Central Nervous System Metastasis in Patients With HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival From SystHERs.

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Central Nervous System Metastasis in Patients With HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival From SystHERs.

Clin Cancer Res. 2018 Dec 28;:

Authors: Hurvitz SA, O'Shaughnessy J, Mason G, Yardley D, Jahanzeb M, Brufsky AM, Rugo HS, Swain SM, Kaufman PA, Tripathy D, Chu L, Li H, Antao V, Cobleigh M

Abstract
Background Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with central nervous system (CNS) metastasis have a poor prognosis. We report treatments and outcomes in patients with HER2-positive MBC and CNS metastasis from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs). Methods SystHERs (NCT01615068) was a prospective, US-based, observational registry of patients with newly diagnosed HER2-positive MBC. Study endpoints included treatment patterns, clinical outcomes, and patient-reported outcomes (PROs). Results Among 977 eligible patients enrolled (2012-2016), CNS metastasis was observed in 87 (8.9%) at initial MBC diagnosis and 212 (21.7%) after diagnosis, and was not observed in 678 (69.4%) patients. White and younger patients, and those with recurrent MBC and hormone receptor-negative disease, had higher risk of CNS metastasis. Patients with CNS metastasis at diagnosis received first-line lapatinib more commonly (23.0% vs. 2.5%), and trastuzumab less commonly (70.1% vs. 92.8%), than patients without CNS metastasis at diagnosis. Risk of death was higher with CNS metastasis observed at or after diagnosis (median overall survival [OS] 30.2 and 38.3 months from MBC diagnosis, respectively) versus no CNS metastasis (median OS not estimable; hazard ratio 2.86 [95% confidence interval 2.05-4.00] and 1.94 [95% confidence interval 1.52-2.49]). Patients with versus without CNS metastasis at diagnosis had lower quality of life at enrollment. Conclusions Despite advances in HER2-targeted treatments, patients with CNS metastasis continue to have a poor prognosis and impaired quality of life. Observation of CNS metastasis appears to influence HER2-targeted treatment choice.

PMID: 30593513 [PubMed - as supplied by publisher]

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Increases in Tumor N-glycan Polylactosamines Associated with Advanced HER2 Positive and Triple Negative Breast Cancer Tissues.

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Increases in Tumor N-glycan Polylactosamines Associated with Advanced HER2 Positive and Triple Negative Breast Cancer Tissues.

Proteomics Clin Appl. 2018 Dec 28;:e1800014

Authors: Scott DA, Casadonte R, Cardinali B, Spruill L, Mehta AS, Carli F, Simone N, Kriegsmann M, Mastro LD, Kriegsmann J, Drake RR

Abstract
Using a recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) method, we have spatially profiled N-linked glycans in human breast cancer formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA). Routinely, 50 or more individual N-glycan species are detected per FFPE tissue, and this number increases significantly with disease severity. Through the combined analysis of breast cancer FFPE tissues and TMAs we have been able to identify histopathology co-localized glycan structural classes specific to stromal, necrotic and tumor regions. N-glycan panels derived from TMAs representing HER2 receptor positive and triple negative breast cancers were compared to identify shared and divergent glycosylation patterns between the two genetic sub-types. Within the tissues, we have identified a series of high-mannose glycans that are predominantly associated with tumor regions, as well as more highly branched and fucosylated glycans in higher grade tumors. In addition to this, we also found a series of polylactosamine glycans with increasing expression in HER2+, triple negative and metastatic breast cancers. The expression of these polylactosamine glycans could provide further mechanistic insights into the development and spread of breast cancer, and provide new research directions for identifying prognostic markers. This article is protected by copyright. All rights reserved.

PMID: 30592377 [PubMed - as supplied by publisher]

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HSP90 inhibitor, AUY922, debilitates intrinsic and acquired lapatinib-resistant HER2-positive gastric cancer cells.

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HSP90 inhibitor, AUY922, debilitates intrinsic and acquired lapatinib-resistant HER2-positive gastric cancer cells.

BMB Rep. 2018 Dec;51(12):660-665

Authors: Park KS, Hong YS, Choi J, Yoon S, Kang J, Kim D, Lee KP, Im HS, Lee CH, Seo S, Kim SW, Lee DH, Park SR

Abstract
Human epidermal growth factor receptor 2 (HER2) inhibitors, such as trastuzumab and lapatinib are used to treat HER2-positive breast and gastric cancers. However, as with other targeted therapies, intrinsic or acquired resistance to HER2 inhibitors presents unresolved therapeutic problems for HER2-positive gastric cancer. The present study describes investigations with AUY922, a heat shock protein 90 (HSP90) inhibitor, in primary lapatinib-resistant (ESO26 and OE33) and lapatinib-sensitive gastric cancer cells (OE19, N87, and SNU-216) harboring HER2 amplification/over-expression. In order to investigate whether AUY922 could overcome intrinsic and acquired resistance to HER2 inhibitors in HER2-positive gastric cancer, we generated lapatinib-resistant gastric cancer cell lines (OE19/LR and N87/LR) by continuous exposure to lapatinib in vitro. We found that activation of HER2 and protein kinase B (AKT) were key factors in inducing intrinsic and acquired lapatinib-resistant gastric cancer cell lines, and that AUY922 effectively suppressed activation of both HER2 and AKT in acquired lapatinib-resistant gastric cancer cell lines. In conclusion, AUY922 showed a synergistic anti-cancer effect with lapatinib and sensitized gastric cancer cells with intrinsic resistance to lapatinib. Dual inhibition of the HSP90 and HER2 signaling pathways could represent a potent therapeutic strategy to treat HER2-positive gastric cancer with intrinsic and acquired resistance to lapatinib. [BMB Reports 2018; 51(12): 660-665].

PMID: 30591093 [PubMed - in process]

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Massive Pulmonary Embolism as the Initial Presentation of Acromegaly: Is Acromegaly a Hypercoagulable Condition?

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Massive Pulmonary Embolism as the Initial Presentation of Acromegaly: Is Acromegaly a Hypercoagulable Condition?

Am J Case Rep. 2018 Dec 29;19:1541-1545

Authors: Elarabi AM, Mosleh E, Alamlih LI, Albakri MM, Ibrahim WH

Abstract
BACKGROUND The clinical presentation in acromegaly is usually insidious, with headaches or visual disturbances being the most common symptoms. Previous studies have shown higher fibrinogen levels, lower protein C and S activity values, and enhanced platelet function in patients with acromegaly compared to a normal population. Nevertheless, the link between hypercoagulability and acromegaly is often overlooked and rarely reported in the literature. CASE REPORT We report a case of a young man with a massive pulmonary embolism as the initial presentation of acromegaly. Extensive workup excluded other causes of thrombophilia. Furthermore, the diagnosis of acromegaly was confirmed by the patient's clinical features as well as laboratory and radiological testing. A literature review on the link between hypercoagulability and acromegaly was performed. CONCLUSIONS This case report shed light on hypercoagulability as an under-recognized serious complication of acromegaly and paves the road for future studies on this topic.

PMID: 30593586 [PubMed - in process]

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An Evaluation of the Clinical and Histological Effects of High Dose Radiosurgery on the Rat Dorsal Root Ganglion.

An Evaluation of the Clinical and Histological Effects of High Dose Radiosurgery on the Rat Dorsal Root Ganglion.

World Neurosurg. 2018 Dec 26;:

Authors: Goldschmidt E, Fellows-Mayle W, Paschel EE, Niranjan A, Flickinger JC, Lunsford LD, Gerszten PC

PMID: 30593969 [PubMed - as supplied by publisher]

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MRI Parameters and Their Impact on the Survival of Patients with Glioblastoma: Tumor Perfusion Predicts Survival.

MRI Parameters and Their Impact on the Survival of Patients with Glioblastoma: Tumor Perfusion Predicts Survival.

World Neurosurg. 2018 Dec 26;:

Authors: Hou BL, Wen S, Katsevman GA, Liu H, Urhie O, Turner RC, Carpenter J, Bhatia S

Abstract
BACKGROUND: Many prognostic factors influence the overall survival (OS) of patients with glioblastoma. Despite gross total resection and Stupp protocol adherence, many patients have poor survival. Magnetic resonance (MR) perfusion imaging may assist in diagnosis, treatment monitoring, and prognostication.
METHODS: This is a retrospective study of 36 patients with glioblastoma assessing pre-operative MR parameters reflecting tumor cell density and vascularity, as well as patient age, on overall survival.
RESULTS: The area under curve (AUC) based on optimal Receiver Operating Characteristic (ROC) curves for perfusion parameters Normalized Relative Tumor Blood Volume (n_rTBV) and Normalized Relative Tumor Blood Flow (n_rTBF) were 0.92 and 0.89, respectively, and the highest among all imaging parameters and age. OS showed strongly negative correlations with n_rTBV_c (R=-0.70; p<0.001) and n_rTBF (R=-0.67; p< 0.001). The Cox model, which included age and imaging parameters, demonstrated that n_rTBV and n_rTBF were most predictive of OS, with hazard ratios of 5.97 (p=0.0001) and 8.76 (p=0.0001), respectively, compared to 1.63 (p=0.19) for age. Eighteen patients with n_rTBV_c≤2.5 (best cutoff value) had a median OS of 15.1 months (confidence interval (CI): 11.34-21.25), compared to 2.8 months (95% CI: 1.48-4.03; p<0.001) for 18 patients with n_rTBV_c>2.5. Twenty-four patients with n_rTBF≤2.79 had a median OS of 12 months (95% CI: 10.46-17.9), compared to 2.8 months for 12 patients with n_rTBF>2.79 (95% CI: 1.31-4.2; p<0.001).
CONCLUSION: The dominant predictors of OS are normalized perfusion parameters n_rTBV and n_rTBF. Pre-operative perfusion imaging may be used as a surrogate to predict glioblastoma aggressiveness and survival independent of treatment.

PMID: 30593971 [PubMed - as supplied by publisher]

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Implementation of intraoperative computed tomography for deep brain stimulation: pitfalls and optimization of workflow, accuracy, and radiation exposure.

Implementation of intraoperative computed tomography for deep brain stimulation: pitfalls and optimization of workflow, accuracy, and radiation exposure.

World Neurosurg. 2018 Dec 26;:

Authors: Carl B, Bopp M, Gjorgjevski M, Oehrn C, Timmermann L, Nimsky C

Abstract
OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for movement disorders. Stereotactic electrode placement can be guided by intraoperative imaging, which also allows an immediate intraoperative quality control. This paper is about implementation and refining a workflow applying intraoperative computed tomography (iCT) for DBS.
METHODS: 18 patients underwent DBS with bilateral implantation of directional electrodes applying a 32-slice movable CT scanner in combination with microelectrode recording.
RESULTS: iCT led to a significant decrease in overall procedural time, despite performing multiple scans. In three of the initial 5 cases iCT caused an adjustment of the final electrodes demonstrating the learning curve and the necessity to integrate road mapping for the exchange of microelectrode to final electrode. Implementation of low-dose CT protocols added microelectrode iCT to the refined workflow, resulting in an intraoperative adjustment of a trajectory in one patient. Low-dose protocols lowered the total effective dose to 1.15 mSv, i.e. a reduction by a factor of 3.5 compared to a standard non-iCT DBS procedure, despite repeated iCTs. Intraoperative lead detection based on final iCT revealed a radial error of 1.04 ± 0.58 mm and a vector error of 2.28 ± 0.97 mm compared to the preoperative planning, adjusted by the findings of microelectrode recording.
CONCLUSIONS: iCT can be easily integrated into the surgical workflow resulting in an overall efficient time saving procedure. Repeated intraoperative scanning ensures reliable electrode placement, while low-dose scanning protocols prevent extensive radiation exposure. iCT of microelectrodes is feasible and led to an adjustment of one electrode.

PMID: 30593970 [PubMed - as supplied by publisher]

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Frontal Sinus Repair Using Polymethyl Methacrylate After Bifrontal Craniotomy.

Frontal Sinus Repair Using Polymethyl Methacrylate After Bifrontal Craniotomy.

World Neurosurg. 2018 Dec 27;:

Authors: Matsuura J, Otsuka T, Nakagawa T, Kai K

Abstract
BACKGROUND: In many cases where bifrontal craniotomy is performed, the frontal sinus is opened and postoperative complications occur. Various methods to close the frontal sinus have been reported. However, all these methods require skills to perform and take time. This study was conducted to report the good results obtained with the closure of the frontal sinus using polymethyl methacrylate, which is a simpler method.
METHOD: From December 2008 to June 2018, 122 patients with ruptured anterior communicating aneurysm were transported to a facility, 52 of whom consecutively underwent bifrontal craniotomy with opening of the frontal sinuses that were filled with polymethyl methacrylate.
RESULTS: The mean follow-up period was 21.8 months. The longest term was 116 months. Complications and cerebrospinal fluid leak were not observed in any case.
CONCLUSION: The method of filling the frontal sinus with PMMA reported in this study is safe and has no complications. Therefore, it needs to be considered as a method of frontal sinus closure.

PMID: 30593968 [PubMed - as supplied by publisher]

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Anatomical variation and hemodynamic evolution of vertebrobasilar arterial system may contribute to the development of vascular compression in hemifacial spasm.

Anatomical variation and hemodynamic evolution of vertebrobasilar arterial system may contribute to the development of vascular compression in hemifacial spasm.

World Neurosurg. 2018 Dec 26;:

Authors: Wang QP, Yuan Y, Xiong NX, Fu P, Huang T, Yang B, Liu J, Chu X, Zhao HY

Abstract
BACKGROUND: Hemifacial spasm (HFS) is caused by vascular compression of the facial nerve. However, the definitive mechanism of offending vessel formation remains unclear. The aim of the study was to explore whether the anatomical and hemodynamic characteristics of the vertebral-basilar artery play a role in problematic vessel formation in HFS.
METHODS: Imaging data of 341 patients with a HFS who underwent microvascular decompression were reviewed retrospectively and compared with 360 controls. The hemodynamics of typical anatomical variations of the vertebral artery (VA) were analyzed using computational fluid dynamics (CFD) software.
RESULTS: Asymmetry of the left and right VAs was prevalent, and the left VA was the most dominant VA. A dominant VA was more prevalent in the HFS group than in the control group (p=0.026). A Left HFS had a significantly higher proportion of a left dominant VA, and a right HFS had a significantly higher proportion of right dominant VA (p<0.001). CFD models showed that angulation and tortuosity of vessels caused remarkable pressure difference between vascular walls of opposite sides. Dynamic clinical observations showed the mode of vessel transposition coincided with biomechanical characteristics.
CONCLUSION: Anatomical variations and hemodynamics of the vertebrobasilar arterial system are likely to contribute to vascular compression formation in a HFS.

PMID: 30593967 [PubMed - as supplied by publisher]

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Neuroprotective effects of tocilizumab on experimentally induced spinal cord ischemia-reperfusion injury.

Neuroprotective effects of tocilizumab on experimentally induced spinal cord ischemia-reperfusion injury.

World Neurosurg. 2018 Dec 26;:

Authors: Karatas Y, Erdi MF, Kaya B, Keskin F, Cüce G, Kılınc I, Uyar M, Izci EK, Kalkan E

Abstract
STUDY DESIGN: Experimental rabbit spinal cord ischemia-reperfusion (I/R) inury model.
OBJECTIVES: We aimed to evaluate neuroprotective effects of tocilizumab on spinal cord I/R inury.
SETTING: Animal Research Laboratory, Necmettin Erbakan University, Meram School of Medicine, Konya, Turkey.
METHODS: Twenty four adult New Zealand rabbits were randomly divided into three groups: Group 1, control group (n=8); Group 2, ischemia-reperfusion (I/R) group and group 3 (n=8), I/R injury+ tocilizumab (4 mg/kg,ip) treatment group. Spinal cord I/R injury was performed by infrarenal aortic cross clamping. Neurological evaluation, spinal cord tissue and plasma tumor necrosis factor (TNF) alpha, total antioxidant status (TAS), total oxidant status (TOS), thiobarbituric acid reactive substances (TBARS), interleukin 6 (IL 6), interleukin 10 (IL 10) levels were analyzed. Spinal cord neuronal damage score and apoptotic cell count were also investigated.
RESULTS: I/R injury significantly increase the plasma and spinal cord tissue TNF alpha, TOS, TBARS, IL6 levels and decrease the plasma and spinal cord tissue TAS and IL10 levels. Tocilizumab treatment significantly reduce the plasma and spinal cord tissue TNF alpha, TOS, TBARS, IL6 levels and increase plasma and tissue TAS and IL10 levels. I/R injury significantly increase spinal cord neuronal damage score and apoptotic cell count. Tocilizumab treatment significantly reduce spinal cord neuronal damage score and apoptotic cell count. Neurological examination scores at 24., 48. and 72. hours were significantly better in treatment group when compared with the I/R group.
CONCLUSION: This study shows significant neuroprotective effects of tocilizumab on rabbit spinal cord I/R injury.

PMID: 30593966 [PubMed - as supplied by publisher]

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Lead failure after vagus nerve stimulation implantation: X-ray examination and revision surgery.

Lead failure after vagus nerve stimulation implantation: X-ray examination and revision surgery.

World Neurosurg. 2018 Dec 26;:

Authors: Zhou H, Liu Q, Zhao C, Ma J, Ye X, Xu J

Abstract
OBJECTIVE: This study aimed to assess the most common types of lead failures, identify causes and discuss potential procedures for revision surgery following vagus nerve stimulator implantation in epilepsy patients.
METHODS: In a retrospective study over an 8-year period, 13 patients underwent revision surgery due to lead failure. Lead failure was classified as either lead intrinsic damage or lead pin disengagement from the generator header. In the X-ray image, the authors defined an RC ratio that represented the portion of rear lead connector in the header receptacle. It was used to quantitatively evaluate the mechanical failure of the lead-header interface. Optimal procedures to identify and manage lead failure were established.
RESULTS: All 13 patients presented with high lead impedance ≥ 9 kOhms at the time of revision. Seven of ten patients with lead damage presented with increased seizure frequency after a period of seizure remission. In contrast to lead damages occurring relatively late (> 15 months), lead pin disengagement was usually found within the early months after device implantation. A significant association was found between an elevated RC ratio (≥ 35%) and lead pin disengagement. The microsurgical technique permitted the removal or replacement of the lead without adverse effects.
CONCLUSIONS: The method of measuring the RC ratio developed in this study is feasible for identifying lead disengagement at the generator level. Lead revision was an effective and safe procedure for patients experiencing lead failure.

PMID: 30593965 [PubMed - as supplied by publisher]

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Does surgical start time or weekend presentation affect clinical outcome for those presenting with neurosurgical pathology?

Does surgical start time or weekend presentation affect clinical outcome for those presenting with neurosurgical pathology?

World Neurosurg. 2018 Dec 26;:

Authors: Linzey JR, Pandey AS

PMID: 30593964 [PubMed - as supplied by publisher]

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Coil embolization for cerebral aneurysms using a semi-jailing technique and open-cell stent.

Coil embolization for cerebral aneurysms using a semi-jailing technique and open-cell stent.

World Neurosurg. 2018 Dec 26;:

Authors: Shirakawa M, Yoshimura S, Uchida K, Yamada K, Sakamoto D, Iida T, Takada Y, Ishikura R

PMID: 30593963 [PubMed - as supplied by publisher]

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Development and validation of prognostic model for patients with acute subdural hematoma-a reliable nomogram.

Development and validation of prognostic model for patients with acute subdural hematoma-a reliable nomogram.

World Neurosurg. 2018 Dec 26;:

Authors: Jin XQ, Du XF, Yang MF, Zhang Q

Abstract
OBJECTIVE: By extracting clinical and CT imaging data of patients with acute subdural hematoma (ASDH) , factors that were significantly associated with poor prognosis were screened and a nomogram model was established and validated.
METHODS: All patients with ASDH who underwent subdural hematoma removal and decompressive craniectomy from January 2014 to March 2018 in Qinghai Provincial People's Hospital were continuously collected. Finally 124 patients were included in the study. According to Glasgow Outcome Scale at 3 months after operation, patients were divided into good prognosis group and poor prognosis group.
RESULTS: Univariate and binary logistic regression analysis were performed to screen out independent predictors that were significantly associated with poor prognosis of ASDH. Based on these factors, a nomogram model was established.
CONCLUSION: The nomogram model had high accuracy for predicting the poor prognosis in patients with ASDH and it was easy to promote. In the future, large sample and multi-center prospective studies are necessary to complement and identify the results.

PMID: 30593962 [PubMed - as supplied by publisher]

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Vertebral Body Rotation in Patient of Lumbar Degenerative Scoliosis; Surgical Implication for Oblique Lumbar Interbody Fusion (OLIF).

Vertebral Body Rotation in Patient of Lumbar Degenerative Scoliosis; Surgical Implication for Oblique Lumbar Interbody Fusion (OLIF).

World Neurosurg. 2018 Dec 26;:

Authors: Kim DB, Shin MH, Kim JT

Abstract
BACKGROUND: To investigate changes of oblique corridor in patients with lumbar degenerative scoliosis (LDS) and determine proper working angle with respect to the direction of vertebral axial rotation during oblique lumbar interbody fusion (OLIF) procedure.
METHODS: Distance of oblique corridor and rotational angle of the left or right apex group were measured on axial T2 MR images and then compared with those of propensity score-matched control group.
RESULTS: Fifty-five patients of the left apex group and 57 patients of the right apex group were compared with equal number of patients of the propensity score-matched control group. The distance of oblique corridor in the left apex group was shorter than that in the control group at levels of L1-2 and L2-3. In contrast, the distance of oblique corridor in the right apex group was longer than that of the control group at level of L2-3. Patients of the left apex group showed vertebral body rotating to the left side from L1-2 to L5-S1 while in the right apex group, the vertebral body rotated to the right side at level of L1-2, L2-3, and L3-4.
CONCLUSIONS: In the left apex group, the oblique corridor was decreased from psoas overlap and coupled axial rotation to the left side might increase the risk of contralateral nerve root injury during orthogonally working. Thus, surgeons should pay attention to the state of coupled vertebral axial rotation of LDS for OLIF procedure.

PMID: 30593961 [PubMed - as supplied by publisher]

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The Role of Collateral Circulation in Branch Vessel Occlusion After Flow Diversion.

The Role of Collateral Circulation in Branch Vessel Occlusion After Flow Diversion.

World Neurosurg. 2018 Dec 26;:

Authors: Raymond SB, Koch MJ, Rabinov JD, Leslie-Mazwi TM, Torok CM, Stapleton CJ, Patel AB

Abstract
OBJECTIVE: Flow diversion for treatment of intracranial aneurysms frequently necessitates covering adjacent branch vessels. Although branch vessel occlusion is common, associated clinical deficits are rare. We and others hypothesize that clinically silent branch vessel occlusion is due to underlying collateral circulation. To study the role of collateral circulation in covered branch vessel occlusion, we assessed collateral vessels and altered branch vessel flow on transfemoral catheter angiography in patients undergoing flow diversion of intracranial aneurysms.
METHODS: Pre-treatment, immediate post-treatment and interval follow-up angiograms were evaluated for branch vessel flow patterns and associated collateral circulation in a consecutive retrospective cohort of 84 patients from 2011-2017 with branch vessel coverage related to aneurysm flow diversion using the Pipeline Embolization Device (PED, Medtronic, Minneapolis, MN, USA).
RESULTS: We identified 142 branch vessels covered by the PED construct for treatment of 89 aneurysms, predominately in the anterior circulation (>90%). Collateral circulation was observed in roughly a third of these vessels and was associated with diminished (P < .001) or absent (P < .001) flow on follow-up angiography. Only 2 of 80 terminal branch vessels (no collaterals) were occluded, and those occurred in a patient with PED construct thrombosis. Altered branch vessel flow was not associated with vascular risk factors, treatment technique, or outcome measures, including new or worsening neurologic deficit.
CONCLUSIONS: Altered flow in branch vessels covered during flow diversion reflects underlying collateral circulation and is not associated with downstream ischemic deficits.

PMID: 30593960 [PubMed - as supplied by publisher]

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Utility of cervical collars following cervical fusion surgery; does it improve fusion rates or outcomes? A systematic review.

Utility of cervical collars following cervical fusion surgery; does it improve fusion rates or outcomes? A systematic review.

World Neurosurg. 2018 Dec 26;:

Authors: Karikari I, Ghogawala Z, Ropper A, Yavin D, Gabr M, Goodwin CR, Abd-El-Barr M, Veeravagu A, Wang MC

PMID: 30593959 [PubMed - as supplied by publisher]

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Association between CD133, CD44, and nestin expression and prognostic factors in high-grade meningiomas.

Association between CD133, CD44, and nestin expression and prognostic factors in high-grade meningiomas.

World Neurosurg. 2018 Dec 26;:

Authors: Kamamoto D, Saga I, Ohara K, Yoshida K, Sasaki H

Abstract
BACKGROUND: Meningioma is the most common primary brain tumor, which is graded I, II or III based on the World Health Organization (WHO) classification of central nervous system (CNS) tumors. Meningiomas, especially those classified as grade II-III, have an aggressive history and a high recurrence rate. Cancer stem cells (CSCs) represent a small subset of tumor cells and are considered to be involved in tumor initiation, growth, or recurrence. To date, CSCs of meningioma are not well established.
METHODS: We assessed 51 grade II/III meningiomas on immunohistochemistry to determine if there was a correlation with prognosis by investigating CD133, CD44 and nestin expression representative of CSC markers, age, gender, initial WHO tumor grade, Simpson grade, and adjuvant radiation therapy.
RESULTS: The median overall survival (OS) was 7.1 years, and the median progression-free survival (PFS) was 1.8 years. Univariate analysis using Cox proportional hazards regression revealed a negative correlation between CD133 and nestin expression and PFS (p = 0.0176 and 0.0138, respectively), and a high expression of CD44 demonstrated a tendency toward shorter PFS (p = 0.0563) as did initial WHO grade and Simpson grade on the initial operation (p = 0.0166 and 0.0333, respectively). Multivariate analysis showed relevance between CD133 and nestin and PFS.
CONCLUSIONS: CD133, nestin, initial WHO grade and Simpson grade were associated with PFS in grade II/III meningioma, which may suggest that these molecules are representative of CSCs in meningioma regarding the aspect of clinical course.

PMID: 30593958 [PubMed - as supplied by publisher]

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Dural artery from the supraclinoid internal carotid artery to the anterior clinoid process: origin, course and clinical implications.

Dural artery from the supraclinoid internal carotid artery to the anterior clinoid process: origin, course and clinical implications.

World Neurosurg. 2018 Dec 26;:

Authors: Salunke P, Singh A, Rekhapalli R

Abstract
BACKGROUND: /objectives: Dura of the anterior clinoid process (ACP) is presumably supplied by the ophthalmic and external carotid artery branches. There is a less recognised artery described by Yasargil that arises directly from the supraclinoid internal carotid artery (ICA) and supplies the ACP dura. We studied the origin and course of this direct branch in patients in whom the carotid cistern was dissected for lesions not involving the carotid cistern and ACP dura. The management implications of this arterial twig have been described.
MATERIALS AND METHODS: Thirty patients operated through transsyvian route for suprasellar lesions were included. The arterial branch from the supraclinoid ICA to clinoidal dura was dissected and studied under high magnification RESULTS: A thin solitary artery could be delineated in 21 patients. In 14 patients, it originated from the dorsomedial surface of ICA at its bifurcation close to the A1 origin. In the remaining 7, it was seen arising from dorso-medial surface of ICA,2-4mm proximal to bifurcation. The artery coursed from medial to lateral and pierced the clinoidal dura, 1-3 mm lateral to the entry of carotid. The artery had no branches.
CONCLUSION: The knowledge of this arterial twig to clinoidal dura is important as this supply may be responsible for feeding the tumour arising from dura arising from anterior clinoid making pre-operative embolization impossible. In addition, the tumour may grow along with this vessel and infiltrate the adventitia of ICA at the origin of this vessel.

PMID: 30593957 [PubMed - as supplied by publisher]

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Analysis of Endoscopic Findings in the Chronic Subdural Hematoma Cavity: Bleeding Factors in Chronic Subdural Hematoma Natural History and as Predictors of Recurrence.

Analysis of Endoscopic Findings in the Chronic Subdural Hematoma Cavity: Bleeding Factors in Chronic Subdural Hematoma Natural History and as Predictors of Recurrence.

World Neurosurg. 2018 Dec 26;:

Authors: Wakuta N, Abe H, Nonaka M, Morishita T, Higashi T, Arima H, Inoue T

Abstract
OBJECTIVE: Possible factors associated with bleeding from endoscopy-detected chronic subdural hematomas (CSDHs) have rarely been analyzed. We therefore evaluated intraoperative endoscopic findings to elucidate the clinical course and assess predictors of CSDH recurrence.
METHODS: Altogether, 540 CSDHs were reviewed in this retrospective study. Six possible signs of bleeding were detected in the cavity: spotty bleeding on the outer membrane, hematoma clots, cerebral parenchymal suspension, stretched cortical vessels, intraluminal trabecular structures, and septa separating the cavity. We evaluated the association of each with the radiological findings, endoscopic features, and interval from trauma to surgery and then assessed the correlation between each endoscopic feature and CSDH recurrence.
RESULTS: Spotty bleeding, cerebral parenchymal suspension, and stretched cortical vessels occurred during every period. Hematoma clots exhibited a two-peak pattern with significant resurgence during the chronic phase. Trabecular structures significantly increased 61 days after the trauma, reaching 71.2% of patients on day 91. Septa were found in the cavity in only 12.5% during the initial 30 days but subsequently increased significantly to 37.3%. At 2 months, an exacerbation stage was inferred. The multivariable analysis revealed that trabecular structures and residual septa were significant independent risk factors for recurrence. We opened most septa intraoperatively. Their recurrence rate was 7.5%, which is lower than has been previously reported.
CONCLUSIONS: Evaluation of the changes in the endoscopic findings and their association with recurrence was useful for clarifying the mechanism of CSDH enlargement, the risk of recurrence, and the potential for endoscopic surgery.

PMID: 30593956 [PubMed - as supplied by publisher]

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DNA damage checkpoint response to aflatoxin B1.

DNA damage checkpoint response to aflatoxin B1.

Environ Toxicol Pharmacol. 2018 Dec 07;65:90-96

Authors: Engin AB, Engin A

Abstract
Although most countries regulate the aflatoxin levels in food by legislations, high amounts of aflatoxin B1 (AFB1)-DNA adducts can still be detected in normal and tumorous tissue obtained from cancer patients. AFB1 cannot directly interact with DNA unless it is biotransformed to AFB1-8, 9-epoxide via cytochrome p450 enzymes. This metabolite spontaneously and irreversibly attaches to guanine residues to generate highly mutagenic DNA adducts. AFB1-induced mutation of ATM kinase results in the deterioration of the cell cycle checkpoint activation at the G2/M checkpoint site. Genomic instability and increased cancer risk due to A-T mutation is the result of diminished repair of DNA double strand breaks. The major point mutation caused by AFB1 is G-to-T transversion that is related with the high frequency of p53 mutation. Majority of AFB1 associated hepatocellular cancer cases carry TP53 mutant DNA, which is an indicator of AFB1 exposure, as well as hepatocellular cancer risk.

PMID: 30594067 [PubMed - as supplied by publisher]

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Urinary cytokine profile to predict response to intravesical BCG with or without HS-410 therapy in patients with non-muscle invasive bladder cancer.

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Urinary cytokine profile to predict response to intravesical BCG with or without HS-410 therapy in patients with non-muscle invasive bladder cancer.

Cancer Epidemiol Biomarkers Prev. 2018 Dec 28;:

Authors: Salmasi A, Elashoff DA, Guo R, Upfill-Brown A, Rosser CJ, Rose JM, Giffin LC, Gonzalez LE, Chamie K

Abstract
BACKGROUND: Despite extensive research to identify biomarkers of response in patients with non-muscle-invasive bladder cancer (NMIBC), there is no biomarker to date that can serve this purpose. Herein, we report how we leveraged serial urine samples to query a panel of cytokines at varying time points in an attempt to identify predictive biomarkers of response in NMIBC.
METHODS: Serial urine samples were collected from 50 patients with intermediate- or high-risk NMIBC enrolled in a phase II study, evaluating intravesical BCG +/- intradermal HS-410 therapy. Samples were collected at baseline, week-7, week-13, week-28 and at end of treatment. 105 cytokines were analyzed in each sample. To predict outcome of time to event (recurrence or progression), univariate and multivariable Cox analyses were performed.
RESULTS: 15 patients developed recurrence and 4 patients progressed during the follow-up period. Among clinicopathologic variables, ever-smoker vs non-smoker status was associated with an improved response rate (HR 0.38, 95%CI 0.14-0.99, p=0.04). In the most clinically relevant model, the percent change (for 100 units) of IL-18 binding protein-a (HR 1.995, 95%CI 1.16-3.44, p=0.01), IL-23 (HR 1.12, 95%CI 1.01-1.23, p=0.03), IL-8 (HR 0.27, 95%CI 0.07-1.08, p=0.06), and interferon-gamma-induced-protein-10 (HR 0.95, 95%CI 0.91-0.99, p=0.04) at week-13 from baseline best predicted time to event.
CONCLUSIONS: Urinary cytokines provided additional value to clinicopathologic features to predict response to immune modulating agents in patients with NMIBC.
IMPACT: This study serves as a hypothesis generating report for future studies to evaluate the role of urine cytokines as a predictive biomarker of response to immune treatments.

PMID: 30593457 [PubMed - as supplied by publisher]

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Elevation of tumor mutation burden in ROS1-fusion lung adenocarcinoma resistant to crizotinib: A case report.

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Elevation of tumor mutation burden in ROS1-fusion lung adenocarcinoma resistant to crizotinib: A case report.

Medicine (Baltimore). 2018 Dec;97(52):e13797

Authors: Yang T, Xu R, Yan B, Li F, Liu H

Abstract
RATIONALE: Although most of non-small cell lung cancer (NSCLC) patients with ROS1-fusions respond to crizotinb, acquired resistance eventually develop. The next-generations of ROS1 inhibitors have made some achievements, but the effects of immunotherapy have not been explored.
PATIENT CONCERNS: A 44-year-old Chinese women presented with cough and dyspnea with a history of advanced lung adenocarcinoma.
DIAGNOSIS: A PET/CT scan revealed primary tumors in bilateral lung lobes and multiple metastases in lymph nodes and bones. And ultrasound-guided left cervical lymph node biopsy revealed the pathological diagnosis was poor differentiated lung adenocarcinoma.
INTERVENTIONS: The patients was started to be treated with 4 cycles of pemetrexed, carboplatin and bevacizumab, followed by one cycle of docetaxel, cisplatin and bevacizumab. As the ROS1-fusion was found by next generation sequencing, the patient received crizotinib treatment about 3 months.
OUTCOMES: After 5 cycles of chemotherapy, CT scans revealed increased size of bilateral lobe nodules indicative of progressive disease (PD). Then the patient received treatment of crizotinib and his progression-free survival reached 3 months. Due to uncontrollable disease progression, the patient expired.
LESSONS: The genetic profile of NSCLC patients might be altered in various therapeutic processes. Thus, repeated genetic testing might be important at each progression. Moreover, immunotherapy might be a powerful weapon to overcome the resistance to Tyrosine kinase inhibitors (TKIs) in future.

PMID: 30593165 [PubMed - in process]

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Sub-lethal effects of waterborne copper in early developmental stages of rainbow trout (Oncorhynchus mykiss).

Sub-lethal effects of waterborne copper in early developmental stages of rainbow trout (Oncorhynchus mykiss).

Ecotoxicol Environ Saf. 2018 Dec 26;170:778-788

Authors: Santos SW, Cachot J, Gourves PY, Clérandeau C, Morin B, Gonzalez P

Abstract
The aim of this work was to study the impact of copper during a sub-chronic exposure to environmental concentrations in the early life stages of rainbow trout (Oncorhynchus mykiss). Eyed-stage embryos of rainbow trout, at 265 °D, were exposed in semi-static conditions to sub-lethal concentrations of CuSO4 up to the larval stage (528 °D) under laboratory-controlled conditions. During 3 weeks, they were exposed to the environmentally-realistic concentration of 2 µg/L Cu and to a 10-fold higher concentration, 20 µg/L Cu. Several biological (survival, hatching success, malformation, growth) and behavioral (swimming activity) and molecular endpoints (genotoxicity and gene transcription) were studied. Exposure to 20 µg/L Cu had an inhibitory effect on hatching and increased half-hatched embryos (25%). At the end of the exposure, no significant differences were observed in growth of the larvae exposed to the highest Cu concentration. However, larvae exposed to 2 µg/L Cu exhibited increased growth in comparison with non-exposed larvae. The percentage of malformed larvae was significantly higher for both copper conditions, with skeletal malformations being the most observed. Expression of several genes was evaluated in whole larvae using quantitative real-time PCR. Genes involved in detoxification (gst, mt1 and mt2) and in cell cycle arrest (p53) were significantly repressed in both copper conditions when compared to control. In addition, potential genotoxic effects on larvae were investigated by the comet assay on blood cells, but this test did not demonstrate any significant DNA damage on larvae exposed to copper. This study confirms the adverse effects of copper on early life stages of rainbow trout even at the lowest environmentally relevant tested concentration.

PMID: 30593991 [PubMed - as supplied by publisher]

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Elevated WBP2 expression in HER2-positive breast cancers correlates with sensitivity to trastuzumab-based neo-adjuvant therapy:A Retrospective and Multicentric Study.

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Elevated WBP2 expression in HER2-positive breast cancers correlates with sensitivity to trastuzumab-based neo-adjuvant therapy:A Retrospective and Multicentric Study.

Clin Cancer Res. 2018 Dec 28;:

Authors: Kang SA, Guan JS, Tan HJ, Chu T, Thike AA, Bernadó Morales C, Arribas J, Wong CY, Tan PH, Gudi M, Putti TC, Sohn J, Lim SH, Lee SC, Lim YP

Abstract
PURPOSE: Trastuzumab-based chemotherapy has shown remarkable clinical benefits for HER2-positive breast cancer patients. However, treatment regimens involving trastuzumab had little or no effect for a subset of patients. Preliminary studies revealed WW-binding protein 2 (WBP2), an oncogenic transcription co-activator, to be co-amplified with HER2 in 36% of HER2-positive breast cancers. We hypothesize that WBP2 regulates and correlates with the response of HER2-positive breast cancer to trastuzumab.
EXPERIMENTAL DESIGN: The co-expression of WBP2 and HER2 in breast tumors was validated using immunohistochemistry. The role and mechanism of WBP2 in regulating breast cancer response to trastuzumab was elucidated using in vitro, patient-derived xenograft and murine xenograft models. A multi-center retrospective study involving 143 patients given neoadjuvant trastuzumab-based chemotherapy was conducted to determine if WBP2 expression correlates with pathologic complete response.
RESULTS: Elevated expression of WBP2 significantly enhanced breast cancer's response to trastuzumab by augmenting trastuzumab-induced downregulation of HER2 and arrest of cell cycle via inhibition of cyclin D expression. High level of WBP2 correlated with better pathologic complete response (67.19%) compared to low WBP2 level (26.58%). The highest response was observed in subgroups of patients with high WBP2-expressing tumors and also aged below 50 years (77.78%) or were pre-menopausal in status (73.33%). Retrospectively, WBP2 demonstrated sensitivity of 80 to 81% and specificity of 76.5 to 80% in discriminating between patients showing pCR and non-pCR.
CONCLUSIONS: WBP2 expression correlates with the response of HER2-positive breast cancer to trastuzumab-based neoadjuvant chemotherapy.

PMID: 30593516 [PubMed - as supplied by publisher]

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Submerged plus maze: A novel test for studying anxiety-like behaviour in fish

Publication date: Available online 30 December 2018

Source: Behavioural Brain Research

Author(s): Brittany V. Hope, Trevor J. Hamilton, Peter L. Hurd

Abstract

The elevated plus maze is a prominent and well-documented test for studying anxiety in rodents. Fish are becoming more prevalent in studies of anxiety, yet the elevated plus maze has not been adapted and validated for fish. In the present study, we created an aquatic version of the elevated plus maze called the 'submerged plus maze,' which is shaped like a plus symbol with four arms alternating between black and transparent walls. We used convict cichlid fish (Amatitlania nigrofasciata) and administered diazepam to validate the apparatus for studying anxiety-like behaviour. After diazepam exposure, fish spent more time in and entered more open arms than after vehicle exposure, consistent with the effect of benzodiazepines on rodents in the elevated plus maze. The submerged plus maze maintains construct validity for testing anxiety in convict cichlid fish.

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Treadmill exercise intervention improves gait and postural control in alpha-synuclein mouse models without inducing cerebral autophagy

Publication date: Available online 30 December 2018

Source: Behavioural Brain Research

Author(s): Georgia Minakaki, Fabio Canneva, Frédéric Chevessier, Frederik Bode, Stefanie Menges, Ivanna K. Timotius, Liubov S. Kalinichenko, Holger Meixner, Christian P. Müller, Bjoern M. Eskofier, Nicolas Casadei, Olaf Riess, Rolf Schröder, Jürgen Winkler, Wei Xiang, Stephan von Hörsten, Jochen Klucken

Abstract

Gait and postural control dysfunction are prototypical symptoms compromising quality of life for patients with Parkinson's disease (PD). Hallmarks of cellular pathology are dopaminergic degeneration and accumulation of the cytosolic protein alpha-synuclein, linked to impaired autophagy-lysosome pathway (ALP) clearance. Physical exercise improves gait in PD patients and motor function in rodent lesion models. Moreover, exercise is considered neuroprotective and ALP induction has been reported, e.g. in human skeletal muscle, rodent peripheral and cerebral tissues. A combined analysis of how distinct exercise paradigms affect motor and central biochemical aspects of PD could maximize benefits for patients. Here we examine the effect of 4 weeks treadmill exercise intervention in 7-8 month non-lesioned mice on a) distinct gait categories, b) ALP activity, c) dopaminergic and alpha-synuclein homeostasis. The study includes wild type, alpha-synuclein knockout, and mice exclusively expressing human alpha-synuclein. Parameters of gait regularity and stability, activity, and dynamic postural control during unforced walk, were assessed by an automated system (CatWalk XT). At baseline, alpha-synuclein mouse models exhibited irregular and less active gait, with impaired dynamic postural control, compared to wild type mice. Treadmill exercise particularly improved speed and stride length, while increasing dual diagonal versus three-paw body support in both the alpha-synuclein knockout and transgenic mice. Biochemical analyses showed higher striatal tyrosine hydroxylase immuno-reactivity and reduced higher-order alpha-synuclein species in the cerebral cortex. However, no significant cerebral ALP induction was measured. In summary, treadmill exercise improved gait activity and postural stability, and promoted dopaminergic and alpha-synuclein homeostasis, without robustly inducing cerebral ALP.

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The Co-occurrence of Pitch and Rhythm Disorders in Congenital Amusia

Publication date: Available online 30 December 2018

Source: Cortex

Author(s): Marie-Élaine Lagrois, Isabelle Peretz

Abstract

The most studied form of congenital amusia is characterized by a difficulty with detecting pitch anomalies in melodies, also referred to as pitch deafness. Here, we tested for the presence of associated deficits in rhythm processing, beat in particular, in pitch deafness. In Experiment 1, participants performed beat perception and production tasks with musical excerpts of various genres. The results show a beat finding disorder in six of the ten assessed pitch-deaf participants. In order to remove a putative interference of pitch variations with beat extraction, the same participants were tested with percussive rhythms in Experiment 2 and showed a similar impairment. Furthermore, musical pitch and beat processing abilities were correlated. These new results highlight the tight connection between melody and rhythm in music processing that can nevertheless dissociate in some individuals.

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Anatomic conditions for bypass surgery between rostral (T7-T9) and caudal (L2, L4, S1) ventral roots to treat paralysis after spinal cord injury.

Publication date: Available online 30 December 2018

Source: Annals of Anatomy - Anatomischer Anzeiger

Author(s): Habib BENDELLA, RINK Svenja, Aliona WÖHLER, Janna FEISER, Andre WILDEN, Maria GROSHEVA, Hans-Jürgen STOFFELS, Carolin MEYER, Marilena MANTHOU, Makoto NAKAMURA, Doychin N. ANGELOV

Abstract

Severe spinal cord injuries cause permanent neurological deficits and are still considered as inaccessible to efficient therapy. Injured spinal cord axons are unable to spontaneously regenerate. Re-establishing functional activity especially in the lower limbs by reinnervation of the caudal infra-lesional territories might represent an effective therapeutic strategy.

Numerous surgical neurotizations have been developed to bridge the spinal cord lesion site and connect the intact supra-lesional portions of the spinal cord to peripheral nerves (spinal nerves, intercostal nerves) and muscles. The major disadvantage of these techniques is the increased hypersensitivity, spasticity and pathologic pain in the spinal cord injured patients, which occur due to the vigorous sprouting of injured afferent sensory fibers after reconstructive surgery.

Using micro-surgical instruments and an operation microscope we performed detailed anatomical preparation of the vertebral canal and its content in five human cadavers. Our observations allow us to put forward the possibility to develop a more precise surgical approach, the so called "ventral root bypass" that avoids lesion of the dorsal roots and eliminates sensitivity complications.

The proposed kind of neurotization has been neither used, nor put forward. The general opinion is that radix ventralis and radix dorsalis unite to form the spinal nerve inside the dural sac. This assumption is not accurate, because both radices leave the dural sac separately. This neglected anatomical feature allows a reliable intravertebral exposure of the dura-mater ensheathed ventral roots and their damage-preventing end-to-side neurorrhaphy by interpositional nerve grafts. (239 words)

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Numerical Investigations of Bone Remodelling Around the Mouse Mandibular Molar Primordia

Publication date: Available online 30 December 2018

Source: Annals of Anatomy - Anatomischer Anzeiger

Author(s): Junliang Chen, Yun He, Ludger Keilig, Susanne Reimann, Istabrak Hasan, Joachim Weinhold, Ralf Radlanski, Christoph Bourauel

Abstract

The formation of the alveolar bone, which houses the dental primordia, and later the roots of tooth, may serve as a model to approach general questions of alveolar bone formation. In this respect, this study aimed to investigate the potential interactions between the alveolar bone formation and tooth eruption by using finite element (FE) methods, and to figure out whether the expanding tooth systems induce shear stresses that lead to alveolar bone formation. 3D geometric surface models were generated from the 3D histological data of the heads of mice (C57 Bl/6J) ranging from stages embryonic (E) to postnatal (P) stages E15 to P20 using the reconstruction software 3-Matic. Bone, dentin, enamel and dental follicle around the primordia were generated and converted into 3D FE models. Models were imported into the FE software package MSC.Marc/Mentat. As material parameters of embryonic dentine, pulp, enamel, dental follicle, and bony structures basically are unknown, these were varied from 1% to 100% of the corresponding known material parameters for humans and a sensitivity analysis was performed. Surface loads were applied to the outside surface of dental follicle ranging from 0.1 to 5.0 N/mm². The validity of the model was analysed by comparing the activity pattern of the alveolar bone as determined in the histological study with the loading pattern from the numerical analysis. The results show that when varying the surface loads, the distribution of shear stresses remained same, and while varying the material properties of the hard tissues, the location of highest shear stresses remained stable. Comparison of the histologically determined growth regions with the distribution of shear stresses computed in the numerical model showed a very close agreement. The results provide a strong proof to support Blechschmidt's hypothesis that the bone in general is created under the influence of shear forces.

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Evaluation of the Chemopreventive Activity of Grape Skin Extract Using Medium-term Oral Carcinogenesis Assay Induced by 4-Nitroquinoline 1-Oxide.

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Evaluation of the Chemopreventive Activity of Grape Skin Extract Using Medium-term Oral Carcinogenesis Assay Induced by 4-Nitroquinoline 1-Oxide.

Anticancer Res. 2019 Jan;39(1):177-182

Authors: DE Moura CFG, Soares GR, Ribeiro FAP, Silva MJD, Vilegas W, Santamarina AB, Pisani LP, Estadella D, Ribeiro DA

Abstract
BACKGROUND/AIM: The aim of this study was to evaluate the chemoprotective potential of grape skin extract following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO).
MATERIALS AND METHODS: Male Wistar rats were distributed into four groups (n=5, per group): Control Group: free access to commercial diet and drinking water for 12 weeks; 4NQO Group: received 4NQO diluted in drinking water daily, for 12 weeks; Grape Skin Extract Group: free access to water and received grape skin extract incorporated with diet for 12 weeks; 4NQO + Grape Skin Extract Group: received 4NQO in drinking water daily and grape extract incorporated with diet for 12 weeks.
RESULTS: Animals treated with grape skin extract revealed a significant reduction in epithelial dysplasia. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and ki-67 immunoexpression was reduced in animals treated with grape skin extract. Western blot analysis showed a significant decrease of p-NFκB p50 and MyD88 protein expression in the groups treated with grape skin extract. Copper-zinc superoxide dismutase, manganese superoxide dismutase, and catalase gene expression did not present any statistically significant differences (p>0.05).
CONCLUSION: Grape skin extract displayed chemopreventive activity in oral carcinogenesis assays as depicted by its antioxidant, anti-proliferative and anti-inflammatory properties.

PMID: 30591456 [PubMed - in process]

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Valproic acid and epilepsy: from molecular mechanisms to clinical evidences.

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Valproic acid and epilepsy: from molecular mechanisms to clinical evidences.

Curr Neuropharmacol. 2018 Dec 27;:

Authors: Romoli M, Mazzocchetti P, D'Alonzo R, Siliquini S, Rinaldi VE, Verrotti A, Calabresi P, Costa C

Abstract
After more than a century from its discovery, valproic acid (VPA) still represents one of the most efficient antiepileptic drugs (AEDs). Pre and post-synaptic effects of VPA depend on a very broad spectrum of actions, including the regulation of ionic currents and the facilitation of GABAergic over glutamatergic transmission. As a result, VPA indirectly modulates neurotransmitter release and strengthens the threshold for seizure activity. However, even though participating to the anticonvulsant action, such mechanisms seem to have minor impact on epileptogenesis. Nonetheless, VPA has been reported to exert anti-epileptogenic effects. Epigenetic mechanisms, including histone deacetylases (HDACs), BDNF and GDNF modulation are pivotal to orientate neurons toward a neuroprotective status and promote dendritic spines organization. From such broad spectrum of actions comes constantly enlarging indications for VPA. It represents a drug of choice in child and adult with epilepsy, with either general or focal seizures, and is a consistent and safe IV option in generalized convulsive status epilepticus. Moreover, since VPA modulates DNA transcription through HDACs, recent evidences point to its use as an anti-nociceptive in migraine prophylaxis, and, even more interestingly, as a positive modulator of chemotherapy in cancer treatment. Furthermore, VPA-induced neuroprotection is under investigation for benefit in stroke and traumatic brain injury. Hence, VPA has still got its place in epilepsy, and yet deserves attention for its use far beyond neurological diseases. In this review, we aim to highlight, with a translational intent, the molecular basis and the clinical indications of VPA.

PMID: 30592252 [PubMed - as supplied by publisher]

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Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia: Clinical characteristics, risk factors, course, and outcome of disease.

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Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia: Clinical characteristics, risk factors, course, and outcome of disease.

Pediatr Blood Cancer. 2018 Dec 27;:e27594

Authors: Anastasopoulou S, Eriksson MA, Heyman M, Wang C, Niinimäki R, Mikkel S, Vaitkevičienė GE, Johannsdottir IM, Myrberg IH, Jonsson OG, Als-Nielsen B, Schmiegelow K, Banerjee J, Harila-Saari A, Ranta S

Abstract
BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a distinct entity with incompletely known predisposing factors. The aim of this study is to describe the incidence, risk factors, clinical course, and outcome of PRES in childhood acute lymphoblastic leukemia (ALL).
PROCEDURE: Patients aged 1.0 to 17.9 years diagnosed with ALL from July 2008 to December 2015 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol were included. Patients with PRES were identified in the prospective NOPHO leukemia toxicity registry, and clinical data were collected from the medical records.
RESULTS: The study group included 1378 patients, of whom 52 met the criteria for PRES. The cumulative incidence of PRES at one month was 1.7% (95% CI, 1.1-2.5) and at one year 3.7% (95% CI, 2.9-4.9). Older age (hazard ratios [HR] for each one-year increase in age 1.1; 95% CI, 1.0-1.2, P = 0.001) and T-cell immunophenotype (HR, 2.9; 95% CI, 1.6-5.3, P = 0.0005) were associated with PRES. Central nervous system (CNS) involvement (odds ratios [OR] = 2.8; 95% CI, 1.2-6.5, P = 0.015) was associated with early PRES and high-risk block treatment (HR = 2.63; 95% CI, 1.1-6.4, P = 0.033) with late PRES. At follow-up of the PRES patients, seven patients had epilepsy and seven had neurocognitive difficulties.
CONCLUSION: PRES is a neurotoxicity in the treatment of childhood ALL with both acute and long-term morbidity. Older age, T-cell leukemia, CNS involvement and high-risk block treatment are risk factors for PRES.

PMID: 30592147 [PubMed - as supplied by publisher]

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The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential.

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The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential.

Brain Stimul. 2018 Dec 14;:

Authors: Warren CM, Tona KD, Ouwerkerk L, van Paridon J, Poletiek F, van Steenbergen H, Bosch JA, Nieuwenhuis S

Abstract
BACKGROUND: Transcutaneous vagus nerve stimulation (tVNS) is a new, non-invasive technique being investigated as an intervention for a variety of clinical disorders, including epilepsy and depression. It is thought to exert its therapeutic effect by increasing central norepinephrine (NE) activity, but the evidence supporting this notion is limited.
OBJECTIVE: In order to test for an impact of tVNS on psychophysiological and hormonal indices of noradrenergic function, we applied tVNS in concert with assessment of salivary alpha amylase (SAA) and cortisol, pupil size, and electroencephalograph (EEG) recordings.
METHODS: Across three experiments, we applied real and sham tVNS to 61 healthy participants while they performed a set of simple stimulus-discrimination tasks. Before and after the task, as well as during one break, participants provided saliva samples and had their pupil size recorded. EEG was recorded throughout the task. The target for tVNS was the cymba conchae, which is heavily innervated by the auricular branch of the vagus nerve. Sham stimulation was applied to the ear lobe.
RESULTS: P3 amplitude was not affected by tVNS (Experiment 1A: N = 24; Experiment 1B: N = 20; Bayes factor supporting null model = 4.53), nor was pupil size (Experiment 2: N = 16; interaction of treatment and time: p = .79). However, tVNS increased SAA (Experiments 1A and 2: N = 25) and attenuated the decline of salivary cortisol compared to sham (Experiment 2: N = 17), as indicated by significant interactions involving treatment and time (p = .023 and p = .040, respectively).
CONCLUSION: These findings suggest that tVNS modulates hormonal indices but not psychophysiological indices of noradrenergic function.

PMID: 30591360 [PubMed - as supplied by publisher]

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Laser interstitial thermotherapy (LiTT) in pediatric epilepsy surgery.

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Laser interstitial thermotherapy (LiTT) in pediatric epilepsy surgery.

Seizure. 2018 Dec 18;:

Authors: Hoppe C, Helmstaedter C

Abstract
Laser interstitial thermotherapy (LiTT) is a novel stereotactic approach to the surgical treatment of severe drug-resistant focal epilepsies. This review extends our recent general review on this topic (Hoppe et al. Laser interstitial thermotherapy [LiTT] in epilepsy surgery. Seizure 2017; 48:45-52) with a focus on children (age <18 years). A PubMed search retrieved 25 uncontrolled case series reports that included a total of 179 pediatric patients as well as 7 review papers that specifically referred to using LiTT in pediatric epilepsy surgery (due August 31, 2018). Hypothalamic hamartomas (HH) represented the most frequent indication (64.2%) while therapeutic evidence for other more frequent etiologies underlying severe focal childhood epilepsies (e.g. focal cortical dysplasia, mesiotemporal sclerosis) is still scarce (n<20). For the published cases, the rate of severe complications was 3.4% and the overall complication rate was 23.5%. The seizure freedom rate (Engel class 1) was 57.5% (including patients with early follow-up and repeat thermoablations). None of the studies included the systematic evaluation of the cognitive outcome. Overall, the published evidence does not yet allow a scientific or clinical judgement on the utility of LiTT for pediatric epilepsy surgery. LiTT is likely to extend the neurosurgical toolbox with regard to deep brain lesions (e.g. HH). However, in cases that are equally accessible for both approaches therapeutic superiority of LiTT over open resective surgery still remains to be demonstrated. Recommendations for controlled though non-randomized outcome studies are provided.

PMID: 30591281 [PubMed - as supplied by publisher]

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Never say never: circumventing a contraindication to control apnoea-induced epileptic events with a mandibular advancement device.

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Never say never: circumventing a contraindication to control apnoea-induced epileptic events with a mandibular advancement device.

J Laryngol Otol. 2018 Nov;132(11):1036-1038

Authors: Fenton JE, Fitzgerald C, Dillon PJ, O'Shea D

Abstract
BACKGROUND: The benefit of mandibular advancement devices in patients with sleep-disordered breathing and as a potential option for obstructive sleep apnoea syndrome is well recognised. Their use in the setting of epilepsy or other seizure disorders is typically contraindicated.Case reportA 48-year-old patient with a history of poorly controlled epilepsy and obstructive sleep apnoea syndrome was referred for ENT review for possible tracheostomy. The patient was wheelchair-bound with 24-hour continuous positive airway pressure, but sleep studies demonstrated persistent, severe episodes of apnoea and notable sleep disturbance. Sleep nasendoscopy demonstrated marked improvement on capnography with the laryngeal mask airway in situ, and this was maintained with mandibular advancement using jaw thrust following removal of the laryngeal mask airway. A mandibular advancement device was subsequently trialled; this had no subjective benefit for the patient, but the seizures resolved and control of apnoea was achieved with the combination of a mandibular advancement device and continuous positive airway pressure.
CONCLUSION: This paper highlights a novel application of mandibular advancement devices, used in combination with continuous positive airway pressure, which resulted in complete resolution of sleep deprivation and apnoea-induced epileptic events.

PMID: 30394239 [PubMed - indexed for MEDLINE]

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[Functional hemispherectomy: long-term follow-up in a series of five patients].

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[Functional hemispherectomy: long-term follow-up in a series of five patients].

Rev Neurol. 2018 Mar 01;66(5):147-153

Authors: Rodriguez-Osorio X, Lopez-Gonzalez FJ, Eiris-Punal J, Frieiro-Dantas C, Gomez-Lado C, Peleteiro-Fernandez M, Prieto-Gonzalez A

Abstract
INTRODUCTION: Functional hemispherectomy consists in palliative epilepsy surgical procedure usually performed in patients with pharmaco-resistant epilepsy and hemispheric syndromes. It is based on the neural disconnection of the affected hemisphere with preservation of the vascular supply.
AIM: To analyze long-term prognosis and safety of the hemispherectomies performed in our institution.
PATIENTS AND METHODS: Retrospective analysis collecting the following variables: age, gender, age of epilepsy onset, type of seizures, etiology, age of epilepsy surgery, prognosis and potential surgical complications. All patients had a minimum of five years of follow up.
RESULTS: Five patients (60% females) underwent hemispherotomy between 1999 and 2010. Age of epilepsy onset was 36 months and time of evolution until surgery was 7 years. The most frequent type of seizures were simple motor seizures with secondary generalization (n = 5). Three patients remained seizure free persistently after surgery and another patient had a more than 90% improvement. Time of follow up was 13 years. One patient suffered a bacterial meningitis without sequelae. Six years after surgery a patient suffered hydrocephalous requiring ventriculoperitoneal shunt.
CONCLUSIONS: Functional hemispherectomy constitutes an effective method to treat patients with pharmaco-resistant epilepsy, extensive unihemispheric pathology and seizures limited to that hemisphere. Late complications may occur thus long-term follow-up is needed.

PMID: 29480510 [PubMed - indexed for MEDLINE]

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Human Reproductive Sciences

http://www.jhrsonline.org/currentissue.asp?sabs=n

From the editors desk Madhuri Patil Journal of Human Reproductive Sciences 2018 11(4):303-305

Preimplantation genetic testing: Its evolution, where are we today? Firuza Rajesh Parikh, Arundhati Sitaram Athalye, Nandkishor Jagannath Naik, Dattatray Jayaram Naik, Rupesh Ramesh Sanap, Prochi Fali Madon Journal of Human Reproductive Sciences 2018 11(4):306-314 Preimplantation genetic testing (PGT) is an early form of prenatal genetic diagnosis where abnormal embryos are identified, thereby allowing transfer of genetically normal embryos. This technology has become an integral part of Assisted Reproductive Technology (ART) procedures. Initial experiments with animals as early as 1890 and those in the mid and later part of the last century paved the forward path of ART and PGT. This review article covers the evolution of PGT and is a pointer toward current and fast-evolving technology, allowing scientists and doctors to better comprehend human reproduction, and ensure healthy pregnancy outcomes.

Psychosocial aspects of therapeutic donor insemination Ansha Patel, P. S. V. N. Sharma, Pratap Kumar Journal of Human Reproductive Sciences 2018 11(4):315-319 The experience of delays in conception or possibility of remaining childless has the potential to create considerable psychological discomfort. In couples with severe male factor infertility, therapeutic intrauterine insemination using donor sperms (TDI) is offered as a treatment, second to in vitro fertilization using donor sperms. TDI is lucrative, less invasive, and a hopeful treatment. However, there are intricacies associated with it. Its immediate outcomes involve limited success rates, nonresponse, and chances of implantation failures, miscarriages, and multifetal pregnancies. Due to this, couples experience distress when they are advised to undergo three to six cycles of TDI in order to meet the expectations of having a baby. TDI has long-term issues on the triad comprising the “recipients,” the “donors,” and the “the children born out of TDI.” Nevertheless, managing psychosocial needs for couples undergoing TDI and other treatments in Indian clinics are grey areas of the conventional treatment pathway. The present review expands on the psychological issues and needs in couples opting for TDI.

"In cycles of dreams, despair, and desperation:" Research perspectives on infertility specific distress in patients undergoing fertility treatments Ansha Patel, P. S. V. N. Sharma, Pratap Kumar Journal of Human Reproductive Sciences 2018 11(4):320-328 “Emotional distress in infertility” is a broad expression that loosely denotes anxiety, depression, grief, crisis, depleting psychological well-being, and all forms of affective and interpersonal disturbances faced by individuals with infertility. The distress is usually associated with involuntary childlessness as it is an unwelcoming event. The developmental crisis associated with childlessness poses a threat to one's sense of self at all levels (individual, family and social). Distress may begin before or during treatments as a person experiences the loss of control over attaining parenthood, anxiety or dejection after the diagnosis, treatments, its complications particularly its limited success rates. This paper reviews the basic concepts, theoretical models related to infertility specific distress (ISD). It elaborates on the effects of individual and treatment-specific variables on ISD with special highlights gathered from the national and international research.

Examination of Y-chromosomal microdeletions and partial microdeletions in idiopathic infertility in East Hungarian patients Attila Mokánszki, Anikó Ujfalusi, Éva Gombos, István Balogh Journal of Human Reproductive Sciences 2018 11(4):329-336 Purpose: The aim of this study was to establish the Y chromosome microdeletion and partial AZFc microdeletion/duplication frequency firstly in East Hungarian population and to gain information about the molecular mechanism of the heterogeneous phenotype identified in males bearing partial AZFc deletions and duplications. Materials and Methods: Exactly determined sequences of azoospermia factor (AZF) region were amplified. Lack of amplification was detected for deletion. To determine the copy number of DAZ and CDY1 genes, we performed a quantitative analysis. The primers flank an insertion/deletion difference, which permitted the polymerase chain reaction products to be separated by polyacrylamide gel electrophoresis. Statistical Analysis Used: Mann–Whitney/Wilcoxon two-sample test, Kruskal–Wallis test, and two-sample t-probe were used for statistical analysis. Results: AZFbc deletion was detected only in the azoospermic cases; AZFc deletion occurred significantly more frequently among azoospermic patients, than among oligozoospermic males. The frequency of gr/gr deletions was significantly higher in the oligozoospermic patients than in the normospermic group. The b2/b3 deletion and partial duplications were not different among our groups, while b1/b3 deletion was found only in the azoospermic group. In infertile males and in normozoospermic controls, similar Y haplogroup distribution was detected with the highest frequency of haplogroup P. The gr/gr deletion with P haplogroup was more frequent in the oligozoospermic group than in the normozoospermic males. The b2/b3 deletion with E haplogroup was the most frequent, found only in the normozoospermic group. Conclusions: Y microdeletion screening has prognostic value and can affect the clinical therapy. In case of Y chromosome molecular genetic aberrations, genetic counseling makes sense also for other males in the family because these types of aberrations are transmittable (from father to son 100% transmission).

A study on balanced chromosomal translocations in couples with recurrent pregnancy loss Pritti K Priya, Vineet V Mishra, Priyankur Roy, Hetvi Patel Journal of Human Reproductive Sciences 2018 11(4):337-342 Background: Recurrent pregnancy loss (RPL) is an obstetric complication that affects couples in their reproductive age. Chromosomal abnormalities, mainly balanced rearrangements, could commonly be present in couples with RPL. Aim: The purpose of this study is to evaluate the contribution of chromosomal abnormalities and balanced reciprocal translocations, in particular occurring in either of the partners, resulting in RPL. Materials and Methods: A retrospective cytogenetic study was carried out on 152 individuals (76 couples) having a history of RPL. The cases were analyzed using G-banding and fluorescence in situ hybridization, wherever necessary. Results: Chromosomal abnormalities were observed in 3.2% of the total RPL cases, of which balanced translocations were observed in 4 (80%) individuals and marker chromosome was detected in 1 (20%) individual. All balanced translocations comprised reciprocal translocations, and no cases of Robertsonian translocations were detected in our study. Among reciprocal translocation carriers, three were male and one was female. Polymorphic variants were noted in 8 (5.3%) individuals. Conclusions: Chromosomal analysis is an important etiological investigation in couples with RPL. Balanced translocations are the most commonly detected chromosomal abnormalities in such couples. Thus, these couples are the best candidates for offering prenatal genetic diagnosis, thereby ensuring a better reproductive outcome.

Circulating levels of vitamin D3 and leptin in lean infertile women with polycystic ovary syndrome Ayman Shehata Dawood, Adel Elgergawy, Ahmed Elhalwagy Journal of Human Reproductive Sciences 2018 11(4):343-347 Objective: The objective of this study is to measure levels of Vitamin D3 and leptin and assess their relation of each to the pathogenesis of polycystic ovary syndrome (PCOS). Design: This was a cohort observational study. Settings: This study was conducted at the Department of Obstetrics and Gynecology, Tanta University. Materials and Methods: Ninety lean women were enrolled in this study and were allocated into two groups with 45 patients in each group: the first group (study group) who are lean women with PCOS and the second group (control group) who are the lean infertile patients without PCOS. Blood samples were collected and tested for study parameters. Results: There were no significant differences regarding demographic characteristics between both groups. The differences were in ovarian volume and hormonal profiles. Serum leptin was found to be significantly increased in lean PCOS than in control groups. Vitamin D3 levels were found to be lower in the lean PCOS group than in control group. Conclusion: Lean PCOS women are a unique group with specific hormonal profiles different from the typical PCOS profiles. Leptin and Vitamin D3 may have a role in the pathogenesis of lean PCOS, but large studies are still required regarding this unique group.

Effect of insulin sensitizers on raised serum anti-mullerian hormone levels in infertile women with polycystic ovarian syndrome Neeti Chhabra, Sonia Malik Journal of Human Reproductive Sciences 2018 11(4):348-352 Context: Increased circulating insulin levels contribute to hyperandrogenism in polycystic ovarian syndrome (PCOS) which causes a derangement in folliculogenesis, thus contributing to polycystic morphogenesis of the ovaries and a higher than normal anti-Mullerian hormone (AMH). A high AMH is an indicator of either stubborn anovulation or a predictor of ovarian hyperstimulation syndrome. Hence, it is postulated that the use of insulin sensitizers will reduce insulin resistance, hyperandrogenism, and subsequently serum AMH levels and will convert anovulatory cycles to ovulatory. Aim: To study the effect of insulin sensitizers on raised serum AMH levels in infertile women with PCOS. Settings and Design: This was a prospective interventional randomized single tertiary center study. Methodology: The study was conducted from August 2015 to April 2016. Infertile patients with PCOS as defined by the Rotterdam criteria with raised AMH (>5 ng/ml) levels were enrolled in the study under strict inclusion and exclusion criteria. The sample size was 105 patients. Cycle regularity, day 2–antral follicle count (AFC), luteinizing hormone, AMH levels, modified Ferriman–Gallwey score (mFGS), and acne score were recorded before starting the intervention. Patients were randomized into three equal groups of 35 each. Group A received metformin alone, Group B metformin plus myoinositol, and Group C only myoinositol. After completion of 3 months of pretreatment, the same parameters were rechecked. Statistical Analysis Used: Univariate analysis and Chi-square test were used for statistical analysis. Results: Of 105 patients, 95 completed treatment and the rest 10 dropped out. There was a reduction in AMH in all groups of insulin sensitizers with significant fall in the metformin only group. Cycle regularity, reduction in AFC, mFGS, and grade of acne were also obtained. Conclusions: Therapy with insulin sensitizers in PCOS women with raised AMH reduces the AMH levels, converts irregular menstrual cycles to regular, and reduces clinical hyperandrogenism.

Window of implantation is significantly displaced in patients with adenomyosis with previous implantation failure as determined by endometrial receptivity assay Nalini Mahajan, Simrandeep Kaur, Maria Ruiz Alonso Journal of Human Reproductive Sciences 2018 11(4):353-358 Background: Adenomyosis is associated with implantation failure and poor reproductive performance in IVF/ICSI cycles. Aims: To compare if window of implantation (WOI) is displaced in patients having adenomyosis compared to controls using endometrial receptivity array (ERA) test. Settings and Design: Retrospective Case control study. 374 patients with previous one or more IVF failures who underwent ERA test between 2013-2016 at our centre were enrolled. Patients were divided into two groups; Group A-36 patients with adenomyosis (study group) and Group B- 338 patients without adenomyosis (controls). Statistical Analysis: Normality assumptions for continuous variables were tested using Kolmogorov Smirnov test. Mean values of two groups were compared using Student's t-independent test. Frequency data by categories were compared using Chi-square/Fisher's exact test. Risk ratio and 95% confidence limits were calculated. P < 0.05 was considered for statistical significance. Results: WOI was displaced (Non Receptive ERA) significantly in adenomyosis 47.2% (17/36) compared to controls 21.6% (73/338) (P < 0.001, CI-8.7%-42.5%) making risk ratio of displaced WOI in adenomyosis versus controls to be 2:1. The incidence of RIF was 66.6% in adenomyosis compared to 34.9% in controls (P < 0.001, CI- 15.5%-47.9%). Pregnancy rate after personalized embryo transfer in adenomyosis group was 62.5%, signifying displaced WOI as a cause of implantation failure in adenomyosis patients with previous implantation failure. Conclusions: Our study suggests it is prudent to evaluate Endometrial receptivity before embryo transfer in patients with adenomyosis to avoid wastage of good embryos.

Knowledge about age-related decline in fertility and oocyte cryopreservation: A national survey Karissa C Hammer, Alyssa N Kahan, Louis F Fogg, Mark A Walker, Jennifer E Hirshfeld-Cytron Journal of Human Reproductive Sciences 2018 11(4):359-364 Context: Women worldwide are delaying childbearing, but are they aware of the age-related decline in fertility? Aims: The aim of this study is to investigate awareness of age-related decline in fertility and oocyte cryopreservation. Settings and Design: A primary analysis of a cross-sectional electronic survey with a nationally representative sample of nulliparous women aged 25–45 years. Subjects and Methods: A national online survey performed March 4–March 9, 2016. Statistical Analysis Used: A linear regression model and ANOVA tests were performed. Results: A total of 1213 women completed the survey. A significant difference was discovered in fecundity knowledge between women who identified as in a partnership compared to those who did not. Partnered women were more likely to respond “know a lot” about the age-related decline in fertility, whereas unpartnered women were more likely to respond “never heard of it” (P < 0.01). Partnered women are also more likely to respond that they would have made different life choices had they been more knowledgeable about fertility at a younger age (P = 0.01). The majority of the survey population had heard of oocyte cryopreservation but did not know much about it. Conclusions: Slightly over half of participants had an understanding of the natural age-related decline in fertility. Having a partner significantly increased the likelihood that a woman reported more knowledge about fertility. More effort is necessary to educate all women on assisted reproductive technologies and the natural age-related decline in fertility, specifically single women of childbearing age.

Spontaneous Septostomy in a Twin Pregnancy Causing Fatal Amniotic Band Syndrome

Complications due to spontaneous septostomy of the dividing membrane in monochorionic diamniotic pregnancies are rarely described. Herein, we report the case of a preterm female neonate from a monochorionic diamniotic twin pregnancy delivered by caesarean section at 32 weeks of gestation. She was born with a broad band of a transparent membrane-like material firmly attached to her lower abdomen. Postnatally, she developed respiratory distress syndrome and persistent pulmonary hypertension, complicated by bilateral pneumothorax. She died due to respiratory failure when she was 1 day old. Her twin sister survived with no malformations. At postmortem examination, the neonate had severe lung hypoplasia, and the attached material was diagnosed as the dividing septum. We hypothesize that the lung hypoplasia was secondary to local oligohydramnios, which developed as a consequence of the twin being firmly stuck in the defect of the dividing membrane. To our best knowledge, spontaneous septostomy causing an ultimately fatal amniotic band syndrome has not previously been described.

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Dyspnea in Pregnancy: A Case Report of a Third Trimester Mediastinal Mass in Pregnancy.

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Dyspnea in Pregnancy: A Case Report of a Third Trimester Mediastinal Mass in Pregnancy.

Am J Case Rep. 2018 Dec 28;19:1536-1540

Authors: Reeder CF, Hambright AA, Fortner KB

Abstract
BACKGROUND Dyspnea in pregnancy is common and attributable to a variety of etiologies including normal physiology. The obstetric provider is challenged with distinguishing between physiologic versus pathologic dyspnea. CASE REPORT A 31-year-old G2 P1001 female at 34 weeks gestation presented with dyspnea, tachycardia, and inability to lie supine. Imaging revealed a large heterogeneous anterior mediastinal mass (14.8×11.5 cm). Multidisciplinary coordinated care led to diagnosis of B cell lymphoma, delivery via cesarean section under regional anesthesia in steep Trendelenberg position, followed by chemotherapy postpartum. CONCLUSIONS Dyspnea in pregnancy is common but might represent underlying pathology. While an obstetrician is knowledgeable of physiologic pregnancy changes, he or she should remain vigilant for underlying pathologic causes of dyspnea, including malignancy. Anterior mediastinal masses propose unique anesthetic challenges including respiratory impairment and cardiopulmonary collapse requiring collaborative care and planning.

PMID: 30591704 [PubMed - in process]

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L-Carnosine protects against Oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: A perspective on targeting Nrf-2 and NF-κB pathways.

L-Carnosine protects against Oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: A perspective on targeting Nrf-2 and NF-κB pathways.

Toxicol Appl Pharmacol. 2018 Dec 25;:

Authors: Magdy R, Saleh S, El Abhar H, Shafik A, Schaalan M

Abstract
BACKGROUND: Chemotherapy-induced peripheral neuropathy is a common side effect afflicting cancer patients treated with oxalipatin based chemotherapy.
AIM: The study investigated the potential prophylactic effect of L-carnosine against acute oxaliplatin neurotoxicity in colorectal cancer patients with emphasis on the redox (Nrf-2, MDA), inflammatory (NF-κB, TNF-α), and apoptotic (caspase-3) parameters.
METHODS: In this pilot study, 65 patients were recruited using a prospective randomized controlled study design and enrolled randomly into two arms; Arm A, 31 patients received FOLFOX-6 regimen (oxaliplatin, 5FU & leucovorin) and Arm B, 34 patients received FOLFOX-6 regimen and daily oral L-carnosine (500 mg) along the treatment period. Patients were followed up for three months, then both arms were analyzed for neuropathy incidence/grade and any additional toxicities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC version 4).
RESULTS: The neuropathy grading evaluation of Arm B vs Arm A revealed that 17 patients (56.7%) vs 11 patients (35.5%) suffered grade 1, one patient (3.3%) vs 19 patients (61.3%) suffered grade 2, while 12 patients (40%) vs one patient (3.2%) were normal. In arm B, the addition of L-carnosine decreased significantly the levels/activity of NF-κB (27%) and TNF-α (36.6%); this anti-inflammatory effect entailed also its anti-oxidative and anti-apoptotic effects, thus MDA level (51.8%) and caspase-3 activity (49%) were also reduced, whereas Nrf-2 was increased (38.7%) as compared to Arm A. In both arms a significant correlation was only evident between TNF-α and the neuropathy grading score (P < .03); the correlation analysis was significantly positive between NF-κB and both Nrf-2 and caspase 3.
CONCLUSION: L-Carnosine exerted a neuroprotective effect against oxaliplatin-induced peripheral neuropathy in colorectal cancer patients by targeting Nrf-2 and NF-κB pathways.

PMID: 30592963 [PubMed - as supplied by publisher]

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Relationship between cyclosporine area-under-the curve and acute graft versus host disease in pediatric patients undergoing hematopoietic stem cell transplant: A prospective, multicenter study.

Relationship between cyclosporine area-under-the curve and acute graft versus host disease in pediatric patients undergoing hematopoietic stem cell transplant: A prospective, multicenter study.

Pediatr Hematol Oncol. 2018 Dec 28;:1-9

Authors: Schechter T, Lewis VA, Schultz KR, Mitchell D, Chen S, Seto W, Teuffel O, Gibson P, Doyle JJ, Gassas A, Sung L, Lee Dupuis L

Abstract
Traditionally in hematopoietic stem cell transplant (HSCT), cyclosporine doses are individualized using cyclosporine trough concentrations (C0) while area under the concentration vs time curve (AUC) is used in solid organ transplant. AUC potentially has an important relationship with the development of acute graft-versus-host-disease (aGVHD). We conducted a prospective study to describe the relationship between severe (grade III-IV) aGVHD and cyclosporine AUC in pediatric HSCT recipients. Pediatric patients who underwent allogeneic myeloablative HSCT and scheduled to receive cyclosporine for aGVHD prophylaxis participated in this multicenter study. Cyclosporine doses were adjusted based on C0 according to each center's standard of care. Cyclosporine AUC was determined weekly until neutrophil engraftment or Day +42, whichever was later. Associations between severe aGVHD and cyclosporine AUC and other patient and treatment-related factors were evaluated. Of the 110 children enrolled, 97 were evaluable. Thirty-seven (38%) children developed aGVHD; 13 (13.4%) had severe aGVHD. On univariate analysis, there was no association between severe aGVHD and cyclosporine AUC at any time point before engraftment. Future research should focus on refinement of C0 targets for cyclosporine therapeutic drug monitoring in HSCT.

PMID: 30592246 [PubMed - as supplied by publisher]

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Promoting shared decision making in advanced cancer: Development and piloting of a patient communication aid.

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Promoting shared decision making in advanced cancer: Development and piloting of a patient communication aid.

Patient Educ Couns. 2018 Dec 14;:

Authors: Henselmans I, Brugel SD, de Haes HCJM, Wolvetang KJA, de Vries LM, Pieterse AH, Baas-Thijssen MCM, de Vos FYF, van Laarhoven HWM, Smets EMA

Abstract
OBJECTIVE: To learn how to configure a patient communication aid (PCA) to facilitate shared decision-making (SDM) about treatment for advanced cancer.
METHODS: The PCA consists of education about SDM, a question prompt list, and values clarification methods. Study 1. A first version was presented to 13 patients, 8 relatives and 14 bereaved relatives in interviews. Study 2. A second version was used by 18 patients in a pilot study. Patients and oncologists were interviewed, patients were surveyed, and consultations were audio-recorded.
RESULTS: Respondents reported that the aid facilitated patient control over information, raised choice awareness and promoted elaboration. Risks were identified, most importantly that the aid might upset patients. Also, some respondents reported that the PCA did not, or would not support decision making because they felt sufficiently competent, did not perceive a role for themselves, or did not perceive that the decision required elaboration.
CONCLUSIONS: Opinions on the usefulness of the PCA varied. It was challenging to raise awareness about the presence of a choice, and to find a balance between comprehensive information and sensitivity.
PRACTICE IMPLICATIONS: A future study should demonstrate whether the PCA can improve SDM, and whether this effect is stronger when oncologists receive training.

PMID: 30591283 [PubMed - as supplied by publisher]

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CD38 targeted treatment for multiple myeloma.

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CD38 targeted treatment for multiple myeloma.

Vnitr Lek. 2018;64(10):939-948

Authors: Jelínek T, Mihályová J, Hájek R

Abstract
CD38 antigen is highly and uniformly expressed on plasma cells and thus represents an ideal target for the treatment of multiple myeloma (MM) with anti-CD38 monoclonal antibodies (mAbs). Daratumumab is the most advanced anti-CD38 mAb in the clinical development with approval in several indications, nevertheless isatuximab that targets completely different epitope of CD38 molecule is also very promising drug. Anti-CD38 possess pleiotropic mechanism of action that have been described also in other mAbs, but quite specific, novel and very important seems to be the immunomodulatory effect provided by depletion of several CD38+ immunosuppressive immune cell populations. CD38-targeted mAbs induce partial response or better in approximately 30 % of heavily pre-treated myeloma patients as monotherapy. Based on their favourable toxicity profile and distinct mechanism of action, anti-CD38 mAbs represents very attractive partner to back-bone anti-myeloma drugs. Indeed, daratumumab is already approved as a part of three distinct combination regimens in relapsed setting. The combination of daratumumab with lenalidomide and dexamethasone is considered to be the best treatment option in relapsed myeloma with unprecedented prolongation of median PFS, including high rate of good quality responses. CD38 targeted therapy is rapidly moving toward the first line treatment. Anti-CD38 mAbs have been also successfully tested in other plasma cell dyscrasias (such as AL amyloidosis), and they are examined in other hematological malignancies (such as CLL, ALL, AML, etc.) and even in solid oncology as well as in autoimmune disorders. Implementation of CD38 targeted mAbs have been significant milestone in the treatment of MM, similar to that of CD20 targeted mAbs in CLL or non-Hodgkin lymphomas. We believe that this drug may eventually help to reach the cure at least in a subset of MM patients in the near future. Key words: acute myeloid leukemia - CD38 - daratumumab - isatuximab - multiple myeloma.

PMID: 30590941 [PubMed - in process]

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