Five-Year-Old Boy With Behavioral Changes and Papilledema.

A 5-year-old boy had initial symptoms of behavioral changes, nausea, vomiting, headache, weight loss, and progressive vision failure. Brain MRI revealed abnormal signal intensity in both optic nerves, the optic chiasm, the right medial temporal lobe, and tissues surrounding the right supraclinoid internal carotid artery with associated leptomeningeal and spinal cord enhancement. After nondiagnostic dural and spinal arachnoid biopsies, a temporal lobe biopsy was diagnostic for a rare malignant peripheral nerve sheath tumor. (C) 2017 by North American Neuro-Ophthalmology Society

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Nonsurgical Management of Retained Needlefish Jaw.

While scuba diving, the left medial canthus of a 53-year-old man was pierced by a needlefish. He immediately lost vision in his left eye. An orbital computed tomographic scan showed the needlefish jaw in the left optic canal. The left medial orbit was explored surgically but no foreign object was removed. One month later, MRI confirmed the presence of the retained needlefish jaw. A conservative approach was taken and the patient remained stable over 3 months of follow-up. (C) 2017 by North American Neuro-Ophthalmology Society

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Laughter-Induced Transient Vision Loss in a Patient With Silent Sinus Syndrome.

Background: To report a patient with silent sinus syndrome (SSS) who experienced transient ipsilateral monocular vision loss during intense laughter. Methods: Case report. Results: Our patient's transient vision loss completely resolved after maxillary sinus decompression and during 7 months of follow-up. Conclusions: Although the precise mechanism of our patient's vision loss remains undetermined, we suspect that the vascular supply to the eye and/or the optic nerve was compromised as the result of the combination of laughter (causing Valsalva maneuver and increased intrathoracic pressure) and SSS. (C) 2017 by North American Neuro-Ophthalmology Society

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Why a One-Way Ticket to Mars May Result in a One-Way Directional Glymphatic Flow to the Eye.

No abstract available

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Why a One-Way Ticket to Mars May Result in One-Way Directional Glymphatic Flow to the Eye: Response.

No abstract available

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Clinical and Oculographic Analysis of Inferior Oblique Myokymia.

A 63-year-old man experienced transient vertical oscillopsia lasting several seconds for 2 months. Examination disclosed paroxysmal excyclotorsion of the right eye, spontaneously or triggered by adduction. Eye movements using 3D video-oculography showed intermittent, monocular phasic movements which consisted of excyclotorsion of the right eye mixed with a small amount of supraduction and abduction, and a tonic movement with excyclotorsion and slight elevation. Orbital and brain MRI was unremarkable. Administration of oxcarbazepine markedly decreased the severity and frequency of the episodes. The oculographic characteristics in our patient may indicate that inferior oblique myokymia may be attributed to aberrant, spontaneous discharges in the inferior oblique motor unit. (C) 2017 by North American Neuro-Ophthalmology Society

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International Consensus Statement on the Clinical and Therapeutic Management of Leber's Hereditary Optic Neuropathy.

Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON. To address these issues, a consensus conference with a panel of experts from Europe and North America was held in Milan, Italy, in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. We report the conclusions of this conference, providing the guidelines for clinical and therapeutic management of LHON. (C) 2017 by North American Neuro-Ophthalmology Society

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Investigating psychological and physiological responses to the Trier social stress test in young adults with insomnia: a preliminary study

Publication date: Available online 7 October 2017
Source:Sleep Medicine
Author(s): Ivy Y. Chen, Denise C. Jarrin, Hans Ivers, Charles M. Morin
ObjectiveStress and hyperarousal both contribute to insomnia. Elevated stress-related sleep reactivity is associated with hyperarousal, and might constitute a vulnerability to future insomnia. The present study examined acute stress-induced arousal and its association with nocturnal sleep.MethodsParticipants were 30 healthy adults (66.7% female, Mage = 26.7 years): 10 with insomnia (INS) and 20 good sleepers with high vulnerability (HV) or low vulnerability (LV) to insomnia. They underwent two consecutive nights of polysomnography. During the evening preceding the second night the Trier social stress test (TSST) was administered, and psychological and physiological arousal indices were assessed.ResultsThe TSST elicited an increase in psychological and physiological arousal in all three groups. The INS group showed greater acute cortisol response (p<0.05) and secretion at bedtime (p<0.05), and higher pre-sleep cognitive arousal (p<0.01) than the LV group; HV participants did not significantly differ from those in INS or LV group. Increased cortisol response and elevated sympatho-vagal imbalance (ie, low frequency/high frequency ratio) were each significantly associated with longer nocturnal awakenings (p=0.048, p=0.037, respectively). Heightened blood pressure was significantly associated with prolonged sleep onset latency, and reduced total sleep time and sleep efficiency (all ps<0.05).ConclusionsThese findings supported the hyperarousal conceptualization of insomnia and indirectly suggested that increased stress reactivity and bedtime hyperarousal might represent a trait-like vulnerability in certain good sleepers. More research is warranted to validate and expand these preliminary findings.



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Rational Inference of Beliefs and Desires From Emotional Expressions

Abstract

We investigated people's ability to infer others' mental states from their emotional reactions, manipulating whether agents wanted, expected, and caused an outcome. Participants recovered agents' desires throughout. When the agent observed, but did not cause the outcome, participants' ability to recover the agent's beliefs depended on the evidence they got (i.e., her reaction only to the actual outcome or to both the expected and actual outcomes; Experiments 1 and 2). When the agent caused the event, participants' judgments also depended on the probability of the action (Experiments 3 and 4); when actions were improbable given the mental states, people failed to recover the agent's beliefs even when they saw her react to both the anticipated and actual outcomes. A Bayesian model captured human performance throughout (rs ≥ .95), consistent with the proposal that people rationally integrate information about others' actions and emotional reactions to infer their unobservable mental states.

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Future Horizons in Allergy

There are several advances in diagnosis and management for the otolaryngologist treating allergy. These include new technologies and the refinement of current techniques, and reflect overall trends in health care toward personalized medicine. Local immunoglobulin, urinary leukotriene E4, lipidomics, microRNA within extracellular vesicles, and optical rhinometry all offer to improve the diagnostic accuracy of allergy and related nonallergic conditions. New delivery systems for intranasal steroids and antihistamines, recombinant allergens, advances in allergen immunotherapy delivery, and biologics will improve current management options. These developments will aid the otolaryngologist in diagnosing and treating allergy and related diseases.

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The Role of Allergy in Otologic Disease

Allergy is commonly associated with conditions such as rhinitis, sinusitis, and asthma, but the relationship between allergy and otologic diseases is less clear. This article examines the evidence for a relationship between allergic disease and several common otologic conditions, including otitis media with effusion, eosinophilic otitis media, and Ménière's disease.

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Laparoscopic cholecystectomy versus transvaginal natural orifice transluminal endoscopic surgery cholecystectomy: results of a prospective-comparative single-center study

Laparoscopic cholecystectomy (LC) in female individuals has been recently challenged by transvaginal NOTES cholecystectomy (TVC). TVC has not been widely accepted as a standard procedure, even though it is reported to be a safe and painless alternative to LC. This prospective-comparative study aims to not only prove equality of TVC and LC but to underline the advantages of TVC over LC with regard to postoperative pain.

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Endoscopic submucosal dissection for early Barrett’s neoplasia: a meta-analysis

The role of endoscopic submucosal dissection (ESD) in Barrett's esophagus (BE) is not well established. This meta-analysis aimed to evaluate the safety and efficacy of ESD for the management of early BE neoplasia.

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Rebamipide solution: a novel submucosal injection material to promote healing speed and healing quality of ulcers induced by endoscopic submucosal dissection

Rebamipide was administered perorally to protect the gastric mucosa. We assessed the efficacy and safety of a novel rebamipide solution as a submucosal injection material for endoscopic submucosal dissection (ESD) using an in vivo porcine model.

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Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: An analysis of patients treated on the RICOVER-60 trial

Abstract

Background

The prognosis of elderly patients with aggressive B-NHL after first lymphoma-related treatment failure (TF-L) is not well described.

Methods

We analysed patient characteristics including presence of MYC rearrangements and MYC-expression (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 to 80 years who had been treated on the RICOVER-60 trial.

Results

TF-L occurred in 301 of 1222 (24.6%) patients; 297 patients could be analyzed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (≤12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared to CHOP (23.0% vs. 36.4% at 2 years, p = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% vs. 0% at 2 years, p < 0.001) or negative MYC-IHC (41.0% vs. 16.8% at 2 years, p = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (p < 0.001). The benefit of R was significant after first-line CHOP (2-year-OS 49.6% vs. 19.1%, p < 0.001) as well as after R-CHOP (2-year-OS 33.1% and 22.5%, p = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen.

Conclusion

MYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy, however survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.

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Micro-autologous fat transplantation for rejuvenation of the dorsal surface of the ageing hand

Rejuvenation of the dorsal surface of the hand for various conditions, such as cutaneous dyschromia, fine wrinkling, skin laxity, visible extensor tendons, and varicosities appear vital to prevent wrist and digit flexion resulting from hiding of the aged appearance of the hand. Numerous fillers have been applied to re-contour the ageing dorsal surface of the hand; the results were variable. The micro-autologous fat transplantation (MAFT) technique, proposed by Lin et al. in 2006, has demonstrated its feasibility in facial rejuvenation.

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Integrated Health Care Management of Moderate to Severe TBI in Older Patients—A Narrative Review

Abstract

Purpose of Review

Traumatic brain injuries are common, especially within the elderly population, which is typically defined as age 65 and older. This narrative review aims at summarizing and critically evaluating important aspects of their health care management in covering the entire pathway from prehospital care to rehabilitation and beyond.

Recent Findings

The number of older patients with traumatic brain injury (TBI) is increasing, and there seem to be differences in all aspects of care along their pathway when compared to younger patients. Despite a higher mortality and a generally less favorable outcome, the current literature shows that older TBI patients have the potential to make significant improvements over time.

Summary

More research is needed to evaluate the most efficient and integrated clinical pathway from prehospital interventions to rehabilitation as well as the optimal treatment of older TBI patients. Most importantly, they should not be denied access to specific treatments and therapies only based on age.

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The expression profile and clinicopathological significance of Notch1 in patients with colorectal cancer: a meta-analysis

Future Oncology, Ahead of Print.


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Cancer-directed therapy and potential impact on survivals in nonresected hepatocellular carcinoma: SEER-Medicare population study

Future Oncology, Ahead of Print.


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Central nervous system complications after allogeneic hematopoietic stem cell transplantation

Future Oncology, Ahead of Print.


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Latest advances in adult gastrointestinal stromal tumors

Future Oncology, Ahead of Print.


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Comprehensive characterization of differentially expressed genes in thyroid cancer

Future Oncology, Ahead of Print.


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Sanger Institute series: uncovering the genetics of cancer: an interview with David Adams

Future Oncology, Ahead of Print.


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PD-L1 in immune-escape of breast and prostate cancers: from biology to therapy

Future Oncology, Ahead of Print.


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Prognostic impact of germline mutations in inherited cancer syndromes

Future Oncology, Ahead of Print.


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The current status of adjuvant treatment for high-risk renal cell carcinoma

Future Oncology, Ahead of Print.


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Subsequent malignant neoplasms in the survivor of childhood cancer: where we have been and where we are going?

Future Oncology, Ahead of Print.


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Why should we perform a D2 lymphadenectomy in gastric cancer?

Future Oncology, Ahead of Print.


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Advances in systemic therapy for malignant mesothelioma: future perspectives

Future Oncology, Ahead of Print.


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S100A6 promotes proliferation of intrahepatic cholangiocarcinoma cells via the activation of the p38/MAPK pathway

Future Oncology, Ahead of Print.


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Comparative Study of Head and Neck Mucosal Melanoma in 66 patients vs. 226 patients with Cutaneous Melanoma: A survival analysis

Abstract

Sixty-six patients (22%) had HNMM and 226 (78%) HNCM and the higher prevalence was seen in females with a similar distribution amongst the two diagnoses (p=0.8).

Symptoms were present in all patients with HNCM and in only 15% of patients with HNMM (p=0.000).

Lymph node involvement at diagnosis was present in 51% of HNMM vs. 33% of HNCM (p=0.007) and were bilateral in 44% of HNMM while in HNCM they were only ipsilateral (p=0.000).

Metastatic disease at diagnosis was similar in both groups (p=0.9).

Relapses were more frequent in the HNMM group in ~70% of the cases compared with 23% in HNCM group (p=0.000).

When comparing HNCM vs. HNMM, Overall Survival is similar, without statistical difference.

This article is protected by copyright. All rights reserved.

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Neuronal activity patterns in the ventral thalamus: comparison between Parkinson’s disease and cervical dystonia

The thalamus plays a crucial role in many brain functions, serving as an information gate for afferent sensory signals, efferent programmes and intercortical interactions. Along with a complex inner structure, the thalamus has widespread connections with subcortical structures (basal ganglia, cerebellum, midbrain and others), different cortical regions and the peripheral nervous system (Jones, 2007; Sherman and Guillery, 2013). Thus, such extensive connectivity implies a complexity and diversity of neuronal activity patterns.

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Progression of adverse effects over consecutive sessions of transcranial direct current stimulation

We read the paper by Antal et al. (2017) with great interest, and felt that it provided an excellent overview of the safety aspects of transcranial electrical stimulation (tES). However, we noticed that while multi-day stimulation studies were discussed, potential changes in adverse effects (AEs) over consecutive sessions were not, and the lack of knowledge on the matter was pointed out by the authors. We recently completed an experiment in which we investigated this issue.

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Super-selective cervical nerve root stimulation in contralateral C7 transfer: an intraoperative study

Intraoperative electrophysiological examination of the healthy brachial plexus in contralateral C7 transfer (cC7) procedures contributed substantially to the anatomical understanding of functional motor innervation of cervical nerve roots (Gu 1997; Gu et al. 2003; Hu et al. 2008; Li et al. 2011; Yin et al. 2012; Zhang et al. 2012). Results of intraoperative cervical nerve root stimulation showed that C5 mainly innervates the deltoid (axillary nerve), C6 the biceps brachii (musculocutaneous nerve), C7 the triceps brachii (radial nerve), and C8 the flexor digitorum superficialis and profundus muscles (median nerve) (Gu 1997).

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iMAX: a new tool to assess peripheral motor axonal hypoexcitability

In routine electrodiagnostic procedures, classical parameters allow assessment of motor unit loss/reinnervation (CMAP amplitude) and motor conduction slowing (motor distal latency, motor conduction velocity, F waves), but none evaluates peripheral motor axon hypoexcitability. Yet everyone has experienced that in a demyelinating neuropathy it is often necessary to increase above normal the amount of current to obtain a supramaximal motor response. Excitability properties of human peripheral nerves can be assessed by various neurophysiological methods (Brismar, 1985; Kiernan et al, 2000; Burke et al, 2001), but they are not often used in daily practice because they are time consuming and they require a specific collection system and software.

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Added clinical value of the inferior temporal EEG electrode chain

In 1958, the standardized 10-20 EEG electrode positioning system was proposed by Herbert H. Jasper and his co-workers (Jasper, 1958), and in 1999 this has been reported as a guideline of the International Federation of Clinical Neurophysiology (Klem et al. 1999). Distances were measured from prominent skull landmarks (nasion, inion, preauricular points) and evenly distributed electrode positions were determined using 10% and 20% segments of these distances (Klem et al. 1999). Jasper's 10-20 system was developed using cadaver skulls.

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Learned control over spinal nociception: Transfer and stability of training success in a long-term study

The descending pain inhibition is a system of endogenous pain control, able to reduce incoming nociceptive signals at the spinal dorsal horn level (Fields and Basbaum, 2006). It can be modulated by cognitive and emotional processes (Tracey and Mantyh, 2007; Bingel and Tracey, 2008; Wiech and Tracey, 2009). Recently, we have shown that healthy young adults can learn to use cognitive-emotional strategies to suppress their spinal nociception as quantified by the nociceptive flexor reflex (RIII reflex) when they are given visual feedback on their RIII reflex size, likely by learning to deliberately activate their descending pain inhibition (Ruscheweyh et al., 2015a; Ruscheweyh et al., 2015b).

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The relationship between sacral slope and symptomatic isthmic spondylolysis in a cohort of high school athletes: a retrospective analysis

Spondylolysis with and without anterolisthesis are the most common causes of structural back pain in children and adolescents, but few predictive factors have been confirmed. An association between abnormal sacro-pelvic orientation and both spondylolysis and spondylolisthesis has been supported in the literature. Sacral slope and other sacro-pelvic measurements are easily accessible variables that could aid clinicians in assessing active adolescents with low back pain, particularly when the diagnosis of spondylolysis is suspected.

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Investigating psychological and physiological responses to the Trier social stress test in young adults with insomnia: a preliminary study

Stress and hyperarousal both contribute to insomnia. Elevated stress-related sleep reactivity is associated with hyperarousal, and might constitute a vulnerability to future insomnia. The present study examined acute stress-induced arousal and its association with nocturnal sleep.

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Effects of Homocysteine on white matter diffusion parameters in Alzheimer’s disease

The clinical features of Alzheimer's disease (AD) are related to brain network degeneration, and hyperhomocysteinemia is related to greater white matter hyperintensities. We investigated the changes in four di...

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Identification of VPS35 p.D620N mutation-related Parkinson’s disease in a Taiwanese family with successful bilateral subthalamic nucleus deep brain stimulation: a case report and literature review

Vacuolar protein sorting 35 (VPS35) was recently reported to be a genetic cause for late-onset autosomal dominant Parkinson's disease (PD). However, VPS35 mutations are rarely reported in Asian populations. Herei...

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Self-rated health and associated factors in elderly patients with non-Hodgkin lymphoma

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Lívia Maria Santiago, Daniel Richard Mercante, Inês Echenique Mattos
BackgroundSelf-rated health is a useful indicator for understanding health issues in elderly populations and considered to be a predictor of adverse health outcomes in this group. This study aims to identify factors associated with self-rated health in elderly people with non-Hodgkin's lymphoma.MethodsCross-sectional study performed at a cancer referral hospital in Rio de Janeiro, Brazil, included 162 patients, aged 60 or more years. All patients received a Multidimensional Geriatric Assessment, including seven health dimensions, and socio-demographic, epidemiological and it were collected clinical data. Descriptive analyses were performed and prevalence ratios were calculated to assess associations between self-rated health and the independent variables. Multivariate analysis was performed using Poisson's regression, to a ≤0.05 level of statistical significance.ResultsThe study population mean age was 68.8 (SD=7.1) years; most were women, lived with a partner and had little education. Prevalence of fair/poor self-rated health was 33.6%. Being female, not living with a partner, functional dependence, depressive symptoms and nutritional risk/malnutrion showed associations with fair/poor self-rated health. In the multiple model, dependence in instrumental activities of daily living (PR 2.96; 95%CI 1.66-5.30) and presence of depressive symptoms (PR 1.78; 95%CI 1.15-2.75) remained associated with fair/poor health.ConclusionVariation in perceived health status supports the hypothesis that self-rated health is related to multiple issues, regardless of disease status. The risk profile for poor self-rated health identified may be a useful tool in care for older cancer patients, as it points to those at higher risk of adverse health outcomes.



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Krüppel-Like Factor 8 Overexpression Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

Abstract

Krüppel-like factor 8 (KLF8) plays a key role in cancer progression. However, its expression pattern and relationship with clinicopathological characteristics in non-small cell lung cancer (NSCLC) has not been completely elucidated. The study aimed to investigate the expression of KLF8 and its correlation with clinical pathologic features in NSCLC and to explore the potential mechanism. The expression of KLF8 in NSCLC was detected by RT-PCR, Western blot and immunohistochemistry. The expression of Vimentin and E-cadherin, epithelial-mesenchymal transition (EMT) markers, were detected by immunohistochemistry in the NSCLC. The relationship between KLF8 expression and various clinicopathological features or EMT markers was investigated. The results showed m-RNA and protein of KLF8 were overexpressed in NSCLC and the percent of KLF8 positive cells was positively correlated with TNM stage, lymph node metastasis and poor overall survive. Moreover, high expression of KLF8 correlated with E-cadherin low expression, and Vimentin overexpression. Additionally, COX multivariate regression analysis suggested that TNM stage, KLF8, E-cadherin and Vimentin were independent prognostic indicators for overall survival of patients with NSCLC. The data demonstrate that KLF8 is overexpressed in NSCLC. KLF8 overexpression promotes the malignancy of NSCLC, which mechanism may be involved in EMT. KLF8 maybe serve as a potential therapeutic target for NSCLC.

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Copper Chelation Inhibits BRAFV600E-driven Melanomagenesis and Counters Resistance to BRAFV600E and MEK1/2 Inhibitors

MEK1/2 and BRAFV600E inhibitors are used to treat BRAFV600E-positive melanoma, with other cancers under evaluation. Genetic perturbation of copper import or pharmacological reduction of copper with the clinical copper chelator TTM inhibits MEK1/2 kinase activity and reduces BRAFV600E-driven tumorigenesis. In this study, we report that TTM inhibited transformed growth of melanoma cell lines resistant to BRAF or MEK1/2 inhibitors and enhanced the antineoplastic activity of these inhibitors. TTM also provided a survival advantage in a genetically engineered mouse model of melanoma, and when accounting for putative overdosing, trended towards an increase in the survival benefit afforded by BRAF inhibition. This effect was phenocopied by genetically inhibiting copper import in tumors, which was linked to a reduction in MAPK signaling. Thus, TTM reduces copper levels and MAPK signaling, thereby inhibiting BRAFV600E-driven melanoma tumor growth. These observations inform and support clinical evaluation of TTM in melanoma.

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Loss of FOXO1 cooperates with TMPRSS2-ERG overexpression to promote prostate tumorigenesis and cell invasion

E26 transformation-specific (ETS) transcription factor ERG is aberrantly overexpressed in approximately 50% of all human PCa due to TMPRSS2-ERG gene rearrangements. However, mice with prostate-specific transgenic expression of PCa-associated ERG alone fail to develop PCa, highlighting that ERG requires other lesions to drive prostate tumorigenesis. Forkhead box (FOXO) transcription factor FOXO1 is a tumor suppressor that is frequently inactivated in human PCa. Here we demonstrate that FOXO1, but not other FOXO proteins (FOXO3 and FOXO4), binds and inhibits the transcriptional activity of PCa-associated ERG independently of FOXO1 transcriptional activity. Knockdown of endogenous FOXO1 increased invasion of TMPRSS2-ERG fusion positive VCaP cells, an effect completely abolished by ERG knockdown. Patient specimen analysis demonstrated that FOXO1 and ERG protein expression inversely correlated in a subset of human PCa. Although human ERG transgene expression or homozygous deletion of Foxo1 alone in the mouse prostate failed to promote tumorigenesis, concomitant ERG transgene expression and Foxo1 deletion resulted in upregulation of ERG target genes, increased cell proliferation and formation of high-grade prostatic intraepithelial neoplasia (HGPIN). Overall, we provide biochemical and genetic evidence that aberrantly activated ERG cooperates with FOXO1 deficiency to promote prostate tumorigenesis and cell invasion. Our findings enhance understanding of PCa etiology and suggest that the FOXO1-ERG signaling axis can be a potential target for treatment of PCa.

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Chemotherapeutic dose scheduling based on tumor growth rates provide a case for low-dose metronomic high entropy therapies

We extended the classical tumor regression models such as Skipper's laws and the Norton-Simon hypothesis from instantaneous regression rates to the cumulative effect over repeated cycles of chemotherapy. To achieve this end, we used a stochastic Moran process model of tumor cell kinetics coupled with a prisoner's dilemma game-theoretic cell-cell interaction model to design chemotherapeutic strategies tailored to different tumor growth characteristics. Using the Shannon entropy as a novel tool to quantify the success of dosing strategies, we contrasted maximum tolerated dose (MTD) strategies as compared with low-dose, high-density metronomic strategies (LDM) for tumors with different growth rates. Our results show that LDM strategies outperformed MTD strategies in total tumor cell reduction (TCR). This advantage was magnified for fast growing tumors that thrive on long periods of unhindered growth without chemotherapy drugs present and was not evident after a single cycle of chemotherapy but grew after each subsequent cycle of repeated chemotherapy. The evolutionary growth/regression model introduced in this paper agrees well with murine models. Overall, this model supports the concept of designing different chemotherapeutic schedules for tumors with different growth rates and develops quantitative tools to optimize these schedules for maintaining low volume tumors.

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Astrocytes promote medulloblastoma progression through hedgehog secretion

Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. While astrocytes have been frequently detected in brain tumors, including medulloblastoma (MB), their functions in tumorigenesis are not clear. Here we demonstrate that astrocytes are essential components of the MB tumor microenvironment. Tumor-associated astrocytes (TAA) secreted the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1). Shh drove expression of Nestin in MB cells through a Smoothened-dependent, Gli1-independent mechanism. Ablation of TAA dramatically suppressed Nestin expression and blocked tumor growth. These findings demonstrate an indispensable role for astrocytes in MB tumorigenesis and reveal a novel Ptch1-independent Shh pathway involved in MB progression.

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Potential role of polymorphisms in the transporter genes ENT1 and MATE1/OCT2 in predicting TAS-102 efficacy and toxicity in patients with refractory metastatic colorectal cancer

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Mitsukuni Suenaga, Marta Schirripa, Shu Cao, Wu Zhang, Dongyun Yang, Vincenzo Dadduzio, Lisa Salvatore, Beatrice Borelli, Filippo Pietrantonio, Yan Ning, Satoshi Okazaki, Martin D. Berger, Yuji Miyamoto, Roel Gopez, Afsaneh Barzi, Toshiharu Yamaguchi, Fotios Loupakis, Heinz-Josef Lenz
BackgroundTrifluridine (FTD) is an active cytotoxic component of the metastatic colorectal cancer (mCRC) drug TAS-102, and thymidine phosphorylase inhibitor (TPI) inhibits the rapid degradation of FTD. We tested whether single nucleotide polymorphisms (SNPs) in genes involved in FTD metabolism and TPI excretion could predict outcome in patients with mCRC treated with TAS-102.Patients and methodsWe investigated three different cohorts: a training cohort (n = 52) and a testing cohort (n = 129) both receiving TAS-102 and a control cohort (n = 52) receiving regorafenib. SNPs of TK1, ENT1, CNT1, MATE1, MATE2 and OCT2 were analysed by polymerase chain reaction-based direct DNA sequencing.ResultsIn the training cohort, patients with any ENT1 rs760370 G allele had a significantly longer progression-free survival (PFS; 3.5 versus 2.1 months, respectively, hazard ratio [HR] 0.44, P = 0.004) and overall survival (OS; 8.7 versus 5.3 months, respectively, HR 0.27, P = 0.003) than the A/A genotype. These findings were validated in the testing cohort (P = 0.021 and 0.009 for PFS and OS, respectively). In addition, the combination of ENT1 rs760370, MATE1 rs2289669 and OCT2 rs316019 SNPs significantly stratified patients with the risk of PFS and OS in both cohorts (P < 0.001 for PFS and OS in the training cohort; P = 0.053 and 0.025 for PFS and OS, respectively, in the testing cohort). No significant differences were observed in the control group.ConclusionsThe combination of ENT1, MATE1 and OCT2 SNPs may serve as a predictive and prognostic marker in mCRC patients treated with TAS-102.



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A Novel Technology to Model Pressure-Induced Cellular Injuries in the Brain

Publication date: Available online 6 October 2017
Source:Journal of Neuroscience Methods
Author(s): Michael E. Smith, Ramin Eskandari
BackgroundElevated intracranial pressure (ICP) accompanying a number of neurological emergencies is poorly understood, and lacks a model to determine cellular pathophysiology. This limits our ability to identify cellular and molecular biomarkers associated with the pathological progression from physiologic to pathologic ICP.New MethodWe developed an ex vivo model of pressure-induced brain injury, which combines 3D neural cell cultures and a newly developed Pressure Controlled Cell Culture Incubator (PC³I). Human astrocytes and neurons maintained in 3D peptide-conjugated alginate hydrogels were subjected to pressures that mimic both physiologic and pathologic levels of ICP for up to 48hours to evaluate the earliest impacts of isolated pressure on cellular viability and quantify early indicators of pressure-induced cellular injury.ResultsCompared to control cell cultures grown under physiologic pressure, sustained pathologic pressure exposure increased the release of intracellular ATP in a cell-specific manner. Eighteen hours of sustained pressure resulted in increased ATP release from neurons but not astrocytes.Comparison with Existing MethodsCell culture incubators maintain cultures at normal atmospheric pressure. Based on multiple literature searches, we are not aware of any other cell culture incubator systems that modify the pressure at which primary CNS cells are maintained.ConclusionThis model simulates the clinical features of elevated ICP encountered in patients with hydrocephalus, and provides a first estimate of the pathological signaling encountered during the earliest perid of progression in neonatal hydrocephalus. This model should provide a means to better understand the pathological biomarkers associated with the earliest stages of elevated ICP.

Graphical abstract

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Preparation of polysomal fractions from mouse brain synaptoneurosomes and analysis of polysomal-bound mRNAs

Publication date: Available online 6 October 2017
Source:Journal of Neuroscience Methods
Author(s): Bozena Kuzniewska, Magdalena Chojnacka, Jacek Milek, Magdalena Dziembowska
BackgroundHere we describe a detailed, reliable protocol for isolation of polysomal fractions from mouse brain synaptoneurosomes. This method is an important tool to study local protein synthesis in neurons.New MethodWe combined rapid preparation of synaptoneurosomes by filtration with polysome profiling. We provide a detailed protocol highlighting difficulties and critical steps of: i) preparation of synaptoneurosomes; ii) polyribosome fractionation from synaptoneurosomes; iii) extraction of proteins and RNA from sucrose gradient fractions.Resultsand Comparison with Existing Methods We fractionated polyribosomes from synaptoneurosomes and detected the association of Mmp9, Camk2a and Stx1B mRNA with polysomes in the unstimulated conditions. Synaptic stimulation led to increased levels of Mmp9 and Camk2a mRNA in the heavy polysomal fractions. We compared our protocol with existing methodsConclusionsWe have developed a reliable, effective method to prepare polyribosomal fractions from synaptoneurosomes to study polyribosomal binding of mRNAs as an aspect of synaptic translation in vitro.



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Mucous Membrane Pemphigoid Causing Central Airway Obstruction

Mucous membrane pemphigoid (MMP) is a rare variant of the skin disease pemphigoid, which predominantly involves the mucous membranes. This rare autoimmune disease that infrequently affects the respiratory tract is characterized by subepithelial blister formation that may result in scarring. Immunopathologic examination of mucous membranes reveals the deposition of immunoglobulins and complement within the subepithelial basement membrane. We describe a patient with undiagnosed MMP, with a near-fatal presentation of central airway obstruction causing acute respiratory distress. The patient was successfully treated with emergent rigid bronchoscopic resection of a ball valve-like endotracheal mass, and diagnosed with a rare variant of pemphigoid disease, MMP. The patient was treated with mycophenolate and was clinically in remission, with bronchoscopically stable lesions at 1 year of follow-up.

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Usefulness of Medical Thoracoscopy in the Management of Pleural Effusion Caused by Chronic Renal Failure

Introduction: Although pleural effusion (PE) can be caused by several pathologies like congestive heart failure, infections, malignancies, and pulmonary embolism, it is also a common finding in chronic kidney disease (CKD). Diagnostic thoracentesis is of limited value in the differential diagnosis, and the role of more invasive investigations like medical thoracoscopy (MT) is still unclear. Aim: To evaluate the usefulness of MT in unexplained PE in CKD. Materials and Methods: In the electronic database of our Institution, we retrospectively searched for patients with CKD who underwent MT for unexplained PE between January 2008 and August 2016. Results: Ten patients were included in the present study. The average age was 72.4 years, the male:female ratio 9:1 and the average blood creatinine value 5.96 mg/dL. The average follow-up was 18 months. A thoracentesis showed an exudate was found in 9 patients and in 1 case pleural fluid characteristics were not recorded for technical reasons; in none of them the cytologic or microbiological analyses were considered diagnostic. The clinical suspicion was a neoplastic (5) or an infectious disease (5). In 4 patients with recurrent PE, MT was performed to obtain talc pleurodesis. No immediate procedure-related complications were recorded; 1 patient developed empyema after 2 months. In 6 cases final diagnosis was chronic uremic pleuritis, hydrothorax in 2, and chronic lymphocytic pleurisy in 2. Conclusions: MT represents a safe and effective diagnostic and therapeutic procedure in patients with CKD, that itself is a common cause of exudative effusion, and those patients may not require MT.

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Airway Stenting Revisited: 30 Years, the Age of Reason?

No abstract available

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In situ hybridization detection methods for HPV16 E6/E7 mRNA in identifying transcriptionally active HPV infection of oropharyngeal carcinoma: an updating

Publication date: Available online 6 October 2017
Source:Human Pathology
Author(s): Chiara C. Volpi, Chiara M. Ciniselli, Ambra V. Gualeni, Maddalena Plebani, Salvatore Alfieri, Paolo Verderio, Laura Locati, Federica Perrone, Pasquale Quattrone, Antonino Carbone, Silvana Pilotti, Annunziata Gloghini
The aim of this study is comparing two in situ hybridization (ISH) detection methods for human papilloma virus (HPV) 16 E6/E7 mRNA, i.e. the RNAscope® 2.0 High Definition (HD) and the upgraded RNAscope® 2.5 HD version. The RNAscope® 2.5 HD has recently replaced the RNAscope® 2.0 HD detection kit. Therefore, this investigation starts from the need to analytically validate the new mRNA ISH assay and, possibly, to refine the current algorithm for HPV detection in oropharyngeal squamous cell carcinoma (OSCC) with the final goal to apply it to daily laboratory practice. The study was based on HPV status and on generated data, interpreted by a scoring algorithm. The results highlighted that the compared RNAscope HPV tests had a good level of interchangeability and enabled to identify OSCC that are truly driven by high risk-HPV infection. This was also supported by the comparison of the RNAscope HPV test with HPV E6/E7 mRNA real time reverse transcriptase-polymerase chain reaction (RT-PCR), in a fraction of cases where material for HPV E6/E7 mRNA real time RT-PCR was available. Furthermore, the algorithm that associates p16 immunohistochemistry (IHC) with the identification of HPV mRNA by RNAscope was more effective than the one that associated p16 IHC with the identification of HPV DNA by ISH.



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The CD4/CD8 Ratio of Tumor-infiltrating Lymphocytes at the Tumor-host Interface Has Prognostic Value in Triple Negative Breast Cancer

Publication date: Available online 6 October 2017
Source:Human Pathology
Author(s): Kai Wang, Tiansheng Shen, Gene P Siegal, Shi Wei
Compelling evidence has demonstrated the prognostic value of tumor-infiltrating lymphocytes (TILs), especially in triple-negative breast cancer (TNBC). However, only a limited number of studies to investigate the importance of the subsets of T cells in TILs has been carried out, less so the significance of the location of these TILs. In this study, we explored in a cohort of 42 consecutive TNBC cases the prognostic significance of TIL subsets at the tumor-host interface (within one high power field [0.5 μm] of the invasive front) and compared them to TILs within the intratumoral stroma. Given the reported importance of TILs in HER2-overexpressing breast cancer, a subset of such tumors were also included for comparison. The range was wide in both locations, never-the-less the mean CD4⁺ and CD8⁺ T cell count was significantly higher at the tumor-host interface than that found within the intratumoral stroma (both P<.0001). The number of CD4⁺ or CD8⁺ T cells at either location was not significantly associated with distant relapse-free or overall survival. However, the CD4/CD8 ratio at the tumor-host interface was significantly associated with both relapse-free survival (hazard ratio [HR] 0.2, P=.002) and overall survival (HR 0.13, P=.002), while this association was not seen for the CD4/CD8 ratio within the intratumoral stroma. As expected, both tumor size and nodal status were significantly associated with survival outcomes. The findings further support the contention that TILs, as a marker of regional immune escape, is of prognostic importance in TNBC progression, and that the CD4/CD8 ratio of TILs at the tumor-host interface plays a distinctive role, thus appearing to be of clinical relevance.



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Therapies for Inner Ear Disorders Are One Step Closer to Reality

Spiral Therapeutics (http://ift.tt/2xooDek), a pre-clinical stage company developing first-in-class therapies targeting inner ear disorders, has received positive feedback from the U.S. Drug and Food Administration (FDA) regarding its first Pre-Investigational New Drug (Pre-IND) package submission.  The FDA answered Spiral's product development questions related to manufacturing and non-clinical testing, and concurred with the company's clinical development plans for its LPT99 program for preventing chemotherapy-induced hearing loss in pediatric patients. Pre-IND is a program through which the FDA's Office of Antimicrobial Products could provide advice on drug development before it begins. Spiral plans to raise additional funds for an initial Phase 1 trial, the development of new preclinical data, and the company's operations for the next 18 months.​

Published: 10/6/2017 1:51:00 PM

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Can STN DBS protect both nigral somata and innervation of the striatum?

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Reply to Can STN DBS protect both nigral somata and innervation of the striatum?

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The Rhythm is Going to Get’Cha (o eh, o eh, o eh, oo aah)

Recent research out of McGill University has demonstrated that motor regions of the brain actually sharpen sound perception and this effect is increased when we move in rhythm with the sound.

The investigators examined participants as they listened to a complex tone sequence when the participant was still or tapped in rhythm with the target, all while magnetoencephalography (MEG) was recorded.  

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Cardiac cycle efficiency and dicrotic pressure variations: new parameters for fluid therapy: An observational study

BACKGROUND: During a fluid challenge, the changes in cardiac performance and peripheral circulatory tone are closely related to the position of the ventricle on the Frank–Starling curve. Some patients have a good haemodynamic response to a fluid challenge, others hardly any response. The early haemodynamic effects of a fluid challenge could predict the final response before the entire fluid volume has been administered. OBJECTIVE: To assess whether a multivariate logistic regression model, including pulse pressure variation (PPV), cardiac cycle efficiency (CCE), arterial elastance and the difference between the dicrotic pressure and both systolic and mean arterial pressure (SAP − Pdic and MAP − Pdic) can predict cardiac responsiveness early during a fluid challenge in comparison with the standard procedure described elsewhere. DESIGN: Observational study. SETTING: Elective surgical patients undergoing laparotomy, enrolled in two Italian University Hospitals. PATIENTS: Fifty adult surgical patients, ventilated with a lung protective strategy, were enrolled and data from 46 were analysed. INTERVENTIONS: A fluid challenge consisting of 500 ml of crystalloid infused over 10 min. MAIN OUTCOME MEASURES AND ANALYSIS: The changes in CCE, arterial elastance, SAP − Pdic and MAP − Pdic were compared using analysis of variance. A multivariate logistic regression analysis utilising baseline values and the first minute measuring a variation statistically significant for the considered variables. RESULTS: At baseline, PPV correctly identified 70% of patients (89% of non-responders; 42% of responders). The model, including baseline PPV, ΔCCE and ΔSAP − Pdic, correctly identified the efficiency of fluid challenge in 87% of patients (84.2% of responders; 92.5 of non-responders) after 5 min from fluid challenge infusion. CONCLUSION: In this pilot study conducted in a population of surgical patients mechanically ventilated with a VT less than 8 ml kg−1, a dynamic model of fluid challenge assessment, including PPV, ΔCCE and ΔSAP − Pdic, enhances the prediction of fluid challenge response after 5 min of a 10-min administration. TRIAL REGISTRATION: ACTRN12616001479493.

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Continuous non-invasive haemodynamic monitoring: a beneficial impact on patient outcome is needed to gain ‘confidence in the technology’

No abstract available

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The impact of continuous non-invasive arterial blood pressure monitoring on blood pressure stability during general anaesthesia in orthopaedic patients: A randomised trial

BACKGROUND: In patients undergoing general anaesthesia, intraoperative hypotension occurs frequently and is associated with adverse outcomes such as postoperative acute kidney failure, myocardial infarction or stroke. A history of chronic hypertension renders patients more susceptible to a decrease in blood pressure (BP) after induction of general anaesthesia. As a patient's BP is generally monitored intermittently via an upper arm cuff, there may be a delay in the detection of hypotension by the anaesthetist. OBJECTIVE: The current study investigates whether the presence of continuous BP monitoring leads to improved BP stability. DESIGN: Randomised, controlled and single-centre study. PATIENTS: A total of 160 orthopaedic patients undergoing general anaesthesia with a history of chronic hypertension. INTERVENTION: The patients were randomised to either a study group (n = 77) that received continuous non-invasive BP monitoring in addition to oscillometric intermittent monitoring, or a control group (n = 83) whose BP was monitored intermittently only. The interval for oscillometric measurements in both groups was set to 3 min. After induction of general anaesthesia, oscillometric BP values of the two groups were compared for the first hour of the procedure. Anaesthetists were blinded to the purpose of the study. MAIN OUTCOME MEASURE: BP stability and hypotensive events. RESULTS: There was no difference in baseline BP between the groups. After adjustment for multiple testing, mean arterial BP in the study group was significantly higher than in the control group at 12 and 15 min. Mean ± SD for study and control group, respectively were: 12 min, 102 ± 24 vs. 90 ± 26 mmHg (P = 0.039) and 15 min, 102 ± 21 vs. 90 ± 23 mmHg (P = 0.023). Hypotensive readings below a mean pressure of 55 mmHg occurred more often in the control group (25 vs. 7, P = 0.047). CONCLUSION: Continuous monitoring contributes to BP stability in the studied population. TRIAL REGISTRATION: NCT02519101.

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Effects of dexamethasone on early cognitive decline after cardiac surgery: A randomised controlled trial

BACKGROUND: Postoperative cognitive decline (POCD), a very common complication after cardiac surgery, is characterised by impairment of both memory function and intellectual ability as well as being associated with increased use of healthcare resources. The investigators focused on the role of the inflammatory response to a surgical procedure as a potential factor involved in the pathogenesis of POCD. OBJECTIVE: The use of prophylactic dexamethasone to attenuate the inflammatory response was hypothesised to reduce the risk of POCD. DESIGN: Randomised controlled study. SETTING: Single university teaching hospital, from March 2015 to January 2016. PATIENTS: A total of 169 patients scheduled for elective cardiac surgery were enrolled, and 161 patients were included in the analyses. INTERVENTION: Patients were randomised to receive a single intravenous bolus of 0.1 mg kg−1 dexamethasone (n = 85) or placebo (n = 84) 10 h before the surgery. MAIN OUTCOME MEASURES: The primary outcome measure in both groups was the incidence of POCD on the 6th day after surgery. The investigators also evaluated the effect of dexamethasone on the incidence of systemic inflammatory response syndrome, postoperative C-reactive protein levels and postoperative serum S100β protein levels. RESULTS: Compared to the placebo group, the dexamethasone group showed statistically significant reductions in the incidence of POCD (relative risk, 0.43; 95% confidence interval, 0.21 to 0.89; P = 0.02), the incidence of systemic inflammatory response syndrome (30.0 versus 58.0%, P 

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Re-evaluation of peri-operative cardiac risk (the MET REPAIR study): Study protocol of a prospective, multicentre cohort study sponsored by the European Society of Anaesthesiology

No abstract available

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The relative effects of dexmedetomidine and propofol on cerebral blood flow velocity and regional brain oxygenation: A randomised noninferiority trial

BACKGROUND: Dexmedetomidine constricts cerebral blood vessels without a concomitant reduction in cerebral metabolic oxygen consumption. Its safety as a sedative in patients with neurological diseases thus remains uncertain. OBJECTIVE: Our primary objective was to test the hypothesis that dexmedetomidine is noninferior to propofol as regards cerebral blood flow (CBF) velocity and brain oxygenation. DESIGN: Unblinded randomised trial. SETTING: Cleveland Clinic Hospital, Cleveland, from November 2010 to July 2013. PATIENTS: Forty-four patients scheduled for insertion of a deep-brain stimulating electrodes. INTERVENTIONS: Patients were randomised to receive either dexmedetomidine or propofol sedation during deep-brain stimulating electrode insertion. MAIN OUTCOME MEASURES: Intraoperative CBF velocity was measured with transcranial Doppler, and brain oxygenation was assessed with near-infrared spectroscopy. Noninferiority of dexmedetomidine to propofol was defined as a less than 20% difference in means. RESULTS: Twenty-three patients were given dexmedetomidine and 21 propofol. Baseline characteristics and operative management were similar in each group. Dexmedetomidine was noninferior to propofol on both CBF and brain oxygenation, confirming our primary hypothesis. For cerebral flood flow, the estimated ratio of means (dexmedetomidine/propofol) was 0.94 [90% CI: 0.84 to 1.05], P = 0.011 for noninferiority. For brain oxygenation, the estimated ratio of means was 0.99 [90% CI: 0.96 to 1.02], P 

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Sevoflurane attenuates systemic inflammation compared with propofol, but does not modulate neuro-inflammation: A laboratory rat study

BACKGROUND: Septic encephalopathy is believed to be a result of neuro-inflammation possibly triggered by endotoxins, such as lipopolysaccharides (LPS). Modulation of the immune system is a property of volatile anaesthetics. OBJECTIVE: We aimed to investigate the systemic and cerebral inflammatory response in a LPS-induced sepsis model in rats. We compared two different sedation strategies, intravenous propofol and the volatile anaesthetic sevoflurane, with the hypothesis that the latter may attenuate neuro-inflammatory processes. DESIGN: Laboratory rat study. SETTING: Basic research laboratories at the University Hospital Zurich and University Zurich Irchel between August 2014 and June 2016. PATIENTS: A total of 32 adult male Wistar rats. INTERVENTIONS: After tracheotomy and mechanical ventilation, the anaesthetised rats were monitored before sepsis was induced by using intravenous LPS or phosphate-buffered saline as control. Rats were sedated with propofol (10 mg kg−1 h−1) or sevoflurane (2 vol%) continuously for 12 h. MAIN OUTCOME MEASURES: Systemic inflammatory markers such as cytokine-induced neutrophil chemo-attractant protein 1, monocyte chemo-tactic protein-1 and IL-6 were determined. The same cytokines were measured in brain tissue. Cellular response in the brain was assessed by defining neutrophil accumulation with myeloperoxidase and also activation of microglia with ionised calcium-binding adaptor molecule-1 and astrocytes with glial fibrillary acidic protein. Finally, brain injury was determined. RESULTS: Animals were haemodynamically stable in both sedation groups treated with LPS. Blood cytokine peak values were lower in the sevoflurane-LPS compared with propofol-LPS animals. In brain tissue of LPS animals, chemoattractant protein-1 was the only significantly increased cytokine (P = 0.003), however with no significance between propofol and sevoflurane. After LPS challenge, cerebral accumulation of neutrophils was observed. Microglia activation was pronounced in the hippocampus of animals treated with LPS (P = 0.006). LPS induced prominent astrogliosis (P 

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Evaluation of preoperative oral carbohydrate administration on insulin resistance in off-pump coronary artery bypass patients: A randomised trial

BACKGROUND: In fasting cardiac surgery patients, preoperative carbohydrate (CHO) drink intake attenuated insulin resistance and improved cardiac metabolism, although its beneficial effects were not evident after cardiac surgery possibly due to cardiopulmonary bypass-related extreme systemic inflammation. OBJECTIVE: We aimed to evaluate whether preoperative CHO intake affected insulin resistance and free-fatty acid (FFA) concentrations in off-pump coronary revascularisation. DESIGN: A randomised controlled trial. SETTING: Primary care in a university hospital in Korea from January 2015 to July 2016. PATIENTS: Sixty patients who underwent elective multi-vessel off-pump coronary revascularisation were randomised into two groups. Three patients were excluded from analysis and 57 patients completed study. INTERVENTION: The CHO group received oral CHO (400 ml) the prior evening and 2 to 3 h before surgery, and the control group was fasted from food and water according to standard protocol. MAIN OUTCOME MEASURES: Insulin resistance was assessed twice, after anaesthetic induction and after surgery via short insulin tolerance test. FFA, C-reactive protein and creatine kinase-myocardial band concentrations were determined serially for 48 h after surgery. RESULTS: Insulin sensitivity was greater (P = 0.002) and plasma FFA concentrations were lower (P = 0.001) after anaesthetic induction in the CHO group compared with the Control group, although there were no intergroup differences after surgery. The postoperative peak creatine kinase-myocardial band concentration was significantly lower in the CHO group compared with the Control group [8.8 (5.4 to 18.2) vs. 6.4 (3.5 to 9.7) ng ml−1, P = 0.031]. CONCLUSION: A preoperative CHO supplement significantly reduced insulin resistance and FFA concentrations compared with fasting at the beginning of the surgery, but these benefits were lost after off-pump coronary revascularisation. Despite their transient nature, these beneficial effects resulted in less myocardial injury, mandating further studies focused on the impact of preoperative CHO on myocardial ischaemia and cardiac function after coronary revascularisation. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT 02330263.

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Comparing C-MAC videolaryngoscope with direct laryngoscopy for emergency intubation

No abstract available

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Echocardiography and passive leg raising in the postoperative period: A prospective observational study

BACKGROUND: Signs of hypovolaemia are frequent in the postoperative period, but not all patients need or respond to fluid administration. An increase in cardiac output (CO) after passive leg raising (PLR) has been demonstrated to be useful as a volume response predictor in non-surgical, spontaneously breathing patients. OBJECTIVE: The objective of this study was to evaluate the accuracy of transthoracic echocardiography after PLR to predict fluid responsiveness in post-surgical patients. DESIGN: A prospective observational study. SETTING: A tertiary hospital between January and July 2015. PATIENTS: Fifty-one spontaneously breathing postoperative patients with suspected hypovolaemia (arterial hypotension, oliguria, tachycardia or delayed capillary refill) were considered for the study. INTERVENTION: Demographic and personal data were collected, as well as heart rate variations, mean arterial pressure during PLR and after administering 500 ml of Ringer's lactate solution. CO was measured by transthoracic echocardiography. MAIN OUTCOME MEASURES: The primary outcome was measurement of CO before and after PLR and Ringer's lactate administration. RESULTS: Forty-one patients were included in the study (six patients were excluded because of a poor echocardiographic window and four because of misalignment of the Doppler and outflow tract of the left ventricle). Twenty-two patients (54%) were considered responders to fluid therapy, with an increase of stroke volume greater than or equal to 15% after 500 ml lactated Ringer's infusion. The highest area under the curve was found for an increase in CO (0.91 ± 0.05; 95% confidence interval 0.78 to 0.97). An increase in CO greater than 11% after the PLR manoeuvre predicts a volume response with 68% sensitivity and 100% specificity. CONCLUSION: This is the first study showing that measurement of CO after PLR can predict volume response in spontaneously breathing postoperative patients.

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Oh Excellent Air Bag - Under the influence of Nitrous Oxide, 1799–1920

No abstract available

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Sirolimus precipitating diabetes mellitus in a patient with congenital hyperinsulinaemic hypoglycaemia due to autosomal dominant ABCC8 mutation

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Cadaverless Anatomy Class: Mixed Reality Medical School

New technology allows students to see a 3D representation of a human body, reducing learning time and the cost of maintaining anatomy labs.
Medscape Medical News

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Technology to Target Skin Cancer Mortality

Apps that evaluate a single mole or lesion won't do the trick because people don't know which lesions to target. A whole-body surveillance approach is needed.
Medscape Dermatology

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Dynamics of oogenesis in ghost shrimp Callichirus major (Crustacea: Axiidea): a morphofunctional and histochemical study

Publication date: Available online 6 October 2017
Source:Acta Histochemica
Author(s): Tugstênio L. Souza, Adriane A. Braga, Laura S. López-Greco, Erika T. Nunes
Callichirus major, popularly known as ghost shrimp, is a species of great importance in the fishing industry, because of its use as live bait. This study aimed to describe the different stages of the developing ovaries in C. major. Shrimps were collected along the Corujão beach, Piuma, Brazil (20°50'41.6"S 40°44'15.7"W), and the gonads were dissected for histological and histochemical analysis. The ovary consists of two elongated filaments covered by a connective tissue that divides the organ into lobules, where somatic and germ cells are found. It was possible to classify five types of germ cells: Oogonia (Oog), previtellogenic oocyte (Oc1), early vitellogenic oocyte (Oc2), late vitellogenic oocyte (Oc3) and mature oocyte (Oc4) based on their vitellogenic stage, cytoplasmic, nuclear and morphometric characteristics. The histochemical analysis demonstrated an intense reaction for proteins and polysaccharides in peripheral cytoplasm of Oc3 comparing to others cell types. According to size, volume, color intensity and distribution of oocyte types the gonads were classified into: immature, developing, developed and spent, being in females at this last stage, observed empty follicles and oocytes in reabsorption process. During oogenesis was observed a gradual increase in cytoplasmic acidophilia due to accumulation of yolk granules and the intense histochemical reaction in periphery of Oc3, which indicate the beginning of an extravitellogenic source of nutrients. Based on the microscopic analysis of the vitellogenesis, shrimp C. major showed the initial short phase of oocyte growth following with a fast vitellogenic cycle.



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The Surgical Apgar Score Predicts Not Only Short-Term Complications But Also Long-Term Prognosis After Esophagectomy

Abstract

Background

The surgical Apgar score (SAS) quantifies three intraoperative factors and predicts postoperative complications, but few reports describe its usefulness in esophagectomy, and no studies to date show its correlation with long-term prognosis after esophagectomy.

Methods

This study investigated 400 cases in which esophagectomy was performed on esophageal malignant tumors at the authors' hospital from January 2007 to January 2017. In this study, SAS was defined as the sum of the scores of three parameters, namely, estimated blood loss, lowest mean arterial pressure, and lowest heart rate, with values extracted from medical records. Postoperative complications classified as Clavien–Dindo grade 3 or higher were also extracted. The study retrospectively compared the relationship of SAS to postoperative complications and survival.

Results

Univariate analysis showed that postoperative complications were significantly associated with hypertension (p = 0.017), thoracotomy (p = 0.012), and SAS ≤ 5 (p < 0.0001), and multivariate analysis showed that hypertension (p = 0.049) and SAS ≤ 5 (p < 0.0001) were significant predictive factors for complications. In the prognostic analysis, log-rank analysis showed that patients with an SAS ≤ 5 had a significantly poorer prognosis than those with a SAS > 5 (p = 0.043), especially for complications classified as clinical stage 2 or higher (p = 0.027). In the multivariate analysis, SAS ≤ 5 was identified as a significantly poor prognostic factor for complications classified as clinical stage 2 or higher (p = 0.029).

Conclusion

In this study, SAS was useful not only for predicting short-term complications, but also as a long-term prognostic factor after esophagectomy.

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Total Mesenteric Peritonectomy for Peritoneal Metastases (with video)

ABSTRACT

Background

Complete cytoreductive surgery (CRS), combining organ resection and peritonectomy, is the only potentially curative treatment for patients with peritoneal metastases (PM).1 ^,2 Diffuse mesenteric PM usually represents a contraindication for CRS.3 This report presents a standardized total mesenteric peritonectomy, which provides a therapeutic option of complete CRS for patients with diffuse mesenteric PM.

Patient

A 73-year-old man had a diagnosis of PM caused by an urachal adenocarcinoma (signet cell type). Initial assessment found a 60-mm urachal tumor above the dome of the urinary bladder. Dedicated magnetic resonance imaging (MRI)4 and explorative laparoscopy confirmed the presence of diffuse mucinous PM suspected of pseudomyxoma peritonei arising from urachus. The patient was treated by a systemic induction chemotherapy including cisplatin, fluorouracil, and docetaxel, with an almost full regression of the PM shown on control MRI. The man then was treated with CRS and hyperthermic intraperitoneal chemotherapy.5

Technique

Exploration found persistent diffuse macro-nodular PM with a good response to chemotherapy, a 16/39 peritoneal cancer index,6 and no digestive tract or other organ involvement. The CRS procedure included complete urachus resection, together with appendicectomy, cholecystectomy, omentectomy, and a total parietal and mesenteric peritonectomy, with a completeness of cytoreduction score6 of 1, as illustrated in the video. At this writing, after 6 months of follow-up evaluation, the patient remains free of symptomatic peritoneal disease or local recurrence.

Conclusion

Total mesenteric peritonectomy can be safely performed with the reported technique irrespective of how widespread PM is along the mesentery as long as few small bowel serous membranes are involved.

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The Surgical Apgar Score Predicts Not Only Short-Term Complications But Also Long-Term Prognosis After Esophagectomy

Abstract

Background

The surgical Apgar score (SAS) quantifies three intraoperative factors and predicts postoperative complications, but few reports describe its usefulness in esophagectomy, and no studies to date show its correlation with long-term prognosis after esophagectomy.

Methods

This study investigated 400 cases in which esophagectomy was performed on esophageal malignant tumors at the authors' hospital from January 2007 to January 2017. In this study, SAS was defined as the sum of the scores of three parameters, namely, estimated blood loss, lowest mean arterial pressure, and lowest heart rate, with values extracted from medical records. Postoperative complications classified as Clavien–Dindo grade 3 or higher were also extracted. The study retrospectively compared the relationship of SAS to postoperative complications and survival.

Results

Univariate analysis showed that postoperative complications were significantly associated with hypertension (p = 0.017), thoracotomy (p = 0.012), and SAS ≤ 5 (p < 0.0001), and multivariate analysis showed that hypertension (p = 0.049) and SAS ≤ 5 (p < 0.0001) were significant predictive factors for complications. In the prognostic analysis, log-rank analysis showed that patients with an SAS ≤ 5 had a significantly poorer prognosis than those with a SAS > 5 (p = 0.043), especially for complications classified as clinical stage 2 or higher (p = 0.027). In the multivariate analysis, SAS ≤ 5 was identified as a significantly poor prognostic factor for complications classified as clinical stage 2 or higher (p = 0.029).

Conclusion

In this study, SAS was useful not only for predicting short-term complications, but also as a long-term prognostic factor after esophagectomy.

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Expanding horizons in complement drug discovery: challenges and emerging strategies

Abstract

The complement system is best known for its role in innate immunity, providing a first line of defence against infection, maintaining tissue homeostasis by flagging apoptotic cells and debris for removal, and orchestrating crosstalk between adaptive and innate immunity. In a growing number of diseases, complement is known to drive pathogenesis or to contribute as an inflammatory amplifier of a disease trigger. Association of complement with common and devastating diseases has driven an upsurge in complement drug discovery, but despite a wealth of knowledge in the complexities of the cascade, and many decades of effort, very few drugs have progressed to late-stage clinical studies. The reasons for this are becoming clear with difficulties including high target concentration and turnover, lack of clarity around disease mechanism and unwanted side effects. Lessons learnt from drugs which are either approved, or are currently in late-stage development, or have failed and dropped off the drug development landscape, have been invaluable to drive a new generation of innovative drugs which are progressing through clinical development. In this review, the challenges associated with complement drug discovery are discussed and the current drug development landscape is reviewed. The latest approaches to improve drug characteristics are explored and those agents which employ these technologies to improve accessibility to patients are highlighted.

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A chamber study of alkyl nitrate production formed by terpene ozonolysis in the presence of NO and alkanes

Publication date: Available online 6 October 2017
Source:Atmospheric Environment
Author(s): Stephen R. Jackson, Joel C. Harrison, Jason E. Ham, J.R. Wells
Organic nitrates are relatively long-lived species and have been shown to have a potential impact on atmospheric chemistry on local, regional, and even global scales. However, the significance of these compounds in the indoor environment remains to be seen. This work describes an impinger-based sampling and analysis technique for organic nitrate species, focusing on formation via terpene ozonolysis in the presence of nitric oxide (NO). Experiments were conducted in a Teflon film environmental chamber to measure the formation of alkyl nitrates produced from α-pinene ozonolysis in the presence of NO and alkanes using gas chromatography with an electron capture detector. For the different concentrations of NO and O3 analyzed, the concentration ratio of [O3]/[NO] around 1 was found to produce the highest organic nitrate concentration, with [O3] = 100 ppb & [NO] = 105 ppb resulting in the most organic nitrate formation, roughly 5 ppb. The experiments on α-pinene ozonolysis in the presence of NO suggest that organic nitrates have the potential to form in indoor air between infiltrated ozone/NO and terpenes from household and consumer products.



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Effects of inorganic seeds on secondary organic aerosol formation from photochemical oxidation of acetone in a chamber

Publication date: December 2017
Source:Atmospheric Environment, Volume 170
Author(s): Shuangshuang Ge, Yongfu Xu, Long Jia
Photochemical oxidations of acetone were studied under different inorganic seed (NaCl, (NH4)2SO4 and NaNO3) conditions in a self-made chamber. The results show that no secondary organic aerosol (SOA) can be formed in the experiments either in the absence of artificially added seed particles or in the presence of solid status of the added particles. Liquid water content is the key factor for the formation of SOA in the experiments with seeds. The amount of SOA was only about 4–7 μg m⁻³ in the experiments with the initial acetone of ∼15 ppm under different seed conditions. The analysis of SOA compositions by Exactive-Orbitrap mass spectrometer equipped with electro-spray interface (ESI-MS) shows that chlorine-containing and sulfur-containing compounds were detected in SOA formed from the experiments with NaCl and (NH4)2SO4 seeds, respectively, which were not identified in SOA from those with NaNO3. The compositions of SOA were mainly esters, organonitrates, hydroperoxides, etc. It is concluded that inorganic seed particles participated into the formation of SOA. Acetone SOA was mainly formed in the aqueous phase in which dissolved SOA precursors underwent further oxidation reactions, esterification reactions and/or radical-radical reactions. Our experiments further demonstrate that low-molecular-weight VOCs, such as acetone, can form SOA under certain conditions in the atmosphere, although their contributions to SOA may not be large.



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Statistical partitioning of a three-year time series of direct urban net CO2 flux measurements into biogenic and anthropogenic components

Publication date: Available online 6 October 2017
Source:Atmospheric Environment
Author(s): Olaf Menzer, Joseph P. McFadden
Eddy covariance flux measurements are increasingly used to quantify the net carbon dioxide exchange (FC) in urban areas. FC represents the sum of anthropogenic emissions, biogenic carbon release from plant and soil respiration, and carbon uptake by plant photosynthesis. When FC is measured in natural ecosystems, partitioning into respiration and photosynthesis is a well-established procedure. In contrast, few studies have partitioned FC at urban flux tower sites due to the difficulty of accounting for the temporal and spatial variability of the multiple sources and sinks. Here, we partitioned a three-year time series of flux measurements from a suburban neighborhood of Minneapolis-Saint Paul, Minnesota, USA. We segregated FC into one subset that captured fluxes from a residential neighborhood and into another subset that covered a golf course. For both land use types we modeled anthropogenic flux components based on winter data and extrapolated them to the growing season, to estimate gross primary production (GPP) and ecosystem respiration (Reco) at half-hourly, daily, monthly and annual scales. During the growing season, GPP had the largest magnitude (up to − 9.83 g C m⁻² d⁻¹) of any component CO2 flux, biogenic or anthropogenic, and both GPP and Reco were more dynamic seasonally than anthropogenic fluxes. Owing to the balancing of Reco against GPP, and the limitations of the growing season in a cold temperate climate zone, the net biogenic flux was only 1.5%–4.5% of the anthropogenic flux in the dominant residential land use type, and between 25% - 31% of the anthropogenic flux in highly managed greenspace. Still, the vegetation sink at our site was stronger than net anthropogenic emissions on 16–20 days over the residential area and on 66–91 days over the recreational area. The reported carbon flux sums and dynamics are a critical step toward developing models of urban CO2 fluxes within and across cities that differ in vegetation cover.

Graphical abstract

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Modification of the Surgical Strategy for the Dissection of the Recurrent Laryngeal Nerve Using Continuous Intraoperative Nerve Monitoring

Abstract

Background

The aim of this study was to describe first experiences and changes in management using continuous intraoperative neuromonitoring (C-IONM) in thyroid and parathyroid surgery.

Method

Retrospective analysis of patients who underwent surgery with C-IONM since 2012. Surgical maneuvers were modified when electrophysiologic events occurred. Patients with persistent loss of signal (LOS) underwent postoperative laryngoscopy.

Results

One hundred and one patients (of 1586 neck surgeries) were included and 19 had events: In 13 these were temporary (resolved before end of surgery) and led to intraoperative modifications in surgical approach; in all cases traction was released, and in 8, recurrent laryngeal nerve (RLN) approach was changed [superior approach (2), inferior approach (2), both (4)]. Six patients had persistent LOS (5.9%, present at end of procedure), with RLN palsy (RLNP) on postoperative day 1: In three, LOS occurred at electrode placement on the vagus nerve, leading to distal placement of the electrode allowing ipsilateral dissection under continuous monitoring; all three had complete recovery at 6 months. In the three other patients, LOS occurred on the RLN: one probable thermal, one traction lesion and one accidental section of the anterior RLN branch. The RLN recovered within 6 months in two patients, and in the third, RLNP persisted after 6 months (1/101 = 1%).

Conclusion

C-IONM provides real-time evaluation of the RLN function, allowing for adaptation of surgical maneuvers to prevent RLNP. It seems particularly useful in difficult cases like redo neck surgery, invasive thyroid cancer and intrathoracic or large goiter. Care should be given at electrode placement on the vagus nerve.

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Preparation Ferrule Design Effect on Endocrown Failure Resistance

Abstract

Purpose

To evaluate the effect of preparation ferrule inclusion with fracture resistance of mandibular molar endocrowns.

Materials and Methods

Recently extracted mandibular third molars were randomly divided into 3 groups (n = 12) with the coronal tooth structure removed perpendicular to the root long axis approximately 2 mm above the cemento-enamel junction with a slow-speed diamond saw. The pulp chamber was exposed using a diamond bur in a high-speed handpiece with pulpal remnants removed and canals instrumented using endodontic hand instruments. The chamber floor was restored using a resin core material with a two-step, self-etch adhesive and photopolymerized with a visible light-curing unit to create a 2 mm endocrown preparation pulp chamber extension. One and two millimeter ferrule height groups were prepared using a diamond bur in a high-speed handpiece following CAD/CAM guidelines. Completed preparation surface area was determined using a digital measuring microscope. Scanned preparations were restored with lithium disilicate restorations with a self-adhesive resin luting agent. All manufacturer recommendations were followed. Specimens were stored at 37°C/98% humidity and tested to failure after 24 hours at a 45° angle to the tooth long axis using a universal testing machine. Failure load was converted to MPa using the available bonding surface area with mean data analyzed using Kruskal-Wallis/Dunn (p = 0.05).

Results

Calculated failure stress found no difference in failure resistance among the three groups; however, failure load results identified that the endocrown preparations without ferrule had significantly lower fracture load resistance. Failure mode analysis identified that all preparations demonstrated a high number of catastrophic failures.

Conclusions

Under the conditions of this study, ferrule-containing endocrown preparations demonstrated significantly greater failure loads than standard endocrown restorations; however, calculated failure stress based on available surface area for adhesive bonding found no difference between the groups. Lower instances of catastrophic failure were observed with the endocrown preparations containing 1 mm of preparation ferrule design; however, regardless of the presence of ferrule, this study found that all endocrown restorations suffered a high proportion of catastrophic failures but at loads greater than reported under normal masticatory function.

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A Systematic Review of the Survival and Complication Rates of All-Ceramic Resin-Bonded Fixed Dental Prostheses

Abstract

Purpose

The aim of this systematic review was to investigate the survival and complication rates of all-ceramic resin-bonded fixed dental prostheses (RBFDPs).

Materials and Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied. A systematic search was conducted by an electronic search in PubMed, EMBASE, Cochrane Library, and CNKI databases complemented by a manual search. Only clinical studies on all-ceramic RBFDPs with a mean follow-up period of at least 3 years qualified for data analyses.

Results

Among 1503 screened articles, one randomized controlled trial (RCT) and seven prospective or retrospective cohort studies were included in this study. The estimated 5-year survival rate of all-ceramic RBFDPs was 91.2%. Debonding and framework fracture were the two most frequent technical complications, and the estimated 5-year debonding rate and fracture rate were 12.2% and 4.8%, respectively. Additionally, cantilevered all-ceramic RBFDPs had a higher survival rate (p < 0.01), lower debonding rate, (p < 0.05), and fracture rate (p < 0.01) compared with two-retainer all-ceramic RBFDPs. Zirconia ceramic RBFDPs had a lower incidence of failure but a higher debonding rate compared with glass-ceramic RBFDPs (p < 0.01).

Conclusion

Within the limitations of this systematic review, although all-ceramic RBFDPs have a favorable 5-year survival rate, this rate cannot represent the complete success of the treatment, since it may include typical complications such as debonding and fractures. There is an urgent need for long-term clinical studies, especially for well-designed RCTs on all-ceramic RBFDPs.

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Fluid distribution in ankle and midfoot joints: MR findings in asymptomatic volunteers

Abstract

Purpose

The purpose of this study is to assess the amount of fluid in the joints of the ankle and midfoot on MR imaging in asymptomatic volunteers.

Materials and methods

Twenty-one healthy asymptomatic volunteers (42 ankles) were evaluated with MRI imaging. There were 13 men and 8 women. The mean age was 24.7 years (19–42 years). MR imaging was performed on a 3T MR system using proton density weighted images with fat saturation (TR 2969, TE 30 ms, NA 2, slice thickness 2.5 mm). Images were obtained in three orthogonal planes. The images were interpreted by two radiologists in two sessions. The maximum size of the joint effusion was measured in one plane. Descriptive statistics and variation between interpretation sessions were calculated.

Results

Fluid in the anterior tibiotalar joint had a mean size of 2.0 mm (0.0–5.5 mm), in the posterior tibiotalar joint 3.1 mm (0.0–6.3 mm), in the talonavicular joint 0.7 mm (0.0–2.9 mm), and in the anterolateral recess 2.0 mm (0.0–4.3 mm). Fluid in the posterior aspect of the posterior subtalar joint had a mean size of 2.6 mm (0.0–9.4 mm), in the anterior aspect of the posterior subtalar joint 1.9 mm (0.0–6.6 mm), at the middle subtalar joint 0.1 mm (0.0–1.7 mm), and at the anterior subtalar joint 1.6 mm (0.0–6.0 mm). Fluid in the tibiofibular joint had a mean height of 8.1 mm (0.0–16.4 mm).

Conclusion

In asymptomatic volunteers, moderate to large amounts of fluid were common in all joint recesses of ankle and midfoot, and most pronounced in the anterior and posterior tibiotalar joint, anterolateral recess, and posterior subtalar joint. This should not be mistaken for evidence of a pathological condition.

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Flortaucipir tau PET imaging in semantic variant primary progressive aphasia

Objective

The semantic variant of primary progressive aphasia (svPPA) is typically associated with frontotemporal lobar degeneration (FTLD) with longTAR DNA-binding protein (TDP)-43-positive neuropil threads and dystrophic neurites (type C), and is only rarely due to a primary tauopathy or Alzheimer's disease. We undertook this study to investigate the localisation and magnitude of the presumed tau Positron Emission Tomography (PET) tracer [¹⁸F]Flortaucipir (FTP; also known as T807 or AV1451) in patients with svPPA, hypothesising that most patients would not show tracer uptake different from controls.

Methods

FTP and [¹¹C]Pittsburgh compound B PET imaging as well as MRI were performed in seven patients with svPPA and in 20 controls. FTP signal was analysed by visual inspection and by quantitative comparison to controls, with and without partial volume correction.

Results

All seven patients showed elevated FTP uptake in the anterior temporal lobe with a leftward asymmetry that was not observed in healthy controls. This elevated FTP signal, largely co-localised with atrophy, was evident on both visual inspection and quantitative cortical surface-based analysis. Five patients were amyloid negative, one was amyloid positive and one has an unknown amyloid status.

Conclusions

In this series of patients with clinical profiles, structural MRI and amyloid PET imaging typical for svPPA, FTP signal was unexpectedly elevated with a spatial pattern localised to areas of atrophy. This raises questions about the possible off-target binding of this tracer to non-tau molecules associated with neurodegeneration. Further investigation with autopsy analysis will help illuminate the binding target(s) of FTP in cases of suspected FTLD-TDP neuropathology.

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International multicentre validation of the arteriovenous malformation-related intracerebral haemorrhage (AVICH) score

Objective

The recently published arteriovenous malformation-related intracerebral haemorrhage (AVICH) score showed better outcome prediction for patients with arteriovenous malformation (AVM)-related intracerebral haemorrhage (ICH) than other AVM or ICH scores. Here we present the results of a multicentre, external validation of the AVICH score.

Methods

All participating centres (n=11) provided anonymous data on 325 patients to form the Spetzler-Martin (SM) grade, the supplemented SM (sSM) grade, the ICH score and the AVICH score. Modified Rankin score (mRS) at last follow-up (mean 25.6 months) was dichotomized into favourable (mRS 0-2, n=210) and unfavourable (mRS 3-6;n=115). Univariate and AUROC analyses were performed to validate the AVICH score.

Results

Except nidus structure and AVM size, all single parameters forming the SM, sSM, ICH and AVICH score and the scores itself were significantly different between both outcome groups in the univariate analysis. The AVICH score was confirmed to be the highest predictive outcome score with an AUROC of 0.765 compared with 0.705 for the ICH score and 0.682 for the sSM grade.

Conclusion

The multicentre-validated AVICH score predicts clinical outcome superior to pre-existing scores. We suggest the routine use of this score for future clinical outcome prediction and in clinical research.

Trial registration number

NCT02920645.

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Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinsons disease: the PPMI cohort

Objective

To examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson's disease (PD) compared with healthy controls (HC).

Methods

Parkinson's Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging.

Results

423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Aβ1–42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy.

Conclusions

This study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Aβ1–42 level is an important finding that will have to be replicated in other cohorts.

Trial registration

ClinicalTrials.gov identifier: NCT01141023.

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Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis

Objective

Functional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages.

Methods

A cohort of 121 patients with early relapsing–remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes.

Results

Patients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability.

Conclusion

Increased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease.

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Quality of life in inflammatory neuropathies: the IN-QoL

Background

No consensus exists which quality of life (QoL) measure should be used in patients with inflammatory neuropathies. Moreover, most QoL measures are ordinal-based scales with their known deficiencies.

Objectives

To establish a new disease-specific interval-based QoL questionnaire in inflammatory neuropathies (IN-QoL) using the Rasch model and evaluate its scientific properties (validity, reliability and responsiveness).

Methods

264 patients with inflammatory neuropathies completed six commonly used QoL questionnaires. The obtained data were stacked and subjected to Rasch analysis. Responsiveness was determined by using the concept of minimum clinically important differences related to varying individually obtained SEs (responsiveness definition: MCID-SE≥1.96 after 1-year follow-up compared with baseline).

Results

The IN-QoL fulfilled all Rasch's model requirements with high internal reliability values (patient separation index of 0.94), except being multidimensional. Additional factor analysis resulted in two (functional and mental) subsets that were unidimensional on their own. The IN-QoL showed good correlation with the EuroQol-health quality visual analogue scale (EQ-VAS) (Spearman's rho 0.72). It demonstrated acceptable responsiveness in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), as did the EQ-VAS. In patients with monoclonal gammopathy-related neuropathy and multifocal motor neuropathy, hardly any changes were seen over time.

Conclusion

The IN-QoL questionnaire fulfils modern clinimetric requirements and correlates strongly with a patient's self-assessment of their own quality of health, while also showing responsiveness in patients with GBS and CIDP. We propose using the IN-QoL and the EQ-VAS for assessing the QoL of patients with inflammatory neuropathies in future studies.

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Intravenous alteplase and endovascular clot retrieval following reversal of dabigatran with idarucizumab

Introduction

Dabigatran etexilate (dabigatran) is a direct thrombin inhibitor that has been shown to prevent stroke in patients with atrial fibrillation. Idarucizumab is a humanised monoclonal antibody fragment developed to reverse the anticoagulant effects of dabigatran. Idarucizumab binds dabigatran 350 times more avidly than dabigatran binds thrombin, and completely reverses dabigatran's biological activity within a few minutes.1 To date there have been only a handful of patients in whom dabigatran have been reversed with idarucizumab prior to treatment with intravenous alteplase, and none prior to endovascular clot retrieval.2 3

Methods

All New Zealand patients treated with alteplase must be entered into a national database, and this has noted whether idarucizumab was used prior to alteplase or clot retrieval since 2016. All patients treated with dabigatran and presenting within the 4.5-hour alteplase, or 6-hour endovascular clot retrieval treatment windows, had blood samples taken for thrombin clotting...

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Fluid distribution in ankle and midfoot joints: MR findings in asymptomatic volunteers

Abstract

Purpose

The purpose of this study is to assess the amount of fluid in the joints of the ankle and midfoot on MR imaging in asymptomatic volunteers.

Materials and methods

Twenty-one healthy asymptomatic volunteers (42 ankles) were evaluated with MRI imaging. There were 13 men and 8 women. The mean age was 24.7 years (19–42 years). MR imaging was performed on a 3T MR system using proton density weighted images with fat saturation (TR 2969, TE 30 ms, NA 2, slice thickness 2.5 mm). Images were obtained in three orthogonal planes. The images were interpreted by two radiologists in two sessions. The maximum size of the joint effusion was measured in one plane. Descriptive statistics and variation between interpretation sessions were calculated.

Results

Fluid in the anterior tibiotalar joint had a mean size of 2.0 mm (0.0–5.5 mm), in the posterior tibiotalar joint 3.1 mm (0.0–6.3 mm), in the talonavicular joint 0.7 mm (0.0–2.9 mm), and in the anterolateral recess 2.0 mm (0.0–4.3 mm). Fluid in the posterior aspect of the posterior subtalar joint had a mean size of 2.6 mm (0.0–9.4 mm), in the anterior aspect of the posterior subtalar joint 1.9 mm (0.0–6.6 mm), at the middle subtalar joint 0.1 mm (0.0–1.7 mm), and at the anterior subtalar joint 1.6 mm (0.0–6.0 mm). Fluid in the tibiofibular joint had a mean height of 8.1 mm (0.0–16.4 mm).

Conclusion

In asymptomatic volunteers, moderate to large amounts of fluid were common in all joint recesses of ankle and midfoot, and most pronounced in the anterior and posterior tibiotalar joint, anterolateral recess, and posterior subtalar joint. This should not be mistaken for evidence of a pathological condition.

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Independent association among suicidal ideation, asthma, and bronchial hyperresponsiveness in adolescents

Abstract

Asthma is a known risk factor for suicide-related behaviors in adolescents.¹ In particular, an association between asthma and suicidal behaviors has been reported in US high school students² and Taiwanese³ adolescents. However, most previous studies have used self-reported questionnaires to determine whether asthma was present², and others used hospital registries.³ Moreover, the role of potential confounders has not been fully investigated.

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