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IntroductionAnti-N-methyl-D-aspartate receptor (anti-NMDA-R) encephalitis is well-characterised autoimmune encephalitis with prominent psychiatric manifestations, neurological manifestations like speech dysfunction, seizures, dyskinesias and other movement abnormalities, decreased level of consciousness and autonomic instability. This disorder affects primarily children and adults up to 45 years. Females are 4 times more common than males and may have association with ovarian teratoma.ObjectivesTo identify anti-NMDA receptor encephalitis based on clinical features, facilitate early screening and relevant investigations to prevent delay in treatment.MethodsA case study of 36 year old female presented with clinical manifestations of autoimmune encephalitis syndrome.ResultsDiagnosis confirmed by presence of NMDA receptor antibodies in serum and cerebrospinal fluid.ConclusionsEarly recognition of clinical features of Anti-NMDA receptor encephalitis and early initiation of treatment has shown to improve outcomes, speed recovery and reduce the risk of relapses.DisclosureNo significant relationships.

Arterial base deficit (BD) has been widely used in trauma patients since 1960. However, trauma management has also evolved significantly in the last 2 decades. The first objective of this study was to systematically review the literature on the relationship between arterial BD as a prognostic marker for trauma outcomes (mortality, significant injuries, and major complications) in the acute setting. The second objective was to evaluate arterial BD as a prognosis marker, specifically, in the elderly and in patients with positive blood alcohol levels. MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were searched from January 1, 1990, to August 6, 2015. Bibliographies of articles were also hand searched for relevant citations. Thirty-four studies were included in this review. The studies consistently showed that a higher arterial BD was associated with increased mortality, significant injuries, and major complications. The threshold BD value of 6 mmol/L was also useful in discriminating for poorer outcomes. The presence of alcohol did not affect the ability of arterial BD to discriminate between major and minor injuries. Elderly patients had higher mortality in all arterial BD categories compared to the younger age group. Despite the advances in trauma care in the last 2 decades, arterial BD remains a useful prognostic marker in trauma patients, even in elderly patients and in patients who had consumed alcohol. The threshold BD value of 6 mmol/L was useful to prognosticate poorer outcomes.

IntroductionThere has recently been increased interest in the assessment of body composition in patients with gastric cancer for the purpose of prognostication. This systematic review and meta-analysis aim to evaluate the current literature on body composition assessment in patients with gastric cancer and its impact on peri-operative outcomes.MethodsA systematic literature search was conducted for studies reporting assessment of body composition in patients with gastric cancers. Meta-analysis of postoperative outcomes (overall and major complications, anastomotic leaks, pulmonary complications) and survival was performed using random effects models.ResultsThirty-nine studies reported the assessment of body composition in 8402 patients. Methods used to assess body composition in patients with gastric cancers were computerized tomography (n = 26), bioelectrical impedance analysis (n = 9), and dual-energy-X-ray-absorptiometry (n = 3). Only 21 studies reported the impact of pre-operative sarcopenia on post-operative outcomes. Sarcopenic patients have significantly higher rates of postoperative major complications (n = 12, OR 1.67, CI95% 1.14–2.46, p = 0.009), and pulmonary (n = 8, OR 4.01, CI95% 2.23–7.21, p < 0.001) complications after gastrectomy. Meta-analysis of nine studies reporting overall survival after gastrectomy identified significantly worse survival in patients with pre-operative sarcopenia (HR 2.12, CI95% 1.89–2.38, p < 0.001).ConclusionsAssessment of body composition has the potential to become a clinically useful tool that could support decision-making in patients with gastric cancer. However, variation in methods of assessing and reporting body composition in this patient group limits assessment of current post-operative outcomes

Differentiating status epilepticus (SE) from prolonged psychogenic nonepileptic seizures (pPNES) can be difficult clinically. We aimed to define the utility of peripheral cell counts, cell ratios, and lactate levels in distinguishing SE from pPNES. Retrospective two-center study investigating the sensitivity and specificity of acute (≤12 h of event offset) peripheral cell counts, cell ratios (neutrophil-lymphocyte ratio, neutrophil-monocyte ratio, monocyte-lymphocyte ratio, platelet-lymphocyte ratio, systemic immune-inflammatory index [SII], systemic inflammatory response index [SIRI]), and lactate levels in differentiating SE from pPNES. Patients were identified from two tertiary hospitals, with one forming the development cohort and the other the validation cohort. Using generalized additive models to generate biomarker vs time curves, optimal blood collection times were defined for set parameters. Three diagnostic scores combining neutrophil count, SII, or SIRI with lactate levels were developed and validated in separate cohorts. For the development cohort, 1262 seizure-like events were reviewed and 79 SE and 44 pPNES events were included. For the validation cohort, 241 events were reviewed and 20 SE and 11 pPNES events were included. Individually, the biomarkers generally had low sensitivity and reasonable specificity for differentiating SE from pPNES, with the neutrophil count, SIRI, and SII performing best with sensitivities of 0.65-0.84, specificities of 0.64-0.89, and ROC AUCs of 0.78-0.79. Lactate levels peaked at 60 min, while cell counts and ratios peaked after 240 min. Combining early peaking lactate levels and later peaking neutrophil count, SIRI or SII resulted in three scores that improved predictive potential with sensitivities of between 0.75 and 0.79, specificities between 0.93 and 1.00, and ROC AUCs of 0.89-0.91. Lactate levels peak early post-SE, whereas cell counts and ratios do so later. The differing post-event time profiles of lactate levels vs neutrophil count, SIRI, and SII allow incorporation into three separate scores which can assist in differentiating SE from pPNES.

Background: ERG rearrangements and PTEN (phosphatase and tensin homolog deleted on chromosome 10) loss are two of the most common genetic alterations in prostate cancer. However, there is still significant controversy regarding the order of events of these two changes during the carcinogenic process. We used immunohistochemistry (IHC) to determine ERG and PTEN status, and calculated the fraction of cases with homogeneous/heterogeneous ERG and PTEN staining in a given tumor. Methods: Using a single standard tissue section from the index tumor from radical prostatectomies ( N =77), enriched for relatively high grade and stage tumors, we examined ERG and PTEN status by IHC. We determined whether ERG or PTEN staining was homogeneous (all tumor cells staining positive) or heterogeneous (focal tumor cell staining) in a given tumor focus. Results: Fifty-seven percent ( N =44/77) of tumor foci showed ERG positivity, with 93% of these ( N =41/44) cases showing homogeneous ERG staining in which all tumor cells stained positively. Fifty-three percent ( N =41/77) of tumor foci showed PTEN loss, and of these 66% ( N =27/41) showed heterogeneous PTEN loss. In ERG homogeneously positive cases, any PTEN loss occurred in 56% ( N =23/41) of cases, and of these 65% ( N =15/23) showed heterogeneous loss. In ERG-negative tumors, 51.5% ( N =17/33) showed PTEN loss, and of these 64.7% ( N =11/17) showed heterogeneous PTEN loss. In a subset of cases, genomic deletions of PTEN were verified by fluorescence in situ hybridization in regions with PTEN protein loss as compared with regions with intact PTEN protein, which did not show PTEN genomic loss. Conclusions: These results support the concept that PTEN loss tends to occur as a subclonal event within a given established prostatic carcinoma clone after ERG gene fusion. The combination of ERG and PTEN IHC staining can be used as a simple test to ascertain PTEN and ERG gene rearrangement status within a given prostate cancer in either a research or clinical setting.

An ideal anaesthetic for electroconvulsive therapy (ECT) should have rapid onset and offset with no effect on seizure duration, and provide cardiovascular stability during the procedure. Propofol is commonly used, even though it has been shown to shorten seizure duration which might affect the efficacy of ECT. Etomidate has been advocated as an alternative. This prospective, randomised, single-blind, crossover study was conducted to compare the effects of etomidate (Etomidate-®Lipuro, B. Braun Ltd, Melsungen, Germany) and propofol (Diprivan®, AstraZeneca, UK) on seizure duration as well as haemodynamic parameters in patients undergoing ECT. Twenty patients aged between 18 and 70 years were recruited. Group I received etomidate 0.3 mg/kg for the first course of ECT (Group IA) and propofol 1.5 mg/kg for the second ECT (Group IB), while Group II received propofol for the first ECT (Group IIA) and etomidate for the second ECT (Group IIB). There was a washout period of two to three days in between procedures. Parameters recorded included motor seizure duration, electroencephalogram seizure duration, blood pressure and heart rate. Analysis demonstrated neither period effect nor treatment period interaction. Etomidate was associated with a significantly longer motor and electroencephalogram seizure duration compared with propofol (P <0.01). Neither drug demonstrated consistent effects in suppressing the rise in heart rate or blood pressure during ECT. Myoclonus and pain on injection were the most common adverse effects in etomidate group and propofol group respectively. Etomidate is a useful anaesthetic agent for ECT and should be considered in patients with inadequate seizure duration with propofol.

We report our initial experience using Profilnine SD, a 3-Factor prothrombin complex concentrate (PCC) in combination with fresh frozen plasma and vitamin K in seven patients admitted to our neurointensive care unit with oral anticoagulation therapy-related intracranial haemorrhage over a six-month period, to achieve rapid normalisation of the international normalised ratio (INR) and allow surgical evacuation when indicated. Four patients presented with subdural haematomas while three had intracerebral haematomas. Six of seven patients had admission INR in the appropriate therapeutic range for oral anticoagulation therapy. The median dose of PCC administered was 28.5 IU/kg body weight (interquartile range 21.3 to 38.5 IU/kg). All four patients with subdural haematoma underwent surgical evacuation once INR was less than 1.5. Median time from computed tomography diagnosis to surgery was 275 minutes (range 102 to 420 minutes). The median time to INR normalisation post-PCC administration was shorter, at 85 minutes (range 50 to 420 minutes) for the four patients who survived, versus 10 hours (range 9 to 44 hours) in the three patients who died. Two of the three patients who died had haematoma increase, worsening midline shift and subfalcine herniation, leading to withdrawal of therapy. Prothrombin complex concentrates should be considered for use in the urgent reversal of INR in oral anticoagulation therapy-related intracranial haemorrhage, potentially halting haematoma expansion and expediting urgent neurosurgical intervention, although data from randomised controlled trials is still lacking. The literature supporting the use of PCC is reviewed and a protocolised emergent treatment algorithm is proposed, which may help achieve earlier consistent normalisation of the INR.

Background Cachexia affects the majority with advanced cancer. Based on current demographic and clinical factors, it is not possible to predict who will develop cachexia or not. Such variation may, in part, be due to genotype. It has recently been proposed to extend the diagnostic criteria for cachexia to include a direct measure of low skeletal muscle index (LSMI) in addition to weight loss (WL). We aimed to explore our panel of candidate single nucleotide polymorphism (SNPs) for association with WL +/− computerized tomography‐defined LSMI. We also explored whether the transcription in muscle of identified genes was altered according to such cachexia phenotype Methods A retrospective cohort study design was used. Analysis explored associations of candidate SNPs with WL (n = 1276) and WL + LSMI (n = 943). Human muscle transcriptome (n = 134) was analysed using an Agilent platform. Results Single nucleotide polymorphisms in the following genes showed association with WL alone: GCKR, LEPR, SELP, ACVR2B, TLR4, FOXO3, IGF1, CPN1, APOE, FOXO1, and GHRL. SNPs in LEPR, ACVR2B, TNF, and ACE were associated with concurrent WL + LSMI. There was concordance between muscle‐specific expression for ACVR2B, FOXO1 and 3, LEPR, GCKR, and TLR4 genes and LSMI and/or WL (P < 0.05). Conclusions The rs1799964 in the TNF gene and rs4291 in the ACE gene are new associations when the definition of cachexia is based on a combination of WL and LSMI. These findings focus attention on pro‐inflammatory cytokines and the renin–angiotensin system as biomarkers/mediators of muscle wasting in cachexia.

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) have become a truly global challenge. In addition to the long-known healthcare-associated clones, novel strains have also emerged outside of the hospital settings, in the community as well as in livestock. The emergence and spread of virulent clones expressing Panton-Valentine leukocidin (PVL) is an additional cause for concern. In order to provide an overview of pandemic, epidemic and sporadic strains, more than 3,000 clinical and veterinary isolates of MRSA mainly from Germany, the United Kingdom, Ireland, France, Malta, Abu Dhabi, Hong Kong, Australia, Trinidad & Tobago as well as some reference strains from the United States have been genotyped by DNA microarray analysis. This technique allowed the assignment of the MRSA isolates to 34 distinct lineages which can be clearly defined based on non-mobile genes. The results were in accordance with data from multilocus sequence typing. More than 100 different strains were distinguished based on affiliation to these lineages, SCCmec type and the presence or absence of PVL. These strains are described here mainly with regard to clinically relevant antimicrobial resistance- and virulence-associated markers, but also in relation to epidemiology and geographic distribution. The findings of the study show a high level of biodiversity among MRSA, especially among strains harbouring SCCmec IV and V elements. The data also indicate a high rate of genetic recombination in MRSA involving SCC elements, bacteriophages or other mobile genetic elements and large-scale chromosomal replacements.

In multiple myeloma, abnormal plasma cells establish oncogenic niches within the bone marrow by engaging the NF-κB pathway to nurture their survival while they accumulate pro-proliferative mutations. Under these conditions, many cases eventually develop genetic abnormalities endowing them with constitutive NF-κB activation. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire. Furthermore, through targeted disruption of p52, we characterise how such enhancers are complicit in the formation of super-enhancers and the establishment of cis -regulatory interactions with myeloma dependencies during constitutive activation of p52. Finally, we functionally validate the pathological impact of these cis -regulatory modules on cell and tumour phenotypes using in vitro and in vivo models, confirming RGS1 as a p52-dependent myeloma driver. We conclude that the divergent epigenomic reprogramming enforced by aberrant non-canonical NF-κB signalling potentiates transcriptional programs beneficial for multiple myeloma progression. The downstream molecular mechanisms following the activation of the NF-κB pathway in multiple myeloma (MM) remain to be characterised. Here, it is shown that aberrant non-canonical NF-κB signalling causes epigenomic reprogramming leading to transcriptional changes that favour MM progression.