monitoring is becoming a more common strategy in the management of critically ill patients with Gram-negative infection.
Prolonged beta-lactam infusion may not benefit all patients but only for those who are critically ill and/or immunocompromised, who are also more likely to have less susceptible Gram-negative infections.
Prolonged beta-lactam infusion may not benefit all patients but only for those who are critically ill and/or immunocompromised, who are also more likely to have less susceptible Gram-negative infections.
Data on the infectious complications of anti-CD19 chimeric antigen receptor-modified T-cell (CAR-T-cell) therapies are scant. The approaches to preventing and managing infections among CAR-T-cell recipients are extrapolated from those of patients with other hematological malignancies. Understanding the incidence and risk factors of infections in these patients will improve clinical outcomes.
Infections occur in 23-42% of CAR-T-cell recipients and are most frequent in the first month after infusion, declining sharply thereafter. Risk factors include preinfusion (e.g., prior hematopoietic cell transplant, underlying malignancy) and postinfusion variables (e.g., cytokine release syndrome [CRS], neutropenia). Neutropenic fever after CAR-T-cell therapy is nearly universal but is confounded by CRS. The timeline of infections can be divided into preinfusion (because of the preparative regimen); 0-30 days after infusion, when bacterial infections predominate; and 30 days onwards, when respiratory viral infections predominate. Fungal and herpesviridae infections are uncommon.
Recent studies have shed light on the epidemiology of infections after CAR-T-cell therapy. Future efforts should focus on identifying modifiable risk factors for infection, defining neutropenic fever in the setting of CRS, determining the benefit of antimold prophylaxis, and identifying the optimal approach to viral monitoring, vaccination, and immunoglobulin replacement.
Recent studies have shed light on the epidemiology of infections after CAR-T-cell therapy. Future efforts should focus on identifying modifiable risk factors for infection, defining neutropenic fever in the setting of CRS, determining the benefit of antimold prophylaxis, and identifying the optimal approach to viral monitoring, vaccination, and immunoglobulin replacement.
Mixed venous oxygen saturation (SvO2) is important when evaluating the balance between oxygen delivery and whole-body oxygen consumption. Monitoring SvO2 has so far required blood samples from a pulmonary artery catheter. By combining volumetric capnography, for measurement of effective pulmonary blood flow, with the Fick principle for oxygen consumption, we have developed a continuous noninvasive method, capnodynamic SvO2, for assessment of SvO2. The objective of this study was to validate this new technique against the gold standard cardiac output (CO)-oximetry SvO2 measurement of blood samples obtained from a pulmonary artery catheter and to assess the potential influence of intrapulmonary shunting.
Eight anesthetized mechanically ventilated domestic-breed piglets of both sexes (median weight 23.9 kg) were exposed to a series of interventions intended to reduce as well as increase SvO2. Simultaneous recordings of capnodynamic and CO-oximetry SvO2 as well as shunt fraction, using the Berggren formula, were performed throughout the protocol. CHIR-99021 inhibitor Agreement of absolute values for capnodynamic and CO-oximetry SvO2 and the ability for capnodynamic SvO2 to detect change were assessed using Bland-Altman plot and concordance analysis.
Overall bias for capnodynamic versus CO-oximetry SvO2 was -1 percentage point (limits of agreement -13 to +11 percentage points), a mean percentage error of 22%, and a concordance rate of 100%. Shunt fraction varied between 13% at baseline and 22% at the end of the study and was associated with only minor alterations in agreement between the tested methods.
In the current experimental setting, capnodynamic assessment of SvO2 generates absolute values very close to the reference method CO-oximetry and is associated with 100% trending ability.
In the current experimental setting, capnodynamic assessment of SvO2 generates absolute values very close to the reference method CO-oximetry and is associated with 100% trending ability.
Pneumonia is a common lower respiratory tract infection (LRI) and the leading cause of pediatric hospitalization in the United States. Given its frequency, children with pneumonia may require surgery during their hospital course. This poses serious anesthetic and surgical challenges because preoperative pulmonary status is among the most important risk factors for postoperative complications. Although recent adult data indicated that preoperative pneumonia was associated with poor surgical outcomes, comparable data in children are lacking. Therefore, our objective was to investigate the association of preoperative pneumonia with postoperative mortality and morbidity in children.
Using the National Surgical Quality Improvement Program database, we assembled a retrospective cohort of children (<18 years) who underwent inpatient surgery between 2012 and 2015. Our primary outcome was the time to all-cause 30-day postoperative mortality that we evaluated using Cox proportional hazards regression models. For the secondary outcomes, including 30-day postoperative morbidity events, we used Fine-Gray models to account for competing risk by mortality.
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