bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Selection by Nonantibiotic Stressors to Sensitize Bacteria to Antibiotics
Authors: Maltas Jeff , Krasnick Brian , Wood Kevin B
Published: December 2019

Evolutionary adaptation of bacteria to nonantibiotic selective forces, such as osmotic stress, has been previously associated with increased antibiotic resistance, but much less is known about potentially sensitizing effects of nonantibiotic stressors. In this study, we use laboratory evolution to investigate adaptation of Enterococcus faecalis, an opportunistic bacterial pathogen, to a broad collection of environmental agents, ranging from antibiotics and biocides to extreme pH and osmotic stress. We find that nonantibiotic selection frequently leads to increased sensitivity to other conditions, including multiple antibiotics. Using population sequencing and whole-genome sequencing of single isolates from the evolved populations, we identify multiple mutations in genes previously linked with resistance to the selecting conditions, including genes corresponding to known drug targets or multidrug efflux systems previously tied to collateral sensitivity. Finally, we hypothesized based on the measured sensitivity profiles that sequential rounds of antibiotic and nonantibiotic selection may lead to hypersensitive populations by harnessing the orthogonal collateral effects of particular pairs of selective forces. To test this hypothesis, we show experimentally that populations evolved to a sequence of linezolid (an oxazolidinone antibiotic) and sodium benzoate (a common preservative) exhibit increased sensitivity to more stressors than adaptation to either condition alone. The results demonstrate how sequential adaptation to drug and nondrug environments can be used to sensitize bacteria to antibiotics and highlight new potential strategies for exploiting shared constraints governing adaptation to diverse environmental challenges.
A novel use of random priming-based single-strand library preparation for whole genome sequencing of formalin-fixed paraffin-embedded tissue samples
Authors: Saunderson Emily A , Baker Ann-Marie , Williams Marc , Curtius Kit , Jones J Louise , Graham Trevor A , Ficz Gabriella
Published: December 2019

The desire to analyse limited amounts of biological material, historic samples and rare cell populations has collectively driven the need for efficient methods for whole genome sequencing (WGS) of limited amounts of poor quality DNA. Most protocols are designed to recover double-stranded DNA (dsDNA) by ligating sequencing adaptors to dsDNA with or without subsequent polymerase chain reaction amplification of the library. While this is sufficient for many applications, limited DNA requires a method that can recover both single-stranded DNA (ssDNA) and dsDNA. Here, we present a WGS library preparation method, called ‘degraded DNA adaptor tagging’ (DDAT), adapted from a protocol designed for whole genome bisulfite sequencing. This method uses two rounds of random primer extension to recover both ssDNA and dsDNA. We show that by using DDAT we can generate WGS data from formalin-fixed paraffin-embedded (FFPE) samples using as little as 2 ng of highly degraded DNA input. Furthermore, DDAT WGS data quality was higher for all FFPE samples tested compared to data produced using a standard WGS library preparation method. Therefore, the DDAT method has potential to unlock WGS data from DNA previously considered impossible to sequence, broadening opportunities to understand the role of genetics in health and disease.
Laser interstitial thermal therapy
Authors: Holste Katherine G , Orringer Daniel A
Published: December 2019

Background

Laser interstitial thermal therapy (LITT) is becoming an increasingly popular technique for the treatment of brain lesions. More minimally invasive that open craniotomy for lesion resection, LITT may be more appropriate for lesions that are harder to access through an open approach, deeper lesions, and for patients who may not tolerate open surgery.

Methods

A search of the current primary literature on LITT for brain lesions on PubMed was performed. These studies were reviewed and updates on the radiological, pathological, and long-term outcomes after LITT for brain metastases, primary brain tumors, and radiation necrosis as well as common complications are included.

Results

Larger extent of ablation and LITT as frontline treatment were potential predictors of favorable progression-free and overall survival for primary brain tumors. In brain metastases, larger extent of ablation was more significantly associated with survival benefit, whereas tumor size was a possible predictor. The most common complications after LITT are transient and permanent weakness, cerebral edema, hemorrhage, seizures, and hyponatremia.

Conclusions

Although the current literature is limited by small sample sizes and primarily retrospective studies, LITT is a safe and effective treatment for brain lesions in the correct patient population.
CBMS-07 SERINE SYNTHESIS AND ONE-CARBON METABOLISM IN GLIOMA CELLS TO SURVIVE GLUTAMINE STARVATION
Authors: Tanaka Kazuhiro , Sasayama Takashi , Uno Takiko , Fujita Yuichi , Hashiguchi Mitsuru , Irino Yasuhiro , Kohmura Eiji
Published: December 2019

Cancer cells optimize nutrient utilization to supply energetic and biosynthetic pathways. These metabolic processes also include redox maintenance and epigenetic regulation through nucleic acid and protein methylation, enhancing tumorigenicity and clinical resistance. But less is known about how cancer cells exhibit metabolic flexibility to sustain cell growth and survival from nutrient starvation. Here, we identify a key role for serine availability and one-carbon metabolism in the survival of glioma cells from glutamine deprivation. To identify metabolic response to glutamine deprivation in glioma cells, we analyzed metabolites using gas chromatography and mass spectroscopy (GC/MS) in glioma cells cultured in glutamine-deprived medium and examined gene expression of key enzymes for one-carbon units using RT-PCR and western blotting methods. These expressions were also confirmed by immunohistochemical staining in glioma clinical samples Metabolome studies indicated serine, cysteine, and methionine as key differentiating amino acids between control and glutamine-deprived groups. Serine synthesis was mediated through autophagy rather than glycolysis. Gene expression analysis identified upregulation of Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) to regulate serine synthesis and one-carbon metabolism. Importantly, suppression of this metabolite impaired glioma cell survival in glutamine deprivation. In human glioma samples. MTHFD2 expressions were highest in poorly nutrient regions around “pseudopalisading necrosis”. Serine-dependent one-carbon metabolism has a key role for glioma cells to survive glutamine starvation. These results may suggest the new therapeutic strategies targeting critical glioma cells adapting the tumor microenvironment.
SPDR-01 INHIBITION OF HOMOLOGOUS RECOMBINATION, PARP INHIBITOR, OR DIANHYDROGALACTITOL OVERCOMES TEMOZOLOMIDE-RESISTANCE IN GLIOMA CELLS
Authors: Ohba Shigeo , Hirose Yuichi
Published: December 2019

Glioblastoma is one of the most aggressive tumors, with 5-year survival rates of less than 10%. The standard therapy for glioblastomas is maximal safe resection, followed by radiation therapy and chemotherapy with temozolomide (TMZ). The poor prognosis is partially contributed to the acquisition of resistance to TMZ and intratumoral heterogeneity. The mechanisms of resistance to TMZ are various due to tumor heterogeneity. TMZ is a DNA-methylating agent, delivering a methyl group to DNA (O6-guanine, N7-guanine and N3-adenine). The primary cytotoxic lesion, O6-methylguanine, mispairs with thymine, leading to futile DNA mismatch repair (MMR), formation of double strand breaks (DSBs) and eventual cell death, when O6-methylguanine DNA methyltransferase (MGMT) is absent. N7-methylguanine and N3-methyladenine are repaired by base excision repair (BER). The object of the study was to reveal the mechanisms of resistance to TMZ and to find the way to overcome the resistance in glioma. Several clones of TMZ-resistant U251 or U87 were obtained and analyzed. Increased homologous recombination (HR) and deficiency of MMR system, not MGMT were revealed to be contributed to the resistance to TMZ. Inhibition of HR resensitized cells with high HR to TMZ, but it could not resensitize cells with deficient MMR. For the cells with deficient MMR, Inhibition of BER by PARP inhibitor was revealed to potentiate the TMZ-induced cytotoxicity. PARP inhibitors also potentiate the cytotoxicity of TMZ to cells with expressed MGMT. Dianhydrogalactitol (DAG) is a bifunctional DNA-targeting agent, forming N7 alkylguanine and inter-strand DNA crosslinks. DAG reduced the proliferation of cells independent of MGMT and MMR, inducing DNA DSBs, G2/M arrest, and apoptosis in TMZ-resistant glioma cells. Inhibition of chk1, or HR could enhance the cytotoxicity of DAG, increasing apoptosis cells. By selecting the appropriate treatments to the types of resistant mechanisms, these new treatments have the potential to improve the prognosis of glioblastoma.
TB-09 MRNA-SEQ FOR PERICYTES FROM IN VITRO BRAIN METASTASIS AND BLOOD-BRAIN BARRIER MODEL
Authors: Ujifuku Kenta , Fujimoto Takashi , Sato Kei , Morofuji Yoichi , Muto Hideki , Masumoto Hiroshi , Nakagawa Shinsuke , Niwa Masami , Matsuo Takayuki
Published: December 2019

BACKGROUND

Metastatic brain tumors associated with poor prognosis and limited treatment options. The blood-brain barrier (BBB) is supposed to play a major role in brain metastasis. However, little is known about the role of pericytes in brain metastasis formation. This study aimed to reveal the expression profile of interaction between pericytes, endothelial cells, and cancer cells.

METHODS

The Institutional review board approved this study. We established an in vitro BBB model with rat primary cultured BBB-related cells (endothelial cells and pericytes) and investigated the gene expression of pericytes under the lung cancer cell’s coculture circumstances. Pericytes showed inhibition of the KNS-62 cell proliferation significantly (p < 0.05). RNA was extracted from the pericytes using miRNeasy mini kit. Complementary DNA library preparation was performed with QuantSeq 3 ‘mRNA-Seq Library Prep Kit. RNA-seq was performed with MiSeq using MiSeq Reagent Kit v3. Sequencing reads were analyzed on the Maser (TopHat2-CuffLinks2-CummeRbund, TopHat2-HTSeq) and TCC-GUI (EdgeR, DESeq, baySeq) platform. Enrichment analysis was performed at Metascape, and the results were analyzed concerning the OMIM and KEGG databases.

RESULT

The RIN value of RNA < 8.0 was confirmed. Data quality was acceptable in Fast QC analysis. In TCC differential expressed gene (DEG) analysis, cluster analysis showed that the influence of pericyte lot difference was stronger than the change between cell lines and control. Therefore, lot-specific DEG analysis was performed; the data were pretreated and re-analyzed to try to identify genes involved in the suppression of cancer cell growth.

DISCUSSION

This study revealed that some expression profiles of brain pericytes implemented in the prevention of metastatic lung cancer cell proliferation in the brain. Pericytes exert an anti-metastatic effect and thus have the potential for the preventive treatment of brain metastasis.
BOT-02 2-METHYLTHIO MODIFICATION OF N6-ISOPENTENYLADENOSINE IN MITOCHONDRIAL TRNAS BY CDK5RAP1 PROMOTES THE MAINTENANCE OF GLIOMA-INITIATING CELLS
Authors: Yamamoto Takahiro , Fujimura Atsushi , Fan-Yan Wei , Kai Keitarou , Takezaki Tatsuya , Ohta Kazutaka , Kuroda Jun-Ichirou , Shinojima Naoki , Tomizawa Kazuhito , Mukasa Akitake
Published: December 2019

2-Methylthio-N6-isopentenyl modification of adenosine (ms2i6A) is an evolutionally conserved modification that is found in mitochondrial (mt)-tRNAs. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) specifically converts N6-isopentenyladenosine (i6A) to ms2i6A at position A37 of four mt-DNA-encoded tRNAs, and the modification regulates efficient mitochondrial translation and energy metabolism in mammals. Here, we report that the ms2 conversion mediated by CDK5RAP1 in mt-tRNAs is required to sustain glioma-initiating cell (GIC)-related traits. CDK5RAP1 maintained the self-renewal capacity, undifferentiated state, and tumorigenic potential of GICs. This regulation was not related to the translational control of mt-proteins. CDK5RAP1 abrogated the antitumor effect of i6A by converting i6A to ms2i6A and protected GICs from excessive autophagy triggered by i6A. The elevated activity of CDK5RAP1 contributed to the amelioration of the cytotoxic effect of i6A and promoted GIC maintenance. The hypoxic microenvironment in the tumor core activated CDK5RAP1, whose activity was inversely correlated with the oxygen concentration because of two [4Fe-4S] clusters in the enzyme. This work demonstrates that CDK5RAP1 is crucial for the detoxification of endogenous i6A and that GICs readily utilize this mechanism for survival.
STMO-10 SURGICAL RESECTION FOR PRIMARY MOTOR CORTEX GLIOMA, TWO CASE REPORTS
Authors: Kijima Noriyuki , Kinoshita Manabu , Hirayama Ryuichi , Umehara Tohru , Yokota Chisato , Kagawa Naoki , Kishima Haruhiko
Published: December 2019

Primary motor cortex glioma is usually considered unresectable because of its high risk for motor deficit. However recent reports suggest that surgical resections for primary motor cortex brain tumor is feasible for selected patients. In this case report, we report two cases we can successfully resected primary motor cortex glioma by awake surgery without neurological worsening.

Case1 was 32 year-old woman with right primary motor cortex oligodendroglioma. We could only perform biopsy at initial surgery, however the patient got worsening of left hemiparesis which were gradually improved by rehabilitation. The patient underwent 50 Gy of radiation therapy and 6 courses of PCV chemotherapy. 60 months after the initial surgery, the tumor recurred and the she underwent 12 courses of temozolomide chemotherapy, but tumor continued to grow. She underwent second surgery 13 years after the initial biopsy. We resected primary motor cortex tumor by awake surgery without neurological complication.

Case2 was 31 year-old woman with left primary motor cortex oligodendroglioma. We could only perform biopsy at initial surgery, however the patient got mild right hemiparesis which were improved by rehabilitation. The patient underwent 4 courses of PAV chemotherapy and 54 Gy of Intensity Modulated Radiation Therapy (IMRT). 21 months after IMRT, the tumor recurred and the she underwent second surgery. We resected primary motor cortex tumor by awake motor mapping without severe neurological complication.

In conclusion, surgical resections for primary motor cortex glioma is feasible in selected patients without severe neurological complication. Neural plasticity is the reason for this, but careful intraoperative awake mapping is necessary to achieve maximum resections.
NI-11 PATHOLOGICAL ASSESSMENT IN THE IMPACT OF ONE-SHOT BEVACIZUMAB ON UPTAKE OF 11C-METHIONINE
Authors: Beppu Takaaki , Sato Yuichi , Ogasawara Kuniaki
Published: December 2019

BACKGROUND

This study aimed to clarify how one-time administration of bevacizumab (BEV) changes histological features in glioblastoma, and how histological changes affect the uptake of 11C-methyl-L-methionine (11C-met) as an amino-acid tracer.

MATERIALS AND METHODS

Subjects were 18 patients with newly diagnosed glioblastoma who were assigned to 2 groups: BEV group, single intravenous administration of BEV before surgical tumor removal; and control group, surgical tumor removal alone. After surgery, we compared the densities of tumor cells and microvessels, and microvascular structures including vascular pericytes and L-type amino acid transporter-1 (LAT1), between the BEV and control groups. Correlations between 11C-met uptake on positron emission tomography before surgery, microvascular density, and LAT1 expression were assessed in each group.

RESULTS

BEV induced significant reductions in microvascular density, while tumor cell density and proliferation were retained in the BEV group. Percentages of vessels with pericytes and vascular endothelium with LAT1 expression were lower in the BEV group than in controls. Uptake of 11C-met correlated significantly with microvascular density in the BEV group, but not with LAT1expression.

CONCLUSIONS

The present study showed that even one course of BEV administration induced reductions in microvessels, vascular pericytes, and LAT1 expression in glioblastomas. One course of BEV therapy also reduced 11C-met uptake, which might have been largely attributed to reductions in microvessels rather than reductions in LAT1 expression, in addition to reduction of vascular permeability.
NI-22 IMPROVED DELINEATION OF THE SUPERFICIAL CEREBRAL VENOUS SYSTEM IN BRAIN CT ANGIOGRAPHY BY ULTRAHIGH-RESOLUTION CT FOR ASSISTING BRAIN TUMOR SURGERY
Authors: Koyanagi Masamichi , Suzuki Mitsuru , Kikuyama Satoshi , Nakanishi Akihito , Gomyou Miho , Machida Haruhiko , Yokoyama Kenichi , Tsuchiya Kazuhiro , Kobayashi Keiichi , Shiokawa Yoshiaki , Nagane Motoo
Published: December 2019

BACKGROUND

In brain CT angiography (CTA) for assisting brain tumor surgery, delineation of the superficial cerebral venous system is critical for selecting the optimal surgical approach. This delineation is, however, limited using conventional CT scanners, including an area-detector CT (ADCT) scanner, due to their insufficient spatial resolution. Since March 2017, a state-of-the-art ultrahigh-resolution CT (UHRCT) scanner has been clinically available to improve in- and through-plane spatial resolution compared with conventional CT scanners, mainly due to smaller slice thickness from 0.5 mm to 0.25 mm, larger channel number from 896 to 1792, and smaller x-ray focus from 0.9 x 0.8 mm to 0.4 x 0.5 mm.PurposeWe assessed usefulness of UHRCT to improve delineation of the superficial cerebral venous system in brain CTA for assisting brain tumor surgery compared with conventional ADCT.

METHODS

We retrospectively enrolled patients with intra- and/or extra-axial brain tumors who underwent preoperative brain CTA for assisting brain tumor surgery by UHRCT or ADCT using our routine technique and generated the CTA to delineate the superficial cerebral venous system using the same technique. Two reviewers by consensus subjectively counted the number of the superficial sylvian veins and the cortical veins draining into these veins and the maximal bifurcation order of the cortical veins draining into the superior sagittal sinus. We compared these numbers and the maximal bifurcation order in the CTA between the UHRCT and ADCT groups using the intraoperative findings as the reference.

RESULTS

The numbers and the maximal bifurcation order in the UHRCT group were significantly greater and more accurate than those in the ADCT group.

CONCLUSIONS

Use of UHRCT can be clinically useful for better delineating the superficial cerebral venous system in brain CTA and assisting brain tumor surgery.
ML-12 MECHANISMS OF CELL DEATH INHIBITION THROUGH CHANGE IN SUBCELLULAR LOCALIZATION OF PIM-1 BY PIM1 GENE MUTATION RECURRENTLY FOUND IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Sasaki Nobuyoshi , Ichimura Koichi , Nagane Motoo , Tomiyama Arata
Published: December 2019

BACKGROUNDS

In a study of Next Generation Sequencing in primary central nervous system lymphoma (PCNSL), we have previously reported several mutations of high frequency, in comparison with systemic diffuse large B cell lymphoma (DLBCL)s. Consequences of these specific mutations in PCNSL are unknown. In this study, we have analyzed the functional consequence of mutations in the PIM1 gene, observed in 100% of PCNSL patients, which encodes a serine/threonine kinase and is known to drive tumorigenesis in several malignancies.

METHODS

Four most frequent mutations of PIM1 in PCNSL, S77N, K115N, P216S, L275F, were chosen from our previous study, and each mutant was generated by site directed mutagenesis in PIM1 cDNA cloned in an expression vector. Resulting vectors were transiently transfected into human cancer cell lines. Functional studies were carried out using various biochemical methods.

RESULTS

Among the four mutants, increased phosphorylation of BCL-2 associated death promoter (BAD) at Ser112, which is a phosphorylation target of Pim-1, was observed by expression of K115N mutant compared with wild type PIM1 in Hela and Nagai cells expressing endogeneous BAD. Decreased cell death under campthothecin treatment was also observed in K115N mutant expressing Nagai cells compared with wild type PIM1-expressed cells. We also observed a significant shift in subcellular localization of Pim-1 carrying K115N mutant; from the nucleus, main sublocalization for wild type Pim-1, into the cytosol determined by immunocytochemistry and immunoblotting of nuclear and cytosolic fraction of the cells. Augmented cytosolic localization of Pim-1 carrying K115N mutant was suppressed by inhibition of glycosylation.

DISCUSSION

It is suggested that PIM1 K115N mutant may drive chemoresistance through increased BAD phosphorylation that suppresses cell death compared with wild-type PIM1 through modification of its subcellular localization, which might be regulated by its glycosylation status.
MET-05 PRELIMINARY REPORT OF RADIOTHERAPY FOR BRAIN METASTASES FROM GASTRO-INTESTINAL CANCERS USING MASK SYSTEM OF LEKSELL GAMMA KNIFE ICON
Authors: Kawabe Takuya , Sato Manabu
Published: December 2019

OBJECT

Leksell Gamma Knife Icon enables us to apply new methods of immobilization using mask fixation and the option of fractionated treatment. This provides exceptional accuracy and precision of radiosurgery, making it a possibility for many more disease types and many more patients to be treated.

METHODS

We retrospectively analyzed 50 patients (71 times) with brain metastases from gastro-intestinal cancers who underwent Gamma Knife Icon using mask fixation between September 25th, 2017 and June 30th, 2019 at Rakusai Shimizu Hospital. Patients with small, few, newly diagnosed, and non-eloquent area tumors were treated in a single session. If the tumor volume was larger than 5.0 ml, recurrence, or the location was in an eloquent area, we applied a fractionated schedule. If the tumor number was large, we selected a multisession schedule. The most common origin was colon (19 patients), followed by rectum (11), stomach (7), esophagus (5) and others (8).

RESULTS

13 cases were treated in a single session, 53 with fractionation, and five with multiple sessions. We selected fractionated schedules as follows; 7.0 Gy x 5Fr (5–10 ml), 4.2Gy x 10Fr (10-20ml), 3.7Gy x 10Fr (20-30ml), 3.2Gy x 10Fr (30ml-) for malignant tumors, and 2.7Gy x 10Fr for benign tumors. Median tumor number was two (1–40) and median tumor size was 8.1 (0.03–67.5) ml. Median survival times after Icon treatment was 13.5 months and local control rate after 6-month Icon treatment was 80%.

CONCLUSIONS

Although these results are limited to short periods, survival rates, local control rates and qualitative survival rated in patients unsuitable for stereotactic radiosurgery, such as those with large, recurrent, and eloquent site lesions, were within the acceptable ranges.
BT-02 MULTIDISCIPLINARY TREATMENT FOR EPENDYMOMA
Authors: Hirokawa Daisuke , Hayashi Tomoko , Sato Hironobu , Keino Dai , Yokosuka Tomoko , Gotou Hiroaki , Yamamoto Tetsuya
Published: December 2019

BACKGROUND

In intracranial ependymoma, the effectiveness of chemotherapy and radiation therapy is unclear, and the degree of tumor removal contributes to the improvement of life prognosis. Methods: We examined ependymoma cases treated in our institution from July 1998 to March 2017.

RESULTS

There were 18 boys and 7 girls. The average age at the time of surgery is 5.3 ± 3.6 years. The pathological diagnosis was Grade II for 8 cases and Grade III for 17 cases. Genetic analysis was performed in 16/25 cases (64%). Of the infratentorial cases, 10/11 cases (90.1%) were PFA and PFB were one case. Of the supratentorial cases, 3/5 cases (60%) were positive for RELA fusion. As chemotherapy, 19 patients were VCR + VP-16 + CDDP + CPA. Irradiation was performed in all cases, local irradiation (50.4–55.8Gy) in 22 cases (88%), and craniospinal irradiation in 2 cases (8%). The 7-year OS was 74.6 ± 9% and the 7-year PFS was 59.7 ± 10.5%. Grade III showed a short OS (p = 0.053). GTR and NTR were obtained in the first excision in 14 cases (56%), and OS and PFS were not significantly different from those in the STR group (p = 0.219, p = 0.248). GTR and NTR including 2nd-look surgery were obtained in 18 cases (72%), and significant improvement of OS was observed compared with STR group (p = 0.02). In patients with hydrocephalus preoperatively, OS tended to be short (p = 0.057), especially in cases requiring VP shunt placement, OS was significantly shortened (p = 0.017).

CONCLUSION

Even if it is not GTR or NTR at the first operation, improvement of OS is expected by total excision after chemotherapy. The importance of chemotherapy was suggested to be suppression of tumor growth until reoperation and reduction of blood loss during surgery.
BT-06 CENTRAL NERVOUS SYSTEM HEMANGIOBLASTOMA; DIFFERENCES IN CLINICAL PICTURE OF SPORADIC CASES AND VON-HIPPEL LINDAU DISEASE IN 184 CASES
Authors: Takami Hirokazu , Burns Terry , Parney Ian
Published: December 2019

INTRODUCTION

Central nervous system hemangioblastoma (CNS HGB) is a rare neoplasm, which predominantly arise in the posterior fossa and spinal cord. The etiology is divided into sporadic and von-Hippel Lindau (VHL) disease. The difference in clinical picture of these 2 types of HGB and differentiation of treatment have not been extensively unraveled yet.

METHODS

Retrospective analysis of consecutive, neurosurgically managed CNS HGB at Mayo Clinic, 1988–2018.

RESULTS

117 sporadic and 67 VHL HGBs were treated by Mayo Clinic. No significant difference in sex was observed. Compared with sporadic cases, VHL cases were younger (51.8 vs 36.0 years old, p<0.0001), had more frequent family history (0.0 vs 41.5 %, p<0.0001), and higher frequency of germline alteration (0.0 vs 84.2 %, p<0.0001). Regarding imaging findings, VHL cases had multiple lesions at presentation more frequently (3.4 vs 82.1 %, p<0.0001), it was more common for sporadic lesions to contain cysts (72.2 vs 51.0 %, p=0.0004), the solid portion rate in the entire lesion was larger in VHL lesions (60.2 vs 69.5 %, p=0.02), and the volume was larger in sporadic cases (15.1 vs 6.6 cc, p<0.0001). Regarding treatment, 131 and 123 surgeries were performed for sporadic and VHL cases, respectively, among which the indication of surgery was preventative in 8.4 and 47.3 %, respectively (p<0.0001). VHL cases had higher number of treatments per case in the follow-up (1.3 vs 2.1, p<0.0001). Recurrence-free survival of sporadic cases was significantly longer than that of VHL cases (p=0.007) and overall survival was longer in sporadic cases than VHL, but not significant (p=0.07).

CONCLUSION

Clinical presentation and tumor appearance on imaging are highly dependent on the etiology. Differences in clinical manifestations require further study, but may reflect contrasting tumor biology that are tied to genetic differences.
CS-08 A CASE OF CD 57 NEGATIVE OLFACTORY GROOVE SCHWANNOMA IN WHICH SCHWANN / 2 E AND SOX10 WAS USEFUL FOR DISTINGUISHING FROM OEC TUMOR: A CASE REPORT AND REVIEW OF THE LITERATURES
Authors: Masuda Hiroyuki , Nemoto Masaaki , Matsuzaki Ryo , Matsura Chie , Terazono Sayaka , Mikai Masataka , Ando Shumpei , Harada Masasi , Kondo Kosuke , Harada Naoyuki , Sugo Nobuo
Published: December 2019

INTRODUCTION

In the case of the differentiate between olfactory groove schwannomas(OGS) and olfactory ensheathing cell (OEC) tumors, CD57 which is the marker which is specific for Schwann cell is useful. We experienced a case of OGS that was negative for CD57.

CASE PRESENTATION

This case was a 13-year-old girl. Medical history: She visited the pediatric department with a chief complaint of headache. On the magnetic resonance image (MRI), a tumorous lesion was found in the anterior skull base and was referred to our department. No dysosmia, visual impairment, or cafe au lait spots were observed. Past history: As a medical history, she has developed acute lymphocytic leukemia at the age of 1 and has achieved complete remission after chemotherapy. At that time, radiation treatment to the head was not performed. Neuroradiological findings: The tumor was strongly enhanced heterogeneously in Gadolinium (Gd) enhanced MRI and the angiography showed hypovascular. Progress after hospitalization: The tumor was clearly demarcated from the surrounding brain surface and adhered strongly to the cribriform plate. Eventually, all tumors were removed and the patient was discharged on the 10th postoperative day. Five years have passed since the operation, and no recurrence of the tumor has been confirmed by MRI. Pathological findings: Antoni A and Antoni B were seen by Hematoxylin & Eosin (H & E) staining. Immunostaining showed S-100 strong positive, Schwann / 2E and Sox10 positive, and CD57 negative. Discussion: In our case, CD57 (Leu7) was negative, but Schwann / 2E and Sox10 were positive, so OGS was diagnosed.

CONCLUSION

We experienced a case of OGS that was negative for CD57 (Leu7) but positive for Schwann / 2E and Sox10. For pathological differentiation between OGS and the OEC tumor, Schwann / 2E and Sox10 immunostaining would also be necessary in addition to H & E stain and CD57 (Leu7).
COT-20 PERIOPERATIVE STATUS OF SERUM D-DIMER LEVEL AND VENOUS THROMBOSIS IN PATIENTS WITH MALIGNANT BRAIN TUMOR
Authors: Shimada Daisuke , Kobayashi Keiichi , Saito Kuniaki , Matsumoto Yoshie , Iijima Shohei , Shiokawa Yoshiaki , Nagane Motoo
Published: December 2019

BACKGROUNDS

The patients with malignant brain tumors frequently show the hypercoagulability state and a decrease in fibrinolysis ability with an elevation in D-dimer. This is partially due to tumor-related hemiparesis or surgical stress including long-term bed-ridden positioning during and after operation,which could lead to development and extension of deep venous thrombosis (DVT) in lower extremities and eventually fatal pulmonary embolism.

METHODS

We retrospectively examined the pre- and postoperative serum D-dimer levels and DVT state in 75 consecutive patients with malignant brain tumors (i.e. glioma,malignant lymphoma; mean age 64 yo,28 females) operated at our hospital from January 2015 to April 2017. Serial D-dimer levels were measured with the latex agglutination method (Roche) at 2 days before and right after operation,postoperative day (POD) 1,3,and 7. Lower limb venous ultrasound (LVUS) or contrast CT was performed if preoperative D-dimer was 0.5μg/ml or higher.

RESULTS

Average BMI was 21.3,nine patients with diabetes mellitus,10 had recurrent diseases after chemotherapy,and 10 presented paresis in the lower extremities preoperatively while two developed transient paresis postoperatively. While two patients had prior DVT history,central and calf DVTs were identified preoperatively in one and 12 (15%) patients,respectively. Among four patients with re-elevation of D-dimer after POD 7,infection (2 patients),new DVT (2),and hemorrhagic events (gastrointestinal 2,including 1 death; epistaxis 2) developed,where a cut-off value D-dimer > 1.69 yielded sensitivity 100% and specificity 80%. Intraoperative intermittent calf compression prevented perioperative pulmonary embolism in those with calf DVT.

CONCLUSIONS

Appropriate perioperative DVT managements could prevent development of pulmonary embolisms in all patients with”high-risk” malignant brain tumors. Not only D-dimer > 1.5,but age of 80 or older,high preoperative D-dimer levels with calf DVT and taking DOAC may be risk factors for postoperative venous thromboembolism.
Nitrogen Fertilization Reduces Nitrogen Fixation Activity of Diverse Diazotrophs in Switchgrass Roots
Authors: Bahulikar Rahul A. , Chaluvadi Srinivasa R. , Torres-Jerez Ivone , Mosali Jagadish , Bennetzen Jeffrey L. , Udvardi Michael
Published: December 2019

The use of synthetic nitrogen fertilizers to grow biofuel crops adds to the economic and environmental costs of biomass production. Biological nitrogen fixation provides an alternative, eco-friendly source of nitrogen for leguminous plants and some nonlegumes. With the objective of characterizing and eventually harnessing nitrogen-fixing bacteria in switchgrass roots, we assayed nitrogenase activity and surveyed nifH-expressing bacteria in roots of switchgrass grown under agricultural conditions. Plants were cultivated at two separate locations in Oklahoma in different soil types for 5 years with three nitrogen fertilizer regimes (0, 90, and 180 kg of N ha−1 year−1). Nitrogenase activity associated with roots cleaned of soil was found to be highest in plants grown with no N fertilizer and lowest or not detectable for plants grown at the highest level of N fertilizer. A total of 454 abundant nifH operational taxonomic units (OTUs) were identified in the switchgrass roots. Diversity analysis of active nifH-expressing bacteria showed that the most common orders were Burkholderiales (171 OTUs), Desulfovibrionales (55 OTUs), and Rhizobiales (44 OTUs). OTUs belonging to Azonexus, Pseudacidovorax, Desulfovibrio, Dechloromonas, and Bradyrhizobium were enriched in roots of plants grown under low nitrogen conditions. Analysis of significant OTUs showed distinct nifH-expressing microbial communities at the two field locations, as well as a unique community in roots of unfertilized soil at Frederick that exhibited the highest rates of nitrogen fixation.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Efficacy of Ethaboxam as a Soybean Seed Treatment Toward Phytophthora, Phytopythium, and Pythium in Ohio
Authors: Scott Kelsey , Eyre Meredith , McDuffee Dair , Dorrance Anne E.
Published: December 2019

Phytophthora, Phytopythium, and Pythium species that cause early-season seed decay and pre-emergence and post-emergence damping off of soybean are most commonly managed with seed treatments. The phenylamide fungicides metalaxyl and mefenoxam, and ethaboxam are effective toward some but not all species. The primary objective of this study was to evaluate the efficacy of ethaboxam in fungicide mixtures and compare those with other fungicides as seed treatments to protect soybean against Pythium, Phytopythium, and Phytophthora species in both high-disease field environments and laboratory seed plate assays. The second objective was to evaluate these seed treatment mixtures on cultivars that have varying levels and combinations of resistance to these soilborne pathogens. Five of eight environments received adequate precipitation in the 14 days after planting for high levels of seedling disease development and treatment evaluations. Three environments had significantly greater stands, and three had significantly greater yield when ethaboxam was used in the seed treatment mixture compared with treatments containing metalaxyl or mefenoxam alone. Three fungicide formulations significantly reduced disease severity compared with nontreated in the seed plate assay for 17 species. However, the combination of ethaboxam plus metalaxyl in a mixture was more effective than either fungicide alone against some Pythium and Phytopythium species. Overall, our results indicate that the addition of ethaboxam to a fungicide seed treatment is effective in reducing seed rot caused by these pathogens commonly isolated from soybean in Ohio but that these effects can be masked when cultivars with resistance are planted.
Intensive Care Neonates and Evidence to Support the Elimination of Hats for Safe Sleep
Authors: Fulmer Megan , Zachritz Whitney , Posencheg Michael A.
Published: December 2019

Background:

Although the incidence of sudden unexplained infant deaths has decreased over time with the use of safe sleep practices, one area that remains unclear is the safety of hats during infant sleep.

Purpose:

Decrease the risk of overheating or suffocation by removing NICU infants' hats during sleep without increasing the relative risk of hypothermia during transition to an open crib.

Methods:

Removal of hats for routine thermoregulation, beyond the initial infant resuscitation and stabilization of NICU infant was implemented in 2015. Retrospective chart audits were conducted on all NICU infants between February 2015 and December 2016. Hypothermia (≤ 97.6°F) data during transition to an open crib was collected. Exclusion criteria included concurrent diagnosis of: sepsis, hyperbilirubinemia, congenital anomaly inhibiting infants thermoregulation and noncompliance with unit guideline for weaning infant to open crib.

Findings:

Over 18 months, 2.7% of infants became hypothermic (≤ 97.6°F) during transition to open crib, requiring return to isolettes.

Implications for Practice:

Hats were found to be unnecessary in maintaining thermoneutrality after weaning infants toan open crib in our NICU. By avoiding the use of hats in an open crib, it's possible infants will avoid overheating and a risk of suffocation, creating a safer sleep environment.

Implications for Research:

The removal of hats during sleep to promote infant health should be considered for all infants.
Debates in gout management
Authors: Abhishek Abhishek
Published: December 2019

Purpose of review

This review discusses the findings of recently published translational research studies that have the potential to directly impact on the management of gout patients.

Recent findings

Recent research suggests that treat-to-target urate-lowering treatment (ULT) alongside individualized education about gout, and shared decision making results in excellent adherence with ULT and prevents gout flares in the long term. Such interventions should preferentially be delivered face-to-face rather than remotely. The recently published CARES study raises the possibility that febuxostat increases the risk of death in people with preexisting major cardiovascular diseases, and, allopurinol should remain the first-choice ULT. There is paucity of data on the dosing of ULT for managing hyperuricaemia in gout patients with chronic kidney disease. However, recent research suggests that the dose of allopurinol can be gradually increased to above the conventional renal dose in people with chronic kidney disease without allopurinol hypersensitivity syndrome. However, additional larger studies are needed in this field.

In summary, long-term treat-to-target ULT prevents gout flares and improves quality of life. Given the recent safety concerns, gradually up-titrated allopurinol remains the first-line urate-lowering drug.
Should Thoracolumbar Junction Be Always Avoided as Upper Instrumented Vertebra in Long Instrumented Fusion for Adult Spinal Deformity?
Authors: Park Se-Jun , Lee Chong-Suh , Park Jin-Sung , Lee Kyung-Jun
Published: December 2019

Study Design.

Retrospective study.

Objective.

The aim of this study was to investigate the risk factors for proximal junctional failure (PJF) following long instrumented fusion stopping at thoracolumbar junction (TLJ) in adult spinal deformity (ASD) and to determine which cases are suitable for TLJ stop without increasing the risk for PJF.

Summary of Background Data.

PJF following long fusion for ASD is a well-recognized complication that negatively affects clinical outcomes. Generally, the uppermost instrumented vertebra (UIV) at the TLJ is associated with the risk of PJF. Little is known about the risk factors for PJF in case with the UIV at TLJ.

Methods.

Radiographic and clinical data of 63 consecutive patients who underwent instrumented fusion from sacrum to TLJ (T11, T12, and L1) for the treatment of ASD with a minimum 2-year follow-up were analyzed to identify the risk factors for PJF, which was defined as proximal junctional angle (PJA) ≥20°, fracture at UIV or UIV+1, failure of UIV fixation, myelopathy, or ‘need for proximal extension of fusion.

Results.

During the average follow-up duration of 51.7 months, PJF developed in 23 patients (36.5%) at a mean of 9.3 months after surgery. Multivariate analysis revealed that age >70 years (odds ratio [OR]: 1.119), osteoporosis (OR: 4.459), and preoperative kyphotic PJA (OR: 1.138) were significant risk factors for the development of PJF. No PJF occurred in 14 patients lacking any risk factors. The last follow-up clinical results were significantly inferior in the PJF group than in the non-PJF group in terms of Oswestry Disability Index and Scoliosis Research Society-22 score.

Conclusion.

Age >70 years, osteoporosis, and PJA greater 0° were identified as significant risk factors for PJF. Therefore, the TLJ level can be considered as UIV selectively for patients younger than 70 years without osteoporosis and with lordotic preoperative PJA.

Level of Evidence: 3
Utilizing 2.0 mm Plates as a Supplemental Fixation Aid: A Technique For Complex Fractures
Authors: Telgheder Zachary L. , Sullivan Matthew P.
Published: December 2019

Direct reduction and rigid fixation of periarticular fractures such as those about the distal humerus present unique challenges to the orthopedic surgeon. Obtaining reduction of fracture fragments with conventional methods such as reduction forceps and Kirschner wires may obscure visualization, impede further reduction, and compromise placement of rigid implants. The use of the 2.0 mm mini-fragment nonlocking plate, a commonly available implant produced by several manufacturers, is presented as a method to address these challenges. Early clinical results from our series demonstrate the clinical utility of this technique.
DIABETIC MACULAR ISCHEMIA
Authors: Tsai Andrew S. H. , Gan Alfred T. L. , Ting Daniel S. W. , Wong Chee Wai , Teo Kelvin Y. C. , Tan Anna C. S. , Lee Shu Yen , Wong Tien Yin , Tan Gavin S. W. , Gemmy Cheung Chui Ming
Published: December 2019

Purpose:

To examine the relationship between macular microvasculature parameters and functional changes in persons with diabetic retinopathy (DR).

Methods:

Cross-sectional study of 76 eyes with varying levels of DR. Optical coherence tomography angiography (OCTA) quantified superficial and deep perifoveal vessel densities and foveal avascular zone areas. Retinal sensitivity was measured using microperimetry. Optical coherence tomography angiography parameters and retinal sensitivity were correlated.

Results:

Deep perifoveal vessel density decreased with increasing severity of DR (adjusted mean 51.93 vs. 49.89 vs. 47.96, P-trend = 0.005). Superficial and deep foveal avascular zone area increased with increasing DR severity (adjusted mean: 235.0 µm2 vs. 303.4 µm2 vs. 400.9 µm2, P-trend = 0.003 [superficial]; 333.1 µm2 vs. 513.3 µm2 vs. 530.2 µm2, P-trend = 0.001 [deep]). Retinal sensitivity decreased with increasing DR severity (adjusted mean: 25.12 dB vs. 22.34 dB vs. 20.67 dB, P-trend = 0.003). Retinal sensitivity correlated positively with deep perifoveal vessel density (Pearson's ρ = 0.276, P = 0.020) and inversely with superficial foveal avascular zone area (Pearson's ρ = −0.333, P = 0.010).

Conclusion:

Alterations in retinal microvasculature can be observed with OCTA with increasing severity of DR. These changes are correlated with reduced retinal sensitivity. Optical coherence tomography angiography is useful to detect and quantify the microvasculature properties of eyes with diabetic macular ischemia.
OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS AND VISUAL PROGNOSIS IN TWO PATIENTS WITH POSTERIOR MICROPHTHALMOS
Authors: Pineles Stacy L. , Davila-Gonzalez Juan P. , Gorin Michael , Lee Hane , Sarraf David , Velez Federico G.
Published: December 2019

Background/Purpose:

Posterior microphthalmos is a rare ocular condition characterized by a disproportionately small posterior segment and multiple retinal abnormalities. The diagnosis can be challenging, and novel findings on optical coherence tomography (OCT) angiography may help to identify this unusual disorder. The purpose of this study is to report OCT and OCT angiography findings in two siblings with posterior microphthalmos.

Methods:

Case series at an academic eye institute including two affected siblings with posterior microphthalmos.

Results:

The results of OCT testing in two siblings with posterior microphthalmos illustrated bilateral papillomacular retinal fold and loss of the foveal depression. Optical coherence tomography angiography findings included loss of the foveal avascular zone and complete vascularization across the fovea.

Conclusion:

Unique OCT angiography findings in posterior microphthalmos are described herein. These findings may support the diagnosis of posterior microphthalmos and aid in the understanding of the pathogenesis of this disease.
Home Use Medical Devices
Authors: Waheed Saphia
Published: December 2019

More than 7 million people in the United States each year receive healthcare in the home setting from a wide variety of devices, from relatively simple devices such as urine collector bags to complex infusion pumps. As more patients require the use of home use medical devices, the devices being used in the home are also increasing in complexity, creating a greater opportunity for adverse events. In addition, the uncontrolled, often unsupervised environment of home use medical devices comes with its own safety considerations. Clinical engineers and healthcare technology managers play an important role in identifying problems with home use medical devices, particularly when patients bring their devices from the home to the hospital with them that can be reported to the device manufacturer and US Food and Drug Administration (FDA). Detecting and reporting these problems will allow the hospital, FDA, and device manufacturer to work together to address device problems. The following analysis of MedSun reports involving home healthcare devices determines the most common home use medical devices that are reported on, as well as the most common types of failure modes for these devices and implications of such failures. When these failures are assessed and reported to the FDA, the FDA can work with the clinical community and device manufacturers to promote the safety and effectiveness of home use medical devices and the patients they serve.
Prognosis of Incomplete Avulsion of the Proximal Hamstring Tendon Is Determined by the Avulsion Location of the Proximal Hamstring Tendon Footprint
Authors: Saito Masayoshi , Niga Sadao , Suzuki Kaoru , Ikezawa Yuji , Tsukada Sachiyuki
Published: December 2019

Objective:

To test the hypothesis that prognosis of incomplete avulsion of the proximal hamstring tendon would be worse whether avulsion location reached the proximal part of the conjoined tendon (CJ) footprint or not.

Design:

Retrospective chart review.

Setting:

Outpatient specialty clinic.

Patients:

We reviewed 345 consecutive athletes with hamstring injury.

Interventions:

Based on magnetic resonance imaging, incomplete avulsion of the proximal hamstring tendon was divided into 2 cases according to avulsion location without (cases A) or with (cases B) avulsion of the proximal part of the CJ footprint.

Outcome Measures:

We compared the time until return to play, subjective outcomes, and success rate of avoiding surgery between cases.

Results:

Incomplete avulsion of the proximal hamstring tendon was detected in 47 athletes (13.6%). Thirty-four athletes were classified as cases A, and 13 as cases B. Forty-two athletes (89.4%) were followed up until return to play. The median time from pain onset to return to play was significantly longer in cases B than in cases A (B, 39.3 weeks; A, 8.0 weeks; P = 0.00015). Subjective outcomes at return to play were significantly poorer in cases B than in cases A (P = 0.00054). Success rate of avoiding surgery were significantly poorer in cases B (55%) than in cases A (100%) (P = 0.00062).

Conclusions:

Incomplete avulsion of the proximal hamstring tendon was observed in 13.6% of hamstring injuries. Return to play, subjective outcomes, and success rate of avoiding surgery were significantly poorer with avulsion of the proximal part of the CJ footprint.