Pediatric Keloids and Review of the Efficacy of Current Treatment Modalities.

BACKGROUND: Keloids and hypertrophic scars are the result of excessive fibroblast proliferation and collagen deposition in the wound healing process, leaving patients with irritating and cosmetically displeasing lesions. Despite there being numerous modalities for treatment, keloids are notoriously recalcitrant to therapy and recurrence rates are high. OBJECTIVE: Because many keloids begin to develop during childhood and adolescence, it is important to better understand which treatment options may be best suited toward the pediatric population specifically. METHODS: We reviewed 13 studies that focus specifically on effectiveness of treatment options for keloids and hypertrophic scars in the pediatric population. These studies cover 545 keloids in 482 patients, all aged 18 and younger. RESULTS: Many treatment modalities were used, with multimodal treatment being the most common (76%). There were 92 instances of recurrence, with a total recurrence rate of 16.9%. CONCLUSION: Data from the combined studies suggest that keloid development is less common before adolescence and that higher rates of recurrence are observed among patients who have received monotherapy compared with those who received multimodal treatments. More well-designed studies with standardized ways of assessing outcomes are needed to expand our understanding on how to optimally treat keloids in the pediatric population.

Unpacking the Role of Extracellular Vesicles in Ischemic and Hemorrhagic Stroke: Pathophysiology and Therapeutic Implications.

Stroke is a leading cause of death and disability worldwide. Inflammation and microvascular dysfunction have been associated with brain injury and long-term disability after both ischemic and hemorrhagic stroke. Recent studies have suggested a potential role of extracellular vesicles (EVs) as a link underlying these pathogenic processes. EVs are cell-derived particles enveloped by a lipid bilayer, containing proteins, lipids, and nucleic acids. From a functional standpoint, EVs can facilitate intercellular communication, including across the blood-brain barrier (BBB). Recent advances in EV research have shown a preferential release of EVs from specific cell types in the context of stroke, some of which were associated with increased neuroinflammation, microvascular dysfunction, and neuronal cytotoxicity while others offered a degree of neuroprotection. However, one historic challenge in the studies of EVs in stroke is the lack of consistent definitions and methods to analyze EVs, only recently updated in the MISEV2018 guidelines. Given limitations and complexity in the treatment of stroke, particularly delivery of therapeutics across the BBB, increasing attention has been paid towards manipulating EVs as one vehicle that can permit targeted therapeutic delivery to the central nervous system. These discoveries point towards a future where a better understanding of EVs will advance our knowledge of stroke-associated mechanisms of cerebral and systemic injury and contribute to the development of novel treatments. Here, we review the role that EVs play in ischemic and hemorrhagic stroke.

Elevated Serum Leukocytes are Predictive of Cardiac Injury Following Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVES: Aneurysmal subarachnoid hemorrhage (aSAH) accounts for 5% of strokes but results in significant morbidity and mortality. In addition to systemic inflammation, up to half of patients develop cardiac injury; however, the relationship between systemic inflammation and cardiac injury after aSAH is unknown. We investigated changes in leukocyte counts in relation to cardiac dysfunction MATERIALS AND METHODS: We reviewed the records of consecutive patients with SAH at our large academic medical referral center. The inclusion criteria were aSAH and available cardiac troponin I (cTnI) levels within 48 h of admission. The primary outcome was cardiac injury, defined as cTnI ≥0.04 ng/mL (lab reference range 0.01-0.03 ng/mL). We compared baseline characteristics, including serum leukocyte counts and performed univariable and multivariable logistic regression analysis to determine whether changes in leukocyte subpopulations predict cardiac injury. RESULTS: Of 288 SAH patients, 250 met inclusion criteria. Of these, 116 (46.4%) had elevated cTnI. In univariable analysis, total leukocyte count (p < 0.001), absolute neutrophil count (ANC, p < 0.001), and absolute monocyte count (p = 0.013), were associated with elevated cTnI. in multivariable analysis, total leukocyte count (OR=1.079, p = 0.037) and ANC (OR=1.081, p = 0.044) remained predictors of elevated cTnI. Adjusted ANC distinguishes between aSAH patients with normal and elevated TnI (area under the curve=0.766, p < 0.001) with specificity of 89.2%. CONCLUSIONS: Elevated total leukocytes and ANC are independently associated with cardiac injury in aSAH. Systemic inflammatory responses after aSAH may play a role in cardiac dysfunction, warranting additional studies to further characterize how cardiac inflammation after aSAH drives subsequent morbidity and mortality.

Systemic Immune-Inflammation Index Predicts Delayed Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral vasospasm is a feared complication of aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE: To investigate the relationship of systemic inflammation, measured using the systemic immune-inflammation (SII) index, with delayed angiographic or sonographic vasospasm. We hypothesize that early elevations in SII index serve as an independent predictor of vasospasm. METHODS: We retrospectively reviewed the medical records of 289 SAH patients for angiographic or sonographic evidence of delayed cerebral vasospasm. SII index [(neutrophils × platelets/lymphocytes)/1000] was calculated from laboratory data at admission and dichotomized based on whether or not the patient developed vasospasm. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to determine the ability of SII index to predict the development of vasospasm. RESULTS: A total of 246 patients were included in our study, of which 166 (67.5%) developed angiographic or sonographic evidence of cerebral vasospasm. Admission SII index was elevated for SAH in patients with vasospasm compared to those without (P < .001). In univariate logistic regression, leukocytes, neutrophils, lymphocytes, neutrophil-lymphocyte ratio (NLR), and SII index were associated with vasospasm. After adjustment for age, aneurysm location, diabetes mellitus, hyperlipidemia, and modified Fisher scale, SII index remained an independent predictor of vasospasm (odds ratio 1.386, P = .003). ROC analysis revealed that SII index accurately distinguished between patients who develop vasospasm vs those who do not (area under the curve = 0.767, P < .001). CONCLUSION: Early elevation in SII index can independently predict the development of delayed cerebral vasospasm in aneurysmal SAH.

Inflammasome Caspase-1 Activity is Elevated in Cerebrospinal Fluid After Aneurysmal Subarachnoid Hemorrhage and Predicts Functional Outcome.

BACKGROUND/OBJECTIVE: Subarachnoid hemorrhage (SAH) is a devastating neurological injury, further complicated by few available methods to objectively predict outcomes. With the recent shift in focus to neuroinflammation as a potential cause of adverse outcomes following SAH, we investigated the inflammasome-derived enzyme, caspase-1, as a potential biomarker for poor functional outcome. METHODS: SAH patients were recruited from a regional stroke referral center. Cerebrospinal fluid (CSF) samples from 18 SAH subjects were collected via an external ventricular drain and obtained as close as possible to admission (within 72 h). For control subjects, we collected CSF from 9 patients undergoing lumbar puncture with normal CSF. Caspase-1 activity was measured using commercially available luminescence assays. SAH subjects were categorized at hospital discharge into those with good outcomes (Glasgow Outcome Scale, GOS, of 4-5) and poor outcomes (GOS of 1-3). RESULTS: CSF analysis demonstrated a nearly seven-fold increase in caspase-1 activity in SAH patients compared to controls (p < 0.0001). Within the SAH group, 10 patients (55.6%) had good outcomes and 8 patients (44.4%) had poor outcomes. Mean caspase-1 activity in the poor outcome group was approximately three-times higher than the good outcome group (p = 0.001). Caspase-1 activity was significantly correlated with GOS score (r = - 0.705, p = 0.001). Receiver operating characteristic curve analysis showed that caspase-1 activity can accurately differentiate between patients with good versus poor functional outcome (area under the curve 0.944, p = 0.002). CONCLUSIONS: Inflammasome-derived caspase-1 activity is elevated in the CSF of SAH patients compared to controls and higher levels correlate with worse functional outcome.