Increasing angiotensin-converting enzyme concentrations and absent angiotensin-converting enzyme activity are associated with adverse kidney outcomes in pediatric septic shock.

BACKGROUND: Sepsis-induced endothelial dysfunction is proposed to cause angiotensin-converting enzyme (ACE) dysfunction and renin-angiotensin-aldosterone system (RAAS) derangement, exacerbating vasodilatory shock and acute kidney injury (AKI). Few studies test this hypothesis directly, including none in children. We measured serum ACE concentrations and activity, and assessed their association with adverse kidney outcomes in pediatric septic shock. METHODS: A pilot study of 72 subjects aged 1 week-18 years from an existing multicenter, observational study. Serum ACE concentrations and activity were measured on Day 1; renin + prorenin concentrations were available from a previous study. The associations between individual RAAS components and a composite outcome (Day 1-7 severe persistent AKI, kidney replacement therapy use, or mortality) were assessed. RESULTS: 50/72 subjects (69%) had undetectable ACE activity (< 2.41 U/L) on Day 1 and 27/72 (38%) developed the composite outcome. Subjects with undetectable ACE activity had higher Day 1 renin + prorenin compared to those with activity (4533 vs. 2227 pg/ml, p = 0.017); ACE concentrations were no different between groups. Children with the composite outcome more commonly had undetectable ACE activity (85% vs. 65%, p = 0.025), and had higher Day 1 renin + prorenin (16,774 pg/ml vs. 3037 pg/ml, p < 0.001) and ACE concentrations (149 vs. 96 pg/ml, p = 0.019). On multivariable regression, increasing ACE concentrations (aOR 1.01, 95%CI 1.002-1.03, p = 0.015) and undetectable ACE activity (aOR 6.6, 95%CI 1.2-36.1, p = 0.031) retained associations with the composite outcome. CONCLUSIONS: ACE activity is diminished in pediatric septic shock, appears uncoupled from ACE concentrations, and is associated with adverse kidney outcomes. Further study is needed to validate these findings in larger cohorts.

Exogenous nitric oxide delivery protects against cardiopulmonary bypass-associated acute kidney injury: Histologic and serologic evidence from an ovine model.

OBJECTIVE: Several human studies have associated nitric oxide administration via the cardiopulmonary bypass circuit with decreased incidence of cardiopulmonary bypass-associated acute kidney injury, but histopathologic and serologic evidence of nitric oxide efficacy for acute kidney injury attenuation are lacking. METHODS: By using a survival ovine model (72 hours), acute kidney injury was induced by implementing low-flow cardiopulmonary bypass for 2 hours, followed by full-flow cardiopulmonary bypass for 2 hours. The nitric oxide cohort (n = 6) received exogenous nitric oxide through the cardiopulmonary bypass circuit via the oxygenator, and the control group (n = 5) received no nitric oxide. Serial serologic biomarkers and renal histopathology were obtained. RESULTS: Baseline characteristics (age, weight) and intraoperative parameters (cardiopulmonary bypass time, urine output, heart rate, arterial pH, and lactate) were equivalent (P > .10) between groups. Postoperatively, urine output, heart rate, respiratory rate, and peripheral arterial saturation were equivalent (P > .10) between groups. Post-cardiopulmonary bypass creatinine elevations from baseline were significantly greater in the control group versus the nitric oxide group at 16, 24, and 48 hours (all P < .05). Histopathologic evidence of moderate/severe acute kidney injury (epithelial necrosis, tubular slough, cast formation, glomerular edema) occurred in 60% (3/5) of the control group versus 0% (0/6) of the nitric oxide group. Cortical tubular epithelial cilia lengthening (a sensitive sign of cellular injury) was significantly greater in the control group than in the nitric oxide group (P = .012). CONCLUSIONS: In a survival ovine cardiopulmonary bypass model, nitric oxide administered with cardiopulmonary bypass demonstrated serologic and histologic evidence of renal protection from acute kidney injury. These results provide insight into 1 potential mechanism for cardiopulmonary bypass-associated acute kidney injury and supports continued study of nitric oxide via cardiopulmonary bypass circuit for prevention of acute kidney injury.

Manual single lumen alternating micro-batch dialysis achieves reliable clearance via diffusion.

BACKGROUND: Acute kidney injury is a cause of preventable deaths in low resource settings due to lack of dialysis access and cost. A manual single lumen alternating micro-batch (mSLAMB) dialysis technique performs kidney replacement therapy using single lumen access, low-cost bags/tubing, intravenous fluids, and a filter without electricity, a battery, or a pump. We propose a protocol whereby mSLAMB can perform diffusive clearance simply and efficiently to bring dialysis to underserved populations. METHODS: Expired packed red blood cells mixed with crystalloid solution were spiked with urea and anticoagulated with heparin. A Static diffusion Technique (with short flushes of fluid before each filter pass) was compared to a Dynamic diffusion Technique (with fluid running through the filter during the forward pass) to assess urea and potassium clearance. Passive ultrafiltration was the difference between the 200 mL batch volume and volume returned to the blood bag per cycle. RESULTS: Five cycles achieved urea reduction ratios (URR) between 17-67% and potassium clearance of 18-60%, with higher percentages achieved from higher proportions of batch volume dialyzed to patient volume. Dynamic Technique increased clearance over the Static Technique. Passive ultrafiltration volumes were 2.5-10% of batch volume. CONCLUSION: mSLAMB dialysis performs diffusive clearance and passive ultrafiltration efficiently, while preserving resources and available manpower. IMPACT: mSLAMB is a dialysis technique that can perform efficient diffusive clearance and passive ultrafiltration without electricity, batteries, or a pump. With basic medical supplies and limited manpower, mSLAMB is a cost-effective means of providing emergency dialysis in low resource areas. We propose a basic algorithm for safe and cost-effective dialysis for people of different ages and sizes.

Acute kidney injury biomarker olfactomedin 4 predicts furosemide responsiveness.

BACKGROUND: Acute kidney injury (AKI) is associated with increased morbidity and mortality in critically ill patients. Olfactomedin 4 (OLFM4), a secreted glycoprotein expressed in neutrophils and stressed epithelial cells, is upregulated in loop of Henle (LOH) cells following AKI. We hypothesized that urine OLFM4 (uOLFM4) will increase in patients with AKI and may predict furosemide responsiveness. METHODS: Urine from critically ill children was collected prospectively and tested for uOLFM4 concentrations with a Luminex immunoassay. Severe AKI was defined by KDIGO (stage 2/3) serum creatinine criteria. Furosemide responsiveness was defined as > 3 mL/kg/h of urine output in the 4 h after a 1 mg/kg IV furosemide dose administered as part of standard of care. RESULTS: Fifty-seven patients contributed 178 urine samples. Irrespective of sepsis status or AKI cause, uOLFM4 concentrations were higher in patients with AKI (221 ng/mL [IQR 93-425] vs. 36 ng/mL [IQR 15-115], p = 0.007). uOLFM4 concentrations were higher in patients unresponsive to furosemide (230 ng/mL [IQR 102-534] vs. 42 ng/mL [IQR 21-161], p = 0.04). Area under the receiver operating curve for association with furosemide responsiveness was 0.75 (95% CI, 0.60-0.90). CONCLUSIONS: AKI is associated with increased uOLFM4. Higher uOLFM4 is associated with a lack of response to furosemide. Further testing is warranted to determine whether uOLFM4 could identify patients most likely to benefit from earlier escalation from diuretics to kidney replacement therapy to maintain fluid balance. A higher resolution version of the Graphical abstract is available as Supplementary information.

Stability of novel urinary biomarkers used for lupus nephritis.

Background: The Renal Activity Index for Lupus (RAIL) is a composite score of six urinary biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), ceruloplasmin, adiponectin, and hemopexin) used to monitor lupus nephritis activity in children. We tested stability of RAIL biomarkers prior to meaningful clinical use. Methods: Urine samples were tested by ELISA under shipping conditions, freeze/thaw, ambient and longer-term storage. Statistical analysis was performed via Deming Regression, Bland-Altman and Spearman Correlation Coefficient. Results: Biomarker concentration were comparable to freshly collected urine following storage at -80 °C for up to 3 months, and at 4 or 25 °C up to 48 h followed by -80 °C. Neither shipping on dry or wet ice exposure nor addition of two freeze-thaw cycles led to loss of signal, with excellent Spearman Correlation coefficients under all conditions. Conclusions: RAIL biomarkers are stable following short-term storage at clinically relevant conditions.

Hepatic failure and death due to new onset T cell lymphoma.

INTRODUCTION: Liver involvement is commonly seen in disseminated T cell lymphoma; however, it is rarely the presenting organ. Here, we describe a case of T cell lymphoma presenting as acute hepatobiliary disease leading to hepatic failure and death. DISCUSSION: Forty-seven-year-old male with history of cirrhosis (etiology undetermined), diabetes mellitus, and pancytopenia was admitted to ICU for hypotension and failure to thrive. He had icterus, minimal ascitis, and hepatosplenomegaly on physical examination. No lymphadenopathy was noted. Laboratory workup on admission showed elevated total bilirubin (10.1 mg/dl) and liver enzymes. Serology for acute viral hepatitis, human immunodeficiency virus, Epstein-Barr virus, and autoimmune hepatitis was negative. CT abdomen showed cirrhotic liver with heterogeneous arterial enhancement of the liver without definite mass lesions. Hospital course was complicated by progressively worsening hypotension, respiratory failure, profound acidosis, disseminated intravascular coagulation, and multi-organ system failure leading to death on hospital day 12. Autopsy of the liver showed cirrhotic changes with infiltration with atypical small lymphocytes confined to septa which were CD3 and CD5 positive (CD4 weakly positive, CD8, CD20, CD57, CD56, CD30, Alk-1, granzyme B, TIA1, and S100 negative). Unusual clinical/histological features include (1) initial clinical presentation of hepatic dysfunction without obvious physical signs of lymphoma, (2) negative workup for viral, toxic, autoimmune, and metabolic liver disease, (3) involvement of the entire liver, observed as heterogeneous enhancement of liver without any focal mass lesion as seen on CT scan, (4) an aggressive nature of disease, and (5) autopsy of liver with T cell infiltration confined to septa. Initial diagnosis was challenging due to unusual clinical presentation suggesting inflammatory hepatobiliary disease and the absence of enlarged lymph nodes. CONCLUSION: In conclusion, early suspicion of this aggressive lymphoma is important and should be considered in the evaluation of a patient whose course is atypical for hepatitis. Even in the absence of a mass lesion or lymphadenopathy, hepatosplenic T cell lymphoma should be included in the differential diagnosis of acute hepatic dysfunction in a patient who has no evidence of viral, toxic, autoimmune, or metabolic liver disease.

Ganglioglioma in the cerebellopontine angle of an adult without seizures.

We present a rare case of an adult patient without seizures who is found to have a ganglioglioma occurring in the cerebellopontine angle. A 52-year-old woman with ataxia, headaches, and falling episodes underwent neuroimaging. Magnetic resonance imaging (MRI) revealed a smooth, somewhat lobulated mass in the left cerebellopontine angle. The mass was hypointense on T1-weighted imaging, hyperintense on T2-weighted imaging, and did not enhance after administration of gadolinium. Left retromastoid craniectomy was performed, and the mass was noted to be exophytic from the brain stem. The exophytic component was resected. Light microscopic findings were consistent with ganglioglioma. This was confirmed with immunohistochemical studies. Ganglioglioma is a rare tumor of the central nervous system that typically presents with seizures in children and young adults. Occurrence of this tumor in the cerebellopontine angle is extremely unusual; this rarity is magnified by its occurrence in an adult patient without a history of seizures. Our case illustrates that ganglioglioma should be considered in the differential diagnosis of cerebellopontine angle masses at any age. This appears to be especially true when dealing with masses that are non-enhancing on imaging.

Amiodarone induced liver cirrhosis. Report of two cases.

Amiodarone is used commonly in patients with cardiac diseases. Common side effects include thyroid dysfunction and hepatic abnormalities. However, recently there has been concern for developing liver cirrhosis secondary to amiodarone therapy. We present two cases of liver cirrhosis in patients taking amiodarone. Their clinical presentation as well as histological features are discussed in detail.

Recurrence of pediatric cerebral arteriovenous malformations after angiographically documented resection.

Angiographically confirmed surgical resection is believed to be the 'gold standard' for cure in the treatment of intracranial arteriovenous malformations (AVMs). However, rare exceptions of recurrent AVMs have been documented. We are aware of 11 reported cases of recurrent AVMs in which complete resection of the initial lesion was confirmed by postoperative angiography. Eight of these cases were in the pediatric population. In this report, we present 2 additional cases of such recurrent lesions, review the clinical and scientific literature on this rare phenomenon and provide suggested management guidelines.

Topographic mapping of the superior transverse scapular ligament: a cadaver study to facilitate suprascapular nerve decompression.

Division of the superior transverse scapular ligament for decompression of suprascapular nerve entrapment can be curative. However, the superior transverse scapular ligament can be difficult to locate, and large incisions are often required. This study was designed to determine the topographic coordinates of the superior transverse scapular ligament to permit reproducible surgical localization and reduce incision size. In 20 cadavers, the superior transverse scapular ligament was identified through a superior approach. Measurements were obtained from the superior transverse scapular ligament to external landmarks. The superior transverse scapular ligament was located 1.3 +/- 0.3 cm (+/- SD) posterior to the posterior border of the clavicle and 2.9 +/- 0.8 cm from the acromioclavicular joint in a two-dimensional surface plane. The depth of the superior transverse scapular ligament from the skin surface was 3.9 +/- 0.7 cm. An incision (mean length, 6.3 +/- 0.7 cm) derived from a novel system of planning marks facilitated access to the superior transverse scapular ligament. The authors conclude that the superior transverse scapular ligament can be located consistently through an incision located on the superior aspect of the shoulder on the basis of palpable topographic landmarks. The superior approach permits small incision size and the maintenance of local muscle anatomic integrity.