Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke.

BACKGROUND: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood. METHODS: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications. RESULTS: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p = 0.1; mRS 0-2: 47% vs 50%, p = 0.41) but higher mortality (26% vs 17%, p = 0.008). After PSM, there were no significant differences in outcomes between the two groups. CONCLUSION: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates.

Measuring CSF shunt flow with MRI using flow enhancement of signal intensity (FENSI).

PURPOSE: To develop and validate a noninvasive imaging technique for accurately assessing very slow CSF flow within shunt tubes in pediatric patients with hydrocephalus, aiming to identify obstructions that might impede CSF drainage. THEORY AND METHODS: A simulation of shunt flow enhancement of signal intensity (shunt-FENSI) signal is used to establish the relationship between signal change and flow rate. The quantification of flow enhancement of signal intensity data involves normalization, curve fitting, and calibration to match simulated data. Additionally, a phase sweep method is introduced to accommodate the impact of magnetic field inhomogeneity on the flow measurement. The method is tested in flow phantoms, healthy adults, intensive care unit patients with external ventricular drains (EVD), and shunt patients. EVDs enable shunt-flow measurements to be acquired with a ground truth measure of CSF drainage. RESULTS: The flow-rate-to-signal simulation establishes signal-flow relationships and takes into account the T1 of draining fluid. The phase sweep method accurately accounts for phase accumulation due to frequency offsets at the shunt. Results in phantom and healthy human participants reveal reliable quantification of flow rates using controlled flows and agreement with the flow simulation. EVD patients display reliable measures of flow rates. Shunt patient results demonstrate feasibility of the method and consistent flow rates for functional shunts. CONCLUSION: The results demonstrate the technique's applicability, accuracy, and potential for diagnosing and noninvasively monitoring hydrocephalus. Limitations of the current approach include a high sensitivity to motion and strict requirement of imaging slice prescription.

Novel technique of stent placement via gateway balloon in intracranial atherosclerosis-associated large vessel occlusion.

BACKGROUND AND PURPOSE: Neuroform Atlas stent can be deployed directly via gateway balloon for angioplasty and stent placement without the need for exchange maneuver required for Wingspan stent use. We present our initial experience of this strategy in intracranial atherosclerosis-associated large vessel occlusions. METHODS: Patients were identified through mechanical thrombectomy (MT) database from January 2020 to June 2022 at our institutions. Due to reocclusion or impending occlusion, rescue angioplasty with stent placement was performed after initial standard MT. Primary outcomes were good angiographic recanalization with modified thrombolysis in cerebral infarction (mTICI) score of 2b-3, rate of intracranial hemorrhage (ICH), and favorable functional outcome at 3 months, that is, modified Rankin Scale (mRS) score of 0-3. RESULTS: We identified 22 patients treated using this technique. Among those, 11 were females with their average age at 66 years (range: 52-85). Initial median National Institute of Health Stroke Scale score was 11 (range: 5-30) and all patients received loading doses of aspirin and P2Y12 inhibitor. After performing submaximal angioplasty and Neuroform Atlas stent deployment through the gateway balloon, we achieved final mTICI of 2b-3 in 20 (90%) patients. One patient had ICH post-op that was asymptomatic. Eight (36%) patients had mRS of 0-3 at 90 days. CONCLUSION: Our preliminary experience suggests possible safety and feasibility of deploying Neuroform Atlas stent through a compatible Gateway balloon microcatheter without the need for ICH-associated microcatheter exchange. Further studies with long-term clinical and angiographic follow-up are warranted to corroborate our initial findings.

Ruptured arteriovenous malformation mortality: Incidence, risk factors, and inpatient outcome score.

BACKGROUND: Limited literature exists on the morbidity and mortality of AVM associated intracerebral hemorrhage (ICH) compared with non-AVM ICH. OBJECTIVE: We examine morbidity and mortality in cAVM in a large nationwide inpatient sample to create a prognostic inpatient ruptured AVM mortality score. METHODS: This retrospective cohort study from 2008 to 2014 compares outcomes in cAVM related hemorrhages and ICH utilizing the National Inpatient Sample database. Diagnostic codes for ICH and AVM underlying ICH were identified. We compared case fatality according to medical complications. Multivariate analysis was used to derive hazard ratios and 95% confidence intervals to assess odds of mortality. RESULTS: We identified 6496 patients with ruptured AVMs comparing them to 627,185 admitted with ICH. Mortality was lower for ruptured AVMs (11%) compared to ICH (22%) [p < 0.01]. Mortality associated factors were liver disease (OR 2.64, CI 1.81-3.85, p < .001), diabetes mellitus (OR 2.42, CI 1.38-4.22, p = 0.002), alcohol abuse (OR 1.81, CI 1.31-2.49, p = 0.001), hydrocephalus (OR 3.35 CI 2.81-4.00, p < 0.001), cerebral edema (OR 1.5, 1.25-1.85, p < 0.001), cardiac arrest (OR 15, CI 7.9-30, p < 0.001), and pneumonia (OR 1.93, CI 1.51-2.47, p < 0.001). A 0-5 ruptured AVM mortality score was developed: Cardiac arrest (=3), age >60 (=1), Black race (=1), chronic liver failure (=1) diabetes mellitus (=1), pneumonia (=1), alcohol abuse (=1) and cerebral edema (=1). Mortality increased with score. No patient with 5 or more points survived. CONCLUSION: The Ruptured AVM Mortality Score allows for risk stratification on patients with ICH due to ruptured AVM. This scale could prove useful in prognostication and patient education.

Unicystic ameloblastoma of mural variant crossing the midline.

Unicystic ameloblastoma (UCA) refers to cystic lesions that show gross features of a jaw cyst but on histologic examination show a typical ameloblastomatous epithelium lining part of the cyst cavity, with or without luminal and/or mural tumor growth. Even though the lesion is not as aggressive as the solid ameloblastoma, an accurate histopathologic diagnosis is essential for the treatment and prognosis. This case report illustrates a case of UCA of mural variant in the anterior region of the mandible crossing the midline, which is usually an unusual site of occurrence.

Endoscopic Transnasal Transmaxillary Approach to Orbital Apex through the Meningo-Orbital Band: A Cadaveric Feasibility Study.

Background: Extradural transcranial release of the meningo-orbital band occupying the lateral part of the superior orbital fissure is used to approach the orbital apex and middle cranial fossa. The authors tested the feasibility of the release of the meningo-orbital band via an endonasal transmaxillary approach. Materials and Methods: Five injected cadaveric heads were assessed for dimensions of superior orbital fissure by computerized tomography. An endonasal transsphenoid transpterygoid approach was done to the superior orbital fissure and annulus of Zinn medially, down to the maxillary nerve. The periorbita was dissected superolaterally to expose the greater wing of the sphenoid and the meningo-orbital band. The superior orbital fissure was decompressed inferiorly by drilling the greater wing of the sphenoid and the maxillary strut after transposition of the maxillary nerve. The meningoorbital band was cut at the junction of the lateral part of the superior orbital fissure and the periorbita exposing the frontotemporal dural junction. The edge of the lesser wing of the sphenoid was drilled toward the annulus of Zinn and the optic canal. The temporal lobe dura was separated from the periorbita and lateral cavernous dural wall at the meningo-orbital band and the ophthalmic nerve. Results: The superior orbital fissure had an oblique angle (mean: 39 ± 2.75 degrees) to the midsagittal plane, the length of its lateral part corresponding to the meningo-orbital band was (mean: 6.08 ± 2.58 mm) and the distance from its lateral end to midline was (mean 2.97 ± 0.11 cm). The meningo-orbital band was released in 10 cadaveric head sides with a distinct plane between the periorbita and the dura propria. Transmaxillary endoscopy provided less orbital retraction and better visualization of the lateral wall of the cavernous sinus. Conclusion: Endonasal transmaxillary release of the meningoorbital band is feasible, allowing exposure of the orbital apex and the middle cranial fossa.

Endovascular thrombectomy with and without preceding intravenous thrombolysis for treatment of large vessel anterior circulation stroke: A cross-sectional analysis of 50,000 patients.

INTRODUCTION: The safety and efficacy of intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) for large vessel occlusion stroke remains a highly contested and unanswered clinical question. We aim to characterize the clinical profile, complications, and discharge disposition of EVT patients treated with and without preceding IVT using a large, nationally-representative sample. METHODS: The National Inpatient Sample was queried from 2015 to 2018 to identify adult patients with anterior circulation stroke treated with EVT with and without preceding IVT. Multivariable logistic regression analysis and propensity-score matching were employed to assess adjusted associations with clinical endpoints and to address confounding by indication for IVT, respectively. RESULTS: Among 48,525 patients identified, 40.7% (n = 19,735) received IVT prior to EVT. On unadjusted analysis, patients treated with IVT bridging therapy experienced higher rates of intracranial hemorrhage (26% vs. 24%, p = 0.003) and routine discharge to home with or without services (33% vs. 27%, p < 0.001), a lower frequency of thromboembolic complications (3% vs. 5%, p < 0.001), and lower rates of extended hospital stays (eLOS) (20% vs. 24%, p < 0.001). Multivariable logistic regression analysis adjusting for demographic and baseline clinical characteristics demonstrated independent associations of IVT bridging therapy with intracranial hemorrhage (aOR 1.28, 95% CI 1.15, 1.43; p < 0.001), thromboembolic complications (aOR 0.66, 95% CI 0.53, 0.83; p < 0.001), routine discharge (aOR 1.27, 95% CI 1.15, 1.40; p < 0.001), and eLOS (aOR 0.76, 95% CI 0.68, 0.85; p < 0.001). Sensitivity testing confirmed these findings. CONCLUSION: Preceding IVT was associated with favorable functional outcomes following endovascular therapy. Prospective randomized clinical trials are warranted for further evaluation.

Brain stiffness following recovery in a patient with an episode of low-pressure hydrocephalus: case report.

The authors describe a follow-up to a case of a 19-year-old female with shunted aqueductal stenosis who presented with low-pressure hydrocephalus during a shunt malfunction. Shortly after management with CSF drainage at negative pressure, a magnetic resonance elastography scan was performed and revealed very low brain stiffness (high compliance). Here we present the case of the same patient seen 2 years later, now 21 years old, who again received a magnetic resonance elastography scan after receiving treatment for another shunt malfunction, this time with high intracranial pressure. This scan revealed recovery of brain stiffness to a near normal value for the patients' age. This observation suggests the low brain stiffness observed during the low-pressure hydrocephalus event is reversible. The authors discuss these findings in relation to biomechanical hypotheses of low-pressure hydrocephalus.

Experience With the Pipeline Embolization Device for Posterior Circulations Aneurysms: A Multicenter Cohort Study.

BACKGROUND: The Pipeline Embolization Device (PED; Medtronic) has been used off-label for the treatment of challenging posterior circulation aneurysms. Data on this modality are primarily limited to small retrospective single-center series. OBJECTIVE: To assess safety and efficacy of this treatment by establishing an international, multicenter collaboration. METHODS: Consecutive posterior circulation aneurysms treated with the PED from 2012 to 2019 across 11 neurovascular centers were retrospectively reviewed. Baseline demographics, aneurysm and treatment characteristics, complications, occlusion status, and functional outcome were assessed. RESULTS: There were 149 posterior circulation aneurysms treated with PED in 146 patients. A total of 24 (16.4%) patients presented with subarachnoid hemorrhage. Most aneurysms were dissecting/blister (36.2%) in morphology, followed by saccular (35.6%) and fusiform (28.2%). The most common locations were the vertebral (51.7%) and basilar arteries (22.8%). Complete or near-complete occlusion (>90%) was achieved in 90.9% of aneurysms at a median follow-up of 12 mo. Dissecting/blister aneurysms were most likely to occlude (P = .06). Symptomatic neurologic complications occurred in 9.4% of aneurysms, associated with larger size, ruptured presentation, presentations with brain stem compression, cranial nerve palsy, or stroke. Favorable functional outcome (modified Rankin Score 0-2) was achieved in 86.2% of patients. There were 6 fatalities of which 4 occurred in aneurysmal subarachnoid hemorrhage patients. CONCLUSION: This multicenter study shows that PED for the treatment of posterior circulation is preferentially used for the treatment of fusiform and dissecting/blister aneurysm morphologies. Despite the challenges presented by these less-common morphologies, flow diversion may be performed with a neurologic complication rate of about 10% and favorable long-term aneurysm occlusion rates.

Verrucous carcinoma: A clinicopathological study.

OBJECTIVE: The purpose of this study is to identify a co-relation between clinical and histopathological features of verrucous carcinoma. MATERIALS AND METHODS: This study was conducted based on Knowledge Attitude and Practice (KAP) questionnaire comprising of 3 sets of questions covering clinical and histopathological aspects of the oral verrucous carcinoma. The target subjects were specialists in the field of Oral Medicine and Radiology, Oral and Maxillofacial Surgery and Oral Pathology. RESULTS AND CONCLUSION: Verrucous carcinoma is a low grade variant of squamous cell carcinoma and the clinical features of both are very similar. The treatment of both differs widely; we fail to diagnose it correctly. This study correlates the clinic-pathologic features of oral verrucous carcinoma by means of statistically analyzing the varied clinical features and pathological impressions. This is helpful in eliminating the diagnostic dilemma and thus channelizing the data to present a clear treatment planning.

Mobilization of the outer cavernous membrane decreases bleeding and improves resection in spheno-clinoidal meningiomas without cavernous sinus extension: A randomized controlled trial.

OBJECTIVE: The aim of this study was to determine whether adding mobilization of the outer cavernous sinus membrane as a part of the approach, in large spheno-clinoidal meningiomas without cavernous sinus extension, would reduce bleeding and increase the extent of resection. METHODS:: This prospective randomized controlled trial was held between February 2016 and April 2017 at Cairo University Hospitals. The study recruited 94 patients with spheno-clinoidal meningiomas without cavernous sinus involvement. Patients were randomly assigned (by a computer based randomization system) into two groups; the treatment group, in which the patients received mobilization of the outer layer of the lateral wall of the cavernous sinus, prior to opening of the dura; and, the control group, in which the patients were operated by a direct opening of the dura without cavernous sinus dissection. The primary outcome of this study was the difference in the amount of blood lost during surgery between both groups of patients. The secondary outcome variables were the estimated blood loss (EBL) calculated according to Mercurelli's formula, the extent of tumor resection and the amount of blood transfused. RESULTS:: The amount of blood loss and estimated blood loss (EBL) were significantly less in the "with mobilization group" with the P value being 0.00 and 0.013, respectively. Additionally, the amount of residual tumor was compared between both the groups and it showed that the group of patients who have received mobilization of the outer cavernous sinus membrane had a higher rate of radical resection as expressed by a lower volume of residual tumor (P value 0.005). CONCLUSION:: In large spheno-clinoidal meningiomas without cavernous sinus involvement, routine mobilization of the outer cavernous sinus membrane reduces bleeding. This helps in a better visualization of cranial nerves in a relatively avascular field as it enables the performance of neurovascular dissection in an earlier phase of surgery. It also enables a more radical resection.

The "11 O'clock Heel First" technique for microvascular end-to-side anastomosis.

BACKGROUND: The heel of a microvascular end-to-side anastomosis is a common site for technical imperfections. We describe a simple technique to overcome this challenge. The aim of the technique is to insert all the sutures in an inside-to-outside manner at the heel area on the donor side of the anastomosis. This technique has first been tested in a laboratory setting and then was further elaborated in a clinical setting. MATERIALS AND METHODS: One hundred and twenty adult albino Wistar rats of both genders were randomized into the following two groups: (A) Control, 48 rats, representing approximately 40% of the total sample, underwent the usual two anchoring stitch technique; (B) Study group, 72 rats, representing approximately 60% of the total sample, underwent the technique described. Patency was confirmed both clinically and by the use of fluorescein angiography. Rat weight, diameter of both the donor and recipient vessels, type of anastomosis (arterio-arterial or arterio-venous) and angiographic findings were used as variables. A P value of less than 0.05 was considered significant. RESULTS: The proposed technique had increased patency rates as compared to the standard technique, which was statistically significant (P = 0.021). However, there was no difference between the patency rates of arterio-arterial and arterio-venous atastomoses. CONCLUSION: The proposed technique is useful for perfecting the heel area of a microvascular end-to-side anastomosis in both laboratory and clinical settings.

Role of surgery for small petrous apex meningiomas causing refractory trigeminal neuropathy in the minimally invasive era.

BACKGROUND: Radiosurgery seems to be a very appealing option for patients having a small petrous apex meningioma and presenting with trigeminal neuralgia, presumably because of the lower risk and cost involved. The aim of this study was to analyze the results of our surgical series of petrous apex meningioma presenting with trigeminal neuralgia, and to determine the efficacy of neurosurgical treatment with regard to pain control. The procedure-related complication and morbidity rates were also evaluated. MATERIALS AND METHODS: This is a retrospective study of 17 patients with a small (<3 cm) petrous apex meningioma. The included patients were refractory to medical treatment for trigeminal neuralgia and were deemed as surgical candidates. Postoperatively, the patients were assessed for pain relief according to the Barrow Neurological Institute (BNI) scale. A P value of less than 0.05 was considered significant. Magnetic resonance imaging was also performed after 6 weeks to assess the radicality of resection. RESULTS: In a median follow-up of approximately 2 years, the study showed that 14 of the 17 (82.4%) patients had complete pain relief, with very low morbidity and no mortality, and 100% tumor control. According to the Barrow Neurological Institute (BNI) scale for the assessment of postoperative pain relief, 52.9, 23.5, 5.9, 11.8, and 5.9% of patients had grades I, II, IIIa, IIIb, and IV in terms of their pain relief, respectively. CONCLUSIONS: In our population of patients, surgery proved to be successful in providing symptomatic relief, with low morbidity and no mortality, and was comparable with other studies involving the minimally invasive modalities. However, these results warrant further follow-up, with recruitment of more patients, to demonstrate whether or not, surgery should be the primary choice of treatment in this subgroup of patients.

Novel double catheter technique with detachable microcatheter for the treatment of arteriovenous malformations: A technical note.

BACKGROUND: Onyx has improved the safety and efficacy of endovascular treatment in the management of cerebral arteriovenous malformations (AVMs). However, during injection inadvertent reflux around the delivery microcatheter into important normal arterial branches remains a major challenge. METHODS: We describe a new double arterial catheterization technique using a detachable tip microcatheter in conjunction with a second microcatheter to form a proximal antireflux Onyx plug. This novel technique allows for increased amounts of Onyx to be steadily injected while avoiding dangerous backflow in the treatment of AVMs. RESULTS: The patient tolerated the procedure well without changes in hemodynamics. Using the novel double catheter technique, a significant portion of the AVM was embolized and the patient had no complications postoperatively. CONCLUSIONS: The novel double catheter technique with a detachable microcatheter is a safe and effective technique to increase the amount of Onyx embolization material into the AVM nidus.

Isolated synchondrosis fracture of the atlas presenting as rotatory fixation of the neck: Case report and review of literature.

BACKGROUND: Exclusive to the pediatric population, cartilaginous fractures of the atlas are singularly rare. Rarer still are those fractures that produce a fixed, rotational deficit of the neck. Here, the authors present the case of a 4-year-old boy with an isolated fracture of the anterior synchondrosis of C1 with a rotational component following a fall, as well as a review of the literature. Management with serial bedside manipulation, which is unique to our report, helped conservatively correct the rotation of the patient's neck, and, coupled with rigid bracing, demonstrated a comprehensive management strategy that resulted in fracture ossification at 3 months. CASE DESCRIPTION: Our patient is a 4-year-old boy who fell from a bunk bed and complained of severe neck pain. The patient was brought to the emergency room and was found to have an isolated anterior fracture of the right frontal synchondrosis of the atlas. After conservative management with a hard collar and cautious manual reductions at the bedside, rotation of our patient's neck spontaneously resolved on day 3. After 3 months of rigid immobilization, the patient remained at neurological baseline and his fracture was healed. Literature review demonstrated age range between 2 and 6 years, with a subset of patients demonstrating rotational components to their fractures. Complete resolution of nearly all patients treated with rigid immobilization after fracture was documented, yet several patients experienced delayed diagnosis. CONCLUSIONS: Knowledge of the radiographic appearance of the C1 ossification centers as well as the normal timeline and sequence of ossification is essential in differentiating a true synchondrosis fracture from normal, nonossified cervical cartilage. With early diagnosis, immobilization, pain control, and muscle relaxants, patients can recover well with conservative management, can successfully ossify fracture sites, and can recover without sequelae.

Extracranial to intracranial by-pass anastomosis: Review of our preliminary experience from a low volume center in Egypt.

BACKGROUND: Cerebral revascularization is a useful microsurgical technique for the treatment of steno-occlusive intracranial ischemic disease, complex intracranial aneurysms that require deliberate occlusion of a parent artery and invasive skull base tumors. We describe our preliminary experience with extracranial-to-intracranial by-passes at a low volume center; and discuss clinical indications and microsurgical techniques, challenges in comparison to large advanced referral centers. MATERIALS AND METHODS: Twenty-seven patients with hemodynamic ischemia or complex aneurysms or skull base tumors were operated at Cairo University Hospitals in the period between May 2009 and June 2014. All patients operated by a low flow by-pass were operated through a superficial temporal artery to middle cerebral artery (MCA) anastomosis. All patients chosen for a high flow by-pass were operated using a radial artery graft interposed between the MCAs distally and the common or the external carotid artery proximally. Patency was confirmed at the end of surgery using appearance on the table and confirmed after surgery by transcranial color-coded duplex or computed tomography angiography. All patient data were prospectively collected and retrospectively analyzed at the end of surgery. RESULTS: Nineteen patients (70.4%) were operated upon for flow augmentation and eight patients (29.6%) were operated upon for flow replacement. A total of 30 anastomoses were performed. All except one were patent which gives a patency rate of 96.3%. There was one death in the present series resulting from a hyperperfusion syndrome. 89.5% of patients with hemodynamic ischemia stopped having symptoms after surgery. All but one patient operated for hemodynamic ischemia showed a considerable cognitive improvement after surgery. None of the patients operated upon for flow replacement showed improvement of oculomotor nerve function in spite of adequate intraoperative decompression. All patients treated for flow replacement showed the absence of recurrence on follow-up. CONCLUSION: Our initial results for both low and high flow by-pass procedures in our low volume center indicate that such complex surgical procedures are possible with results comparable to those obtained in other larger referral centers throughout the world. This procedure not only represents a more definitive treatment when compared to other endovascular or radiation treatments but is also much less costly when compared to other treatment modalities.

Supratentorial paraventricular schwannoma.

Intraventricular schwannoma in either infra or supratentorial location is an extremely rare tumor with less than 20 cases described in the literature to date. There is no consensus regarding the origin of this tumor. This paper describes an excised supratentorial schwannoma located on the wall of the left lateral ventricle. The relevant literature is reviewed. A 34-year-old man with no significant medical history presented with a recent episode of right focal motor seizures and weakness of the right lower extremity. Magnetic resonance imaging of the brain demonstrated a heterogeneous enhancing mass in the body of left lateral ventricle mass lesion with vasogenic edema in the adjacent brain parenchyma. The patient underwent a left frontoparietal parasagittal craniotomy with neuronavigational guidance to avoid damage to the primary motor cortex. The tumor originated from the ependymal layer and extended to the body of lateral ventricle. Complete surgical excision of the tumor was achieved. Intraventricular schwannomas are rare tumors amenable to complete surgical excision, having a good prognosis without the need for adjuvant therapy. The recognition of this benign and potentially curable neoplasm and its differentiation from other less favorable tumors is of obvious importance.

Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.

Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5'-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na(+) dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

Use of a customized 3D "basket" to create a solitary split-thickness cranial graft from numerous split fragments in an infant.

While autologous split calvaria remains the preferred material for use in pediatric cranioplasty, it may be difficult to split the bone neatly into two distinct pieces, especially in infants and young children. In this paper, the authors present a technique in which numerous split pieces of bone can be readily joined together and conformed to the shape of the specific defect using a customized template and 3D trellis-like basket.