Early fluid plus norepinephrine resuscitation diminishes kidney hypoperfusion and inflammation in septic newborn pigs.

ABSTRACT: Sepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Sepsis-induced dysregulation of kidney microcirculation in newborns is unresolved. The objective of this study was to use the translational swine model to evaluate changes in kidney function during the early phase of sepsis in newborns and the impact of fluid plus norepinephrine (NE) resuscitation. Newborn pigs (3-7-day-old) were allocated randomly to three groups: 1) Sham, 2) Sepsis (cecal ligation and puncture; CLP) without subsequent resuscitation, and 3) Sepsis with Lactated Ringer plus NE resuscitation. All animals underwent standard anesthesia and mechanical ventilation. Cardiac output (COP) and glomerular filtration rate (GFR) were measured non-invasively. Mean arterial pressure (MAP), total renal blood flow (RBF), cortical perfusion (coPf), medullary perfusion (mePf), and medullary tissue oxygen tension (mtPO2) were determined for 12 h. CLP decreased MAP and COP by more than 50%, with a proportional increase in renal vascular resistance (RVR) and a 60-80% reduction in RBF, coPf, mePf, and mtPO2 compared to sham. CLP also decreased GFR by ~79% and increased AKI biomarkers. Isolated foci of tubular necrosis were observed in the septic piglets. Except for mtPO2, changes in all these parameters were ameliorated in resuscitated piglets. Resuscitation also attenuated sepsis-induced increases in the levels of plasma C-reactive protein, proinflammatory cytokines, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, and renal NLRP3 inflammasome. These data suggest that newborn pigs subjected to CLP develop hypodynamic septic AKI. Early implementation of resuscitation lessens the degree of inflammation, AKI, and liver injury.

Transdermal Measurement of Glomerular Filtration Rate in Mechanically Ventilated Piglets.

Transdermal measurement of glomerular filtration rate (GFR) has been used to evaluate kidney function in conscious animals. This technique is well established in rodents to study acute kidney injury and chronic kidney disease. However, GFR measurement using the transdermal system has not been validated in pigs, a species with a similar renal system to humans. Hence, we investigated the effect of sepsis on transdermal GFR in anesthetized and mechanically ventilated neonatal pigs. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). The transdermal GFR measurement system consisting of a miniaturized fluorescence sensor was attached to the pig's shaved skin to determine the clearance of fluorescein-isothiocyanate (FITC) conjugated sinistrin, an intravenously injected GFR tracer. Our results show that at 12 h post-CLP, serum creatinine increased with a decrease in GFR. This study demonstrates, for the first time, the utility of the transdermal GFR approach in determining renal function in mechanically ventilated, neonatal pigs.

Value of Blood Cultures in the Management of Children Hospitalized with Community-Acquired Pneumonia.

Background and objectives Current guidelines for the management of community-acquired pneumonia (CAP) in children recommend obtaining a blood culture for children with moderate to severe pneumonia; yet, there is no guidance to assess the severity of the disease. Thus, a blood culture is obtained for the majority of children admitted with CAP, regardless of the severity of their symptoms. The study was designed to investigate and identify the prevalence of bacteremia in pediatric patients hospitalized with CAP and to evaluate the clinical and laboratory variables associated with bacteremia. Methods We conducted a medical record review of children aged from two months to 18 years diagnosed with CAP between January 1, 2013, and December 31, 2017, at our two urban tertiary centers. We used binary logistic regression analysis and chi-square tests to look at factors associated with blood culture positivity. Results A total of 464 patients were admitted with CAP. Blood cultures were obtained in 357 (76.9%) patients; 23 patients had repeated cultures. Fifteen patients had positive cultures: 5/380 (1.3%) were considered true positive results and 10/380 (2.6%) were considered contaminants. Intensive care unit (ICU) admission (OR 5.6 with 95% CI (1- 31), p<0.03), toxic appearance (OR 12.8 with 95% CI (1.3-125), p<0.01), and significantly elevated C-reactive protein (CRP) (>300 mg/L (p<0.01) were associated with bacteremia. Conclusion The prevalence of bacteremia among children admitted for CAP is low. The use of routine blood cultures should be reserved for children with moderate to severe pneumonia. Further studies are required to better risk-stratify children with CAP.

The impact of DaTscan in the diagnosis of Parkinson disease.

PURPOSE: The aim of this study was to evaluate the impact of DaTscan in a heterogeneous group of patients with movement disorders as well as the degree of confidence in scan findings between different readers. PROCEDURES: A retrospective evaluation of consecutive patients who underwent DaTscan during 1 year was performed. The patients' demographics, symptoms, duration, clinical diagnosis, and medications were collected. The scan findings were categorized by 2 blinded observers on a semiquantitative scale as follows: 0, normal; 1, mild; 2, moderate; 3, marked; and 4, absent uptake for each of the caudate heads and putamina separately. A correlation of the scan findings with the clinical symptoms and diagnosis as well as interobserver agreement was performed. Disagreement was considered when a difference greater than 2 in more than 1 area of the basal ganglia was recorded. Descriptive statistics and κ test for interobserver agreement were used for data analysis. RESULTS: Fifty-seven patients were included (mean age, 63.4 years; 29 men, 28 women). Clinical diagnosis of Parkinson disease (PD) was certain in 26 and uncertain in 31 patients. DaTscan was markedly abnormal in 24 (92%) of 26 patients with certain clinical diagnosis of PD and normal in the remaining 2 (8%). In 31 patients with uncertain diagnosis, 15 (48%) had markedly abnormal scans, 5 (16%) had mild abnormalities, and 11 (36%) had normal scans. Each of the sensitivity and positive predictive value of DaTscan in patients who had certain clinical diagnosis of PD (26 patients) is 92%. Interobserver agreement occurred in 52 (91%) of 57 scans and disagreement in 5 (9%) of 57 (κ = 0.82). There was also a good correlation with laterality of symptoms in 32 (82%) of 39 positive studies. CONCLUSIONS: Markedly abnormal DaTscan is confirmed as the diagnostic pattern for PD. This pattern helps confirm the diagnosis in patients with unclear clinical diagnosis. Good interobserver agreement is easily obtained in reading DaTscans.