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William D Tobler,1 Miguel A Melgar,2 Thomas J Raley,3 Neel Anand,4 Larry E Miller,5 Richard J Nasca6 1Department of Neurosurgery, University of Cincinnati College of Medicine, Mayfield Clinic, and The Christ Hospital, Cincinnati, OH, USA; 2Department of Neurosurgery, Tulane University, New Orleans, LA, USA; 3Advanced Spine and Pain, Arlington, VA, USA; 4Spine Trauma, Minimally Invasive Spine Surgery Spine Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 5Miller Scientific Consulting, Inc, Arden, NC, USA; 6Orthopaedic and Spine Surgery, Wilmington, NC, USA Introduction: Previous studies have confirmed the benefits and limitations of the presacral retroperitoneal approach for L5–S1 interbody fusion. The purpose of this study was to determine the safety and effectiveness of the minimally invasive axial lumbar interbody approach (AxiaLIF) for L4–S1 fusion. Methods: In this retrospective series, 52 patients from four clinical sites underwent L4–S1 interbody fusion with the AxiaLIF two-level system with minimum 2-year clinical and radiographic follow-up (range: 24–51 months). Outcomes included back pain severity (on a 10-point scale), the Oswestry Disability Index (ODI), and Odom's criteria. Flexion and extension radiographs, as well as computed tomography scans, were evaluated to determine fusion status. Longitudinal outcomes were assessed with repeated measures analysis of variance. Results: Mean subject age was 52 ± 11 years and the male:female ratio was 1:1. Patients sustained no intraoperative bowel or vascular injury, deep infection, or neurologic complication. Median procedural blood loss was 220 cc and median length of hospital stay was 3 days. At 2-year follow-up, mean back pain had improved 56%, from 7.7 ± 1.6 at baseline to 3.4 ± 2.7 (P < 0.001). Back pain clinical success (ie, ≥30% improvement from baseline) was achieved in 39 (75%) patients at 2 years. Mean ODI scores improved 42%, from 60% ± 16% at baseline to 35% ± 27% at 2 years (P < 0.001). ODI clinical success (ie, ≥30% improvement from baseline) was achieved in 26 (50%) patients. At final follow-up, 45 (87%) patients were rated as good or excellent, five as fair, and two as poor by Odom's criteria. Interbody fusion observed on imaging was achieved in 97 (93%) of 104 treated interspaces. During follow-up, five patients underwent reoperation on the lumbar spine, including facet screw removal (two), laminectomy (two), and transforaminal lumbar interbody fusion (one). Conclusion: The AxiaLIF two-level device is a safe, effective treatment adjunct for patients with L4–S1 disc pathology resistant to conservative treatments. Keywords: AxiaLIF, axial presacral fusion, interbody, outcomes, two-level fusion

The management of febrile neutropenia (FN) in pediatrics is evolving. Our objective was to describe current practices for the care of patients with FN in pediatric oncology centers in Latin America and identify areas for practice improvement. We used an online survey to enroll eligible healthcare providers who treat children with cancer in Latin America. The survey addressed respondents' characteristics, the environment of care, and FN care practices, including risk assessment, criteria for hospitalization, initial management of FN, evaluation, antibiotic administration, and discharge. From 220 surveys sent, we received 109 responses and selected 108 from 19 countries for analysis. Most (94%) respondents were working in specialized oncology centers, oncology units within a pediatric or general care hospital. The cohort included oncologists (42%) and infectious diseases physicians (30%). Most (67%) respondents had available guidelines; they used a risk-stratification scoring system (73%) for severe infection; and their guidelines had locally adapted risk stratification (34%) or published risk stratification (51%). The respondents used diverse FN definitions and concepts, including fever definitions, temperature-obtaining methods, neutropenia values for assigning risk, empiric antimicrobials administration, and length of hospitalization. Overall, we detected common practices aligning with standard published recommendations, as well as care variability. These findings can guide further evaluations of care resources and practices to prioritize interventions, and professional networks can be used for FN discussions and consensus in Latin America., (© 2021. The Author(s).)

Antimicrobial resistance (AMR) is increasing worldwide. We analyzed AMR rates for bacterial species identified from pediatric blood cultures between 2005 and 2019 at a single institution in Guatemala. We found significantly increased rates in Gram-negative resistance, with a high prevalence of carbapenem-resistant Acinetobacter and Klebsiella harboring the New Delhi metallo-beta-lactamase gene., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Multiplex polymerase chain reaction (PCR) platforms have enhanced understanding of intestinal pathogens in low- and middle-income countries (LMICs). However, few such studies have been performed in Latin America, where poverty, poor sanitation, and undernutrition persist. Multiplex PCR (BioFire, Salt Lake City, UT) was used to identify viral, bacterial, and parasitic pathogens in stool collected on day 1 and 31 from children aged 6 to 35 months with acute, non-bloody diarrhea in two locations (rural and urban) in Guatemala. We analyzed correlation between pathogens and clinical, demographic, and socioeconomic variables; described patterns of pathogen acquisition, persistence, and clearance over the 30-day period; and calculated population attributable fractions (PAFs) for diarrheal causation for individual pathogens. We analyzed 316 subjects (144 urban; 172 rural) enrolled between March 2015 and January 2016. Rural subjects had significantly more malnutrition, animal exposure, and unimproved water/sanitation infrastructure. The majority of subjects had multiple pathogens/sample (4.8 rural and 2.7 urban). Few meaningful correlates were identified between individual pathogens and clinical, demographic, or environmental variables. Escherichia coli pathotypes, Shigella , Campylobacter, and Giardia had high rates of persistence between initial and 30-day follow-up. Statistically significant adjusted PAFs were identified for Campylobacter (14.9%, 95% CI: 3.2-23.1), norovirus (10.2%, 95% CI: 0.4-17.1), sapovirus (7.6%, 95% CI: 2.3-10.9), and adenovirus 40/41 (5.6%, 95% CI: 0.3-8.7). These observations further characterize the diversity and complexity of enteric pathogens in children in LMICs. Patterns of chronic symptomatic and asymptomatic infection among Latin American children are similar to those observed in other LMIC regions. Findings have direct implications for practitioners treating individuals with acute infectious diarrhea and should inform regional public health strategies.

Background: Treatments for paediatric diarrhoeal disease are limited. We assessed the impact of a bovine colostrum and egg-based treatment designed to reduce diarrhoea duration through non-specific and pathogen-directed mechanisms in children., Methods: Randomised, double-blind, placebo-controlled trial of PTM202, derived from bovine colostrum and hyperimmune hen's egg on the duration of acute diarrhoeal disease in Guatemalan children. PTM202 contains specific immunoglobulins that target rotavirus, enterotoxigenic Escherichia coli , Shiga toxin-producing E. coli and Salmonella. Children aged 6-35 months presenting to three sites (one rural and two urban) with acute non-bloody diarrhoea were computer randomised to receive three daily doses of PTM202 or placebo. The primary outcome was the post-treatment duration of diarrhoea assessed in the per protocol population. Diarrhoeal pathogens were identified in stool by multiplex PCR (FilmArray Gastrointestinal-Panel, BioFire, Salt Lake City, Utah, USA). Key secondary outcomes included postdiarrhoeal weight gain and impact on diarrhoeal duration stratified by study site and presence of PTM202-targeted organisms in stool at enrolment. Safety was assessed in all participants., Results: From 9 March 2015 to 25 January 2016, 325 children were enrolled, and 301 (154 intervention and 147 placebo) were analysed for the primary outcome. No difference in diarrhoea duration was observed between intervention and placebo in the total population, but a significant reduction was observed in the treatment group among children with at least one targeted pathogen in stool (HR=1.46, P=0.02), an effect most pronounced in urban subjects (HR 2.20, P=0.007) who had fewer stool pathogens and better nutritional status. No impact on 2-week or 4-week weight gain was noted. No adverse events attributed to PTM202 occurred., Conclusion: Results demonstrate the potential to target specific pathogens occurring in children with acute non-bloody diarrhoea and shorten illness duration using a novel, safe, nutrition-based intervention. PTM202 may represent a new tool to ameliorate the effects of acute diarrhoeal disease in low/middle-income populations., Trial Registration Number: NCT02385773; Results., Competing Interests: Competing interests: None declared.

Background: The National Pediatric Oncology Unit (UNOP) is the only pediatric hemato-oncology center in Guatemala., Methods: Patients ages 1 to 17 years with acute lymphoblastic leukemia (ALL) were treated according to modified ALL Intercontinental Berlin-Frankfurt-Münster (IC-BFM) 2002 protocol. Risk classification was based on age, white blood cell count, immunophenotype, genetics (when available), and early response to therapy., Results: From July 2007 to June 2014, 787 patients were treated, including 160 who had standard-risk ALL, 450 who had intermediate-risk ALL, and 177 who had high-risk ALL. The induction death rate was 6.6%, and the remission rate was 92.9%. The rates of death and treatment abandonment during first complete remission were 4.8% and 2.5%, respectively. At a median observation time of 3.6 years, and with abandonment considered an event, the 5-year event-free survival and overall survival estimates ( ± standard error) were 56.2% ± 2.1% and 64.1% ± 2.1%, respectively, with a 5-year cumulative incidence of relapse of 28.9% ± 2.0%. Twenty-one of 281 patients (7.5%) investigated were positive for the ets variant 6/runt-related transcription factor 1 (ETV6/RUNX1) fusion., Conclusions: A well organized center in a low-middle-income country can overcome the disadvantages of malnutrition and reduce abandonment. Outcomes remain suboptimal because of late diagnosis, early death, and a high relapse rate, which may have a partly genetic basis. Earlier diagnosis, better management of complications, and better knowledge of ALL will improve outcomes. Cancer 2017;123:436-448. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Background: Loss of lumbar lordosis has been reported after lumbar interbody fusion surgery and may portend poor clinical and radiographic outcome. The objective of this research was to measure changes in segmental and global lumbar lordosis in patients treated with presacral axial L4-S1 interbody fusion and posterior instrumentation and to determine if these changes influenced patient outcomes., Methods: We performed a retrospective, multi-center review of prospectively collected data in 58 consecutive patients with disabling lumbar pain and radiculopathy unresponsive to nonsurgical treatment who underwent L4-S1 interbody fusion with the AxiaLIF two-level system (Baxano Surgical, Raleigh NC). Main outcomes included back pain severity, Oswestry Disability Index (ODI), Odom's outcome criteria, and fusion status using flexion and extension radiographs and computed tomography scans. Segmental (L4-S1) and global (L1-S1) lumbar lordosis measurements were made using standing lateral radiographs. All patients were followed for at least 24 months (mean: 29 months, range 24-56 months)., Results: There was no bowel injury, vascular injury, deep infection, neurologic complication or implant failure. Mean back pain severity improved from 7.8±1.7 at baseline to 3.3±2.6 at 2 years (p < 0.001). Mean ODI scores improved from 60±15% at baseline to 34±27% at 2 years (p < 0.001). At final follow-up, 83% of patients were rated as good or excellent using Odom's criteria. Interbody fusion was observed in 111 (96%) of 116 treated interspaces. Maintenance of lordosis, defined as a change in Cobb angle ≤ 5°, was identified in 84% of patients at L4-S1 and 81% of patients at L1-S1. Patients with loss or gain in segmental or global lordosis experienced similar 2-year outcomes versus those with less than a 5° change., Conclusions/clinical Relevance: Two-level axial interbody fusion supplemented with posterior fixation does not alter segmental or global lordosis in most patients. Patients with postoperative change in lordosis greater than 5° have similarly favorable long-term clinical outcomes and fusion rates compared to patients with less than 5° lordosis change.

The supraclavicular artery island (SAI) flap is a viable fasciocutaneous option for the reconstruction of head and neck defects. Although authors have reported success using SAI flaps for various reconstructive indications, concerns of a tenuous blood supply and distal ischemia have previously limited its use in the posterolateral skull base. This case series reports the outcomes of 5 consecutive patients receiving SAI flaps for posterolateral skull base reconstruction. All flaps were harvested in less than 1 hour with primary closure of all donor sites. A single patient developed superficial necrosis of the distal flap, which was repaired with a full-thickness skin graft. There were no other complications, and no donor site morbidity was observed. The SAI flap is an excellent option for the reconstruction of posterolateral skull base defects. The close color match, easy harvest within 1 hour, lack of microsurgical anastomosis, and absence of donor site morbidity support its continued utilization.

Instability of the high cervical spine, particularly C1 and C2, is commonly treated via a posterior approach. Access to this region via transoral approaches is often avoided due to the high risk of wound contamination, limited exposure, and lack of experience on the part of the surgeon. We present a 48-year-old man exhibiting complete C2 vertebral body involvement by multiple myeloma with a pathologic fracture, which we treated via the anterolateral/retropharyngeal approach to the high cervical spine. The anterolateral/retropharyngeal approach provides relatively easy access to the anterior arch of C1 and to the vertebral bodies of C2-4 and can be applied to a variety of different conditions. In addition, this approach may be a viable alternative to the transoral route and its associated morbidities.

Objectives: Bilateral carotid artery occlusion associated with lymphocytic hypophysitis is exceedingly rare. We describe this association and review the literature., Methods: The authors describe a 38-year-old woman with a history of severe headaches. Magnetic resonance (MR) imaging showed an intrasellar mass with invasion of both cavernous sinuses. Lymphocytic hypophysitis was diagnosed by transphenoidal biopsy. In the course of the disease, she developed symptoms of cerebral ischemia attributable to bilateral occlusion of her internal carotid arteries in both cavernous sinuses. She underwent bilateral superficial temporal artery-middle cerebral artery bypass surgery., Results: The patient experienced progressive neurological recovery after surgery. A literature search revealed no other cases describing this unique association., Conclusions: Bilateral carotid artery occlusion may develop in the course of lymphocytic hypophysitis with cavernous sinus involvement. If indicated, cerebral revascularization should be performed to reverse cerebral ischemia.

Background: The optimal method to protect the brain from hemodynamic ischemia during carotid endarterectomy (CEA) remains controversial. This study reports our experience with induced arterial hypertension and selective etomidate cerebral protection in a cohort of patients who underwent CEA without shunting and continuous electroencephalography (EEG) monitoring., Methods: We reviewed retrospectively 102 consecutive CEAs performed in 102 patients with routine EEG monitoring and general anesthesia between March 1998 and October 2002. There were 65 (66%) symptomatic and 37 (34%) asymptomatic individuals. A protocol of induced arterial hypertension against EEG ischemic changes during carotid artery cross clamping was followed. Only patients with EEG changes refractory to induced hypertension went into etomidate-induced burst suppression., Results: EEG changes were classified as mild, moderate and severe. Twenty patients (19.6%) developed asymmetric EEG changes, of which the great majority were mild and moderate (75%, p< 0.05). Seven patients with moderate (n=3) and severe (n=4) EEG changes needed etomidate cerebral protection. There were no mortalities and only one stroke (0.98%) is reported in the series. The morbidity rate was 6.8% and included transient cranial nerve palsies (n=5) and wound hematoma (n=1)., Conclusions: Carotid endarterectomy can be safely performed with EEG monitoring and selective induced arterial hypertension and etomidate cerebral protection. Our results suggest that this method may be a good alternative for shunting and its inherent risks.

Medically refractory positional cerebral ischemia (PCI) and concomitant orthostatic hypotension associated with chronic common carotid artery (CCA) occlusion are rare. In this technical report, the authors describe an extracranial bypass in which the thyrocervical trunk was used as a donor vessel to treat three cases of CCA occlusion with PCI. Postoperatively, although orthostatic hypotension remained, ischemia-related symptoms resolved in all three patients and long-term graft patency was demonstrated. It is possible to treat cerebral ischemia due to CCA occlusion with extracranial bypass surgery. In these patients, the thyrocervical trunk proved to be a suitable donor vessel for the reconstitution of blood flow within the external carotid artery.

Objective: In nonrecovery models of cerebral ischemia, blood-brain barrier (BBB) and cerebral blood flow (CBF) changes are known to occur during reperfusion. It is unknown, however, whether those CBF and BBB alterations occur after brief, transient ischemia with neurological recovery. The purpose of this study was to characterize the time course of CBF and BBB ultrastructural changes during reperfusion in an awake, recovery model of transient global forebrain ischemia (GFI)., Methods: Forty-five adult Sprague-Dawley rats were subjected, while awake, to 10 minutes of GFI by the nine-vessel occlusion method. Thirty-five age-matched animals composed a sham-operated group. Normal control (n = 5), sham-operated (n = 5), and nine-vessel occlusion/reperfusion (n = 15) rats were selected for ultrastructural analysis. Electroencephalography was performed, and CBF, mean arterial blood pressure, and intracranial pressure were measured during ischemia and reperfusion up to 24 hours. Quantitative morphological analysis of cortical BBB capillaries was performed by transmission electron microscopy at the same time points at which specific CBF changes occurred during reperfusion., Results: CBF decreased to 6% of preocclusion values during GFI. This correlated with coma and decerebrate rigidity. During reperfusion, short-lived hyperemia (225 +/- 18%, P < 0.001) was characterized by increased intracranial pressure (28.3 +/- 2.6 mm Hg, P < 0.001) and isoelectric electroencephalogram. This was followed by hypoperfusion, which reached a nadir of 59.7% (59.7 +/- 8.8%, P < 0.01) from baseline by 90 minutes. At this time point, the electroencephalogram recovered, and intracranial pressure and mean arterial blood pressure showed no abnormalities. By 8.5 hours, CBF returned to normal, and this coincided with complete recovery of the animal. Ultrastructural BBB analysis revealed astrocyte end-foot process edema and patent capillaries during hyperemia. Severe interstitial BBB edema and capillary lumen collapse was observed during hypoperfusion. Detachment and migration of pericytes was observed during hypoperfusion and beyond., Conclusion: A biphasic CBF response is elicited during reperfusion after brief nonlethal GFI under awake conditions.

Medically refractory positional cerebral ischemia and concomitant orthostatic hypotension associated with chronic common carotid artery (CCA) occlusion are rare. The authors detail their experience with three cases treated exclusively by an extracranial bypass in which the thyrocervical trunk was used as the donor vessel. Postoperatively grafts were patent and symptoms resolved in all three patients, although orthostatic hypotension remained. Postural cerebral ischemia due to CCA occlusion can be treated by extracranial bypass surgery. The thyrocervical trunk is a suitable donor for reconstruction of the external carotid artery in these cases.

This study was performed to test the hypotheses that (a) resection of the temporal lobe epileptic focus, amenable to noninvasive as opposed to invasive localization, is associated with superior seizure outcome and (b) that quadruple (versus lesser degrees of) concordance of seizure focus localizing data predicts superior seizure-free outcome. Eighty-three patients underwent invasive (subdural-EEG) and/or noninvasive (video/scalp-EEG, SPECT, PET, MRI, neuropsychological testing) evaluation. All patients underwent anterior temporal lobectomy and amygdalohippocampectomy (ATL/AH) and seizure outcome was assessed at minimum one-year follow-up. At 34.8 +/- 2.5 months following ATL/AH, outcome was superior for patients in whom the seizure focus was amenable to noninvasive compared to invasive localization (80% versus 40% seizure-free, X2 = 14.03, p < 0.05). Seizure outcome was superior for patients with quadruple, compared to all lesser degrees of, concordance of seizure focus localizing data (85% versus 51% seizure-free, X2 = 7.34, p < 0.05). Post-ATL/AH, seizure outcome is superior in patients (1) harboring an epileptic focus amenable to noninvasive localization and (2) with quadruple concordance of seizure focus localizing data. These findings support the development of temporal lobectomy selection criteria including up to four invasive and/or noninvasive concordant seizure focus localizing techniques.

Anesthesia is an essential element during the induction of ischemia/reperfusion and cerebral blood flow (CBF) measurement in most animal models. Cerebral neuroprotection and intrinsic effects on CBF afforded by anesthetics are confounding variables in those models. A new model of global forebrain ischemia/reperfusion (GFIR) in awake rats is presented and characterized. Rats underwent permanent occlusion of the basilar, and the paired pterygopalatine, external carotid, and occipital arteries. Inflatable balloon occluders were inserted around both common carotids, the nine-vessel occlusion (9VO) preparation. A subgroup of 9VO rats underwent placement of a laser Doppler flowmetry (LDF) probe for measurement of cortical CBF. Twenty-four hours later, while awake, 9VO rats were subjected to 10 min of ischemia by occluding both common carotid arteries. Blood gases, glucose and hematocrit were analyzed before and during ischemia, and for up to 90 min during reperfusion. Behavioral observations and continuous LDF CBF and mean arterial blood pressure determinations during ischemia and reperfusion were made. Rats were rendered comatose and decerebrate rigidity was observed during 9VO. Following balloon deflation, rats immediately regained the righting reflex and achieved complete recovery in the next 24 h. Moderate hyperglycemia was observed at 5 min of ischemia and up to 90 min reperfusion in 9VO rats. LDF CBF decreased to 5% of baseline and remained unchanged during ischemia. The 9VO is a reproducible recovery model of GFIR. Behavioral and LDF CBF correlates are consistent and survival studies are feasible.

The present study was undertaken to ascertain the role of smooth muscles and pericytes in the microcirculation during hyperperfusion and hypoperfusion following ischemia in rats. Paired external carotids, the pterygopalatine branch of the internal carotids and the basilar artery were exposed and divided. Reversible inflatable occluders were placed around the common carotids. After 24 h, the unanesthetized rat underwent 10-min ischemia by inflating the occluders. Continuous cortical cerebral blood flow (c-CBF) was monitored by laser Doppler flowmetry. The measured c-CBF was below 20% of control (P < 0.001) during ischemia. A c-CBF of 227.5 +/- 54.1% (P < 0.001) was obtained during reperfusion hyperemia. A c-CBF of 59.7 +/- 8.8% (P < 0.001) occurred at the nadir of postischemic hypoperfusion, and this was followed by a second hyperemia. The cytoarchitecture of the vascular smooth muscles and pericytes was assessed by scanning electron microscopy. Samples were prepared using a KOH-collagenase digestion method. In control rats, arteriolar muscle cells showed smooth surfaces. Capillary pericytes were closely apposed to the endothelium. Immediately after reperfusion, transverse membrane creases were observed on the smooth muscle surfaces. During maximal hyperemia the creases disappeared. When c-CBF started to decrease the creases became visible again. Throughout the postischemic hypoperfusion the creases remained. Capillary endothelial walls became tortuous in the late phase of hypoperfusion. During the second hyperemia most arteriolar muscle cells showed smooth surfaces. Some pericytes appeared to have migrated from the vascular wall. The morphological changes of smooth muscle membranes suggest that they are related to specific perfusional disturbances during ischemia and reperfusion.

Standard planning for intracranial aneurysm surgery relies on the surgeon's intellectual reconstruction of the three-dimensional (3D) surgical field on the basis of a two-dimensional (2D) imaging modality, biplanar cerebral angiography. This method is relatively imprecise, and it relies on previous experience for optimal results. We describe a stereotactic magnetic resonance angiographic (MRA)-guided method based on computer segmentation techniques for the planning of aneurysm surgery that has the potential of bringing a 3D perspective to the lesion. The method has been evaluated retrospectively on 20 surgical patients in whom the aneurysm orientation and relationship to parent vessels were shown to match presurgical 3D stereotactic display. When it is adapted to frameless interactive surgical navigation, this method may become a useful adjunct in the surgical obliteration of these life-threatening lesions.