Current approaches and future perspectives for advanced-stage follicular lymphoma with a low tumor burden.

Current approaches and future perspectives for advanced-stage follicular lymphoma with a low tumor burden.

Jpn J Clin Oncol. 2019 Jan 31;:

Authors: Fukuhara N, Ishizawa K

Abstract
The introduction of a chimeric anti-CD20 monoclonal antibody, rituximab, for the treatment of follicular lymphoma (FL) has dramatically improved the prognosis of this disease. Despite advances in therapy, the disease remains incurable with current standard therapeutic strategies. For advanced-stage and high-tumor-burden FL patients, a combination of rituximab with chemotherapy has improved the overall survival rates, and subsequent rituximab maintenance following successful rituximab-based chemotherapy induction also prolongs progression-free survival. Conversely, for advanced-stage low-tumor-burden FL patients, watchful waiting remains the appropriate approach, whereas rituximab monotherapy has also been suggested as a good alternative. However, the optimal timing of rituximab monotherapy in low-tumor-burden FL patients has not been clarified. It is important to address this issue for chemo-free treatment strategies. Furthermore, a predictive model for advanced low-tumor-burden patients is required to appropriately identify those patients who may benefit from immediate treatment. In this review, we address the current treatment approaches and present potential future management strategies for advanced-stage, low-tumor-burden patients.

PMID: 30715424 [PubMed - as supplied by publisher]

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Prognostic index score predicts outcome of patients with Stage I non-small cell lung cancer after stereotactic body radiation therapy.

Prognostic index score predicts outcome of patients with Stage I non-small cell lung cancer after stereotactic body radiation therapy.

Jpn J Clin Oncol. 2019 Jan 31;:

Authors: Shi S, Ye L, Zhao Q, Hu Y, Huang Y, Chen G, Zeng Z, He J

Abstract
Objective: Lung cancer is the most common causes of cancer death worldwide and patients with non-small-cell lung cancer (NSCLC) have various prognosis. We conducted this study to identify the prognostic predictors and establish a prognostic index score (PIS) for patients with Stage I NSCLC after stereotactic body radiation therapy (SBRT).
Methods: A total of 131 consecutive patients with Stage I NSCLC who underwent SBRT in our institute were analyzed retrospectively. The Cox proportional hazards regression model was applied to identify the prognostic predictors. Time-dependent receiver operating characteristic analysis was performed to examine cutoff values for survival. The Kaplan-Meier method with log-rank test was used to compare survival curves.
Results: Univariate analysis indicated that tumor location, maximum standardized uptake value (SUVmax), monocyte counts and platelet-to-lymphocyte ratio (PLR) were prognostic factors of overall survival (OS). SUVmax and PLR remained significant in multivariate analysis. Survival analysis indicated both high-SUVmax and PLR correlated with inferior OS and PFS. A PIS was constructed based on pretreatment SUVmax and PLR and a high PIS was also significantly associated with poor outcome.
Conclusion: The pretreatment SUVmax and PLR were independent prognostic factors of OS in patients with Stage I NSCLC after SBRT. PIS provides a convenient and accurate tool for predicting outcome of patients after SBRT.

PMID: 30715411 [PubMed - as supplied by publisher]

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Death, statistics and a disaster zone: the struggle to count the dead after Hurricane Maria

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Risk factors for mortality in elderly and very elderly critically ill patients with sepsis: a prospective, observational, multicenter cohort study

Age has been traditionally considered a risk factor for mortality in elderly patients admitted to intensive care units. The aim of this prospective, observational, multicenter cohort study is to determine the ...

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Long-term effects of intracapsular debulking and adjuvant somatostatin analogs for growth hormone-secreting pituitary macroadenoma: 10 years of experience in a single institute.

Long-term effects of intracapsular debulking and adjuvant somatostatin analogs for growth hormone-secreting pituitary macroadenoma: 10 years of experience in a single institute.

World Neurosurg. 2019 Feb 01;:

Authors: Shen SC, Shen CC, Pu TW, Cheng WY

Abstract
OBJECTIVE: Long-term effects of endoscopic endonasal transsphenoidal intracapsular debulking and adjuvant somatostatin analogs were evaluated in patients with growth hormone secreting pituitary macroadenomas.
METHODS: We retrospectively reviewed the medical records of 45 patients with acromegalic macroadenoma who underwent endonasal endoscopic transsphenoidal intracapsular debulking and received adjuvant somatostatin analogs (octreotide) between 2006 and 2015, who had more than 1 year of follow-up. To evaluate the predictive factors for 1 year and long-term biochemical outcomes, univariate and multivariate analyses were performed.
RESULTS: Biochemical remission was achieved in 1 year in 20 of the 45 (44.4%) patients, and in 31 of the 45 patients after long-term adjuvant somatostatin analog treatment. Tumor control was achieved in 43 of the 45 (93.3%) patients. The univariate analysis showed age (≥55 years), tumor size (diameter ≤1.5 cm), premedication GH levels (≤2.8 ng/ml), premedication IGF-1 levels (≤2 fold of upper limit of normal range), cavernous sinus invasion (Knops Grades 2, 3, and 4), and near-total tumor resection were associated with long-term outcomes. The multivariate analysis showed near-total resection was a significant predictor for long-term outcomes (p = 0.019). There were no new pituitary dysfunctions. The observed complications included one case of CSF leakage and one case of epistaxis requiring intervention.
CONCLUSIONS: Intracapsular debulking and adjuvant somatostatin analogs are a safe and viable treatment for patients with growth-hormone secreting pituitary macroadenoma to achieve biochemical remission and tumor control. Although adjuvant somatostatin analog treatment enhances residual tumor control, cavernous sinus invasion impedes the remission of endocrine.

PMID: 30716503 [PubMed - as supplied by publisher]

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Pre-operative predictors and prognosticators after microsurgical clipping of poor grade subarachnoid hemorrhage: A retrospective study.

Pre-operative predictors and prognosticators after microsurgical clipping of poor grade subarachnoid hemorrhage: A retrospective study.

World Neurosurg. 2019 Feb 01;:

Authors: Ota N, Noda K, Hatano Y, Hashimoto A, Miyazaki T, Kondo T, Kinoshita Y, Kamiyama H, Tokuda S, Kamada K, Tanikawa R

Abstract
BACKGROUND: Contrary to expectations, some patients with poor grade subarachnoid hemorrhage (SAH) show favorable outcomes. However, the factors predictive of good prognosis are unclear. The purposes of this study were to identify factors related to poor grade SAH and to analyze pre-operative prognostic factors.
METHODS: We included 186 patients with SAH who underwent surgical clipping or conservative treatment immediately after SAH diagnosis. Physiological, radiographic, and blood examination data were collected retrospectively. Factors related to poor World Federation of Neurological Societies (WFNS) grade (WFNS IV and V) and poor outcome (modified Rankin Scale scores 3-6) were analyzed.
RESULTS: The subjects (mean age: 61.6 years) included 134 (72%) women. Seventy (38.2%) subjects had poor WFNS scores. On multivariate analysis, age ≥70 years (adjusted odds ratio [OR]: 3.73), midline shift (OR: 4.89), and the absence of cerebrospinal fluid in the high-convexity cortical sulci (OR: 5.47) and ambient cistern (OR: 4.83) were predictive of poor WFNS scores. Age ≥70 years (OR: 8.36), WFNS grade 5 (OR: 15.35), intracerebral hematoma (OR: 3.32), and Evans index (EI) ≥0.3 (OR: 4.40) were predictive of poor outcome. Body mass index (OR: 0.87), intraventricular hemorrhage (OR: 3.86), glycated hemoglobin level (OR: 2.78), and age ≥70 years (OR: 4.12) were predictive of EI ≥0.3.
CONCLUSIONS: Poor outcomes correlated with older age, brain-destructive hemorrhage, and EI ≥0.3. The EI reflects both hydrocephalus and the patient's frailty. Radiographic signs of poor grade SAH were not correlated with poor outcome, suggesting that early decompressive surgery may improve outcome.

PMID: 30716502 [PubMed - as supplied by publisher]

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Intracranial Solitary Fibrous Tumors: a heterogeneous entity with an uncertain clinical behavior.

Intracranial Solitary Fibrous Tumors: a heterogeneous entity with an uncertain clinical behavior.

World Neurosurg. 2019 Feb 01;:

Authors: Gubian A, Ganau M, Cebula H, Todeschi J, Scibilia N, Noel G, Spatola G, Chaussemy D, Nannavecchia B, P G, Coca A, Pop R, Signorelli F, Proust F, Lhermitte B, Chibbaro S

Abstract
Intracranial solitary fibrous tumors (ISFT) are rare mesenchymal neoplasms, originating in the meninges, characterized by very different biological and clinical behaviors. Benign histotypes such as hemangiopericytomas are now considered a cellular phenotypic variant of this heterogeneous group of rare spindle-cell tumors. Due to their rarity and resemblance to other more common brain tumors, ISFTs are often poorly recognized and remain a diagnostic challenge: in fact, ISFT might either have a benign/indolent clinical behavior or show biological aggressivity with local and distant recurrences after surgery. We describe herein a surgical series of 29 patients treated for ISFTs confirmed histologically and through immunohistochemistry. We attempt to provide a focus on the natural history of these pathologies and the need for a tailored management.

PMID: 30716501 [PubMed - as supplied by publisher]

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Predictive accuracy of neutrophil to lymphocyte ratio on long-term outcome in patients with spontaneous intracerebral hemorrhage.

Predictive accuracy of neutrophil to lymphocyte ratio on long-term outcome in patients with spontaneous intracerebral hemorrhage.

World Neurosurg. 2019 Feb 01;:

Authors: Zhang F, Ren Y, Fu W, Yang Z, Wen D, Hu X, Tao C, Li X, You C, Xin T, Yang M

Abstract
BACKGROUND: It is well established that inflammation plays critical roles in the progression of intracerebral hemorrhage (ICH). And recently neutrophil to lymphocyte ratio (NLR) was identified as a predictor for short-term outcome of ICH patients. However, the association of NLR on long-term outcome of patients with ICH remains unrevealed. Here, we aim to assess the relationship between NLR and long-term prognosis of ICH patients.
METHODS: All retrospectively enrolled cases of spontaneous ICH patients were hospitalized at West China Hospital of Sichuan University from October 2013 to May 2017. White blood count, absolute count of neutrophil and lymphocyte are extracted from electronic medical records, and NLR was calculated according to admission neutrophil count (ANC) and lymphocyte count (ALC). The associations between long-term outcomes and laboratory biomarkers were estimated by applying multivariable logistic regression analysis. The receiver operating characteristic curves (ROC) was also performed to compare the predictive power between each inflammatory factor.
RESULTS: A total of 481 ICH patients were included in current study. 204 of them presented with unfavorable outcomes, and 142 of them were dead within 6 months. Age, GCS scores, WBC, ANC, NLR, incidence of hematoma size and hydrocephalus were independently associated with poor prognosis of patients with ICH. By using multiple linear analyses, GCS, hematoma volume, WBC, ANC and ALC were correlated with NLR. Moreover, by comparing with other single laboratorial parameters, NLR also exhibited better predictive capacity for long-term mortality and morbidity, and the best predictive cutoff values are 9.07 and 8.69, respectively.
CONCLUSIONS: NLR independently predicts 180-days morbidity and 180-days mortality in patients with spontaneous ICH.

PMID: 30716500 [PubMed - as supplied by publisher]

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Paradoxical Relations between Basilar Artery Reconfiguration and Superior Cervical Ganglia Ischemia Following Bilateral Common Carotid Artery Ligation.

Paradoxical Relations between Basilar Artery Reconfiguration and Superior Cervical Ganglia Ischemia Following Bilateral Common Carotid Artery Ligation.

World Neurosurg. 2019 Feb 01;:

Authors: Kilic M, Kilic B, Aydin MD, Kanat A, Yilmaz I, Eseoglu M, Gundogdu B

Abstract
ACKGROUND: The relationship between superior cervical ganglia (SCG) ischemia due to bilateral common carotid artery ligation (BCCAL) and basilar artery (BA) reconfiguration was investigated.
METHOD: Twenty-three rabbits were randomly divided into three groups: GIII rabbits underwent BCCAL (n = 13), GII rabbits were sham-operated controls (n = 5), and GI rabbits did not undergo surgery (n = 5). Degenerated neuron densities (DND) within SCG were correlated with the BA vasodilatation index (VDI).
RESULTS: Mean live and DND in SCG of GI rabbits were 11.235 ± 982/μm3 and 11 ± 3/μm3, respectively, with a mean heart rate of 294 ± 21 beats/min. Mean SCG DND and heart rates were 213 ± 42/μm3 and 242 ± 17 beats/min for sham group (Group II) rabbits and 1743 ± 285/μm3 and 199 ± 19 beats/min for study group (Group III) rabbits, respectively. BA VDI values in sham group (Group II) (1.32 ± 0.10) and study group (Group III) rabbits, (0.976 ± 0.112) rabbits significantly differed from those in control group (Group I) (1.65 ± 0.12; P< 0.005 vs sham group (Group II); P< 0.0001 vs BCCAL applied group (Group III) and between Group II and Group III rabbits (P< 0.005).
CONCLUSION: A meaningful and paradoxical correlation was detected between the BA VDI values and degenerated neuron density of SCG following BCCAL. Although a low degenerated neuron density within SCG may provoke excessive sympathetic activity and prevent excessive BA dilatation with steno-occlusive carotid artery diseases, a high degenerated neuron density may cause dangerous vasodilatation of BA.

PMID: 30716499 [PubMed - as supplied by publisher]

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Cerebrovascular reactivity measured with ASL perfusion MRI, ivy sign and regional tissue vascularization in moyamoya.

Cerebrovascular reactivity measured with ASL perfusion MRI, ivy sign and regional tissue vascularization in moyamoya.

World Neurosurg. 2019 Feb 01;:

Authors: Kronenburg A, Bulder MMM, Bokkers RPH, Hartkamp NS, Hendrikse J, Vonken EJ, Kappelle LJ, van der Zwan A, Klijn CJM, Braun KPJ

Abstract
BACKGROUND: and purpose: Arterial spin labeling (ASL) perfusion MRI may be used to determine brain regions at risk for ischemia in patients with moyamoya vasculopathy (MMV) and to identify patients who may benefit from surgical revascularization. We aimed to investigate whether 1) the severity of moyamoya is related to the presence of leptomeningeal collaterals and cerebrovascular reactivity (CVR); 2) the presence of collaterals and ivy sign reflects disturbed CVR; and 3) arterial transit artefacts (ATAs) and ivy sign reflect the presence of collaterals.
METHODS: We determined severity of moyamoya on digital subtraction angiography (DSA) according to the modified Suzuki classification in 20 brain regions and scored regional tissue revascularization using a 4-point scale. Regional CVR and ATAs were assessed on ASL perfusion MRI, ivy sign on FLAIR MRI.
RESULTS: In 11 patients (median age 36 years; 91% female), we studied 203 regions. ATAs were associated with the presence of collaterals on DSA (p<0.01). Of all regions with clearly visible collateral vessels on DSA, however, only 24% had ATAs. Ivy sign was not related to presence or absence of collaterals nor to CVR. In 10% of regions with good vascularization on DSA, CVR was poor or showed steal.
CONCLUSIONS: ATAs were associated with the presence of collaterals on DSA. Although DSA vascularization scores correlated with CVR, 10% of regions with good vascularization on DSA had absent CVR or steal on ASL-MRI. DSA and ivy sign did not provide adequate information on the hemodynamic status of brain tissue in patients with MMV.

PMID: 30716498 [PubMed - as supplied by publisher]

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Thick clot in the inferior limiting sulcus on the CT image as an indicator of the sylvian subpial hematoma in patients with aneurysmal subarachnoid hemorrhage.

Thick clot in the inferior limiting sulcus on the CT image as an indicator of the sylvian subpial hematoma in patients with aneurysmal subarachnoid hemorrhage.

World Neurosurg. 2019 Feb 01;:

Authors: Matsukawa H, Miyazaki T, Kiko K, Kamiyama H, Ota N, Noda K, Takahashi O, Shonai T, Fujisawa T, Tokuda S, Tanikawa R

Abstract
OBJECTIVE: The sylvian subpial hematoma (SSH) was occasionally observed in the aneurysm subarachnoid hemorrhage (aSAH) when accompanying with the thick clot in the inferior limiting sulcus (ILS). We aimed to determine whether the thickness of the clot in the ILS (TCILS) was an indicator of SSH.
METHODS: Data of 150 consecutive aSAH patients was retrospectively analyzed. The relationship between TCILS on axial CT image and the intraoperatively confirmed SSH. In patients without the SSH, the average of the clot thickness of the clot in the bilateral ILS was used. Primary outcome was the SSH.
RESULTS: The median TCILS of the SSH group (n=18, 12%) was larger than that of the non-SSH group (n=132, 88%) (21 mm v.s. 2.1 mm; P < 0.001). The intraclass correlation coefficient for the clot thickness in the right and left ILS between two observers were 0.97 (P < 0.001) and 0.85 (P < 0.001). The TCILS threshold of ≧6.0 mm was associated with the SSH with a sensitivity of 89% and specificity of 99%. The unadjusted and adjusted OR of the SSH of clot thickness in the affected ILS ≧ 6 mm relative to clot thickness in the affected ILS < 6 mm were 263 (95% CI, 46-5063) and 137 (95% CI, 19-3029), respectively.
CONCLUSIONS: The clot thickness in the ILS on CT image was easily measured and could be a marker of the SSH. The SSH assessment could be useful in helping us predict the clinical course in patients with aSAH.

PMID: 30716497 [PubMed - as supplied by publisher]

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Complete Recanalization May Exert The Most Important Effect on Outcomes of Endovascular Treatment in Acute Ischemic Stroke With Small Infarct Core Beyond 6 Hours.

Complete Recanalization May Exert The Most Important Effect on Outcomes of Endovascular Treatment in Acute Ischemic Stroke With Small Infarct Core Beyond 6 Hours.

World Neurosurg. 2019 Feb 01;:

Authors: Yang D, Geng Y, Zhang M, Lin M, Shi Z, Zi W, Hao Y, Wang H, Liu W, Wang W, Xu G, Xiong Y, Liu X, ACTUAL Investigators

Abstract
OBJECTIVE: To explore the differences among grades of recanalization on outcomes of endovascular treatment for acute anterior large vessel occlusion with small infarct core beyond 6 hours time window.
METHODS: Patients beyond 6 hours time window with ASPECTS>7 were retrospectively enrolled from the endovascular treatment for acute anterior circulation ischemic stroke (ACTUAL) registry. They were divided into three groups according to the degree of recanalization: modified treatment in cerebral infarction (mTICI) 0-2a, 2b, and 3. We compared the differences of outcomes among groups on modified Rankin Scale (mRS) score at 90 days, symptomatic intracerebral hemorrhage (sICH) within 72 hours, and mortality.
RESULTS: One hundred and one patients were enrolled. Median of time from onset to groin puncture was 415 minutes (interquartile range [IQR]: 387-497 minutes). Favorable functional outcomes were significantly better in patients with successful recanalization than patients with failed recanalization (mTICI 0-2a, 22.7% [5/22], mTICI 2b, 48.0% [12/25], and mTICI 3, 61.1% [33/54], trend P=0.01). Complete recanalization (mTICI 3) (odds ratio [OR]: 5.34; 95% confidence interval [CI]: 1.71-16.66; P=0.004) was associated with good functional outcome. Mortality was different among groups at 90 days (mTICI 0-2a, 36.4% [8/22], mTICI 2b, 0, [0/25], P=0.001; mTICI 0-2a, 36.4% [8/22], mTICI 3, 9.3% [5/54], P=0.008; and mTICI 2b, 0, [0/25], mTICI 3, 9.3% [5/54], P=0.173). There was no significant differences of sICH among groups (mTICI 0-2a, 22.7% [5/22], mTICI 2b, 12.0% [3/25], and mTICI 3, 9.3% [5/54], P=0.28).
CONCLUSIONS: For acute anterior circulation stroke patients, who were beyond 6h time window yet with small ischemic core, complete recanalization following endovascular treatment may play the most important role on clinical outcome.

PMID: 30716496 [PubMed - as supplied by publisher]

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Neonatal Hyponatremia in the Setting of Untreated Progressive Hydrocephalus: Case Report.

Neonatal Hyponatremia in the Setting of Untreated Progressive Hydrocephalus: Case Report.

World Neurosurg. 2019 Feb 01;:

Authors: Obi M, Onwuzulike K

Abstract
BACKGROUND: Hyponatremia in the neonatal population is an uncommon occurrence and can be associated with significant increase in morbidity and mortality. In the neonatal population, it is typically associated with an excess of antidiuretic hormone (ADH) and rarely has been found to be associated with hydrocephalus short of being caused by the subsequent treatment of hydrocephalus.
CASE: Description: We present a case report of a patient with neonatal hydrocephalus, secondary to intraventricular hemorrhage in the setting of prematurity, treated at our institution, in whom sodium levels reached a nadir as head circumference peaked and subsequent treatment of hydrocephalus resolved the associated hyponatremia.
CONCLUSIONS: Hydrocephalus secondary to intraventricular hemorrhage is a notable complication in the premature neonatal population. Physicians should be aware of its potential association with hyponatremia and consider early neurosurgical intervention when other etiologies of the electrolyte disturbance cannot be identified.

PMID: 30716495 [PubMed - as supplied by publisher]

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Dissociation between 11C-methionine-PET and Gd-MRI in the longitudinal features of Glioblastoma after postoperative radiotherapy.

Dissociation between 11C-methionine-PET and Gd-MRI in the longitudinal features of Glioblastoma after postoperative radiotherapy.

World Neurosurg. 2019 Feb 01;:

Authors: Kawasaki T, Miwa K, Shinoda J, Asano Y, Takei H, Ikegame Y, Yokoyama K, Yano H, Iwama T

Abstract
INTRODUCTION: The aims of this study are to compare the longitudinal radiological changes of Glioblastoma multiforme (GBM) after radiotherapy (RT) between 11C-methionine positron emission tomographic (MET-PET) imaging and gadolinium enhanced MRI (Gd-MRI), and to clarify whether these changes predict patient survival.
METHODS: This study included 30 patients with newly diagnosed GBM, who received MET-PET and Gd-MRI postoperatively before and every three months after RT (30, 28, and 16 patients were followed for 3, 6, and 9 months after RT, respectively). Regardless of the size after surgery, there remained tumor lesions radiologically in all cases on MET-PET and Gd-MRI. The changes of the lesion/normal brain uptake ratio on MET-PET (L/N ratio) and the contrast enhancing lesion volume on Gd-MRI (Gd-vol) were examined.
RESULTS: The L/N ratio was decreased until 9 months after RT with significance until 3 months. The Gd-vol was decreased until 3 months and thereafter increased significantly until 9 months. The variation rates (VRs) of the L/N ratio between pre- and 3 months post-RT significantly differentiated patients with survival more than 23 months from those with survival of 23 months or less. The best cut-off value of the VR was -0.366, while providing a specificity of 94.7% and a sensitivity of 60.0%. The median survivals were 39.5 and 17.0 months in patients with a VR of -0.366 or less and those with a VR of more than -0.366.
CONCLUSIONS: There could be a significant dissociation in the longitudinal changes of GBM after RT between MET-PET and Gd-MRI. The VR of the L/N ratio between pre- and 3 months post-RT, was suggested to be related significantly to patient survival.

PMID: 30716494 [PubMed - as supplied by publisher]

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Delayed Pipeline embolization of a ruptured true internal carotid artery aneurysm presenting with epistaxis: Case report and review of the literature.

Delayed Pipeline embolization of a ruptured true internal carotid artery aneurysm presenting with epistaxis: Case report and review of the literature.

World Neurosurg. 2019 Feb 01;:

Authors: Grandhi R, Brasiliense LBC, Williamson R, Zwagerman NT, Sauvageau E, Hanel RA

Abstract
BACKGROUND: Massive epistaxis from rupture of an intracavernous internal carotid artery (ICA) aneurysm is a potentially fatal event. Although rare, this presentation is seen most often in patients after trauma or iatrogenic injury secondary to transsphenoidal surgery or radiation therapy.
CASE DESCRIPTION: We present our unusual case of a patient with no significant risk factors who had recurrent epistaxis due to a ruptured true cavernous ICA aneurysm. The patient was treated initially with coil embolization followed by placement of a Pipeline Embolization Device (PED). The patient had complete resolution of her bleeding events. A follow-up arteriogram performed 14 months later confirmed aneurysm obliteration, with parent artery preservation and no evidence of in-stent stenosis.
CONCLUSIONS: Our case highlights the importance of evaluating for intracranial pathological conditions in patients who present with refractory epistaxis. In selected patients, the use of flow-diversion technology as an adjunct or alternative to primary coil embolization for treatment should be considered.

PMID: 30716493 [PubMed - as supplied by publisher]

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Intrathecal saline infusion as an effective temporizing measure in the management of spontaneous intracranial hypotension.

Intrathecal saline infusion as an effective temporizing measure in the management of spontaneous intracranial hypotension.

World Neurosurg. 2019 Feb 01;:

Authors: Muram S, Yavin D, DuPlessis S

Abstract
BACKGROUND: Spontaneous intracranial hypotension is a rare condition for which no optimal treatment guidelines have been determined. The most common presentation is orthostatic headaches, but patients can present with a variety of symptoms.
CASE DESCRIPTION: We present a case of a 34 year old male who developed progressive orthostatic headaches and bilateral subdural collections. His symptoms along with imaging of his brain and spine were consistent with SIH. Unfortunately, his symptoms continued to progress, and his level of consciousness became affected. The patient failed both conservative management and epidural blood patching. Due to his worsening condition, a lumbar drain was inserted for the intrathecal infusion of normal saline to prevent tonsillar herniation. Once the infusion was started his level of consciousness improved. It was discovered that his CSF leak was due to an osteophyte within his thoracic spine, which was eroding the dura. He underwent a costo-transversectomy with the removal of the osteophyte and repair of the dural defect. The patient had some improvement after this procedure, but he remained more somnolent then expected. On subsequent imaging, it was found that his subdural collections had increased slightly in size and it was decided to drain them. Both collections were released under high pressure, and he went on to make an excellent recovery.
CONCLUSION: This case demonstrates that an intrathecal saline infusion can be used as an effective temporizing measure in patient's with critical symptoms of SIH and it also alerts clinicians that low pressure subdural collections can progress to subdural collections under high pressure.

PMID: 30716492 [PubMed - as supplied by publisher]

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Resection of Meningiomas Involving Major Dural Venous Sinuses: Classification, Technique and Long Term Results.

Resection of Meningiomas Involving Major Dural Venous Sinuses: Classification, Technique and Long Term Results.

World Neurosurg. 2019 Feb 01;:

Authors: Zeeshan Q, Patel A, Cheng CY, Zhao NH, Barber J, Ghodke BV, Sekhar LN

Abstract
OBJECTIVE: Management of meningiomas with major dural venous sinus involvement is challenging. We present our case series and perspective on reconstruction of the sinuses.
METHODS: 55 patients underwent operations between 2005 and 2016 and the retrospective data were collected and analyzed.
RESULTS: Cohort was younger with a mean of 51.3 years (Range 19 - 72 ) predominantly involving the superior sagittal sinus (44 patients). Sinus involvement was classified into Group 1 (<50% of sinus, n=28), Group 2 (50-99%, n=8) and Group 3 (Total occlusion, n=19). Venous collateralization was present in 100% of Group 2 and 3 and in 36% of Group 1 occlusions. Sinus pericranii was seen in 22 patients. A gross total resection was achieved in 87.2%, and sinus reconstruction followed in thirty eight patients; 24 by direct suture and 14 by a patch graft. Pathology showed 36 (65%) WHO I, 18 (33%) WHO II, and 1 (2%) WHO III tumors. During the mean follow up of 60 months (range 1 -132 months), sinus was patent (74%) or narrowed but patent (24%) in 98% ; two recurrences (3.6%) were observed (at 24 and 120 months) .The Mean pre/postoperative KPS scores and Kaplan Meier cumulative overall/recurrence free survival were 84.2/88.1 and 90.9%/80.1 % respectively.
CONCLUSIONS: These meningiomas present in a younger population, are more likely to be WHO grade II or III, necessitating a more aggressive tumor resection strategy. Aggressive resection coupled with sinus reconstruction results in good long term surgical outcome and low recurrence rates.

PMID: 30716491 [PubMed - as supplied by publisher]

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Cost-utility analysis of surgery and radiotherapy for symptomatic spinal metastases in a Belgian specialist center.

Cost-utility analysis of surgery and radiotherapy for symptomatic spinal metastases in a Belgian specialist center.

World Neurosurg. 2019 Feb 01;:

Authors: Depreitere B, Turner I, Vandoren C, Choi D

PMID: 30716490 [PubMed - as supplied by publisher]

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Daily living activities and their relationship to health-related quality of life in Parkinson's disease patients after subthalamic nucleus deep brain stimulation.

Daily living activities and their relationship to health-related quality of life in Parkinson's disease patients after subthalamic nucleus deep brain stimulation.

World Neurosurg. 2019 Feb 01;:

Authors: Gorecka-Mazur A, Furgała A, Krygowska-Wajs A, Pietraszko W, Kwinta B, Gil K

PMID: 30716489 [PubMed - as supplied by publisher]

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The possible prognostic role of magnetic resonance imaging findings in patients with trigeminal neuralgia and multiple sclerosis submitted to percutaneous balloon compression. Report of our series and literature review.

The possible prognostic role of magnetic resonance imaging findings in patients with trigeminal neuralgia and multiple sclerosis submitted to percutaneous balloon compression. Report of our series and literature review.

World Neurosurg. 2019 Feb 01;:

Authors: Montano N, Gaudino S, Giordano C, Pignotti F, Ioannoni E, Rapisarda A, Olivi A

Abstract
OBJECTIVE: We studied the correlation of magnetic resonance imaging (MRI) findings with the prognosis of multiple sclerosis (MS)-related trigeminal neuralgia (TN) patients submitted to percutaneous balloon compression (PBC). No articles have previously been reported on this topic. We also performed a literature review of the pertinent studies.
METHODS: From a surgical series of 82 TN patients submitted to PBC between January 2013 and June 2017, we identified 16 MS patients (mean age: 54.81±8.51 years and mean follow-up: 38.12±19.86 months). On brain MRI, we evaluated the presence of a lesion in the trigeminal nerve root entry zone and in the trigeminal nuclei and, along with other clinical and procedure-related factors, we studied its impact on the acute pain relief (APR: pain-free at hospital discharge) and on the pain-free survival (PFS).
RESULTS: Fifteen out of sixteen patients (93.75%) reported an APR. Eight patients (50.00%) experienced a recurrence of pain. At latest follow-up, an excellent outcome (BNI I-II) was obtained in 75% of patients and a good outcome (BNI III) in the remaining ones. No patients had an uncontrolled pain. The presence of a pear-like shape of the balloon at the operation (p=0.0053) and the evidence of a MRI detectable lesion in trigeminal pathway (p=0.049) were associated to a higher PFS.
CONCLUSIONS: PBC can be efficient in treating MS-related TN. Some factors such as the pear-like shape of the balloon at the operation and the evidence of a MRI detectable lesion in trigeminal pathway seem to be associated to a higher PFS.

PMID: 30716488 [PubMed - as supplied by publisher]

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Magnetically Controlled Growing Rod for Early Onset Scoliosis: A Systematic Review and Meta-Analysis.

Magnetically Controlled Growing Rod for Early Onset Scoliosis: A Systematic Review and Meta-Analysis.

World Neurosurg. 2019 Feb 01;:

Authors: Tang N, Zhao H, Shen JX, Zhang JG, Li SG

Abstract
BACKGROUND: The goal of the current systematic review and meta-analysis was to explore the utilization of magnetically controlled growing rod (MCGR) for the treatment of early onset scoliosis based on eligible studies demonstrating efficacy.
METHODS: Online electronic databases were searched to identify the eligible studies updated to April 2018 according to the index words. Several literatures that were relevant to the present analysis were also included. Mean difference (MD) or relative risk (RR) along with 95% confidence interval (95% CI) was used to analyze the main outcomes.
RESULTS: Totally, 11 studies were included in the meta-analysis with 186 patients in the MCGR group and 64 patients in the conventionally growing rod (CGR) group; three studies were case-control studies, and eight studies were self-control studies. The results indicated that MCGR had significantly decreased the Cobb angle and thoracic kyphosis, and increased T1-T12 distance, and T1-S1 distance. In addition, the incidence of complications after MCGR therapy was 0.37%. However, there was no significant difference in the change of Cobb angle and the incidence of complications between the MCGR group and the CGR group.
CONCLUSION: We demonstrated that MCGR significantly reduced the Cobb angle and thoracic kyphosis while markedly increase T1-T12 distance and T1-S1 distance. However, a close comparison of MCGR with CGR reveals more high-quality RCTs with a larger sample size and long-term follow-ups are needed to gather more robust evidence on the efficacy of MCGR for early onset scoliosis.

PMID: 30716487 [PubMed - as supplied by publisher]

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The Neural Circuitry: Architecture and Function, a fiber dissection study.

The Neural Circuitry: Architecture and Function, a fiber dissection study.

World Neurosurg. 2019 Feb 01;:

Authors: Shah A, Goel A, Jhawar SS, Patil A, Rangnekar R, Goel A

Abstract
OBJECTIVE: White fiber dissection using a gyrus based approach was performed to study the various association, commissural and projection fiber bundles of the brain METHODS: Ten previously frozen and formalin-fixed cadaveric human brains were used. The fiber dissection techniques described by Klingler were adopted. The primary dissection tools used were thin handmade wooden spatulas, and curved metallic spatulas with tips of various sizes. The fibers were studied by the naked eye and with the use of magnification. The various fiber bundles were studied using a gyrus based approach. The dissection was carried out through each named gyrus and the fiber tracts encountered during the dissection were identified and their relation to other adjacent fiber bundles was studied.
RESULTS: Based on our dissections the white fibers of the brain have been divided architecturally into five groups- four horizontal groups and one vertical group. The four horizontal groups are the superficial, middle, deep and central groups. The association fibers constitute the superficial, middle and deep groups. The commissural fibers form the central group and the projection fibers form the vertical group. The course of the fiber bundles and their functional co-relation is discussed.
CONCLUSIONS: When planning surgical trajectory, knowledge of the location of white matter tracts is essential in order to help minimize post-operative deficits. Fiber dissection using the Klingler technique is useful in gaining an understanding of the complex three dimensional nature of these white matter tracts, and may provide a valuable resource in neurosurgical training.

PMID: 30716486 [PubMed - as supplied by publisher]

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Increased risk of dementia in patients with craniofacial trauma: a nationwide population-based cohort study.

Increased risk of dementia in patients with craniofacial trauma: a nationwide population-based cohort study.

World Neurosurg. 2019 Feb 01;:

Authors: Yang JR, Kuo CF, Chung TT, Liao HT

Abstract
OBJECTIVE: The role of maxillofacial trauma in dementia risk is less well established. The aim of this study was to evaluate the association between craniofacial trauma, including facial bone fracture and TBI, and dementia.
METHODS: Using Taiwan's National Health Insurance Research Database, we identified 501,889 adults, who had had at least one medical record of craniofacial trauma between 2000 and 2010 and did not have a dementia diagnosis at baseline. Diagnoses of craniofacial trauma, including facial bone fracture and TBI, and dementia were made using ICD-9 codes. The standardized incidence ratio (SIR) was used to determine whether craniofacial trauma was associated with a greater risk of incident dementia compared with the general population. The Cox proportional hazards model was used to predict the risk of dementia among the trauma cohort by comparing the patients with and without comorbidities.
RESULTS: A total of 501,889 patients with craniofacial trauma were included, of which 1.5% (n = 7,804) developed dementia. Facial bone fracture (SIR, 1.58 [95% CI, 1.25-2.00]) was shown to be associated with an increased dementia risk compared with the general population. In addition, craniofacial trauma accompanied with postinjury comorbidities were associated with an elevated risk of dementia during follow-up periods compared with the group without comorbidities.
CONCLUSIONS: Craniofacial traumas, especially facial bone fracture, were associated with an increased risk of subsequent dementia. Maintaining a high index of suspicion for associated TBIs in all patients with facial trauma is crucial, even if no obvious initial signs and symptoms of brain injury are observed.

PMID: 30716485 [PubMed - as supplied by publisher]

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Lazy Glass Microsurgical trainer. A frugal solution for microsurgical training.

Lazy Glass Microsurgical trainer. A frugal solution for microsurgical training.

World Neurosurg. 2019 Feb 01;:

Authors: Bedi MS, Bhavthankar T, Rao GM, Babu KJ, Ambati V, Jonalgadda V, Ogando-Rivas E, Konchada K, Chaitanya J, Jvnk A

Abstract
OBJECTIVE: The art of surgery is becoming perpetually complex and dependent on scopes, screens and technology, inviting a complex learning curve and development of hand eye coordination and dexterity amongst other skills.We introduce an affordable, DIY microsurgical simulator which can be setup using a smartphone & a pair of reflective prism glasses. The glasses employ, periscopic prisms on either side which reflect light perpendicularly. When the visual input is combined with the magnification of a smartphone camera. A very real time microsurgical experience can be simulated, sitting at home or any other place of interest.
METHODS: We analyzed the performance of 2 trainee residents in performing first five successful sutures with 5-0 polypropylene thread on the cut ends of a glove, for three months. The module was also subjected to a survey at an international conference of neurosurgeons.
RESULTS: A significant improvement was observed in both residents at the end of each month vs baseline. (p<0.05) A total of 3/27 (11%) survey participants reported access to a training lab in their institute. The module was rated 4/5 in terms of hand eye coordination, 3.5/5 in management of Microsurgical field & 3.5/5 in depth perception.
CONCLUSION: The microsurgical simulation technique proved to be useful in performing complex microsurgical tasks and a significant improvement in microsurgical skills was observed amongst our trainees. The cost of building the module is as low as 5$. We endorse the use of this technique for resident training and skill development, especially in resource challenged environments.

PMID: 30716484 [PubMed - as supplied by publisher]

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A modified technique of two-staged extensor tendon reconstruction in zones 6-8 in a patient with absent palmaris/plantaris tendons: A case report.

A modified technique of two-staged extensor tendon reconstruction in zones 6-8 in a patient with absent palmaris/plantaris tendons: A case report.

Int J Surg Case Rep. 2019 Jan 30;55:99-102

Authors: Al-Qattan MM, Al Mohrij SA

Abstract
INTRODUCTION: The indications for two-staged extensor tendon reconstruction are rare and only 14 previously reported cases were found in the literature. In these cases, silicone rods are inserted in the first stage. Few months later, the palmaris longus / plantaris tendon grafts are usually used to replace the silicone rods.
CASE REPORT: we encountered a patient with major defects of the extensor tendons of all fingers extending from the proximal one third of zone 6 to zone 8. The patient had no palmaris or plantaris tendons. We utilized a modified technique of reconstruction using the split flexor carpi radialis as the tendon graft and the flexor carpi ulnaris as the motor tendon. At final follow-up, there was full active extension of the fingers. However, there was limitation of wrist flexion because of the harvesting of both wrist flexors.
DISCUSSION: We describe a modified technique of two-staged extensor tendon reconstruction which may be used in patients with absent palmaris/ plantaris tendons.
CONCLUSION: In patients with absent palmaris/ plantaris tendons and major defects of the extensor tendons of all fingers, the use of split flexor carpi radialis is an adequate alternative for reconstruction and gives a good functional outcome.

PMID: 30716711 [PubMed - as supplied by publisher]

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A case report of parotid mammary analogue secretory carcinoma and reviews.

A case report of parotid mammary analogue secretory carcinoma and reviews.

Int J Surg Case Rep. 2019 Jan 19;55:88-91

Authors: Sun L, Thorson T, Zhu R, Huo J, Tong J, Rodgers WH, Shemen L

Abstract
INTRODUCTION: Mammary analog secretory carcinoma (MASC) is a new diagnosis of head and neck tumors first reported in 2010. It was often misdiagnosed as salivary acinic cell carcinoma (AciCC). We present a patient with an asymptomatic parotid tumor that underwent deep lobe parotidectomy and postoperative radiation therapy. The final pathology showed MASC.
CASE PRESENTATION: A 57-year-old male presented with an asymptomatic enlarging right parotid mass. A CT neck with IV contrast showed a 1.2 cm heterogeneously enhancing mass in the center of the right parotid gland without extraparotid extension. An FNA showed an epithelial neoplasm with papillary features. The patient underwent a right deep lobe parotidectomy with facial nerve dissection. The final pathology confirmed the diagnosis of MASC. He subsequently completed a 6-week course of radiation therapy and remained asymptomatic at his 30-month follow up.
DISCUSSION/CONCLUSION: Although MASC is considered a low-grade tumor in most cases, recurrence and disseminated disease are not uncommon. No standard treatment protocol has been established. This report aims to enhance the awareness of this diagnosis and provide a review of current treatments for head and neck oncology care providers.

PMID: 30716709 [PubMed - as supplied by publisher]

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Surgical care for ingested cocaine packets: Case report and literature review.

Surgical care for ingested cocaine packets: Case report and literature review.

Int J Surg Case Rep. 2019 Jan 29;55:84-87

Authors: Elkbuli A, Ehrhardt JD, Hai S, McKenney M, Boneva D

Abstract
INTRODUCTION: Body packing is the use of intra-corporeal packages of illicit drugs for the purpose of smuggling, usually through customs. Clinical cases and experience with body packers has increased since the first report appeared in 1971. These cases remain an uncommon cause of acute drug toxicity and/or bowel obstruction.
PRESENTATION OF CASE: A 23 year-old man was brought to the emergency department with seizures. CT imaging revealed numerous intestinal foreign bodies, suspicious for body packing. The patient was stabilized and taken emergently to the operating room for exploratory laparotomy and removal of 34 cocaine packets. Ongoing treatment for cocaine overdose was also utilized. The patient recovered without complications.
DISCUSSION: This case provides insight and awareness for proper diagnosis and management of body packers by physicians and surgeons alike.
CONCLUSION: We present a case report of acute cocaine intoxication in a young man who ingested 34 packets of cocaine for means of drug trafficking. Medical approaches are available for cases in which patients remain asymptomatic, but surgical intervention is necessary for those with signs and symptoms of bowel obstruction or drug overdose.

PMID: 30716708 [PubMed - as supplied by publisher]

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Biliary hyperkinesia, a new diagnosis or misunderstood pathophysiology of dyskinesia: A case report.

Biliary hyperkinesia, a new diagnosis or misunderstood pathophysiology of dyskinesia: A case report.

Int J Surg Case Rep. 2019 Jan 19;55:80-83

Authors: Bates JA, Dinnan K, Sharp V

Abstract
INTRODUCTION: Biliary colic, characterized by intermittent right upper quadrant abdominal pain is a common complaint in the United States population. Patients whose pain is undiagnosed by ultrasound generally undergo hepatobiliary iminodiacetic acid scan with cholecystokinin stimulation (HIDA-CCK) to assess function of the gallbladder and biliary tree. Traditionally, two outcomes are possible based on a measured ejection fraction of the gallbladder: either dyskinesia or normal function is diagnosed. Biliary dyskinesia, or hypokinesia of the gallbladder, is accepted as an ejection fraction less than 35%, while an accepted normal functioning gallbladder ejection fraction is greater than 35%.
CASE: We report a case of a fifteen-year-old female who had functional gallbladder disease per Rome IV criteria due to intermittent biliary colic, with exception to the ejection fraction measurement which was elevated at 96.5%. She underwent laparoscopic cholecystectomy with complete symptom resolution.
DISCUSSION: As demonstrated in the literature reviewed here, these subsets of patients, who present with normal to high ejection fractions, have undergone laparoscopic cholecystectomy with resolution of pain in several case studies.
CONCLUSION: Many unknown variables still exist due to lack of prospective studies, most notably the pathophysiology and definitive indications for surgical treatment. As such, we propose that surgical options should not be limited to those who display the traditional findings of biliary dyskinesia, but also patients who demonstrate typical symptoms with normal to elevated ejection fraction, following work up to rule out the extensive differential diagnoses for right upper quadrant abdominal pain.

PMID: 30716707 [PubMed - as supplied by publisher]

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Anterograde bile duct drainage for intractable bile leakage after hepatectomy in a patient with previous pancreatoduodenectomy: A case report.

Anterograde bile duct drainage for intractable bile leakage after hepatectomy in a patient with previous pancreatoduodenectomy: A case report.

Int J Surg Case Rep. 2019 Jan 29;55:121-124

Authors: Murata R, Kamiizumi Y, Ishizuka C, Kashiwakura S, Tsuji T, Kasai H, Tani Y, Haneda T, Yoshida T, Ito K

Abstract
INTRODUCTION: Endoscopic retrograde drainage is effective for managing bile leakage, which is relatively common after hepatectomy without bile duct reconstruction. However, the procedure is difficult to perform after pancreatoduodenectomy with choledochojejunostomy. We present a case of anterograde bile duct drainage for intractable bile leakage after hepatectomy in a patient with previous pancreatoduodenectomy.
PRESENTATION OF CASE: An 80-year-old woman with a history of pancreatoduodenectomy for distal biliary cancer and adjuvant chemotherapy presented with bile leakage. Six years after the pancreatoduodenectomy, she underwent partial hepatectomy for suspected metastasis or intrahepatic cholangiocarcinoma. On the 9th postoperative day, bile leaked from her drainage tube forming an abscess cavity; this continued until the 28th postoperative day. We attempted selective anterograde drainage from the cut surface of the liver under fluoroscopic guidance using a guidewire and Cobra-type catheter. We selectively cannulated the entrance hole of the bile duct. Twenty days after the drainage, the abscess cavity disappeared. After 41 days, the tube was removed, and the patient was discharged. We suggest this procedure as a possible treatment option for difficult bile leakage cases.
DISCUSSION: A case of intractable bile leakage after hepatectomy in a patient with a previous history of pancreatoduodenectomy is difficult to manage, and usually needs surgical intervention. The effect of selective cannulation of the entrance hole of the bile duct has not been studied.
CONCLUSION: Selective anterograde bile duct drainage for intractable bile leakage after hepatectomy in a patient with a previous history of pancreatoduodenectomy successfully resolved bile duct leakage in our patient.

PMID: 30716706 [PubMed - as supplied by publisher]

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Tension pneumoperitoneum: Case report of a rare form of acute abdominal compartment syndrome.

Tension pneumoperitoneum: Case report of a rare form of acute abdominal compartment syndrome.

Int J Surg Case Rep. 2019 Jan 29;55:112-116

Authors: Cadena M, Solano J, Caycedo N, Gomez D, Vinck EE, Quiroga P, Gaete P

Abstract
INTRODUCTION: Tension pneumoperitoneum is a severe and rare form of pneumoperitoneum with concomitant hemodynamic instability and respiratory failure. It is a variant of abdominal compartment syndrome (ACS) causing an abrupt increase in intra-abdominal pressure.
PRESENTATION OF CASE: We present a case of pneumoperitoneum, after an endoscopic mucosal resection with the development of ACS. The patient was successfully treated with percutaneous decompression.
DISCUSSION: Decompressive laparotomy is the first treatment option for both most forms of pneumoperitoneum and ACS; nevertheless, this issue is controversial. Recent reports have shown that some patients may be candidates for a minimally invasive catheter decompression avoiding major decompressive surgery. Identifying these patients is vital to avoiding unnecessary surgeries.
CONCLUSIONS: Tension pneumoperitoneum is a life-threatening event, early detection and intervention is critical in order to provide prompt and optimal treatment approaches.

PMID: 30716704 [PubMed - as supplied by publisher]

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New technique for the management of anteriorly located midline prostatic cysts causing severe lower urinary tract symptoms: Case report and literature review.

New technique for the management of anteriorly located midline prostatic cysts causing severe lower urinary tract symptoms: Case report and literature review.

Int J Surg Case Rep. 2019 Jan 29;55:107-111

Authors: Al-Nasser KA, Almannie RM

Abstract
INTRODUCTION: Prostatic cysts are uncommon and usually asymptomatic. In most cases, these cysts are found incidentally by imaging. In some cases, these cysts can be symptomatic and missed for years.
CASE REPORT: We report the case of a 36-year-old male patient presented with a 3-year history of weak urine stream, dysuria, frequency and urgency. Ultrasound, computed tomography and magnetic resonance imaging demonstrated a prostatic cyst measuring 1.5*1.2 cm occupying the bladder outlet and causing obstruction. Transverse incision of the cyst provided a satisfactory resolution of the patient's complaint.
CONCLUSION: Incision of a symptomatic midline anterior prostatic cyst is a safe and effective management option with no potential risk of retrograde ejaculation.

PMID: 30716703 [PubMed - as supplied by publisher]

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Successful surgical management of non-perforating acute appendicitis with septic disseminated intravascular coagulation: A case report and review of the literature.

Successful surgical management of non-perforating acute appendicitis with septic disseminated intravascular coagulation: A case report and review of the literature.

Int J Surg Case Rep. 2019 Jan 29;55:103-106

Authors: Komo T, Kohashi T, Aoki Y, Hihara J, Oishi K, Tokumoto N, Kanou M, Nakashima A, Shimomura M, Miguchi M, Mukaida H, Hirabayashi N

Abstract
INTRODUCTION: Perforating appendicitis and abscess-forming appendicitis may cause septic disseminated intravascular coagulation (DIC). However, non-perforating acute appendicitis with septic DIC is extremely rare.
PRESENTATION OF CASE: A 67-year-old man was referred to our hospital one day after starting oral antibiotic treatment for acute appendicitis. Physical examination revealed only slight spontaneous abdominal pain without tenderness and peritoneal irritation. Contrast-enhanced computed tomography demonstrated an enlarged appendix (10 mm in diameter) without fecalith, ascites, intraperitoneal free air, and abscess. There was no evidence of perforating appendicitis. Laboratory analysis revealed septic DIC. The patient was diagnosed with non-perforating acute appendicitis with septic DIC. The patient was distressed regarding whether he should be treated conservatively with an antibiotics-first strategy or undergo an appendectomy. Ultimately, a laparoscopic appendectomy was performed. Histopathological examination showed non-perforating gangrenous appendicitis. He required DIC therapy for 2 days postoperatively. He was discharged on postoperative day 9, and remained in good health 1 month after surgery.
DISCUSSION: There is no absolute index of conversion to surgery with an antibiotics-first strategy of appendicitis treatment. Judging the limit of conservative treatment and determining the best moment to perform surgery is a critically important matter for patients with acute appendicitis.
CONCLUSIONS: The incidence of conservative treatment preceding an antibiotics-first strategy for acute appendicitis is increasing. However, it is thought that appendectomy should be performed when acute appendicitis is complicated with septic DIC, even if it is a non-perforating appendicitis in which improvement with conservative treatment is anticipated.

PMID: 30716702 [PubMed - as supplied by publisher]

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Brain Vital Signs: Expanding From the Auditory to Visual Modality.

Related Articles

Brain Vital Signs: Expanding From the Auditory to Visual Modality.

Front Neurosci. 2018;12:968

Authors: Pawlowski GM, Ghosh-Hajra S, Fickling SD, Liu CC, Song X, Robinovitch S, Doesburg SM, D'Arcy RCN

Abstract
The critical need for rapid objective, physiological evaluation of brain function at point-of-care has led to the emergence of brain vital signs-a framework encompassing a portable electroencephalography (EEG) and an automated, quick test protocol. This framework enables access to well-established event-related potential (ERP) markers, which are specific to sensory, attention, and cognitive functions in both healthy and patient populations. However, all our applications to-date have used auditory stimulation, which have highlighted application challenges in persons with hearing impairments (e.g., aging, seniors, dementia). Consequently, it has become important to translate brain vital signs into a visual sensory modality. Therefore, the objectives of this study were to: 1) demonstrate the feasibility of visual brain vital signs; and 2) compare and normalize results from visual and auditory brain vital signs. Data were collected from 34 healthy adults (33 ± 13 years) using a 64-channel EEG system. Visual and auditory sequences were kept as comparable as possible to elicit the N100, P300, and N400 responses. Visual brain vital signs were elicited successfully for all three responses across the group (N100: F = 29.8380, p < 0.001; P300: F = 138.8442, p < 0.0001; N400: F = 6.8476, p = 0.01). Initial auditory-visual comparisons across the three components showed attention processing (P300) was found to be the most transferrable across modalities, with no group-level differences and correlated peak amplitudes (rho = 0.7, p = 0.0001) across individuals. Auditory P300 latencies were shorter than visual (p < 0.0001) but normalization and correlation (r = 0.5, p = 0.0033) implied a potential systematic difference across modalities. Reduced auditory N400 amplitudes compared to visual (p = 0.0061) paired with normalization and correlation across individuals (r = 0.6, p = 0.0012), also revealed potential systematic modality differences between reading and listening language comprehension. This study provides an initial understanding of the relationship between the visual and auditory sequences, while importantly establishing a visual sequence within the brain vital signs framework. With both auditory and visual stimulation capabilities available, it is possible to broaden applications across the lifespan.

PMID: 30713487 [PubMed]

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Isolated Pulmonic Valve Endocarditis.

Related Articles

Isolated Pulmonic Valve Endocarditis.

Am J Case Rep. 2019 Feb 04;20:151-153

Authors: Samaroo-Campbell J, Hashmi A, Thawani R, Moskovits M, Zadushlivy D, Kamholz SL

Abstract
BACKGROUND Infective endocarditis (IE) has a high mortality rate, even when treated with appropriate antibiotic therapy and surgical intervention. Right-sided endocarditis is in itself rare, with some studies reporting an incidence of 5-10%. The majority of these cases involve the tricuspid valve, and isolated pulmonary valve endocarditis (PVE) is an extremely rare entity affecting less than 2% of patients with infective endocarditis. Identification and early management are crucial to prevent long-term complications and reduce mortality. CASE REPORT We present a patient with a history of essential hypertension and no underlying valvular disease, who underwent dental cleaning and subsequently developed low-grade fever, myalgia, and malaise. This occurred during the flu season, and was initially diagnosed and treated as flu, without any improvement. The patient was later found to be bacteremic with S. mitis, with no identifiable source, and a normal transthoracic echocardiogram (TTE). He was later hospitalized, had a transesophageal echocardiogram, and was found to have a large pulmonic valve vegetation. CONCLUSIONS This case presents an interesting and rare finding of endocarditis, isolated to the pulmonic valve, in an otherwise healthy individual with no predisposing risk factors. The lack of peripheral stigmata, as well as an unremarkable initial outpatient TTE, made the diagnosis more difficult. It should also be noted that current guidelines do not specifically address right-sided endocarditis, and do not specify the role of surgical intervention.

PMID: 30713335 [PubMed - in process]

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Assessing Cognitive Abilities in High-Performing Cochlear Implant Users.

Related Articles

Assessing Cognitive Abilities in High-Performing Cochlear Implant Users.

Front Neurosci. 2018;12:1056

Authors: Hillyer J, Elkins E, Hazlewood C, Watson SD, Arenberg JG, Parbery-Clark A

Abstract
Despite being considered one of the most successful neural prostheses, cochlear implants (CIs) provide recipients with a wide range of speech perception performance. While some CI users can understand speech in the absence of visual cues, other recipients exhibit more limited speech perception. Cognitive skills have been documented as a contributor to complex auditory processing, such as language understanding; however, there are no normative data for existing standardized clinical tests assessing cognitive abilities in CI users. Here, we assess the impact of modality of presentation (i.e., auditory-visual versus visual) for the administration of working memory tests in high-performing CI users in addition to measuring processing speed, cognitive efficiency and intelligence quotient (IQ). Second, we relate performance on these cognitive measures to clinical CI speech perception outcomes. Methods: Twenty one post-lingually deafened, high-performing, adult CI users [age range: 52-88 years; 3 unilateral CI, 13 bimodal (i.e., CI with contralateral hearing aid), 5 bilateral CI] with clinical speech perception scores (i.e., AzBio sentences in quiet for the first-ear CI) of ≥60% were recruited. A cognitive test battery assessing auditory-visual working memory (AVWM), visual working memory (VWM), processing speed, cognitive efficiency and IQ was administered, in addition to clinical measures of speech perception in quiet (i.e., AzBio sentences in quiet). AzBio sentences were assessed in two conditions: first-ear CI only, and best-aided everyday wearing condition. Subjects also provided self-reported measures of performance and benefit from their CI using standardized materials, including the Glasgow Benefit Inventory (GBI) and the Nijmegen Cochlear Implant questionnaire (NCIQ). Results: High-performing CI users demonstrated greater VWM than AVWM recall. VWM was positively related to AzBio scores when measured in the first-ear CI only. AVWM, processing speed, cognitive efficiency, and IQ did not relate to either measure of speech perception (i.e., first-ear CI or best-aided conditions). Subjects' self-reported benefit as measured by the GBI predicted best-aided CI speech perception performance. Conclusion: In high-performing CI recipients, visual presentation of working memory tests may improve our assessment of cognitive function.

PMID: 30713488 [PubMed]

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Correction: LGR5 regulates gastric adenocarcinoma cell proliferation and invasion via activating Wnt signaling pathway

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Removal efficiency of As(V) and Sb(III) in contaminated neutral drainage by Fe-loaded biochar

Abstract

Performance of raw and two Fe-loaded biochars, produced either by evaporation (E-product, 26.9% Fe) or precipitation (P-product, 12.6% Fe), was evaluated in batch and column testing for As(V) and Sb(III) removal from contaminated neutral drainage (CND). Batch testing results showed that sorption capacity of the E-product tripled for As(V) and quintupled for Sb(III), whereas for the P-product, it doubled for both contaminants, relative to the raw biochar. Moreover, As(V) removal by the E-product reached 90% in less than 8 h, for initial concentrations up to 50 mg/L. In column testing, the E-product efficiently treated the influent [pH 6; 1 mg/L As(V)] for more than 286 days. The pH of the final effluent was within the legally allowed limits (6–9.5) while less than 0.3 mg/L Fe leached out. Based on these findings, Fe-loaded biochar by evaporation (E-product) seems promising for As(V) treatment in CND.

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L-α-Phosphatidylcholine attenuates mercury-induced hepato-renal damage through suppressing oxidative stress and inflammation

Abstract

The potential ameliorative effects of L-α-phosphatidylcholine (PC) against mercuric chloride (HgCl₂)-induced hematological and hepato-renal damage were investigated. Rats were randomly allocated into four groups (n = 12): control, PC (100 mg/kg bwt, intragastrically every other day for 30 consecutive days), HgCl₂ (5 mg/kg bwt, intragastrically daily), and PC plus HgCl₂. Hematological and hepato-renal dysfunctions were evaluated biochemically and histopathologically. Hepatic and renal oxidative/antioxidative indices were evaluated. The expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) was also detected by ELISA. HgCl₂ significantly increased serum aminotransferases (ALT, AST), urea, and creatinine levels that are indicative of hepato-renal damage. HgCl₂ also induced a significant accumulation of malondialdehyde (+ 195%) with depletion of glutathione (− 43%) levels in the liver and renal tissues. The apparent hepato-renal oxidative damage was associated with obvious organ dysfunction that was confirmed by impairments in the liver and kidney histoarchitecture. Furthermore, HgCl₂ significantly attenuated the expression of proinflammatory cytokines named tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Conversely, PC treatment attenuated these effects, which improved the hematological and serum biochemical alternations, reduced the oxidative stress and proinflammatory cytokine levels, and ameliorated the intensity of the histopathological alterations in livers and kidneys of HgCl₂-treated rats. It could be concluded that PC displayed potential anti-inflammatory and antioxidant activities against HgCl₂-induced hepato-renal damage via suppression of proinflammatory cytokines and declining oxidative stress.

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In situ evaluation of the NO x removal efficiency of photocatalytic pavements: statistical analysis of the relevance of exposure time and environmental variables

Abstract

In the recent past, the NO_x removal efficiency of photocatalytic materials has been subject of many studies with promising results. However, many of these studies involve laboratory tests carried out under standardized climatic exposure conditions, often not representative of the real-world environment. With the aim to bridge this gap, selected photocatalytic materials have been applied to different substrates in outdoor demonstrator platforms at pilot scale as part of the project LIFE-PHOTOSCALING. The paper presents the results of in situ measurements of NO_x removal efficiency of the materials, performed during 17 months. Statistical models accounting for the influence of exposure time and relevant environmental variables are derived. They suggest that photocatalytic emulsions on the tested asphalt experience a significant loss of activity over time irrespective of climatic conditions. The efficiency of photocatalytic slurries on asphalt and of concrete tiles, with the photocatalyst applied on surface or in bulk, mainly depends on substrate humidity.

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Synthesis of new derivatives of boehmeriasin A and their biological evaluation in liver cancer.

Synthesis of new derivatives of boehmeriasin A and their biological evaluation in liver cancer.

Eur J Med Chem. 2019 Jan 24;166:243-255

Authors: Güzelcan EA, Baxendale IR, Cetin-Atalay R, Baumann M

Abstract
Two series of boehmeriasin A analogs have been synthesized in short and high yielding processes providing derivatives differing either in the alkaloid's pentacyclic scaffold or its peripheral substitution pattern. These series have enabled, for the first time, comparative studies into key biological properties revealing a new lead compound with exceptionally high activity against liver cancer cell lines in the picomolar range for both well (Huh7, Hep3B and HepG2) and poorly (Mahlavu, FOCUS and SNU475) differentiated cells. The cell death was characterized as apoptosis by cytochrome-C release, PARP protein cleavage and SubG1 cell cycle arrest. Subsequent testing associated apoptosis via oxidative stress with in situ formation of reactive oxygen species (ROS) and altered phospho-protein levels. Compound 19 decreased Akt protein phosphorylation which is crucially involved in liver cancer tumorigenesis. Given its simple synthetic accessibility and intriguing biological properties this new lead compound could address unmet challenges within liver cancer therapy.

PMID: 30716712 [PubMed - as supplied by publisher]

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Loss of Peter Pan protein is associated with cell cycle defects and apoptotic events.

Loss of Peter Pan protein is associated with cell cycle defects and apoptotic events.

Biochim Biophys Acta Mol Cell Res. 2019 Feb 01;:

Authors: Keil M, Meyer MT, Dannheisig DP, Maerz LD, Philipp M, Pfister AS

Abstract
The nucleolus is a subnuclear compartment, which governs ribosome biogenesis. Moreover, it functions as hub in the stress response by orchestrating a variety of processes, such as regulation of cell cycle progression, senescence and apoptosis. Emerging evidence links the nucleolus also to the control of genomic stability and the development of human malignancies. Peter Pan (PPAN) is an essential ribosome biogenesis factor localized to nucleoli and mitochondria. We earlier showed that PPAN depletion triggers p53-independent nucleolar stress and apoptosis. In this study we investigated the precise localization of nucleolar PPAN during cell cycle and its function in cell cycle regulation. We show that PPAN knockdown impairs cell proliferation and induces G0/G1 as well as later G2/M cell cycle arrest in cancer cells. Although PPAN knockdown stabilizes the tumor suppressor p53 and induces CDKN1A/p21, the proliferation defects occur largely in a p53/p21-independent manner. We noticed a reduced number of knockdown cells entering cytokinesis and an elevation of binucleation. PPAN knockdown is also associated with increased H2A.X phosphorylation (γH2A.X) in cancer cells. We evaluated a potential signaling axis through the DNA damage response kinases ATM and ATR and alternatively apoptosis as a potent driver of γH2A.X. Interestingly, PPAN knockdown does not involve activation of ATM/ATR. Instead, γH2A.X is generated as a consequence of apoptosis induction in cancer cells. Strikingly, PPAN depletion in human fibroblasts did neither provoke apoptosis nor H2A.X phosphorylation, but recapitulated p53 stabilization. In summary, our data underline the notion that the PPAN-mediated, p53-independent nucleolar stress response has multiple facets.

PMID: 30716409 [PubMed - as supplied by publisher]

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KLF4 sensitizes the colon cancer cell HCT-15 to cisplatin by altering the expression of HMGB1 and hTERT.

KLF4 sensitizes the colon cancer cell HCT-15 to cisplatin by altering the expression of HMGB1 and hTERT.

Life Sci. 2019 Feb 01;:

Authors: Yadav SS, Kumar M, Varshney A, Yadava PK

Abstract
AIMS: Insensitivity of cancer cells to therapeutic drugs is the most daunting challenge in cancer treatment. The mechanism of developing chemo-resistance is only partly understood to date. In continuation of some earlier reports, we hypothesize that KLF4, a key transcription factors that also has a crucial role in maintaining the stemness in cancer cells, may offer a basis for chemo-resistance.
MAIN METHODS: Sensitivity of cells to cisplatin was analyzed by cell proliferation, colony formation, and cell growth assay. Cell cycle analysis and immunophenotyping were used to measure cell cycle arrest and level of reactive oxygen species respectively. Immunoblotting was used to analyze the change in expression hTERT and HMGB1 involved in KLF4 mediated cisplatin resistance.
KEY FINDINGS: We found that KLF4 expression sensitizes cancer cell to cisplatin cytotoxicity. Further, KLF4 promotes the cisplatin-mediated G2/M cell cycle arrest while KLF4 knocked down induces cisplatin-mediated S-phase arrest compared to control. Decreased level of reactive oxygen species (ROS) in cisplatin-treated and KLF4 knocked down HCT-15 cells compared to vector control, accounting for increased cell survival. Immuno-blotting showed that KLF4 positively regulates expression of the survival proteins hTERT and HMGB1 while in presence of cisplatin, expression of HMGB1 and hTERT is negatively regulated by KLF4.
SIGNIFICANCE: This study suggests the involvement of KLF4-HMGB1/hTERT signaling in offering the basis for chemo-resistance in colon cancer cells and KLF4 overexpression as a probable strategy for sensitizing drug-resistant cancer cells to chemotherapy. The present study opens up new avenues for cancer research and therapeutics.

PMID: 30716337 [PubMed - as supplied by publisher]

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A fluorinated indole-based MDM2 antagonist selectively inhibits the growth of p53wt osteosarcoma cells.

A fluorinated indole-based MDM2 antagonist selectively inhibits the growth of p53wt osteosarcoma cells.

FEBS J. 2019 Feb 04;:

Authors: Skalniak L, Twarda-Clapa A, Neochoritis CG, Surmiak E, Machula M, Wisniewska A, Labuzek B, Ali AM, Krzanik S, Dubin G, Groves M, Dömling A, Holak TA

Abstract
The p53 protein is engaged in the repair of DNA mutations and elimination of heavily damaged cells, providing anti-cancer protection. Dysregulation of p53 activity is a crucial step in carcinogenesis. This dysregulation is often caused by the overexpression of negative regulators of p53, among which MDM2 is the most prominent one. Antagonizing MDM2 with small molecules restores the activity of p53 in p53 wild-type (p53wt ) cells and thus provides positive outcomes in the treatment of p53wt cancers. Previously, we have reported the discovery of a panel of fluoro-substituted indole-based antagonists of MDM2. Here, we demonstrate the biological activity and stereoselectivity of the most active compound from this series. Both enantiomers of the esterified form of the compound, as well as its corresponding carboxylic acids, were found active in fluorescence polarization (FP) assay, nuclear magnetic resonance (NMR) and microscale thermophoresis (MST) assay, with Ki and KD values around 1 μM. From these four compounds, the esterified enantiomer (R)-5a was active in cells, which was evidenced by the increase of p53 levels, the induced expression of p53-target genes (CDKN1A and MDM2), the selective induction of cell cycle arrest and selective growth inhibition of p53wt U-2 OS and SJSA-1 compared to p53del SAOS-2 cells. The analysis of the crystal structure of human MDM2 in complex with the compound (R)-6a (carboxylic acid of the active (R)-5a compound) revealed the classical three-finger binding mode. Altogether, our data demonstrate the activity of the compound and provide the structural basis for further structure optimization. This article is protected by copyright. All rights reserved.

PMID: 30715803 [PubMed - as supplied by publisher]

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Moringa peregrina Leaves Extracts Induce Apoptosis and Cell Cycle Arrest of Hepatocellular Carcinoma.

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Moringa peregrina Leaves Extracts Induce Apoptosis and Cell Cycle Arrest of Hepatocellular Carcinoma.

Biomed Res Int. 2019;2019:2698570

Authors: Mansour M, Mohamed MF, Elhalwagi A, El-Itriby HA, Shawki HH, Abdelhamid IA

Abstract
Moringa grows in the tropical and subtropical regions of the world. The genus Moringa belongs to family Moringaceae. It is found to possess various medicinal uses including hypoglycemic, analgesic, anti-inflammatory, hypolipidemic, and antioxidant activities. In this study, we investigated the antimicrobial and the anticancer activity of the Moringa peregrina as well as Moringa oleifera leaves extracts grown locally in Egypt. Results indicated that most of the extracts were found to possess high antimicrobial activity against gram-positive bacteria, gram-negative bacteria, and fungus. The survival rate of cancer cells was decreased in both hepatocellular carcinoma (HepG2) and breast carcinoma (MCF-7) cell lines when treated with Moringa leaves extracts. In addition, the cell cycle progression, apoptosis, and cancer-related genes confirmed its anticancer effect. The toxicity of each extract was also tested using the normal melanocytes cell line HFB4. The toxicity was low in both Moringa peregrina and Moringa oleifera leaves extracts. Furthermore, GC/MS analysis fractionized the phytochemicals content for each potential extract. In conclusion, results suggested that the Moringa peregrina and Moringa oleifera leaves extracts possess antimicrobial and anticancer properties which could be attributed to the bioactive phytochemical compounds present inside the extracts from this plant. These findings can be used to develop new drugs, especially for liver cancer chemotherapy.

PMID: 30713850 [PubMed - in process]

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EGFR deficiency leads to impaired self-renewal and pluripotency of mouse embryonic stem cells.

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EGFR deficiency leads to impaired self-renewal and pluripotency of mouse embryonic stem cells.

PeerJ. 2019;7:e6314

Authors: Yu M, Wei Y, Xu K, Liu S, Ma L, Pei Y, Hu Y, Liu Z, Zhang X, Wang B, Mu Y, Li K

Abstract
Background: Self-renewal and pluripotency are considered as unwavering features of embryonic stem cells (ESCs). How ESCs regulate the self-renewal and differentiation is a central question in development and regenerative medicine research. Epidermal growth factor receptor (EGFR) was identified as a critical regulator in embryonic development, but its role in the maintenance of ESCs is poorly understood.
Methods: Here, EGFR was disrupted by its specific inhibitor AG1478 in mouse ESCs (mESCs), and its self-renewal and pluripotency were characterized according to their proliferation, expression of pluripotency markers, embryoid body (EB) formation, and mRNA expression patterns. We also used another EGFR inhibitor (gefitinib) and RNA interference assay to rule out the possibility of non-specific effects of AG1478.
Results: EGFR inhibition by AG1478 treatment in mESCs markedly reduced cell proliferation, caused cell cycle arrest at G0/G1 phase, and altered protein expressions of the cell cycle regulatory genes (CDK2 (decreased 11.3%) and proliferating cell nuclear antigen (decreased 25.2%)). The immunoreactivities and protein expression of pluripotency factors (OCT4 (decreased 26.9%)) also dramatically decreased, while the differentiation related genes (GATA4 (increased 1.6-fold)) were up-regulated in mESCs after EGFR inhibition. Meanwhile, EGFR inhibition in mESCs disrupted EB formation, indicating its impaired pluripotency. Additionally, the effects observed by EGFR inhibition with another inhibitor gefitinib and siRNA were consistent with those observed by AG1478 treatment in mESCs. These effects were manifested in the decreased expression of proliferative and pluripotency-related genes and the increased expression of genes involved in differentiation. Moreover, RNA-seq analysis displayed that transcript profiling was changed significantly after EGFR inhibition by AG1478. A large number of differentially expressed genes were involved in cell cycle, apoptotic process, epigenetic modification, and metabolic process, which were related to self-renewal and pluripotency, confirming that EGFR deficiency impaired self-renewal and pluripotency in mESCs.
Conclusions: Taken together, our results demonstrated the importance of EGFR in guarding the stemness of mESCs.

PMID: 30713819 [PubMed]

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Transition metal substituted sandwich-type polyoxometalates with a strong metal-C (imidazole) bond as anticancer agents.

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Transition metal substituted sandwich-type polyoxometalates with a strong metal-C (imidazole) bond as anticancer agents.

Chem Commun (Camb). 2019 Jan 22;55(8):1096-1099

Authors: Zhao H, Tao L, Zhang F, Zhang Y, Liu Y, Xu H, Diao G, Ni L

Abstract
Two novel sandwich-type polyoxometalates {Na0.7M5.3(H2O)2(imi)2(Himi)(SbW9O33)2}6- (M = NiII (1), CoII (2), imi = imidazole) containing a strong M-Cimi bond were synthesized by a tetragonal cluster [Na2Sb8W36O132(H2O)4]22- {Sb8W36} precursor. Compound 1 was highly cytotoxic against gastric cancer cells by arresting the cell cycle in the S-phase and inducing cell apoptosis.

PMID: 30620027 [PubMed - indexed for MEDLINE]

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A new pyrrole based small molecule from Tinospora cordifolia induces apoptosis in MDA-MB-231 breast cancer cells via ROS mediated mitochondrial damage and restoration of p53 activity.

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A new pyrrole based small molecule from Tinospora cordifolia induces apoptosis in MDA-MB-231 breast cancer cells via ROS mediated mitochondrial damage and restoration of p53 activity.

Chem Biol Interact. 2019 Feb 01;299:120-130

Authors: Rashmi KC, Harsha Raj M, Paul M, Girish KS, Salimath BP, Aparna HS

Abstract
Approximately 15% of globally diagnosed breast cancers are designated as triple negative breast cancer (TNBC). In this study, we investigated the effect of the natural compound, Bis(2- ethyl hexyl) 1H-pyrrole-3,4-dicarboxylate (TCCP), purified from Tinospora cordifolia on MDA-MB-231, a TNBC cell line. The pro-apoptotic nature of TCCP on MDA-MB-231 was determined by assessing various apoptotic markers. ROS generation, intracellular calcium, mitochondrial membrane potential (ΔΨm), MPTP, cardiolipin peroxidation and caspase activity were determined fluorometrically. BAX, BCL-2, cytochrome c, caspases, and p53 protein expressions were determined by immunoblotting. Further, the effect of TCCP on DNA and cell death was determined by DNA fragmentation assay, annexin-V staining, and cell cycle analysis. TCCP treatment caused endogenous ROS generation, increase in intracellular calcium and phosphorylation of p53 in a concentration-dependent manner, which was reverted upon pre-treatment with pifithrin-μ. This led to the downstream altered expression of Bcl-2 and Bax proteins, mitochondrial membrane depolarization, MPTP, and cardiolipin peroxidation. TCCP induced cytochrome c release into the cytosol, caspase activation, ultimately resulting in DNA fragmentation. Further, induction of apoptosis and morphological alterations were evident from the phosphatidylserine externalization and increase in sub G1 population. The in vivo Ehrlich ascites tumor (EAT) mouse study revealed the effectiveness of TCCP in reducing the tumor burden and resulted in a ~2 fold increase in mice survival with minimal hepato-renal toxicity. Overall, TCCP was shown to be efficient in inducing ROS and mitochondrial-mediated apoptosis by restoring p53 activity in MDA-MB-231 cells and also induced EAT cell death in vivo thereby inhibiting tumor proliferation.

PMID: 30543781 [PubMed - indexed for MEDLINE]

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Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: Design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents.

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Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: Design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents.

Eur J Med Chem. 2019 Jan 15;162:147-160

Authors: Eldehna WM, Abo-Ashour MF, Nocentini A, El-Haggar RS, Bua S, Bonardi A, Al-Rashood ST, Hassan GS, Gratteri P, Abdel-Aziz HA, Supuran CT

Abstract
Herein we report the design and synthesis of novel N-substituted isatins-SLC-0111 hybrids (6a-f and 9a-l). A structural extension approach was adopted via N-alkylation and N-benzylation of isatin moiety to enhance the tail hydrophobic interactions within the carbonic anhydrase (CA) IX active site. Thereafter, a hybrid pharmacophore approach was utilized via merging the pharmacophoric elements of isatin and SLC-0111 in a single chemical framework. As planned, a substantial improvement of inhibitory profile of the target hybrids (KIs: 4.7-86.1 nM) towards hCA IX in comparison to N-unsubstituted leads IVa-c (KIs: 192-239 nM), was achieved. Molecular docking of the designed hybrids in CA IX active site unveiled, as planned, the ability of N-alkylated and N-benzylated isatin moieties to accommodate in a wide hydrophobic pocket formed by T73, P75, P76, L91, L123 and A128, establishing strong van der Waals interactions. Hybrid 6c displayed good anti-proliferative activity under hypoxic conditions towards breast cancer MDA-MB-231 and MCF-7 cell lines (IC50 = 7.43 ± 0.28 and 12.90 ± 0.34 μM, respectively). Also, 6c disrupted the MDA-MB-231 cell cycle via alteration of the Sub-G1 phase and arrest of G2-M stage. Additionally, 6c displayed significant increase in the percent of annexinV-FITC positive apoptotic cells from 1.03 to 18.54%. Furthermore, 6c displayed potent VEGFR-2 inhibitory activity (IC50 = 260.64 nM). Collectively, these data suggest 6c as a promising lead molecule for the development of effective anticancer agents.

PMID: 30445264 [PubMed - indexed for MEDLINE]

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Polyhydroxybutyrate-co-hydroxyvalerate copolymer modified graphite oxide based 3D scaffold for tissue engineering application.

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Polyhydroxybutyrate-co-hydroxyvalerate copolymer modified graphite oxide based 3D scaffold for tissue engineering application.

Mater Sci Eng C Mater Biol Appl. 2019 Jan 01;94:534-546

Authors: Pramanik N, Bhattacharya S, Rath T, De J, Adhikary A, Basu RK, Kundu PP

Abstract
In this study, we have fabricated the PHBV functionalized graphite oxide using freeze drying technique, followed by 'in situ' pay loading of Fe3O4 nanoparticles onto the hydrophobic plate of the composite basal plane; thereby, mechanically and thermally stable, bio-imaging Fe3O4/GO-g-PHBV composites have been developed. The synthesis of Fe3O4/GO-g-PHBV composite was confirmed by field emission SEM and TEM analyses, X-ray diffraction and Fourier transform infrared spectroscopy. The wrapping of PHBV copolymer into the graphene layers was investigated by atomic force microscopy and Raman spectral analyses which provided the shifting of the 2D band with low signal intensity in the range of 2600-3000 cm-1. The bactericidal activities of the Fe3O4/GO-g-PHBV composite films were found to exhibit more efficiency against Gram-negative bacteria strains compared to Gram-positive strains. In vibrating sample magnetometer (VSM) analysis, the zero value of coercivity revealed the super-paramagnetic nature of the Fe3O4/GO-g-PHBV composites. The Phantom agar magnetic resonance imaging analysis revealed the efficiency of Fe3O4 nanoparticles as a negative contrast (T2 contrast) along with higher relaxivity value. The significant fibroblast cell (NIH 3T3) adhesion and proliferation (85%) on the Fe3O4/GO-g-PHBV composite surface indicated the physiological and biocompatible stability of that composite along with the presence of large π conjugated aromatic domain.

PMID: 30423738 [PubMed - indexed for MEDLINE]

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Radical change of apoptotic strategy following irradiation during later period of embryogenesis in medaka (Oryzias latipes).

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Radical change of apoptotic strategy following irradiation during later period of embryogenesis in medaka (Oryzias latipes).

PLoS One. 2018;13(8):e0201790

Authors: Yasuda T, Ishikawa Y, Shioya N, Itoh K, Kamahori M, Nagata K, Takano Y, Mitani H, Oda S

Abstract
Induction of apoptosis in response to various genotoxic stresses could block transmission of teratogenic mutations to progeny cells. The severity of biological effects following irradiation depends on the stage at which embryos are irradiated during embryogenesis. We reported previously that irradiation of medaka embryos 3 days post fertilization (dpf) with 10 Gy of gamma rays induced high incidence of apoptotic cells in the mid-brain, however, the embryos hatched normally and developed without apparent malformations. To determine the severity of biological effects following irradiation during a later period of embryogenesis, embryos of various developmental stages were irradiated with 15 Gy of gamma rays and examined for apoptotic induction at 24 h after irradiation in the brain, eyes and pharyngeal epithelium tissues, which are actively proliferating and sensitive to irradiation. Embryos irradiated at 3 dpf exhibited many apoptotic cells in these tissues, and all of them died due to severe malformations. In contrast, embryos irradiated at 5 dpf showed no apoptotic cells and subsequently hatched without apparent malformations. Embryos irradiated at 4 dpf had relatively low numbers of apoptotic cells compared to those irradiated at 3 dpf, thereafter most of them died within 1 week of hatching. In adult medaka, apoptotic cells were not found in these tissues following irradiation, suggesting that apoptosis occurs during a restricted time period of medaka embryogenesis throughout the life. No apoptotic cells were found in irradiated intestinal tissue, which is known to be susceptible to radiation damage in mammals, whereas many apoptotic cells were found in proliferating spermatogonial cells in the mature testis following irradiation. Taken together, with the exception of testicular tissue, the results suggest a limited period during medaka embryogenesis in which irradiation-induced apoptosis can occur.

PMID: 30075024 [PubMed - indexed for MEDLINE]

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Design, synthesis and evaluation of novel sophoridinic imine derivatives containing conjugated planar structure as potent anticancer agents.

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Design, synthesis and evaluation of novel sophoridinic imine derivatives containing conjugated planar structure as potent anticancer agents.

Bioorg Med Chem. 2018 08 07;26(14):4136-4144

Authors: Xu Y, Jing D, Chen R, Rashid HU, Jiang J, Liu X, Wang L, Xie P

Abstract
Based on our previous study and the binding mode of camptothecin with Topo I, a series of novel sophoridine imine derivatives containing conjugated planar structure were designed, synthesized and tested for their in vitro anticancer activity. The results showed that most of the derivatives displayed potent activity. In particular, compounds 10b exhibited excellent anti-proliferative activities with IC50 5.7 µM and 8.5 µM against HepG-2 and HeLa cell lines, respectively. Molecular docking studies revealed that the introduction of conjugated planar structure could form π-π stacking interaction with DNA, leading to the improvement of biological activity. Its mode of action was to inhibit the activity of DNA Topo I, followed by the G0/G1 phase arrest. This work provides a theoretical basis for structural optimizations and exploring anticancer pathways of this kind of compound and 10b could emerge as promising lead compounds for the development of novel Topo I inhibitors.

PMID: 30007563 [PubMed - indexed for MEDLINE]

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Cell-Cycle Modulation of Transcription Termination Factor Sen1.

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Cell-Cycle Modulation of Transcription Termination Factor Sen1.

Mol Cell. 2018 04 19;70(2):312-326.e7

Authors: Mischo HE, Chun Y, Harlen KM, Smalec BM, Dhir S, Churchman LS, Buratowski S

Abstract
Many non-coding transcripts (ncRNA) generated by RNA polymerase II in S. cerevisiae are terminated by the Nrd1-Nab3-Sen1 complex. However, Sen1 helicase levels are surprisingly low compared with Nrd1 and Nab3, raising questions regarding how ncRNA can be terminated in an efficient and timely manner. We show that Sen1 levels increase during the S and G2 phases of the cell cycle, leading to increased termination activity of NNS. Overexpression of Sen1 or failure to modulate its abundance by ubiquitin-proteasome-mediated degradation greatly decreases cell fitness. Sen1 toxicity is suppressed by mutations in other termination factors, and NET-seq analysis shows that its overexpression leads to a decrease in ncRNA production and altered mRNA termination. We conclude that Sen1 levels are carefully regulated to prevent aberrant termination. We suggest that ncRNA levels and coding gene transcription termination are modulated by Sen1 to fulfill critical cell cycle-specific functions.

PMID: 29656924 [PubMed - indexed for MEDLINE]

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Cadmium Exposure and Blood Telomere Length in Female University Students in Japan

Abstract

Cadmium is a toxic metal found ubiquitously throughout the world. Our study evaluated whether cadmium exposure was associated with telomere length in 73 female university students. Determination of telomere length was performed by quantitative polymerase chain reaction using DNA in blood. Urinary cadmium concentration was measured by inductively coupled plasma mass spectrometry. The students' physiological attributes and lifestyle were surveyed by means of a self-administered questionnaire. The geometric mean of urinary cadmium concentration was 0.312 μg/g creatinine, which was lower than the levels previously reported for Japan. Urinary cadmium concentration was not significantly associated with telomere length, though the exposure level of the present subjects was similar to that of previous study subjects which found significantly negative associations. It is possible that other factors affected telomere length in this study population.

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Cannabidiol (Epidiolex) for epilepsy.

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Cannabidiol (Epidiolex) for epilepsy.

Med Lett Drugs Ther. 2018 Nov 05;60(1559):182-184

Authors:

Abstract

PMID: 30681657 [PubMed - indexed for MEDLINE]

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