Impact of Age and Baseline NIHSS Scores on Clinical Outcomes in the Mechanical Thrombectomy Using Solitaire FR in Acute Ischemic Stroke Study

BACKGROUND AND PURPOSE Age and stroke severity are inversely correlated with the odds of favorable outcome after ischemic stroke. A previously proposed score for Stroke Prognostication Using Age and NIHSS Stroke Scale (SPAN) indicated that SPAN-100-positive patients (ie, age + NIHSS score = 100 or more) do not benefit from IV-tPA. If this finding holds true for endovascular therapy, this score can impact patient selection for such interventions. This study investigated whether a score combining age and NIHSS score can improve patients' selection for endovascular stroke therapy. MATERIALS AND METHODS The SPAN index was calculated for patients in the prospective Solitaire FR Thrombectomy for Acute Revascularization study: an international single-arm multicenter cohort for anterior circulation stroke treatment by using the Solitaire FR. The proportion with favorable outcome (90-day mRS score ≤2) was compared between SPAN-100-positive versus-negative patients. RESULTS Of the 202 patients enrolled, 196 had baseline NIHSS scores. Fifteen (7.7%) patients were SPAN-100-positive. There was no difference in the rate of successful reperfusion (Thrombolysis In Cerebral Infarction 2b or 3) between SPAN-100-positive versus -negative groups (93.3% versus 82.8%, respectively; P = .3). Stroke SPAN-100-positive patients had a significantly lower proportion of favorable clinical outcomes (26.7% versus 60.8% in SPAN-100-negative, P = .01). In a multivariable analysis, SPAN-100-positive status was associated with lower odds of favorable outcome (OR, 0.3; 95% CI, 0.1-0.9; P = .04). A higher baseline Alberta Stroke Program Early CT Score and a short onset to revascularization time also predicted favorable outcome in the multivariable analysis. CONCLUSIONS A significantly lower proportion of patients with a positive SPAN-100 achieved favorable outcome in this cohort. SPAN-100 was an independent predictor of favorable outcome after adjusting for time to treatment and the extent of preintervention tissue damage according to the Alberta Stroke Program Early CT Score.

Juvenile onset central nervous system folate deficiency and rheumatoid arthritis.

Isolated cerebral folate deficiency was detected in a 13-year-old girl with cognitive and motor difficulties and juvenile rheumatoid arthritis. Her serum contains autoantibodies that block membrane-bound folate receptors that are on the choroid plexus and diminish the uptake of folate into the spinal fluid. Whereas her serum folate exceeded 21 ng/mL, her spinal fluid contained 3.2 ng/mL of 5-methyltetrahydrofolate as a consequence of the autoantibodies diminishing the uptake of this folate.

Does Age Matter? Semantic Memory in Healthy Young and Elderly Adults

Background: Semantic memory processes have been well described in literature. However, the available findings are mostly based on relatively young subjects and concrete word material (e.g. tree). Comparatively little information exists about semantic memory for abstract words (e.g. mind) and possible age related changes in semantic retrieval. In this respect, we developed a paradigm that is useful to investigate the implicit (i.e. attentionindependent) access to concrete and abstract semantic memory. These processes were then compared between young and elderly healthy subjects. Methods: A well established tool for investigating semantic memory processes is the semantic priming paradigm, which consists both of semantically unrelated and related word pairs. In our behavioral task these noun-noun word pairs were further divided into concrete, abstract and matched pronounceable non-word conditions. With this premise, the young and elderly participants performed a lexical decision task: they were asked to press a choice of two buttons as an indication for whether the word pair contained a non-word or not. In order to minimize controlled (i.e. attention-dependent) retrieval strategies, a short stimulus onset asynchrony (SOA) of 150ms was set. Reaction time (RT) changes and accuracy to related and unrelated words (priming effect) in the abstract vs. concrete condition (concreteness effect) were the dependent variables of interest. Results and Discussion: Statistical analysis confirmed both a significant priming effect (i.e. shorter RTs in semantically related compared to unrelated words) and a concreteness effect (i.e. RT decrease for concrete compared to abstract words) in the young and elderly subjects. There was no age difference in accuracy. The only age effect was a commonly known general slowing in RT over all conditions. In conclusion, age is not a critical factor in the implicit access to abstract and concrete semantic memory.

Exposure to stallion accelerates the onset of mares' cyclicity.

Horses (Equus caballus) belong to the group of seasonally polyestrous mammals. Estrous cycles typically start with increasing daylight length after winter, but mares can differ greatly in the timing of onset of regular estrus cycles. Here, we test whether spatial proximity to a stallion also plays a role. Twenty-two anestrous mares were either exposed to one of two stallions (without direct physical contact) or not exposed (controls) under experimental conditions during two consecutive springs (February to April). Ovarian activity was monitored via transrectal ultrasound and stallion's direct contact time with each mare was determined three times per week for one hour each. We found that mares exposed to a stallion ovulated earlier and more often during the observational period than mares that were not exposed to stallions. Neither stallion identity nor direct contact time, mare age, body condition, size of her largest follicle at the onset of the experiment, or parasite burden significantly affected the onset of cyclicity. In conclusion, the timing of estrous cycles and cycle frequency, i.e., crucial aspects of female reproductive strategy, strongly depend on how the mares perceive their social environment. Exposing mares to the proximity of a stallion can therefore be an alternative to, for example, light programs or elaborated hormonal therapies to start the breeding season earlier and increase the number of estrous cycles in horses.

Impact of early-onset seizures on grading and outcome in patients with subarachnoid hemorrhage

OBJECT After subarachnoid hemorrhage (SAH), seizure occurs in up to 26% of patients. The impact of seizure on outcome has been studied, yet its impact on grading is unknown. The authors evaluated the impact of early-onset seizures (EOS) on grading of spontaneous SAH and on outcome. METHODS This retrospective analysis included consecutive patients with SAH who were treated at the NeuroCenter, Inselspital, University Hospital Bern, Switzerland, between January 2005 and December 2010. Demographic data, clinical data, and reports of EOS were recorded. The EOS were defined as seizures occurring within 24 hours after ictus. Patients were graded according to the World Federation of Neurosurgical Societies (WFNS) scale pre- and postresuscitation and dichotomized into good (WFNS I-III) and poor (WFNS IV-V) grades. Outcome was assessed at 6 months by using the modified Rankin Scale (mRS); an mRS score of 0-3 was considered a good outcome and an mRS score of 4-6 was considered a poor outcome. RESULTS Forty-one of 425 patients with SAH had EOS. Twenty-seven of those 41 patients (65.9%) had a poor WFNS grade. Twenty-eight (68.3%) achieved a good outcome, 11 (26.8%) had a poor outcome, and 2 (4.9%) were lost to followup. Early-onset seizures were proven in 9 of 16 electroencephalograms. The EOS were associated with poor WFNS grade (OR 2.81, 97.5% CI 1.14-7.46; p = 0.03) and good outcome (OR 4.01, 97.5% CI 1.63-10.53; p = 0.03). Increasing age, hydrocephalus, intracerebral hemorrhage, and intraventricular hemorrhage were associated with poor WFNS grade, whereas only age, intracerebral hemorrhage (p < 0.001), and poor WFNS grade (p < 0.001) were associated with poor outcome. CONCLUSIONS Patients with EOS were classified significantly more often in a poor grade initially, but then they significantly more often achieved a good outcome. The authors conclude that EOS can negatively influence grading. This might influence decision making for the care of patients with SAH, so grading of patients with EOS should be interpreted with caution.

Early-onset Crohn's disease is a risk factor for smaller final height.

OBJECTIVES Growth retardation is a frequent complication of paediatric inflammatory bowel disease (IBD). Only a few studies report the final height of these patients, with controversial results. We compared adult height of patients with paediatric IBD with that of patients with adult-onset disease. METHODS Height data of 675 women 19-44 years of age and 454 men 23-44 years of age obtained at inclusion in the Swiss IBD cohort study registry were grouped according to the age at diagnosis: (a) prepubertal (men≤13, women≤11 years), (b) pubertal (men 13-22, women 11-18 years) and (c) adult (men>22, women>18 years of age), and compared with each other and with healthy controls. RESULTS Male patients with prepubertal onset of Crohn's disease (CD) had significantly lower final height (mean 172±6 cm, range 161-182) compared with men with pubertal (179±6 cm, 161-192) or adult (178±7 cm, 162-200) age at onset and the general population (178±7 cm, 142-204). Height z-scores standardized against heights of the normal population were significantly lower in all patients with a prepubertal diagnosis of CD (-0.8±0.9) compared with the other patient groups (-0.1±0.8, P<0.001). Prepubertal onset of CD emerged as a risk factor for reduced final height in patients with prepubertal CD. No difference for final height was found between patients with ulcerative or unclassified IBD diagnosed at prepubertal, pubertal or adult age. CONCLUSION Prepubertal onset of CD is a risk for lower final height, independent of the initial disease location and the necessity for surgical interventions.

Sporadic late-onset nemaline myopathy with MGUS: long-term follow-up after melphalan and SCT.

OBJECTIVE Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS. METHODS We performed a retrospective case series study (n = 8) on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT (HDM-SCT) on survival, muscle strength, and functional capacities. RESULTS Seven patients showed a lasting moderate-good clinical response, 2 of them after the second HDM-SCT. All of them had a complete, a very good partial, or a partial hematologic response. One patient showed no clinical or hematologic response and died. CONCLUSIONS This case series shows the positive effect of HDM-SCT in this rare disorder. Factors that may portend an unfavorable outcome are a long disease course before the hematologic treatment and a poor hematologic response. Age at onset, level and type of M protein (κ vs λ), and severity of muscle weakness were not associated with a specific outcome. CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT increases the probability of survival and functional improvement.

Age, trauma and the critical shoulder angle accurately predict supraspinatus tendon tears.

BACKGROUND The pathogenesis of full-thickness tears of the rotator cuff remains unclear. Apart from age and trauma, distinct scapular morphologies have been found to be associated with rotator cuff disease. The purpose of the present study was to evaluate whether a score formed using these established risk factors was able to predict the presence of a rotator cuff tear reliably. METHODS We retrospectively assessed a consecutive series of patients with a minimal age of 40 years old, who had true antero-posterior (AP) radiographs of their shoulders, as well as a magnetic resonance (MR) gadolinium-arthrography, between January and December 2011. In all of these patients, the critical shoulder angle (CSA) was determined, and MR images were assessed for the presence of rotator cuff tears. Additionally, the patients' charts were reviewed to obtain details of symptom onset. Based on these factors, the so-called rotator cuff tear (RCT) score was calculated. RESULTS Patients with full-thickness RCTs were significantly older and had significantly larger CSAs than patients with intact rotator cuffs. Multiple logistic regression, using trauma, age and CSA as independent variables, revealed areas under the curve (AUCs) for trauma of 0.55, for age of 0.65 and for CSA of 0.86. The combination of all three factors was the most powerful predictor, with an AUC of 0.92. CONCLUSION Age, trauma and the CSA can accurately predict the presence of a posterosuperior RCT. LEVEL OF EVIDENCE Level IV. Case series with no comparison groups.

Late onset and pregnancy-induced congenital thrombotic thrombocytopenic purpura.

UNLABELLED We report on our patient (case 2) who experienced a first acute episode of thrombotic thrombocytopenic purpura (TTP) at the age of 19 years during her first pregnancy in 1976 which ended in a spontaneous abortion in the 30th gestational week. Treatment with red blood cell concentrates was implemented and splenectomy was performed. After having suffered from several TTP episodes in 1977, possibly mitigated by acetylsalicylic acid therapy, an interruption and sterilization were performed in 1980 in her second pregnancy thereby avoiding another disease flare-up. Her elder sister (case 1) had been diagnosed with TTP in 1974, also during her first pregnancy. She died in 1977 during her second pregnancy from a second acute TTP episode. DIAGNOSIS In 2013 a severe ADAMTS13 deficiency of <10% without detectable ADAMTS13 inhibitor was repeatedly found. Investigation of the ADAMTS13 gene showed that the severe ADAMTS13 deficiency was caused by compound heterozygous ADAMTS13 mutations: a premature stop codon in exon 2 (p.Q44X), and a missense mutation in exon 24 (p.R1060W) associated with low but measurable ADAMTS13 activity. CONCLUSION Genetic analysis of the ADAMTS13 gene is important in TTP patients of all ages if an ADAMTS13 inhibitor has been excluded.

Age matters in the prevalence and clinical significance of ultra-high-risk for psychosis symptoms and criteria in the general population: Findings from the BEAR and BEARS-kid studies

Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high-risk symptoms in children and adolescents as compared to adults. We examined ultra-high-risk (UHR) symptoms and criteria in a sample of individuals aged 8-40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non-perceptive APS were differentiated. Psychosocial functioning and current non-psychotic DSM-IV axis I disorders were also surveyed. Well-trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8-15-year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non-perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non-perceptive APS, and their interaction with age, also in terms of conversion to psychosis.

Impact of anti-inflammatory treatment on the onset of uveitis in juvenile idiopathic arthritis: Longitudinal analysis from a nation-wide paediatric rheumatological database

PURPOSE Based on a nation-wide database, this study analysed the influence of methotrexate (MTX), TNF inhibitors and a combination of the two on uveitis occurrence in JIA patients. METHODS Data from the National Paediatric Rheumatological Database in Germany were used in this study. Between 2002 and 2013, data from JIA patients were annually documented at the participating paediatric rheumatological sites. Patients with JIA disease duration of less than 12 months at initial documentation and ≥2 years of follow-up were included in this study. The impact of anti-inflammatory treatment on the occurrence of uveitis was evaluated by discrete-time survival analysis. RESULTS A total of 3,512 JIA patients (mean age 8.3±4.8 years, female 65.7%, ANA-positive 53.2%, mean age at arthritis onset 7.8±4.8 years) fulfilled the inclusion criteria. Mean total follow-up time was 3.6±2.4 years. Uveitis developed in a total of 180 patients (5.1%) within one year after arthritis onset. Uveitis onset after the first year was observed in another 251 patients (7.1%). DMARD treatment in the year before uveitis onset significantly reduced the risk for uveitis: MTX (HR 0.63, p=0.022), TNF inhibitors (HR 0.56, p<0.001) and a combination of the two (HR 0.10, p<0.001). Patients treated with MTX within the first year of JIA had an even a lower uveitis risk (HR 0.29, p<0.001). CONCLUSION The use of DMARDs in JIA patients significantly reduced the risk for uveitis onset. Early MTX use within the first year of disease and the combination of MTX with a TNF inhibitor had the highest protective effect. This article is protected by copyright. All rights reserved.

No Effect of Acupuncture in the Relief of Delayed-Onset Muscle Soreness: Results of a Randomized Controlled Trial

BACKGROUND Delayed-onset muscle soreness (DOMS) is a common symptom in people participating in exercise, sport, or recreational physical activities. Several remedies have been proposed to prevent and alleviate DOMS. DESIGN AND METHODS A five-arm randomized controlled study was conducted to examine the effects of acupuncture on eccentric exercise-induced DOMS of the biceps brachii muscle. Participants were recruited through convenience sampling of students and general public. Participants were randomly allocated to needle, laser, sham needle, sham laser acupuncture, and no intervention. Outcome measures included pressure pain threshold (PPT), pain intensity (visual analog scale), and maximum isometric voluntary force. RESULTS Delayed-onset muscle soreness was induced in 60 participants (22 females, age 23.6 ± 2.8 years, weight 66.1 ± 9.6 kg, and height 171.6 ± 7.9 cm). Neither verum nor sham interventions significantly improved outcomes within 72 hours when compared with no treatment control (P > 0.05). CONCLUSIONS Acupuncture was not effective in the treatment of DOMS. From a mechanistic point of view, these results have implications for further studies: (1) considering the high-threshold mechanosensitive nociceptors of the muscle, the cutoff for PPT (5 kg/cm) chosen to avoid bruising might have led to ceiling effects; (2) the traditional acupuncture regimen, targeting muscle pain, might have been inappropriate as the DOMS mechanisms seem limited to the muscular unit and its innervation. Therefore, a regionally based regimen including an intensified intramuscular needling (dry needling) should be tested in future studies, using a higher cutoff for PPT to avoid ceiling effects.

Are there age-, strain-, and sex-differences in the prolonged exposure to methylphenidate?

Repeated treatment with psychostimulants produces behavioral sensitization that results in increased locomotor responses so that lower drug doses are required to obtain the same effect and cross-sensitization with other stimulants. Methylphenidate (MPD; Ritalin) is most frequently prescribed to treat children having attention deficit hyperactivity disorder (ADHD), a syndrome with onset in childhood characterized by high levels of inattention, hyperactivity, and impulsivity. Little is known of the consequences involving the long-term use of MPD as treatment for ADHD. This study investigates if there are age, genetic/strain, and sex differences in the prolonged exposure to MPD and cross-sensitization with amphetamine. The objective is to determine whether (a) early exposure to MPD in adolescent rats increases their sensitivity to the drug when they are adult rats, (b) there are strain and sex differences in the response to MPD, and (c) treatment with MPD in adolescent and adult Wistar-Kyoto (WKY), spontaneously hyperactive/hypertensive rat (SHR), and Sprague-Dawley (SD) rat results in cross-sensitization with amphetamine. The hypotheses are that (1) early exposure to MPD in adolescent rats increases their sensitivity to the drug when they reach adulthood, and that this hypersensitivity is dose-, strain-, and sex-dependent and (2) adult rats treated with MPD as adolescents will show a greater cross-sensitization to amphetamine than those adult rats treated with saline as adolescents, and that this cross-sensitization is dose-, strain-, and sex-dependent. The study consists of recording and evaluating locomotor activity of female and male WKY, SHR, and SD rats before and after acute and repeated MPD administration when these rats are young and as adults follows by an amphetamine treatment. Results showed that repeated treatment with MPD elicited behavioral sensitization and cross-sensitization with amphetamine in these animals. The study also found that strain and sex play a crucial role in the differentiated sensitivity to the acute and chronic effects of MPD. The development of behavioral sensitization and cross-sensitization are also dependent on the dose of MPD and the age of the rat. ^

Risk of adult-onset asthma in Mexican-American women employed in food preparation or food service

Existing literature examining the association between occupation and asthma has not been adequately powered to address this question in the food preparation or food service industries. Few studies have addressed the possible link between occupational exposure to cooking fumes and asthma. This secondary analysis of cohort study data aimed to investigate the association between adult-onset asthma and exposure to: (a) cooking fumes at work or (b) longest-held employment in food preparation or food service (e.g. waiters and waitresses, food preparation workers, non-restaurant food servers, etc.). Participants arose from a cohort of Mexican-American women residing in Houston, TX, recruited between July 2001 and June 2007. This analysis used Cox proportional-hazards regression to estimate the hazard ratio of adult-onset asthma given the exposures of interest, adjusting for age, BMI, smoking status, acculturation, and birthplace. We found a strong association between adult-onset asthma and occupational exposure to cooking fumes (hazard ratio [HR] = 1.77; 95% confidence interval [CI], 1.15, 2.72), especially in participants whose longest-held occupation was not in the food-related industry (HR = 2.12; 95% CI, 1.21, 3.60). In conclusion, adult-onset asthma is a serious public health concern for food industry workers. ^

Age tie points and geochemistry of sediment cores from the Antarctic continental margin

Few high-latitude terrestrial records document the timing and nature of the Cenozoic "Greenhouse" to "Icehouse" transition. Here we exploit the bulk geochemistry of marine siliciclastic sediments from drill cores on Antarctica's continental margin to extract a unique semiquantitative temperature and precipitation record for Eocene to mid-Miocene (~54-13 Ma). Alkaline elements are strongly enriched in the detrital mineral fraction in fine-grained siliciclastic marine sediments and only occur as trace metals in the biogenic fraction. Hence, terrestrial climofunctions similar to the chemical index of alteration (CIA) can be applied to the alkaline major element geochemistry of marine sediments on continental margins in order to reconstruct changes in precipitation and temperature. We validate this approach by comparison with published paleotemperature and precipitation records derived from fossil wood, leaves, and pollen and find remarkable agreement, despite uncertainties in the calibrations of the different proxies. A long-term cooling on the order of >=8°C is observed between the Early Eocene Climatic Optimum (~54-52 Ma) and the middle Miocene (~15-13 Ma) with the onset of transient cooling episodes in the middle Eocene at ~46-45 Ma. High-latitude stratigraphic records currently exhibit insufficient temporal resolution to reconstruct continental aridity and inferred ice-sheet development during the middle to late Eocene (~45-37 Ma). However, we find an abrupt aridification of East Antarctica near the Eocene-Oligocene transition (~34 Ma), which suggests that ice coverage influenced high-latitude atmospheric circulation patterns through albedo effects from the earliest Oligocene onward.