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Background: To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae. Methods: This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression. Findings: Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation–Sedation Scale score while on invasive mechanical ventilation was –4 (–5 to –3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p

We review two cases of adolescents with orbital cellulitis, sinusitis and SARS- CoV-2 infection presenting to emergency departments within a 24 hour period. SARS-CoV-2 samples obtained within 24 hours were positive, supporting prior infection despite relatively limited early symptoms of COVID-19. Unusual clinical and radiographic characteristics included hemorrhagic abscess with blood of varying age in the first, intracranial epidural abscess in the second, radiographic signal consistent with hemorrhagic or thrombotic phenomena, retro-maxillary antral fat changes, and meningeal enhancement or extension in both cases. Radiographic findings thereby mimic fungal infection, although final cultures and ancillary investigation for allergic and invasive fungal disease have remained negative. These cases highlight two unusual orbital presentations of cellulitis occurring in the context of SARS-CoV-2 co-infection.

PURPOSE To determine which narrative performance level for each general pediatrics entrustable professional activity (EPA) reflects the minimum level clinical competency committees (CCCs) felt should be associated with graduation as well as initial entrustment and compare expected narrative performance levels (ENPLs) for each EPA with actual narrative performance levels (ANPLs) assigned to residents at initial entrustment. METHOD A series of 5 narratives, corresponding to the 5 milestone performance levels, were developed for each of the 17 general pediatrics EPAs. In academic year (AY) 2015-2016, the CCCs at 22 Association of Pediatric Program Directors Longitudinal Educational Assessment Research Network member sites reported ENPLs for initial entrustment and at time of graduation. From AYs 2015-2016 to 2017-2018, programs reported ANPLs for initial entrustment decisions. ENPLs and ANPLs were compared using a logistic mixed effects model. RESULTS ENPLs for graduation and entrustment were most often level 3 (competent) followed by level 4 (proficient). For 8 EPAs, the ENPLs for graduation and entrustment were the same. For the remaining 9, some programs would entrust residents before graduation or graduate them before entrusting them. There were 4,266 supervision level reports for initial entrustment for which an ANPL was provided. ANPLs that were lower than the ENPLs were significantly more likely to be assigned to the medical home-well child (OR = 0.39; 95% CI: 0.26-0.57), transition to adult care (OR = 0.43; 95% CI: 0.19-0.95), behavioral or mental health (OR = 0.36; 95% CI: 0.18-0.71), make referrals (OR = 0.31; 95% CI: 0.17-0.55), lead a team (OR = 0.34; 95% CI: 0.22-0.52), and handovers (OR = 0.18; 95% CI: 0.09-0.36) EPAs. CONCLUSIONS CCCs reported lower ENPLs for graduation than for entrustment for 5 EPAs, possibly indicating curricular gaps that milestones and EPAs could help identify.

Background/aim The Fistula Risk Score (FRS), as other risk scores, is a validated model predicting the development of a clinically relevant post-operative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). We evaluated risk factors related with CR-POPF and correlated four predictive scores with the likelihood of developing CR-POPF in our cohort. Patients and methods The records of 107 patients who underwent PD from 2007 to 2015 were obtained from a prospectively maintained database and reviewed. CR-POPFs were categorized by the International Study Group of Pancreatic Fistula (ISGPF) standards. Firstly, a univariate and multivariate analysis of risk factors related to CR-PPOPF was performed, and then the data were correlated with FRS, Wellner's, Robert's and Yamamoto's scores. Results In total, 30 patients developed a CR-POPF. On multivariate analysis, abdominal thickness (OR=1.02, p=0.010), Wirsung's duct diameter (OR=0.57, p=0.029), pancreatic consistency (OR=3.18, p=0.011) and histological diagnosis of the lesion (OR=1.65, p=0.012) represented independent predictive factors of CR-POPF. FRS (R2=0.596, p=0.001), Wellner's score (R2=0.285, p=0.005) and Roberts' score (R2=0.385, p=0.002) correlated with the likelihood of developing CR-POPF. Conclusion Abdominal thickness, Wirsung's duct diameter, pancreatic consistency and histological diagnosis were independent predictive factors of CR-POPF. Predictive scores reflected the likelihood of CR-POPF, FRS being the score with the highest predictive value.

Background Assessment using entrustable professional activities (EPAs) is currently under study as a joint effort of the American Board of Pediatrics and program director community. However, limited evidence exists for the feasibility of EPA-based assessment in pediatrics. Aim Among pediatric residency programs that implemented EPA-based assessment over 3 academic years (2015-16, 2016-17, 2017-18), determine how often programs were “unable to assess” a resident on a given EPA. Methods 23 programs reported clinical competency committee (CCC) determined EPA supervision level assignments for all residents in their program for a subset of 5-6 of the 17 general pediatrics EPAs biannually (Fall and Spring), except interns who were only assessed at the end of the academic year (Spring). They indicated “unable to assess” whenever applicable. Results Across the 5 data collection cycles, there were 29,643 opportunities to assign an EPA supervision level to 1987 residents from all three post-graduate years. Of these, 4140 assignments (14%) were deemed “unable to assess.” Across all EPAs, this determination was made less often in mid-year reports than year-end reports (p=.005). Post-graduate year 3 (PGY3) residents and PGY2 residents had significantly lower frequencies of “unable to assess” assignments when compared with PGY1 residents (Figure). EPAs with the lowest rates of “unable to assess” included: EPA 4 (patients with acute, common dx) at 0.4%, EPAs 10 (initial resuscitation/stabilization) and 16 (handovers) at 0.9%, EPA 11 (manage information) at 4%, and EPA 13 (practice management) at 5%. EPAs with the highest rates of “unable to assess” included EPA 8 (transition to adult care) at 43%, EPA 17 (procedures) at 27%, EPA 14 (quality improvement) at 20%, and EPAs 12 (make referrals) and 9 (behavioral and mental health) at 14%. Conclusions “Unable to assess” assignments are related to the given EPA, training year, and timing of assessment within the academic year. CCCs may be less likely to assign EPA supervision levels at timepoints viewed as higher stakes, such as transition from one training year to the next. Future work should explore this further and consider the etiology behind high levels of inability to assess some EPAs in particular.

The aim was to evaluate the effects of judo combat on the athletes’ postural control (PC) and physiological loading before, during and after a simulated match. Seventeen under-20 regional and national level athletes completed one modified 7-min match. At baseline, during the combat (3rd and 7th minutes) and 2-min post-match centre of pressure (CoP) parameters were assessed. Heart rate (HR), blood lactate (BLa) and rating of perceived exertion (RPE) and local RPE (LRPE) were collected. Significant increments were observed in CoP mean positioning and velocity at 3rd and 7th minutes, but the CoP deviation in both axes was unaffected. HR and BLa were elevated at 3rd and 7th minutes, and they remained elevated 2-min post-match. However, CoP returned to baseline 2-min post-match. RPE was elevated at 3rd and 7th minutes and the greatest effort was displayed in the Deltoid and Quadriceps. Thus, one simulated judo match stimulates a significant metabolic response and balance is degraded, with the greatest effects on the anterior–posterior axis and it recovers to baseline level after 2 min of passive rest. The physiological load cannot be regarded as a potential predictor variable of CoP. Overall, a judo match predominantly affects the upper body than the other body parts.

Objective To describe the clinical and electromyographic characteristics of blepharospasm caused by selective involvement of the pars pretarsalis of the orbicularis oculi muscle. Methods Clinical assessment and simultaneous electromyographic recordings from levator palpebrae superioris and pars orbitaria and pretarsalis of orbicularis oculi muscles were performed in patients with blepharospasm and primary failure to botulinum toxin injections. Patients with selective abnormal electromyographic activity of the pars pretarsalis of the orbicularis oculi muscle were identified and treated with selective pretarsal injections of botulinum toxin. Results We found 24 patients with pretarsal blepharospasm confirmed by the electromyographic assessment. All of them were functionally blind. Three clinical-electromyographic patterns were identified: (a) Impairment of eyelid opening; (b) Increased blinking; (c) Spasms of eye closure combined with varying degrees of excessive blinking and impairment of eye-opening. Pretarsal injections of botulinum toxin induced a significant improvement in all patients and 50 % regained normal or near-normal vision. The clinical improvement was sustained after repeated pretarsal injections. Conclusions Pretarsal blepharospasm can be suspected on clinical grounds and it can be confirmed by electromyographic recordings. Significance Recognition of this type of blepharospasm is important because of its excellent response to botulinum toxin injections applied into the pretarsal part of the orbicularis oculi muscle.

For children with brainstem encephalitis or encephalomyelitis, clinicians should look for enterovirus and not limit testing to cerebrospinal fluid., We conducted an observational study from January 2016 through January 2017 of patients admitted to a reference pediatric hospital in Madrid, Spain, for neurologic symptoms and enterovirus infection. Among the 30 patients, the most common signs and symptoms were fever, lethargy, myoclonic jerks, and ataxia. Real-time PCR detected enterovirus in the cerebrospinal fluid of 8 patients, nasopharyngeal aspirate in 17, and anal swab samples of 5. The enterovirus was genotyped for 25 of 30 patients; enterovirus A71 was the most common serotype (21/25) and the only serotype detected in patients with brainstem encephalitis or encephalomyelitis. Treatment was intravenous immunoglobulins for 21 patients and corticosteroids for 17. Admission to the pediatric intensive care unit was required for 14 patients. All patients survived. At admission, among patients with the most severe disease, leukocytes were elevated. For children with brainstem encephalitis or encephalomyelitis, clinicians should look for enterovirus and not limit testing to cerebrospinal fluid.

Introduction The American Board of Pediatrics and pediatrics community developed entrustable professional activities (EPAs) defining the foundation of general pediatrics care. We sought to determine the developmental progression of pediatric residents across 3 years of training for the 17 General Pediatrics (GP) EPAs. Methods Over 3 academic years (2015-18), 22 geographically representative residency programs in the APPD LEARN used scales with 5 or 8 anchors, describing levels of supervision from direct to indirect to entrustment, to assess EPAs biannually. Interns were assessed only at the end of Year 1. We fit growth curves to ordinal supervision levels for all 17 EPAs together using a linear mixed model and developed “Denver Developmental” charts to display the proportion of learners who have reached each given level of supervision on each EPA based on the growth curves. Results Figure 1 illustrates examples of the developmental progression for 5 of the 17 EPAs. The graphic demonstrates where 25% (beginning of white box), 75% (where white and blue boxes meet), and 90% (end of blue box) of residents achieve each supervision level for the EPA with the highest ratings (handovers) and 4 EPAs with the lowest ratings (quality improvement, resuscitate/stabilize, behavioral/mental health, and transition to adult care) across 3 years of training. Some levels were achieved by all residents by the end of the intern year (e.g., levels 1-3 for EPA 16, handovers). Most EPAs had one or more advanced levels where the 25%, 75%, or 90% data extended beyond the end of training. In those instances, the percent of residents achieving these levels is indicated on the right-hand side of Figure 1 (e.g., 12% of residents achieved level 8 for EPA 8, transition to adult care, by the end of training). Conclusion The GP EPA “Denver Developmental” progressions may help in early screening for underperforming residents. This is critical information for the learner and the program. For the former, providing feedback provides an opportunity for improvement and for the latter, if a number of learners are not progressing as expected this may indicate curricular gaps.

Chronic neurotoxicity caused by lithium salts can be reversible or irreversible and may appear after years of treatment, even at serum levels considered within the usual therapeutic range. The authors present the case of a patient with bipolar disorder who developed dementia at the age of 54 after being treated with lithium carbonate at therapeutic levels for 4 years. Nevertheless, lithium treatment was continued. At age 56, the patient presented with an acute encephalopathy caused by toxic lithium levels, which resolved only after lithium carbonate was discontinued. Full recovery from the dementia, which had started 2 years earlier, occurred only after cessation of lithium. The authors conclude that when patients treated with lithium develop subacute cognitive impairment, the possibility of lithium toxicity should be considered, even if the serum levels are considered within the therapeutic range. A long duration of neurotoxicity associated with lithium treatment does not necessarily indicate an irreversible prognosis.

Progressive resistance exercise (PRE) can have a positive effect in individuals with Parkinson’s disease (PD). However, the effect of PRE may vary with the clinical subtype of PD. To date, no study has assessed the effects of PRE in the different subtypes of PD. AIM: The aim of the present study was to assess the effects of PRE in PD patients with akinesia and rigidity (AR-subtype). DESIGN: A randomized controlled trial was conducted. SETTING: Outpatients clinics of the Bierzo Parkinson Association (Ponferrada, Spain) and the Asturias Parkinson Association (Oviedo, Spain). POPULATION: Twenty-eight patients with AR-subtype PD were randomized into an Experimental Group (EG, N.=13) and Control Group (CG, N.=15). METHODS: Static posturography (Centre of Pressure -CoP- parameters), gait (the Ten-Meter Walk Test [TMWT]), freezing of gait (the Freezing of Gait Questionnaire [FOG-Q]), the motor portion of the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and patient-perceived quality of life (the 39-item Parkinson’s disease Questionnaire [PDQ39]), were assessed at pre-test, post-test, and re-test. Ratings of perceived exertion (RPE) (Borg >6-20 Scale) were recorded at the end of each PRE training session. RESULTS: The EG displayed significant ameliorations in Length (CoP parameters) from pre- to post-test (P=0.048), in speed of fast rhythm walking (TMWT) from pre- to post-test (P=0.000), and from pre- to re-test (P=0.027), and in the PDQ39 Score from pre- to post-test (P=0.024). No significant differences were detected in Area or Speed (CoP parameters), speed of preferred rhythm walking (TMWT), FOG-Q scores, or the motor portion of the MDS-UPDRS scores. The EG reported a mean RPE of 9.95 (between “very light” and “fairly light”) for the whole training program. CONCLUSIONS: These findings provide support for the use of PRE training in the rehabilitation of individuals with AR-subtype PD, as it can improve static posturography, gait, and quality of life. Furthermore, RPE scores showed that individuals with AR-subtype PD consider that PRE training require only light efforts. CLINICAL REHABILITATION IMPACT: The PRE training can be a helpful and fruitful rehabilitation tool for AR-subtype PD patients. Sin financiación 2.208 JCR (2017) Q1, 15/65 Rehabilitation 0.754 SJR (2017) Q1, 31/125 Rehabilitation; Q2, 53/201 Physical Therapy, Sports Therapy and Rehabilitation No data IDR 2017 UEM

The goal of this study was to specify symptoms frequently neglected in concussion. Health care professionals correctly identified 75% of concussion symptoms, whereas children and caregivers both only correctly identified 31%. Most people correctly identified headache and ataxia, but many missed photophobia, paresthesias, anxiety and depression. This study demonstrates the general lack of knowledge regarding specific signs and symptoms of concussion.

13 p.-6 fig.-1 tab., It has been known for a long time that mitochondria isolated from hepatocytes treated with glucagon or Ca(2+)-mobilizing agents such as phenylephrine show an increase in their adenine nucleotide (AdN) content, respiratory activity, and calcium retention capacity (CRC). Here, we have studied the role of SCaMC-3/slc25a23, the mitochondrial ATP-Mg/Pi carrier present in adult mouse liver, in the control of mitochondrial AdN levels and respiration in response to Ca(2+) signals as a candidate target of glucagon actions. With the use of SCaMC-3 knock-out (KO) mice, we have found that the carrier is responsible for the accumulation of AdNs in liver mitochondria in a strictly Ca(2+)-dependent way with an S0.5 for Ca(2+) activation of 3.3 ± 0.9 μm. Accumulation of matrix AdNs allows a SCaMC-3-dependent increase in CRC. In addition, SCaMC-3-dependent accumulation of AdNs is required to acquire a fully active state 3 respiration in AdN-depleted liver mitochondria, although further accumulation of AdNs is not followed by increases in respiration. Moreover, glucagon addition to isolated hepatocytes increases oligomycin-sensitive oxygen consumption and maximal respiratory rates in cells derived from wild type, but not SCaMC-3-KO mice and glucagon administration in vivo results in an increase in AdN content, state 3 respiration and CRC in liver mitochondria in wild type but not in SCaMC-3-KO mice. These results show that SCaMC-3 is required for the increase in oxidative phosphorylation observed in liver mitochondria in response to glucagon and Ca(2+)-mobilizing agents, possibly by allowing a Ca(2+)-dependent accumulation of mitochondrial AdNs and matrix Ca(2+), events permissive for other glucagon actions., This work was supported in part by Ministerio de Educación y Ciencia Grants BFU2008-04084/BMC and BFU2011-30456, European Union Grant LSHMCT- 2006-518153, and CIBERER Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (an initiative of the ISCIII Instituto de SaludCarlos III) (to J. S.), Comunidad de Madrid Grants S-GEN-0269-2006 and S2010/BMD-2402 MITOLAB-CM (to J. S., E. R., and A. S.), by ISCIII Grant PI080610 (to A. delA), and an institutional grant from the Fundación Ramon Areces to the Centro de Biología Molecular Severo Ochoa.

The aim of this study was to assess whether supervised slackline training reduces the risk of falls in people with Parkinson's disease (PD).Twenty-two patients with idiopathic PD were randomized into experimental (EG, N = 11) and control (CG, N = 11) groups. Center of Pressure (CoP), Freezing of Gait (FOG), and Falls Efficacy Scale (FES) were assessed at pre-test, post-test and re-test. Rate perceived exertion (RPE, Borg's 6-20 scale) and local muscle perceived exertion (LRPE) were also assessed at the end of the training sessions.The EG group showed significant improvements in FOG and FES scores from pre-test to post-test. Both decreased at re-test, though they did not return to pre-test levels. No significant differences were detected in CoP parameters. Analysis of RPE and LRPE scores revealed that slackline was associated with minimal fatigue and involved the major lower limb and lumbar muscles.These findings suggest that slacklining is a simple, safe, and challenging training and rehabilitation tool for PD patients. It could be introduced into their physical activity routine to reduce the risk of falls and improve confidence related to fear of falling. Implications for Rehabilitation Individuals with Parkinson's disease (PD) are twice as likely to have falls compared to patients with other neurological conditions. This study support slackline as a simple, safe, and challenging training and rehabilitation tool for people with PD, which reduce their risk of falls and improve confidence related to fear of falling. Slackline in people with PD yields a low tiredness or fatigue impact and involves the major lower limb and lumbar muscles.

Incorporation of a human bone allograft requires osteoclast activity and growth of recipient osteoblasts. The aim of this work was to study the effects produced by autoclavated and −80°C frozen bone allografts on osteoblast proliferation and synthesis of interleukin 6 (IL6), activator of bone resorption, aminoterminal propeptide of procollagen I (PINP), marker of bone matrix formation, and osteoprotegerin (OPG), inhibitor of osteoclast activity and differentiation. Allografts were obtained from human femoral heads. Human osteoblasts were cultured in the presence (problem group) or in the absence (control group) of allografts during 15 days. Allografts produced a decrease in osteoblast proliferation in the first week of the experiment, and an increase in IL6 mRNA, both at 3 h and 2 days, and an increase in the IL6 released to the culture medium the second day of the experiment. We found a decrease in OPG released to the culture on the 2nd and fourth days. These results suggest an increase in bone resorption and a decrease in bone formation in the first week of the experiment. In the second week, allografts produced an increase in osteoblast proliferation and PINP release to the culture medium, indicating an increase in bone formation; an increase in OPG released to the culture medium, which would indicate a decrease in bone resorption; and a decrease in IL6, indicating a decrease in bone resorption stimulation. These results demonstrate that autoclavated and −80°C frozen bone allografts produce in bone environmemt changes that regulate their own incorporation to the recipient bone. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:200–207, 2008

BACKGROUND. Activation of the NLRP3 inflammasome is associated with metabolic dysfunction, and intermittent fasting has been shown to improve clinical presentation of NLRP3 inflammasome–linked diseases. As mitochondrial perturbations, which function as a damage-associated molecular pattern, exacerbate NLRP3 inflammasome activation, we investigated whether fasting blunts inflammasome activation via sirtuin-mediated augmentation of mitochondrial integrity. METHODS. We performed a clinical study of 19 healthy volunteers. Each subject underwent a 24-hour fast and then was fed a fixed-calorie meal. Blood was drawn during the fasted and fed states and analyzed for NRLP3 inflammasome activation. We enrolled an additional group of 8 healthy volunteers to assess the effects of the sirtuin activator, nicotinamide riboside, on NLRP3 inflammasome activation. RESULTS. In the fasting/refeeding study, individuals showed less NLRP3 inflammasome activation in the fasted state compared with that in refed conditions. In a human macrophage line, depletion of the mitochondrial-enriched sirtuin deacetylase SIRT3 increased NLRP3 inflammasome activation in association with excessive mitochondrial ROS production. Furthermore, genetic and pharmacologic SIRT3 activation blunted NLRP3 activity in parallel with enhanced mitochondrial function in cultured cells and in leukocytes extracted from healthy volunteers and from refed individuals but not in those collected during fasting. CONCLUSIONS. Together, our data indicate that nutrient levels regulate the NLRP3 inflammasome, in part through SIRT3-mediated mitochondrial homeostatic control. Moreover, these results suggest that deacetylase-dependent inflammasome attenuation may be amenable to targeting in human disease. TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02122575","term_id":"NCT02122575"}}NCT02122575 and {"type":"clinical-trial","attrs":{"text":"NCT00442195","term_id":"NCT00442195"}}NCT00442195. FUNDING. Division of Intramural Research, NHLBI of the NIH.

The aim of this work was to evaluate the effects of 24,25-dihydroxyvitamin D3, 24,25(OH)2D3, on alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) activities in fetal rat calvaria cultures. These actions were compared with those of 1,25-dihydroxyvitamin D3, 1,25(OH)2D3, and 25-hydroxyvitamin D3, 25(OH)D3, in similar experimental conditions. At 10 min, 30 min and at 24 h incubation time, 1,25(OH)2D3 (10(-10)M) and 25(OH)D3 (10(-7) M) produced a significant increase in AP and TRAP activities compared to control group (without vitamin D metabolites). However, 24,25(OH)2D3 (10(-7) M) only produced effects on phosphatase activities similar to those produced by 1,25(OH)2D3 and 25(OH)D3, after 24 h incubation time. These findings suggest that 1,25(OH)2D3 and 25(OH)2D3 could carry out actions in minutes (nongenomic mechanism), while 24,25(OH)2D3 needs longer periods of time to perform its biological actions (genomic mechanism).

Title Hemorragia vitrea bilateral asociada a hemorragia pontomesencefalica: un caso extremo de sindrome de Terson.

BACKGROUND The aim of this work was to evaluate the effect produced by conditioned medium from human prostatic carcinoma cell (PC-3) culture on human osteoblast (HOB) interleukin 6 (IL-6) synthesis. METHODS PC-3 cells were cultured in Ham's F12K medium with 10% fetal calf serum (FCS) up to confluence. Medium was changed by Dulbecco modified Eagle medium (DMEM)/F12K (1:1) with 0.1% bovine serum albumin. Cells were cultured for 24 hr, and medium (PC-3-CM) was collected. HOBs were cultured up to confluence, and after 48 hr without FCS, medium was removed and PC-3-CM was added to the wells. After 24 hr, supernatant was collected for the determination of IL-6. In another experiment, HOBs were cultured up to confluence in Petri dishes, and after 48 hr without FCS, PC-3-CM or DMEM/F12K (1:1) was added. After different periods of time, medium was removed, and total RNA was extracted. IL-6 mRNA was quantified using reverse transcription polymerase chain reaction. RESULTS PC-3-CM significantly enhanced IL-6 secretion into HOB culture supernatants (between 1,812% and 372%, depending on the osteoblastic line) with respect to HOBs cultured in DMEM/F12K. PC-3-CM also produced an increase in IL-6 mRNA levels in HOBs. CONCLUSIONS Prostate carcinoma cells (PC-3) produce a factor or factors that enhance the synthesis and release of IL-6, a known activator of bone resorption. Prostate 50: 241–246, 2002. © Wiley-Liss, Inc.

Objectives To describe the clinical and neurophysiological findings in a case of hemimasticatory spasm (HMS) followed during 14 years of evolution. Material and methods A woman suffered from very frequent paroxysmal episodes of painful involuntary occlusion of the jaw. Neurophysiological studies were performed at the 3, 12 and 14 years after the onset of symptoms. They included a needle electromyographic (EMG) evaluation of the main jaw closing and opening muscles, the jaw reflex (JR), the masseteric silent period (MSP) and the masseteric inhibitory reflex (MIR). Results Clinical symptoms remained unchanged throughout the period of observation. Conventional EMG never disclosed neurogenic signs. Voluntary closure of the jaw systematically provoked an abnormal activity with muscle cramps characteristics, restricted to the left masseter muscle. Left JR response was normal in the first evaluation and became delayed and of reduced amplitude in the second. The MSP and MIR were abolished on the left side during the spasmodic episodes whereas they were strictly normal out of them. The MIR abnormalities showed the characteristic pattern of an efferent lesional type. Conclusions Hemimasticatory spasm probably is the consequence of an abnormal trigeminal hyperexcitability likely induced by the demyelinating lesion of its peripheral motor pathway. The main neurophysiological abnormalities may persist unmodified over a long course of the disease and allow the differential diagnosis of HMS from oromandibular dystonia and temporomandibular dysfunction (TMD).

Anorexia nervosa (AN) is a very extended pathology among adolescent girls nowadays. These patients show a high degree of osteopenia; hence, study of their bone remodelling is of great interest. Serum bone alkaline phosphatase (bAP) and aminoterminal propeptide of procollagen I (PINP) provide good sensitivity in the analysis of bone alterations in postmenopausal osteoporosis. The aim of this study was to compare the usefulness of bAP and PINP in the study of bone remodelling in AN, and their possible correlation with the degree of osteopenia in this pathology. In order to help in the interpretation of the results, levels of the beta-isomer of urinary carboxyterminal propeptide of collagen I (beta-CTX) have also been included. Serum bAP (IRMA) Tandem R-Ostase, Hybritech), PINP (RIA, Orion Diagnostica) and CTX (CrossLaps ELISA, Osteometer) were determined in 41 girls with AN, aged 18.5+/-2.2 years (mean+/-SD) and in 31 healthy control women, aged 19+/-2.3 years. Bone mineral density (BMD) in lumbar spine was measured by DEXA in the AN group. We found that 41 of the 43 patients had BMD z-scores under -2. No significant differences were found in the levels of serum bAP nor in PINP and beta-CTX levels between controls and patients, although values in the AN group were highly variable. All the BMD z-score values were negative, and their absolute value correlates positively with bAP (P = 0.0279) and almost with beta-CTX (P = 0.0921) but not with PINP (P = 0.4627). Bone AP correlates with PINP in control girls (P = 0.017), but not in the AN group (P = 0.3573). Patients with AN were divided into three groups according to their levels of bAP: low (I), normal (II) or high (III). Patients with the highest bAP levels also presented the highest increase in bone resorption, according to their beta-CTX levels, and the highest degree of osteopenia. However, values of PINP were similar in the three groups of patients. The bAP/beta-CTX ratios in subgroups I, II and III of AN patients were 0.035, 0.065 and 0.073, a finding that suggests that bAP is not indicating the real degree of bone mineralization in these patients, because it is a contradiction that the formation/resorption ratio should be higher in the patients who have the highest bone loss. These results could suggest that bone loss in AN is produced by an increase in bone resorption (beta-CTX), without variations in bone matrix formation (PINP); bAP levels are a good marker in the follow-up of osteopenia degree, but not a real indicator of bone mineralization, a similar situation to that of osteomalacia.

The aim of this work was to evaluate the usefulness of serum aminoterminal propeptide of type I collagen (PINP) in the early detection of bone metastases associated with prostatic carcinoma. The results were compared with those of bone isoenzyme of alkaline phosphatase (bAP). Levels of total alkaline phosphatase (TAP) and prostatic specific antigen (PSA), related to the existence of bone metastases, are also evaluated. Fifty-five male patients aged 70-80 years were studied. Nine presented a benign prostatic hyperplasia (BPH) and the rest clinically confirmed prostatic cancer. Cancer patients were classified in accordance with the staging grouping of the International Union Against Cancer/American Joint Committee on Cancer TNM 1992 Revision: stage 0 or BPH (n=9), I (n=6), II (n=12), III (n=18) and IV (n=10). According to this classification, patients of groups BPH, I, II and III have no evidence of metastases. Those of stage IV present any type of metastases. In the case of this work, all patients of group IV presented bone metastases. Some patients of group BPH, I and II were untreated. The rest of the patients were under treatment (radical prostatectomy, telecobaltotherapy or hormonal therapy) for a period of between 6 months and 15 years. Serum PSA (Quimioluminiscence, IMMULITE), PINP (RIA, Orion Diagnostica), bAP (IRMA, Tamdem R-Ostase, Hybritech), and TAP (autoanalyzer) were determined. We found the following sensitivities and specificities (relating the presence of bone metastases to values higher than the upper limit of normality and, in the case of PSA, to values higher than 100 microg/L): (1) PINP: 100% (10/10) and 87% (39/45), (2) bAP: 90% (9/10) and 82% (37/45), (3) TAP: 60% (6/10) and 93% (42/45), (4) PSA: 40% (4/10) and 100% (45/45). These results suggest that PINP and bAP are adequate biochemical markers of bone formation to be used in the detection of bone metastases in prostatic carcinoma, improving the sensitivity and specificity of TAP and PSA. With respect to PINP, bAP presents the disadvantage of its cross-reactivity with liver isoenzyme.

The aim of this work was to study the regulation by calcium of the synthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in Walker 256 carcinosarcoma (W256) cells compared to renal phenotype LLC-PK1 cells. We have detected synthesis of 1,25(OH)2D3 and 24,25(OH)2D3 in W256 cells. Levels of 1,25(OH)2D3 in W256 were similar to those of LLC-PK1 cells. Levels of 24,25(OH)2D3 were higher in W256 than in LLC-PK1 cells. High levels of calcium inhibited 1,25(OH)2D3 synthesis in LLC-PK1 cells but not in W256 cells.

A comparative study was performed on the sensitivity of the determination of the available biochemical markers of bone formation--total and bone alkaline phosphatase (TAP and bAP, respectively), osteocalcin (BGP), procollagen I aminoterminal propeptide (PINP) and procollagen I carboxyterminal propeptide (PICP)--in the study of postmenopausal osteoporosis. The comparison between PINP and PICP, due to the recent development of the amino-terminal assay, is of special interest. The study included 26 untreated osteoporotic postmenopausal women, age 59 +/- 6 years (range 46-69 years) and 17 healty control postmenopausal women, age 56 +/- 7 years (range 48-70 years). We found a significant increase in the levels of bAP (p = 0.0021), BGP (p = 0.041), PINP (p = 0.0001) and PCIP (p = 0.0073), but not in the levels of TAP (p = 0.3389), in osteoporotic patients with respect to the control group. Serum PINP and bAP showed the highest diagnostic accuracy among the markers of bone formation studies, as can be deduced from the receiver operating characteristics (ROC) curves. In spite of their similar origin (amino-terminal and carboxy-terminal release from a procollagen molecule), the results obtained by measuring levels of PINP are significantly better than those found with PICP.

Leigh syndrome is clinically and genetically heterogeneous, associated with mutations in mitochondrial and nuclear genes.(1) Diagnostic criteria include progressive disorder with motor and intellectual delay/regression; signs and symptoms of brainstem and/or basal ganglia disease; raised lactate concentration in blood and/or CSF; and one or more of the following: (1) characteristic features on neuroimaging (bilateral symmetrical hyperintensities in brainstem, basal ganglia, dentate nuclei, and optic nerves on T2-weighted MRI); (2) typical neuropathologic changes; and (3) typical neuropathology in a similarly affected sibling.(2) We describe 2 African American siblings who have a mutation in the mitochondrial MT-TL2 gene and a clinical diagnosis of Leigh syndrome. The same mutation is also identified in their neurologically asymptomatic mother.

IntroductionThere is a high frequency of attendance at emergency medical service for suicide attempts.ObjectivesDetermine the type of urgency for suicide attempt in our country.Material and methodsThe present study treats of suicide attempts (n = 248) attended by the Psychiatric Emergency Service of Hospital in our city between 2004–2008. The diagnoses were made by clinical interview following ICD-10 criteria.Results248 suicide attempts (60% women), with age between 15 and 88 years.There are equal proportions of singles and married (a 38%). 53% live with couple with/without children, 30%live with parents and a 10%live alone. >55% of patients have a middle education and socioeconomic level. The average time from suicide attempt until the assessment in the emergency department is 2.71 ± 3.64 hours. The day of the week with more assistance for this reason is Monday. Also it's observed an increase in the months between May and October. The cases are uniformly distributed throughout the month, although there is a decrease in the number of cases in the initial and final days of the month. 60% of patients haven’t history of previous attempts and use an only method that is drug overdose. Personality disorders are the most frequent diagnose and 44% patients need an internment in a psychiatric ward.ConclusionsProfile of the patient who makes a suicide attempt and that is evaluated in the Psychiatric Emergency Service of our Hospital: woman 36 years old, married/with couple and lives with him/her. She comes to emergency department in the first 4 hours after the drug overdose. She hasn’t history of previous attempts.She is diagnosed of emotionally unstable personality disorder.

Parathyroid hormone related peptide (PTHrP) and 1,25-dihydroxyvitamin D are known to be resorptive agents which could contribute to the development of hypercalcemia in humoral hypercalcemia of malignancy (HHM) syndrome in Walker 256 tumor bearing rats. In order to clarify some aspects about the relative contribution of these factors to bone resorption, we have determined the effects produced by PTHrP (1-34) and/or 1,25(OH)2D3 on tartrate resistant acid phosphatase (TRAP), a biochemical marker of bone resorption, in fetal rat calvaria cultures. At the same time, bovine parathyroid hormone (PTH) (1-34) was used as a control in the experiments in order to compare its effects with those produced by the other two agonists. In the present work, 10(-7) M PTH (1-34), 10(-7) M PTHrP (1-34) and 10(-8) M or 10(-10) M 1,25(OH)2D3 produced a significant increase in TRAP activity, when these agonists were added to the calvaria culture. Surprisingly, and in spite of the different ways of action of PTH, PTHrP and 1,25(OH)2D3, their actions are not additive in our experiment. The results of the present work suggest that any of the two implicated factors PTHrP or 1,25(OH)2D3 could be individually responsible for the high rate of bone resorption that takes place in HHM syndrome in Walker 256 carcinosarcoma bearing rats, although other different agents, like TGF, could also be implicated.

BACKGROUND The incidence of neurological complications in the forearm after radial artery harvesting varies in the literature, ranging from 2% to more than 50%. Also, the areas affected and the type of neurological complications differ a lot. Peripheral nerve injuries may be divided into three types: neuroapraxia (conduction block that recovers within 3 months), axonotmesis (recovers 1 ml/day) and neurotmesis (needs surgery for recovering). We decided to perform a neuroelectrophysiological study, before and after surgery, in peripheral nerves of the forearm to find out the real incidence and the type of lesion after radial artery harvesting. METHODS Fifteen consecutive patients whose RA was going to be harvested were selected. Emergency patients, patients with severe liver or renal dysfunction were excluded. A complete neuroelectrophysiological study was performed in the median, ulnar and radial nerve. The amplitude was measured to check mielina status, whereas with the latency and nerve velocity conduction (NVC) we checked the axonal integrity. An electromyogram was also performed in the forearm muscles. A neurological clinical exploration was also performed. All these tests were performed before surgery and two weeks and two months after surgery. RESULTS Median nerve: A significant decrease in the amplitude that improved over time was registered. This decrease was observed in the motor and sensitive part of the nerve. No changes were observed regarding latency or NVC. Ulnar nerve: A decrease in the amplitude of the sensitive part of the nerve was observed (11.7-9.2-10.4 microV; P=0.006). No changes were observed regarding latency or NVC. Radial nerve: A statistical trend decrease observed regarding NVC of the sensitive part of the nerve branch was found (50.9 m/s vs. 47.1 m/s vs. 47.2 m/s; P=0.10). The electromyogram found no alterations. Clinically, three patients presented sensitive disorders in the median nerve territory and one of these also complained of sensitive disorders in the radial territory. Another patient referred dysesthesias in the ulnar nerve territory. All patients with the exception of one were asymptomatic two months after surgery. CONCLUSIONS Although only a few patients refer symptoms, most patients suffer changes in the peripheral nerves of the forearm (especially in the sensitive part) after RA harvesting. In our study the median nerve and the sensitive part of the ulnar and radial nerve were affected. These changes were temporary, affecting mainly the axon. All these data suggest neuroapraxia as the main peripheral nerve type lesion. We think that physicians and patients must be aware of this.

It has been reported that some hypoparathyroid patients with magnesium deficiency showed altered responses to vitamin D treatment. In the same way, in vitro bone studies have demonstrated the existence of a decrease in the 1,25-dihydroxyvitamin D3-induced resorption in bone as a result of magnesium deficiency. These findings suggest some kind of alteration in the 1,25(OH)2D3 in bone in magnesium deficiency. In the present work, using a binding assay based on the 1,25(OH)2D3 and 3H-1,25(OH)2D3 competition for the hormone binding sites in rat calvaria homogenates, a significant decrease in the number of 1,25(OH)2D3 specific binding sites has been found in calvaria incubated in magnesium-deficient medium compared to magnesium-replete ones. Alterations in the hormone-receptor affinity were not found. These results suggest that an alteration in the 1,25(OH)2D3 action on magnesium-deficient bone could be due, at least in part, to a decrease in the number of available vitamin D receptors in bone cells.

La enterolitiasis, cálculos formados primariamente en el intestino, es una rara enfermedad asociada, generalmente, con estasis intestinal. Suele cursar sin síntomas en la mayoría de los casos, pero puede presentar oclusión intestinal y debe ser tenida en cuenta como posible causa de la misma. Presentamos, un caso de enterolitiasis múltiple, patología muy infrecuente, que coexiste con litiasis biliar y vesical en un paciente con adenocarcinoma de colon. El diagnóstico fue realizado por imágenes de Rx y TC. El análisis de los cálculos: químico, por espectroscopia infrarroja, microscopía estereoscópica y espectrometría de emisión atómica, mostró una composición basada en materia orgánica y whilokita (ortofosfato de calcio y magnesio). No se encontraron factores de riesgo para la litogénesis, exceptuando la estasis intestinal ocasionada por la estenosis provocada por el adenocarcinoma. Se sugiere que los factores genéticos podrían ser los principales contribuyentes a la hiperlitogénesis observada en este caso. Profundizamos en el proceso fisiopatológico y revisamos la literatura al respecto.

Background: Early detection of bone metastases in prostatic carcinoma is very useful in treatment and prognosis of the disease. The aim of this work was to evaluate the sensitivity and specificity of a group of bone markers in order to discriminate between prostate carcinoma patients without (M0) and with (M1) bone metastases. Methods: Sixty-seven non-treated patients with: benign prostate hyperplasia (n=21), prostatic carcinoma in several stages without bone metastases (TXM0) (n=31) and with bone metastases (TXM1) (n=15) were studied. The following markers were studied: (A) bone formation: (1) serum bone alkaline phosphatase, IRMA (Tandem Ostase, Beckman); (2) serum procollagen I amino-terminal propeptide (PINP), RIA (Orion Diagnostica); (B) bone resorption: (1) urinary collagen I amino-terminal telopeptide (NTX), ELISA (Ostex); (2) collagen I carboxy terminal telopeptide (CTX): (2A) urinary α-CTX, RIA (Osteometer), (2B) serum β-CTX, Elecsys (Roche); (3) collagen I cross-linked carboxy terminal telopeptide (ICTP), RIA (Orion Diagnostica). Results: Levels of all bone markers were significantly higher in group M1 than in group M0. A complete separation of groups M0 and M1 was achieved with PINP and β-CTX (100% sensitivity and specificity). Conclusions: These results support the use of PINP or β-CTX as a tool to confirm the presence or absence of bone metastases in the first staging of prostatic carcinoma patients.

Methods: Description of a case series. Eight NF1 patients underwent interventions in order to remove spinal roots neurofibromas causing cervical spinal cord compression. A second intervention at the lumbosacral spine was necessary to remove neurofibromas located at the cauda equina in 2 cases. In all cases, IONM by means of motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs, epidural SSEPs), D-Wave monitoring and Bulbocavernosus Reflex (BCR) was performed. Additionally, in order to identify motor nerve roots and to preserve their function during surgery, neural tissues mapping was performed by direct electrical stimulation of the structures with a bipolar probe. Results: A total of 54 neurofibromas at the cervical and lumbosacral spine were removed. Motor nerve roots were identified and subtotally resected, sparing rootlets with small tumour nodules. Tumours on sensitive nerve roots were fully resected. When tumours were located at the cauda equina, nerve roots were also monitored using a train of stimulus to determine if these sensitive roots were critically involved in BCR. BCR was successfully elicited in both patients with tumours involving cauda equina and were preserved after tumour removing. No significant changes occurred in MEPs, SSEPs or D-Wave monitoring during surgeries. Conclusions: IONM provides continuous, real-time information about the function of neural pathways at risk during surgery and helps the surgeon to identify motor neural structures. The importance of BCR for the clinical outcome of the patients requires the use of special techniques intended to intraoperatively maintain the reflex. As opposed to schwannomas, neurofibromas grow encasing neural fibres from motor and sensory nerve roots. Subtotal resection should be performed in motor roots in order to preserve motor function.

Nephrolithiasis is presented in 18-40% of patients with primary hyperparathyroidism. Our work suggests that citrate, an inhibitor of calcium salts, could be involved in the presence of renal lithiasis because hyperparathyroid stone formers show less citrate elimination than nonstone formers.

Fragments derived from degradation of type I collagen C-telopeptide (CTX) can be nonisomerized (alpha) or beta-isomerized (beta) depending on the age of bone; i.e., mainly the alpha form is derived from new bone and the beta form from old bone. We have studied 41 female patients with anorexia nervosa (AN), aged 18.5 +/- 2.2 years (range 16-24 years), and with an evolution time between 1.5 and 11 years, and 31 healthy control females (C), with a mean age of 19 +/- 2.3 years (range 16-24 years). The AN patients showed a significant decrease in bone mass, with a mean Z-score of bone mineral density (BMD) of -3.2 +/- 0.8 (range -0.9 to -5.4). The aim of our study was to determine the levels of urinary alpha- and beta-CTX markers of bone resorption, the alpha/beta ratio (alpha/beta), and the level of bone alkaline phosphatase (bAP), a biochemical marker of bone formation, in order to relate them to the degree of osteopenia and the status of bone remodeling. Statistical analysis was by the Mann-Whitney test. The degree of osteopenia correlated with bAP levels (p = 0.0027) but not with the other parameters. Patients with AN were divided into three groups according to their levels of bAP: high (H), normal (N) or low (L). We found that BMD was significantly lower, and alpha- and beta-CTX were significantly higher, in groups H and N than in group L. Bone AP correlated significantly with alpha-CTX (p = 0.0042) and alpha/beta (0.0095) in the controls, but not with beta-CTX, while in AN patients bAP correlated with beta-CTX (p = 0.0000) and with alpha-CTX (p = 0.022) but not with the alpha/beta ratio. The ratio CTX/bAP (resorption/formation) was similar in AN patients and controls. It is concluded that: (1) patients with AN have a high degree of osteopenia which correlated with bAP levels; (2) urinary CTX fragments found in AN patients seem to come mainly from old bone (beta-CTX), while CTX found in healthy adolescent control females come from new bone (alpha-CTX). For this reason, alpha-CTX is more suitable than beta-CTX for measuring bone resorption in controls and beta-CTX is more suitable in patients with AN; (3) the resorption/formation ratio (CTX/bAP) was similar in AN patients and controls. From points (2) and (3) it is possible to suggest that, although bAP reflects bone formation in control females, this marker does not reflect effective bone mineralization in AN patients, a similar feature to that of patients with osteomalacia.

The aim of this work was to determine bone mineral density (BMD) in a group of patients with ankylosing spondylitis (AS) and to study alterations in bone remodeling in these patients. Eighteen patients (16 males and two females) with AS, mean age 44.7, range 21–75, and 18 age- and sex-matched healthy controls were studied. BMD was evaluated by dual energy X-ray absorptiometry. The following biochemical markers of bone remodeling were studied: formation – serum amino and carboxyterminal propeptides of procollagen I (PINP and PICP); resorption – urinary total and free deoxypyridinoline and pyridinoline (TDpyr, FDpyr, TPyr and FPyr), crosslinked aminoterminal telopeptides of collagen I (NTX), carboxyterminal telopeptide of collagen I (CTX) and serum bone sialoprotein (BSP). Receiver operating characteristic (ROC) curves of markers were also performed. We found a decrease of bone mass and an increase in TPyr, FPyr, TDpyr, FDpyr, NTX and BSP in AS, but no significant differences were found in PICP, PINP and CTX. FDpyr, FPyr and TPyr showed the highest discrimination between patients and controls according to the results of the ROC curves. TPyr/TDpyr was higher in AS than in controls. We found osteopenia, with a normal formation and a significant increase in bone resorption in AS. FDpyr, FPyr and TPyr seem to present the best sensitivity for the study of alterations of bone resorption in this pathology, although NTX, TDpyr and BSP also show significant differences. The elevation in the ratio TPyr/TDpyr in AS compared to controls indicates that in AS there is a type I-collagen degradation in tissues different from bone.