Intracranial pial arteriovenous fistula in infancy: a case report and literature review.

Intracranial pial arteriovenous fistulas (AVF) are rare vascular malformation especially in the first 2 years of life. The pathology in this age group is associated with greater morbidity and mortality. We report a rare case of 36-day-old male infant with a pial AVF associated with an arterial aneurysm, who presented with intraventricular hemorrhage and hydrocephalus. In addition, an online review of the literatures on pediatric pial AVF was performed using PubMed on published case reports and articles from 1980 to April 2013.

Lethal intratumoral haemorrhages of brain metastases during radiosurgery: case reports and literature review.

Gamma Knife surgery (GKS) is an effective and important treatment modality in the management of brain metastases. The short-term complication rate is low and the tumour control rate high. Complications caused by acute radiation-induced oedema are rare and usually benign. In this article, two cases of lethal haemorrhagic event immediately following GKS are described from two centres, which had prompted us to review the literature.

Repurposing the FDA-approved anthelmintic pyrvinium pamoate for pancreatic cancer treatment: study protocol for a phase I clinical trial in early-stage pancreatic ductal adenocarcinoma.

BACKGROUND: Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we report about an ongoing phase I open-label, single-arm, dose escalation clinical trial to determine the safety and tolerability of PP in PDAC surgical candidates. METHODS AND ANALYSIS: In a 3+3 dose design, PP is initiated 3 days prior to surgery. The first three patients will be treated with the initial dose of PP at 5 mg/kg orally for 3 days prior to surgery. Dose doubling will be continued to a reach a maximum of 20 mg/kg orally for 3 days, if the previous two dosages (5 mg/kg and 10 mg/kg) were tolerated. Dose-limiting toxicity grade≥3 is used as the primary endpoint. The pharmacokinetic and pharmacodynamic (PK/PD) profile of PP and bioavailability in humans will be used as the secondary objective. Each participant will be monitored weekly for a total of 30 days from the final dose of PP for any side effects. The purpose of this clinical trial is to examine whether PP is safe and tolerable in patients with pancreatic cancer, as well as assess the drug's PK/PD profile in plasma and fatty tissue. Potential implications include the utilisation of PP in a synergistic manner with chemotherapeutics for the treatment of pancreatic cancer. ETHICS AND DISSEMINATION: This study was approved by the Thomas Jefferson Institutional Review Board. The protocol number for this study is 20F.041 (Version 3.1 as of 27 October 2021). The data collected and analysed from this study will be used to present at local and national conferences, as well as, written into peer-reviewed manuscript publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05055323.

Simultaneous cardio-cerebral infarction: a meta-analysis.

BACKGROUND/INTRODUCTION: Cardio-cerebral infarction (CCI), which involves the simultaneous occurrence of acute ischaemic stroke and acute myocardial infarction, has a reported incidence of 0.0009%. Treatment of CCI presents a dilemma to physicians as both conditions are time critical. Despite the need for standardized treatment protocols, published data are sparse. AIM: We aimed to summarize the reported cardio-cerebral infarction cases in the literature. DESIGN: Meta-analysis. METHODS: Four databases, Pubmed, Embase, Scopus and Google Scholar were searched until 25 August 2020. A title and abstract sieve, full-text review and extraction of data were conducted independently by three authors. RESULTS: A total of 44 cases of CCI were identified from 37 case reports and series; 15 patients (34.1%) were treated using percutaneous coronary intervention (PCI) with stent, 8 patients (18.2%) were treated with a PCI without stent, 10 patients (22.7%) were treated via a cerebral vessel thrombectomy and 8 patients (18.2%) were treated via a thrombectomy of a coronary vessel. For medications, 20 patients (45.5%) were treated with thrombolytics, 10 patients (22.7%) were treated with anticoagulants, 8 patients (18.2%) were treated with antiplatelets and 11 patients (25.0%) were treated with anticoagulants and antiplatelets. Of 44 patients, 10 patients died, and 9 of those were due to cardiac causes. Among the 44 patients, days to death was observed to be a median of 2.0 days (interquartile range (IQR): 1.5, 4.0). The modified Rankin Score was measured in nine patients, with a median score of 2.0 (IQR: 1.0, 2.5) being reported. DISCUSSION/CONCLUSION: The condition of CCI has substantial morbidity and mortality, and further studies are needed to examine the optimal diagnostic and treatment strategies of these patients.

Utilisation of emergency medical service among Singapore patients presenting with ST-segment elevation myocardial infarction: prevalence and impact on ischaemic time.

BACKGROUND: Previous studies in Western countries found that the emergency medical service (EMS) was under-used in patients with myocardial infarction. AIM: We sought to determine the prevalence of immediate EMS utilisation among Singapore patients presenting with ST-segment elevation myocardial infarction (STEMI), and correlated the use of the EMS with the symptom-to-balloon and door-to-balloon times. METHODS: We studied 252 patients admitted with STEMI to our institution from August 2008 to September 2009. Information regarding demographic characteristics, whether EMS was used, reperfusion procedural details and mortality rates were collected prospectively. RESULTS: Among the recruited patients, 89 (35.3%) used the EMS (EMS group) and 163 (64.7%) did not use the EMS (non-EMS group). In the latter group, 98 (60.1%) arrived at our institution through their own transport, 56 (34.4%) first consulted general practitioners, and 9 (5.5%) initially consulted another hospital without acute medical services. Among the 245 (out of 252, 97.2%) patients who received percutaneous coronary intervention (PCI), the EMS group was more likely to undergo primary PCI (P= 0.003) while the non-EMS group was more likely to undergo non-urgent PCI (P= 0.002). In patients who underwent primary PCI, the EMS group had a shorter symptom-to-balloon time (average difference 81.6 min, P= 0.002). The door-to-balloon time was similar for both groups. CONCLUSION: Despite the availability of a centralised EMS, 64.7% of patients with STEMI did not contact EMS at presentation. These patients were less likely to receive primary PCI and had a significantly longer symptom-to-balloon time.

Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing.

Persistent microvascular hyperpermeability to plasma proteins even after the cessation of injury is a characteristic but poorly understood feature of normal wound healing. It results in extravasation of fibrinogen that clots to form fibrin, which serves as a provisional matrix and promotes angiogenesis and scar formation. We present evidence indicating that vascular permeability factor (VPF; also known as vascular endothelial growth factor) may be responsible for the hyperpermeable state, as well as the angiogenesis, that are characteristic of healing wounds. Hyperpermeable blood vessels were identified in healing split-thickness guinea pig and rat punch biopsy skin wounds by their capacity to extravasate circulating macromolecular tracers (colloidal carbon, fluoresceinated dextran). Vascular permeability was maximal at 2-3 d, but persisted as late as 7 d after wounding. Leaky vessels were found initially at the wound edges and later in the subepidermal granulation tissue as keratinocytes migrated to cover the denuded wound surface. Angiogenesis was also prominent within this 7-d interval. In situ hybridization revealed that greatly increased amounts of VPF mRNA were expressed by keratinocytes, initially those at the wound edge, and, at later intervals, keratinocytes that migrated to cover the wound surface; occasional mononuclear cells also expressed VPF mRNA. Secreted VPF was detected by immunofluoroassay of medium from cultured human keratinocytes. These data identify keratinocytes as an important source of VPF gene transcript and protein, correlate VPF expression with persistent vascular hyperpermeability and angiogenesis, and suggest that VPF is an important cytokine in wound healing.

Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue.

Vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), is a potent microvascular permeability enhancing cytokine and a selective mitogen for endothelial cells. It has been implicated in tumor angiogenesis and ascites fluid accumulation. Since development of the destructive synovial pannus in rheumatoid arthritis (RA) is associated with changes in vascular permeability (synovial fluid accumulation), synovial cell hyperplasia, and angiogenesis, we examined synovial fluids (SFs) and joint tissue for the expression and local accumulation of VPF/VEGF. VPF/VEGF was detected in all of 21 synovial fluids examined and when measured by an immunofluorimetric assay, ranged from 6.9 to 180.5 pM. These levels are biologically significant, since < 1 pM VPF/VEGF can elicit responses from its target cells, endothelial cells. Levels of VPF/VEGF were highest in rheumatoid arthritis fluids (n = 10), with a mean value (+/- SEM) of 59.1 +/- 18.0 pM, vs. 21.4 +/- 2.3 pM for 11 SFs from patients with other forms of arthritis (p = 0.042). In situ hybridization studies that were performed on joint tissues from patients with active RA revealed that synovial lining macrophages strongly expressed VPF/VEGF mRNA, and that microvascular endothelial cells of nearby blood vessels strongly expressed mRNA for the VPF/VEGF receptors, flt-1 and KDR. Immunohistochemistry performed on inflamed rheumatoid synovial tissue revealed that the VPF/VEGF peptide was localized to macrophages within inflamed synovium, as well as to microvascular endothelium, its putative target in the tissue. Together, these findings indicate that VPF/VEGF may have an important role in the pathogenesis of RA.

Incinerator bottom ash derived from municipal solid waste as a potential catalytic support for biomass tar reforming.

Environment-friendly and sustainable routes for municipal solid waste (MSW) incineration bottom ash (IBA) recycling and utilization is one of the major concerns for the urbanized countries like Singapore. In this research paper, the possibility of bulk utilization of MSW-IBA as a catalyst support material has been explored for sustainable syn-gas production. The change in the texture of the IBA with simple hydrothermal treatment using NaOH has also been investigated. Furthermore, with hydrothermal treatment for 24 h at 180 °C, the texture of raw IBA with respect to basicity, surface area, total pore volume and reducibility was greatly improved. These textural properties are highly significant for a material to be utilized as a catalyst or catalytic supports for reforming applications. Ni supported on hydrothermally treated IBA was tested for steam reforming of biomass tar reforming reaction between 700 °C and 800 °C at relatively low steam-to-carbon ratio of 2. Among all the catalysts, Ni supported on IBA hydrothermally treated for 24 h gave stable toluene conversion (of 40%) at 700 °C with reduced coke formation (of 7.5 mgC/g·h) than other catalysts. The superior catalytic performance of this catalyst is mainly due to the presence of high amounts of surface Ni° species and improved reducibility and basicity properties among all. The Raman, DT/TGA and XRD analyses on spent catalysts revealed the deposited carbon during steam reforming of tar reaction is majorly amorphous. Due to this, the deposition of carbon did not show any kind of deactivation within the catalyst testing period.

Comparison of generalized autocalibrating partially parallel acquisitions and modified sensitivity encoding for diffusion tensor imaging.

BACKGROUND AND PURPOSE: Diffusion tensor magnetic resonance imaging (DTI) of the brain is usually acquired with single-shot echo-planar imaging, which is associated with localized signal loss, geometric distortions, and blurring. Parallel imaging can lessen these artifacts by shortening the length of the echo-train acquisition. The self-calibrating parallel acquisition techniques, image domain-based modified sensitivity encoding (mSENSE) and k-space-based generalized autocalibrating partially parallel acquisitions (GRAPPA), were evaluated with DTI of the brain in 5 healthy subjects. METHODS: GRAPPA and mSENSE with higher acceleration factors (R) up to 4 were compared with conventional DTI (with and without phase partial Fourier, another method of reducing the echo-train length) on a 1.5T Sonata scanner (Siemens, Erlangen, Germany). The resulting images and diffusion maps were evaluated qualitatively and quantitatively. Qualitative analysis was performed by 3 reviewers blinded to the technique using image sharpness and the level of artifacts as characteristics for scoring each set of images. Quantitative comparisons encompassed measuring signal-to-noise ratio, Trace/3 apparent diffusion coefficient (ADC), and fractional anisotropy (FA) in 6 white-matter (WM) and gray-matter (GM) regions. RESULTS: Reviewers scored the GRAPPA and mSENSE R = 2 images better than images acquired with conventional techniques. FA contrast was improved at the GM/WM junction in peripheral brain areas. Trace/3 ADC and FA measurements were consistent for all methods. However, R = 3,4 images suffered from reconstruction-related artifacts. CONCLUSIONS: GRAPPA and mSENSE (R = 2) minimized the susceptibility and off-resonance effects associated with conventional DTI methods, yielding high-quality images and reproducible quantitative diffusion measurements.

Sublethal concentrations of gemcitabine (2',2'-difluorodeoxycytidine) alter mitochondrial ultrastructure and function without reducing mitochondrial DNA content in BxPC-3 human pancreatic carcinoma cells.

2',2'-Difluorodeoxycytidine (gemcitabine), a pyrimidine nucleoside analog, is used therapeutically in the treatment of pancreatic, non-small cell lung, and breast cancer. The cytotoxic effect of gemcitabine is thought to be due to masked chain termination after the triphosphorylated anabolite of the drug is incorporated into nascent DNA strands. We tested the hypothesis that sublethal concentrations of gemcitabine inhibit DNA polymerase gamma and reduce mitochondrial DNA content in BxPC-3 and MOLT-4 cell lines, and we used 2',3'-dideoxycytidine, a known inhibitor of DNA polymerase gamma as a positive control. The 6-day BxPC-3 cell growth IC(50) for gemcitabine and 2',3'-dideoxycytidine was 0.003 microM (SD +/- 0.0005) and 14.5 microM (SD +/- 4.7), respectively, and in MOLT-4 cells was 0.002 microM (SD +/- 0.001) and 0.86 muM (SD +/- 0.23), respectively. These drug concentrations were anti-proliferative but non-cytotocidal. Electron photomicrographic studies showed deranged mitochondrial cristae patterns in BxPC-3 cells treated with either gemcitabine or 2',3'-dideoxycytidine for 6 days. Mitochondrial oxidative phosphorylation dysfunction was observed as reflected by increased lactate concentration in the media of cells exposed to gemcitabine, but to a much greater extent in cells exposed to 2',3'-dideoxycytidine. PCR analysis showed that gemcitabine did not reduce mitochondrial DNA content in either BxPC-3 or MOLT-4 cells, but 2',3'-dideoxycytidine did. The effect of gemcitabine on mitochondrial ultrastructure and function did not concomitantly yield a reduction in mitochondrial DNA content. Therefore, the molecular target(s) by which gemcitabine and 2',3'-dideoxycytidine produce mitochondrial abnormalities in these cells appear to be different.

Detection of LGI1 and CASPR2 antibodies with a commercial cell-based assay in patients with very high VGKC-complex antibody levels.

BACKGROUND: The presence of VGKC-complex antibodies, without LGI1/CASPR2 antibodies, as a standalone marker for neurological autoimmunity remains controversial. Additionally, the lack of an unequivocal VGKC-complex antibody cut-off level defining neurological autoimmunity makes it important to test for monospecific antibodies. We aim to determine the performance characteristics of a commercial assay (Euroimmun, Lübeck, Germany) for LGI1/CASPR2 antibody detection in patients with very high VGKC-complex antibody levels and report their clinico-serological associations. METHODS: We identified 8 patients in our cohort with the highest VGKC-complex antibody levels (median 2663.5pM, range 933-6730pM) with VGKC-complex antibody related syndromes (Group A). Two other groups were identified; 1 group with suspected neuronal surface antibody syndromes and negative for VGKC-complex antibodies (Group B, n=8), and another group with cerebellar ataxia and negative for onconeuronal antibodies (Group C, n=8). RESULTS: Seven out of 8 patients (87.5%) in Group A had LGI1 and/or CASPR2 antibodies. One Group B patient had LGI1 antibodies but was negative on re-testing with a live cell assay. No Group C patients had monospecific antibodies. Inter-rater reliability was high; combining Groups A and B patients, the kappa statistic was 0.87 and 1.0 for LGI1 and CASPR2 antibodies respectively. CONCLUSION: We demonstrated that a high proportion of patients with very high VGKC-complex antibody levels and relevant clinical syndromes have LGI1 and/or CASPR2 antibodies detected by the commercial assay. Our findings lend support to the use of the assay for rapid and reliable detection of LGI1 and CASPR2 antibodies.

Potential Use of Multiplex PCR in Diagnosis of Tuberculous Meningitis.

Accurate and rapid diagnosis of tuberculous meningitis (TBM) is important for early administration of treatment. In this study, we have evaluated the diagnostic value of smear, culture, multiplex PCR and GeneXpert MTB/RIF to detect M. tuberculosis in cerebrospinal fluid (CSF) samples from patients with suspected TBM registered in Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia. Of the 55 CSF samples collected, 12 (21.8%) samples were positive by multiplex PCR, 3 (5.4%) by GeneXpert MTB/RIF and only 1 (1.8%) by smear and culture. Multiplex PCR showed higher sensitivity to detect M. tuberculosis in patients with suspected TBM and has the potential to be used as a diagnostic method.

MR spectroscopy in sinus mucocele: N-acetyl mimics of brain N-acetylaspartate.

We describe MR spectroscopy in 2 patients with frontal sinus mucoceles that showed a dominant metabolite peak at 2.0-ppm chemical shift, simulating N-acetylaspartate (NAA) of normal neuronal tissue. In vitro analysis of postsurgical mucocele samples confirmed that the signal at 2.0 ppm was arising from the methyl moiety of an N-acetyl compound. This is probably caused by N-acetylgalactosamine or N-acetylglucosamine, which are glycoproteins found in normal respiratory mucus produced by the paranasal sinus epithelium.

'Office-hour' ambulatory blood pressure monitoring is sufficient for blood pressure diagnosis.

We conducted this study to determine whether 'office hour', defined as time period from 0800 to 1800 hours, ambulatory blood pressure monitoring (ABPM) predicts daytime ('waking-hour') and 24-h ABPM results, and to examine the impact of sleep disturbance on ABPM and nocturnal dip. Eighty-four patients (mean age 49+/-18 years, 47 males) were studied. Systolic, diastolic and mean 4-, 6-, 8-, 'office-hour' as well as 'waking-hour' blood pressures (BPs) were obtained from 24-h ABPM readings. Of these, no statistical differences were found between 8-h and 'office-hour' systolic, diastolic and mean BPs compared to 'waking-hour' values. There was complete concordance between 'office-hour' and 'waking-hour' ABPM diagnosis based on British Hypertension Society definitions. Sleep disturbance was found in 22 patients (26%). Although nocturnal dip was not significantly different in either sleep-disturbed or non-disturbed patients, patients who reported sleep disturbance had significantly higher proportion of borderline/abnormal BP diagnosis compared to non-sleep-disturbed counterpart during both 'waking hour' and night time. In patients without sleep disturbance, there was complete concordance between 'office-hour', 'waking-hour' and 24-h ABPM diagnosis based on British Hypertension Society definitions. 'Office-hour' ABPM is predictive of 'waking-hour' and 24-h ambulatory BP readings. Sleep disturbance is common in patients undergoing the test, and significantly raises the BP readings. We therefore propose 'office-hour' ABPM as an accurate, reliable and comfortable method of continual non-invasive BP monitoring, and omitting routine night time BP monitoring.

Pathogenesis of ascites tumor growth: vascular permeability factor, vascular hyperpermeability, and ascites fluid accumulation.

Previous studies have shown that accumulation of tumor ascites fluid results in large part from increased permeability of peritoneal lining vessels (Nagy et al., Cancer Res., 49: 5449-5458, 1989; Nagy et al., Cancer Res., 53: 2631-2643, 1993). However, the specific microvessels rendered hyperpermeable have not been identified nor has the basis of peritoneal vascular hyperpermeability been established. To address these questions, TA3/St and MOT carcinomas, well-characterized transplantable murine tumors that grow in both solid and ascites form, were studied as model systems. Ascites tumor cells of either type were injected i.p. into syngeneic A/Jax and C3Heb/FeJ mice, and ascites fluid and plasma were collected at intervals thereafter up to 8 and 28 days, respectively. Beginning several days after tumor cell injection, small blood vessels located in tissues lining the peritoneal cavity (mesentery, peritoneal wall, and diaphragm) became hyperpermeable to several macromolecular tracers (125I-human serum albumin, FITC-dextran, colloidal carbon, and Monastral Blue B). Increased microvascular permeability correlated with the appearance in ascites fluid of vascular permeability factor (VPF), a tumor cell-secreted mediator that potently enhances vascular permeability to circulating macromolecules. VPF was measured in peritoneal fluid by both a functional bioassay and a sensitive immunofluorometric assay. The VPF concentration, total peritoneal VPF, ascites fluid volume, tumor cell number, and hyperpermeability of peritoneal lining microvessels were found to increase in parallel over time. The close correlation of peritoneal fluid VPF concentration with the development of hyperpermeable peritoneal microvessels in these two well-defined ascites tumors suggests that VPF secretion by tumor cells is responsible, in whole or in part, for initiating and maintaining the ascites pattern of tumor growth.