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BACKGROUND: High-density lipoprotein (HDL)-raising therapies are currently under intense evaluation, but the effects of HDL may be highly heterogeneous. We therefore compared the endothelial effects of HDL from healthy subjects and from patients with type 2 diabetes mellitus and low HDL (meeting the criteria for metabolic syndrome), who are frequently considered for HDL-raising therapies. Moreover, in diabetic patients, we examined the impact of extended-release (ER) niacin therapy on the endothelial effects of HDL. METHODS AND RESULTS: HDL was isolated from healthy subjects (n=10) and patients with type 2 diabetes (n=33) by sequential ultracentrifugation. Effects of HDL on endothelial nitric oxide and superoxide production were characterized by electron spin resonance spectroscopy analysis. Effects of HDL on endothelium-dependent vasodilation and early endothelial progenitor cell-mediated endothelial repair were examined. Patients with diabetes were randomized to a 3-month therapy with ER niacin (1500 mg/d) or placebo, and endothelial effects of HDL were characterized. HDL from healthy subjects stimulated endothelial nitric oxide production, reduced endothelial oxidant stress, and improved endothelium-dependent vasodilation and early endothelial progenitor cell-mediated endothelial repair. In contrast, these beneficial endothelial effects of HDL were not observed in HDL from diabetic patients, which suggests markedly impaired endothelial-protective properties of HDL. ER niacin therapy improved the capacity of HDL to stimulate endothelial nitric oxide, to reduce superoxide production, and to promote endothelial progenitor cell-mediated endothelial repair. Further measurements suggested increased lipid oxidation of HDL in diabetic patients, and a reduction after ER niacin therapy. CONCLUSIONS: HDL from patients with type 2 diabetes mellitus and metabolic syndrome has substantially impaired endothelial-protective effects compared with HDL from healthy subjects. ER niacin therapy not only increases HDL plasma levels but markedly improves endothelial-protective functions of HDL in these patients, which is potentially more important. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov. Identifier: NCT00346970.

BACKGROUND: Non-attendance is common in primary care and previous studies have reported that reminders were useful in reducing broken appointments. OBJECTIVE: To determine the effectiveness of a text messaging reminder in improving attendance in primary care. DESIGN: Multicentre three-arm randomized controlled trial. SETTING: Seven primary care clinics in Malaysia. Participants. Patients (or their caregivers) who required follow-up at the clinics between 48 hours and 3 months from the recruitment date. Interventions. Two intervention arms consisted of text messaging and mobile phone reminders 24-48 hours prior to scheduled appointments. Control group did not receive any intervention. Outcome measures. Attendance rates and costs of interventions. RESULTS: A total of 993 participants were eligible for analysis. Attendance rates of control, text messaging and mobile phone reminder groups were 48.1, 59.0 and 59.6%, respectively. The attendance rate of the text messaging reminder group was significantly higher compared with that of the control group (odds ratio 1.59, 95% confidence interval 1.17 to 2.17, P = 0.005). There was no statistically significant difference in attendance rates between text messaging and mobile phone reminder groups. The cost of text messaging reminder (RM 0.45 per attendance) was lower than mobile phone reminder (RM 0.82 per attendance). CONCLUSIONS: Text messaging reminder system was effective in improving attendance rate in primary care. It was more cost-effective compared with the mobile phone reminder.

BACKGROUND: The present study aimed at investigating the expression of the Na(+)-Ca2+ exchanger and its functional role in human failing myocardium. METHODS AND RESULTS: Na(+)-Ca2+ exchanger mRNA and protein levels were examined in nonfailing (NF, n = 8) and failing human myocardium (New York Heart Association functional class IV) with idiopathic dilated cardiomyopathy (DCM, n = 8) or ischemic heart disease (ICM, n = 6). The inotropic effect of the Na+ channel activator BDF 9148 was determined in electrically driven left ventricular papillary muscle strip preparations (1 Hz, 37 degrees C) from nonfailing (n = 8) and failing (n = 8) human hearts. Na(+)-Ca2+ exchanger mRNA levels were significantly increased, by 79% (P < .001) in DCM and by 58% (P < .01) in ICM compared with NF; protein levels increased by 36% (P < .001) and by 20% (P < .05), respectively. BDF 9148 increased the force of contraction concentration dependently, with a similar maximal effect in NYHA class IV and NF, but was more potent in NYHA class IV as demonstrated by a significantly smaller (P < .01) EC50 value (NYHA class IV, 0.18 [0.16 to 0.22] mumol/L; NF, 1.65 [1.3 to 3.0] mumol/L). In NYHA class IV, BDF 9148 (0.1 mumol/L) restored the positive force-frequency relationship and reduced the frequency-dependent increase in diastolic tension in relation to force of contraction. CONCLUSIONS: The increased expression of the Na(+)-Ca2+ exchanger is a possible explanation for the increased inotropic potency of the Na+ channel activator BDF 9148 in failing human myocardium. The increase in exchanger molecules could be of functional relevance for the modulation of cardiac contractility by agents that increase the intracellular Na+ concentration. Enhancement of Na(+)-Ca2+ exchanger activity might be a powerful mechanism for increasing cardiac contractility in chronic heart failure.

Forty subjects with chronic hepatitis B and hepatitis B e antigen (HBeAg) seroconversion following lamivudine therapy in previous trials were monitored after treatment to assess the durability of serologic responses. Patient follow-up began a median of 4.3 months after completion of therapy in previous trials. At months 2, 4, 6, 9, and 12 of year 1, and every 6 months thereafter, we tested for HBeAg and hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV) DNA, and alanine aminotransferase (ALT). After a median (range) of 36.6 (4.8-45.6) months of follow-up monitoring, HBeAg seroconversion was demonstrated at the last visit by 77% (30 of 39) of patients. In a post hoc analysis of a slightly different population of all 65 patients with HBeAg seroconversion in previous trials, the 3-year durability of HBeAg seroconversion measured from the time immediately after discontinuing lamivudine therapy was 64%. Nine (9 of 40, 23%) patients were HBsAg negative at the last assessment. Seventy-four percent (17 of 23) of patients with baseline undetectable HBV DNA and normal ALT maintained these responses at the last visit. Eight patients (8 of 40, 20%) initiated retreatment for reappearance of HBV markers, and 7 showed biochemical and/or virologic improvement (including regained HBeAg seroconversion in 2). No safety issues of concern emerged. In conclusion, most HBeAg responses achieved during lamivudine therapy were durable, and most responders experienced prolonged clinical benefit after HBeAg seroconversion and subsequent discontinuation of lamivudine. Lamivudine retreatment for reappearance of hepatitis B markers can achieve resumption of viral suppression.

SUMMARY: Pauwels' classification has been in use as a therapeutic guideline since 1935. Although its application is currently limited, it is still referred to and frequently misinterpreted by authors. The causes of this misinterpretation relate first of all to the degrees of the inclination of the fracture line in Degrees II and III of the classification. The correct values of Pauwels' classification are the following: Degree I, up to 30 degrees; Degree II, between 30 and 50 degrees; and Degree III, 50 degrees and more.

The author's work using magnetic resonance imaging to study the relative movements (the kinematics) of the tibia and femur is reviewed. The description is understood best by reference to comparative anatomy and by dividing the flexion arc into three components. Knee activities take place mainly between 10 degrees and 120 degrees. Over this arc, the articulating surfaces of the femoral condyles are circular in sagittal section and rotate around their center. The medial condyle does not move anteroposteriorly (roll-back does not occur medially). The lateral condyle tends to roll back producing tibial internal rotation with flexion. From full extension to 10 degrees to 30 degrees tibial internal rotation is coupled with flexion. The articulating surfaces medially are a larger radiused anterior femoral facet, which articulates with an upward-sloping tibial facet. Laterally, the femoral condyle rolls forward onto the anterior horn. Flexion beyond 120 degrees only can be achieved passively. Medially, the femur rolls up onto the posterior horn. Laterally, the femur and the posterior horn drop over the posterior tibia.

The intakes of nitrate and nitrite of children and their parents from food and drinking water were estimated in a Finnish nation-wide case-control study on the epidemiology of Type 1 diabetes. The study population consisted of 684 case and 595 control children; 548 case-control pairs of fathers; and 620 case-control pairs of mothers. The consumption frequencies of foods which are important sources of nitrate and nitrite were assessed by structured questionnaire. Nitrate and nitrite concentration data were collected from Finnish water works. Diabetic children's and their mothers' daily dietary intake of nitrite was greater compared with that of control children and mothers (for case and control children 0.9 mg vs 0.8 mg, for case and control mothers 0.9 mg vs 0.8 mg, p < 0.001). Case mothers compared with control mothers received less (p < 0.05) nitrate from their diet. No differences were observed in the intake of nitrate or nitrite from drinking water. Dietary nitrite intake of children (odds ratios and 95% confidence intervals for the second, third, and fourth quartile 1.16, 0.82-1.65; 1.49, 1.06-2.10; 2.32, 1.67-3.24, respectively) and mothers (odds ratios and 95% confidence intervals for the second, third, and fourth quartile 1.15, 0.76-1.74; 1.29, 0.87-1.91; 1.98, 1.35-2.90, respectively) was positively associated with the risk for Type 1 diabetes independently from length of mother's education, child's or mother's age, place of residence or mother's smoking status.(ABSTRACT TRUNCATED AT 250 WORDS)

<h3>Objective</h3> To determine the involvement of subcortical regions in human epilepsy by analyzing direct recordings from these regions during epileptic seizures using stereo-EEG (SEEG). <h3>Methods</h3> We studied the SEEG recordings of a large series of patients (74 patients, 157 seizures) with an electrode sampling the thalamus and in some cases also the basal ganglia (caudate nucleus, 22 patients; and putamen, 4 patients). We applied visual analysis and signal quantification methods (Epileptogenicity Index [EI]) to their ictal recordings and compared electrophysiologic with clinical data. <h3>Results</h3> We found that in 86% of patients, thalamus was involved during seizures (visual analysis) and 20% showed high values of epileptogenicity (EI &gt;0.3). Basal ganglia may also disclose high values of epileptogenicity (9% in caudate nucleus) but to a lesser degree than thalamus (<i>p</i> &lt; 0.01). We observed different seizure onset patterns including low voltage high frequency activities. We found high values of thalamic epileptogenicity in different epilepsy localizations, including opercular and motor epilepsies. We found no difference between epilepsy etiologies (cryptogenic vs malformation of cortical development, <i>p</i> = 0.77). Thalamic epileptogenicity was correlated with the extension of epileptogenic networks (<i>p</i> = 0.02, ρ 0.32). We found a significant effect (<i>p</i> &lt; 0.05) of thalamic epileptogenicity regarding the postsurgical outcome (higher thalamic EI corresponding to higher probability of surgical failure). <h3>Conclusions</h3> Thalamic involvement during seizures is common in different seizure types. The degree of thalamic epileptogenicity is a possible marker of the epileptogenic network extension and of postsurgical prognosis.

Sugammadex as a reversal agent for neuromuscular block: an evidence-based review Stefan Josef Schaller,1,2 Heidrun Fink11Klinik für Anaesthesiologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; 2Department of Anesthesia, Massachusetts General Hospital, Boston, MA, USAAbstract: Sugammadex is the first clinical representative of a new class of drugs called selective relaxant binding agents. It has revolutionized the way anesthesiologists think about drug reversal. Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it is able to reverse any depth of neuromuscular block. So far, it has been approved for use in adult patients and for pediatric patients over 2 years. Since its approval in Europe, Japan, and Australia, further insight on its use in special patient populations and specific diseases have become available. Due to its pharmacodynamic profile, sugammadex, in combination with rocuronium, may have the potential to displace succinylcholine as the "gold standard" muscle relaxant for rapid sequence induction. The use of rocuronium or vecuronium, with the potential of reverse of their action with sugammadex, seems to be safe in patients with impaired neuromuscular transmission, ie, neuromuscular diseases, including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence suggesting an economic advantage of using sugammadex and justifying its relatively high cost for an anesthesia-related drug, is missing. Keywords: reversal agent, cyclodextrin, PORC, SRBAs

Atrial fibrillation (AF) is the most common clinical arrhythmia with substantial health and socioeconomic impact on healthcare.1 The number of people affected by this condition was estimated to be 33.5 million in 2010, with an increasing prevalence and incidence over the coming years.2 In 2017, there were 37.6 million [95% confidence interval (CI): 32.5–42.6 million] individuals with AF/atrial flutter globally.3 The estimated number of subjects with AF in 2030 in Europe will be 14–17 million, and the number of new cases of AF per year at 120 000–215 000.4 Atrial fibrillation is independently associated with increased mortality and morbidity from complications such as ischaemic stroke, dementia, and cognitive dysfunction.5 Oral anticoagulation can significantly reduce the risk of stroke, dementia, and death.6 As a part of a holistic or integrated approach to AF care, it is associated with improved outcomes7–9 and is advocated in guidelines.10,11 In many patients, AF can be asymptomatic, and the diagnosis is established after the appearance of a complication typically associated with AF, such as ischaemic stroke/systemic embolic or heart failure. For example, the Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE) study showed that in patients after transient ischaemic attack (TIA) or cryptogenic stroke without known AF, 30 days of non-invasive event-triggered ambulatory electrocardiogram (ECG) monitoring allowed us to diagnose this arrhythmia in 16.1% of 280 individuals. At the same time, standard 24 h ECG revealed AF in only 3.2% of 277 patients.12 In individuals with stroke risk factors, implantable loop recorder (ILR) screening in the Implantable Loop recorder detection of atrial fibrillation to prevent stroke (LOOP) study resulted in a three-fold increase in AF detection and anticoagulation initiation.13 Hence, looking harder and longer with more sophisticated methods increases AF detection. Early diagnosis of AF in some high-risk populations, together with appropriate antithrombotic therapy, could potentially prevent a substantial number of strokes and mortality.14,15 Additionally, it was shown by the results of the Early Rhythm-Control Therapy in Patients with Atrial Fibrillation (EAST) study that early AF detection and effective implementation of rhythm control strategies would reduce both deaths and hospitalizations. This rationalizes the need for active AF screening/search in at-risk populations. This need was reflected in the 2020 ESC guidelines that recommend opportunistic screening in individuals ≥65 years and suggests taking into consideration systematic screening in high-risk individuals and subjects aged ≥75 years to identify patients who could benefit from antithrombotic treatment. However, the recommended method(s) of screening/search that applies to the majority of the general population is not well established.10 The main objectives of the present consensus are to provide an overview of methods of preselection of participants for mass screening, establish the rationale for optimal monitoring time, and assess currently available AF detection methods in different clinical contexts. The diagnosis of AF requires rhythm documentation with an ECG tracing showing AF. A standard 12-lead ECG recording or a single-lead tracing of ≥30 s of heart rhythm with no discernable repeating P waves and irregular R-R intervals (when atrioventricular conduction is not impaired) is diagnostic for clinical AF with high specificity and sensitivity10,16 Implanted devices and wearable monitors allow for detecting atrial high-rate episode (AHRE) and subclinical AF (SCAF), respectively, which, by definition, cannot be regarded as identical to AF at conventional ECG tracings.17 Short monitoring using external devices is less likely to detect AHRE/SCAF. When AHRE/SCAF is detected by a device/wearable, inspection of stored electrograms/ECG rhythm strips is required.10,17 The primary definition and types of AF concerning the diagnostic criteria, the presence of symptoms, time of detection, and the kind of detecting devices or external monitors are presented in Table 1. As per the current ESC AF guidelines, the patient should be evaluated and characterized according to the 4S scheme: stroke, symptoms, severity of AF burden, and substrate.18 Definitions and types of atrial fibrillation AHRE, atrial high-rate episode; AF, atrial fibrillation; ECG, electrocardiogram; AFL, atrial flutter; AT, atrial tachycardia; CIED, cardiac implantable electronic device; Based on 2020 ESC AFib Guidelines.10 Definitions and types of atrial fibrillation AHRE, atrial high-rate episode; AF, atrial fibrillation; ECG, electrocardiogram; AFL, atrial flutter; AT, atrial tachycardia; CIED, cardiac implantable electronic device; Based on 2020 ESC AFib Guidelines.10 A gap of evidence is to establish better the clinical significance of runs of atrial ectopics and atrial tachyarrhythmias lasting <30 s recorded by ECG Holter and other long-term ECG-monitoring devices, thus not fulfilling the criteria for diagnosing AF, and to assess the probability of progression to clinical AF, as well as their potential significance for thromboembolic events. The current AF definition omits to allow a diagnosis of AF based on widely used screening tools based on photoplethysmography (PPG). The PPG signals registered by certified medical devices validated to the gold standard, as is ECG, could be considered comparable with the ECG due to their high sensitivity and specificity.8,9 The currently ongoing ‘Fitbit Heart Study’ is a significant clinical study designed to examine the validity of a novel PPG-based software algorithm for detecting AF.19 Nonetheless, we need to be sure of AF in an individual patient. Reported sensitivities/specificities are not enough to establish a definite diagnosis of AF without an ECG tracing, as suggested by guidelines. The terms AHRE and SCAF are often used interchangeably. There are two ongoing randomized controlled trials (RCTs) dedicated to optimal management of AHRE/SCAF: ARTESiA20 and NOAH–AFNET 621 studies. Upcoming results should fill gaps in our knowledge in this area. Details of these studies are included in Supplementary material online, Table S1. According to current diagnostic criteria, a correct and definite AF diagnosis require electrocardiographic documentation of at least one episode, lasting 30 s or more. This recommendation is consistent with different guidelines.10,22 Due to the frequently asymptomatic nature of AF, current guidelines recommend systematic and opportunistic screening in populations at risk. Other screening methods and tools include pulse self-palpation,23 automated blood pressure monitors,24,25 watches,26,27 smartphone applications,28 single-lead ECG recorders, continuous ECG patches,29 long-term classical Holter, wearable belts30 for ECG recording, and ILRs31 have been postulated to identify individuals with AF effectively. Nonetheless, only some of these methods allow for definitive AF diagnosis. Most methods require further ECG confirmation in individuals suspected to present AF. In this meaning, the main goal of screening is the identification of asymptomatic subjects with AF. If any screening method is to AF with an ECG recording, a further of AF using devices be In patients with AF to classical ECG not provide an active AF using ECG-monitoring devices or ECG is to establish a diagnosis of AF. The requires devices with identification of AF based on or external ECG can be effective in asymptomatic individuals ECG recording is at the time as was in the In in the population of cryptogenic stroke patients with ECG recorders, only of AF ESC guidelines recommend opportunistic screening in individuals aged ≥65 years and the need for systematic screening in individuals ≥75 years to identify individuals who require Nonetheless, screening in subjects and not Based on the results of current the number of individuals to in the general population to detect one AF is estimated at Additionally, detection of AF due to the or frequently asymptomatic nature of the correct of a patient often requires continuous This of to be for clinical risk tools that better the and identify at risk are to increase the of screening based on continuous long-term of atrial or atrial criteria Supplementary material online, Table have been to better subjects with a high risk of AF. However, their is only to populations of patients as patients after stroke or patients to Holter or were due to other The of these criteria for participants of screening to be The need for better of of AF with the of studies ECG, and or to the estimated risk of AF and complications can be was of results of such studies together with the of should the identification of high-risk populations and individuals. for risk of AF have been most are in high-risk populations for screening The of such as the Heart for Heart and in for AF in and is that have been to the long-term risk of AF some of require or not available in the general In the of AF risk the for an improved risk to to the general based on available such as medical be AF risk risk for stroke in patients with AF. a would patients in AF detection and would a In to thus the was a based on clinical to assess AF risk. this to be more for the high-risk population of AF. as a opportunistic screening for of AF been in a population in a and patients in a In the Heart using the associated with was associated with a of In patients with cardiac devices the was of Atrial fibrillation risk are potentially in of the population at risk of atrial fibrillation AF, atrial fibrillation; failure. Atrial fibrillation risk are potentially in of the population at risk of atrial fibrillation AF, atrial fibrillation; failure. The appearance and of of AF in AF are in patients, some of AF For example, a of patients with AF and with that asymptomatic in of patients with symptoms, no evidence of AF was present in recorded ECG or In this of patients were of AF for established and in of AF, or asymptomatic AF lasting h were time lasting This the in optimal monitoring in AF monitoring be to detect Nonetheless, a standard monitoring time for to be for clinical or clinical and studies. The time of monitoring is affected by the by the For devices such as or implantable it is For it is by and a In external devices such as and it is by the patient and Additionally, some of these devices recorded in more For monitoring that allow monitoring standard Holter devices should be as long-term monitoring for AF in the population using methods is to and is not Nonetheless, for high-risk patients as patients after cryptogenic stroke or the of to be In such populations, of monitoring from to an increase in the incidence of AF from to Atrial fibrillation detection by continuous monitoring increased the study and was at with the In study the of in patients, the detection of new AF after days of monitoring was of were detected to This suggests that at least a of monitoring is to identify the number of patients with AF after and using methods such as Nonetheless, of monitoring over year after the to be due to the of stroke and detected AF. results were using an ECG recorder in a patient The detection of AF in was was in the control using 24 h Holter of this the of or to 30 days of external ECG monitoring resulted in a to incidence of AF in the population of patients after cryptogenic stroke or was with the of 24 h or days In screening to detect AF, devices different from devices should be with monitoring In two studies of ECG population screening, the and the a monitoring time was for two of using different monitoring devices in both the AF detection were in the monitoring in the control with and for the and based on as was in increased of AF detection from in to in high The monitoring time in the Heart was longer the irregular pulse in the study population was and in participants aged ≥65 it was In the Heart the to detected AF was days in a population with a with a detection of Hence, monitoring over 30 days would not significantly increase the AF detection in studies. The rationale for optimal monitoring should be by and the clinical significance of detecting an episode of AF in a monitoring As shown in a study that for AF in years individuals with at least one stroke risk stroke, or heart of monitoring time to a of a significant increase in AF detection from in the control to in the Nonetheless, of anticoagulation in individuals with detected AF not reduce stroke or in the control P Due to the number of devices and methods of detecting AF, we to these tools into two screening and diagnostic detection of AF is a and further diagnostic of AF is for the AF confirmation devices, and certified tools and that establish AF diagnosis after AF detection by the or certified pulse blood pressure wearable devices, PPG on a PPG on a or ECG by PPG with of irregular rhythm or long-term non-invasive ECG recording the of ECG, long-term Holter and implantable or with atrial According to the current of AF AF is detected by a screening registered ECG ECG tracing ≥30 s or 12-lead should be as AF by a with in ECG When AF detection is not based on an ECG recording using or in of in the of registered ECG tracing, a diagnosis of AF should be using ECG recording 12-lead ECG, Holter In the of the of this validated tools and could be to the confirmation of AF by ECG health and are currently used for screening and diagnosis. In the of AF by the from screening there is an to the diagnosis of AF using the diagnostic The tools for screening and diagnostic are in Table The of devices and methods for atrial fibrillation AF, atrial fibrillation; ECG, A or on the The of devices and methods for atrial fibrillation AF, atrial fibrillation; ECG, A or on the and other wearable devices such as are used in and provide for the of smartphone can provide from and non-invasive screening on many However, not of the currently have been Most devices can provide PPG by recording the pulse using the or at the of the can detect the pulse that can to diagnose AF early without provide the for long-term AF screening, diagnostic The of PPG-based methods to detect AF is widely with a single-lead ECG recorded by a the study of PPG-based AF detection based on a smartphone a sensitivity of and a specificity of Other studies diagnostic of PPG-based screening, with sensitivity from to and specificity from to with studies have strategies for AF of the most mass screening included who were by the to a detection from the and to for days using the smartphone PPG a were as some AF, or AF was detected in of the further to diagnose AF. studies have evaluated the of current in screening for AF in a of The Heart included subjects without a known of AF who were for an irregular pulse by PPG in the were recorded and by the study was used to the study subjects and the study the from in the years to irregular pulse of the subjects were by an ECG for resulted in AF diagnosis in with most h in The of irregular pulse for recording AF on the ECG was The Heart included individuals for AF based on PPG in wearable at least days of monitoring by the designed PPG of the individuals a were and AF was in of The majority of cases a for integrated AF management in the of anticoagulation in of the The of was However, to to on anticoagulation in asymptomatic patients these new patients should thus be for further risk on an individual the AF to anticoagulation be different in patients with clinical screening should an integrated AF management to patients according to the further in and or new are in the coming clinical The of classical ECG Holter for long-term ECG monitoring is by factors, to Holter with long-term and patient Due to be for for or of is for the patient after and the as a or recording and would be to and to be a long-term ECG recording to detect AF. the study that the of long-term AF was based on the approach of two strategies the approach to ECG recording are loop and cardiac loop ECG lasting from a to and can detect both and asymptomatic using an algorithm cardiac are of or of to the a using The are in a on the of the monitoring using or can events. strategies allow for long-term continuous ECG monitoring for to 30 days with The monitoring be only for a time for of the or and or recorder loop potentially from that are not by or are of of The of long-term ECG recording in AF detection was in studies characterized in Table Most were on patients after cryptogenic stroke, with the monitoring time lasting to 30 The diagnostic of AF detection was to classical h Holter or and was comparable with in implantable devices that long-term electrocardiogram recording in atrial fibrillation that long-term electrocardiogram recording in atrial fibrillation Holter ECG is considered the gold standard for heart rhythm for to is with to and an of at least two different ECG In to devices, ECG methods heart rhythm and will an of the and of The main of Holter ECG is over In a of patients with of patients a Holter ECG for at least of patients to have a Holter ECG after the time of ECG will increase the diagnostic of Holter for rhythm that are The optimal of monitoring for AF, after a stroke, is to be current evidence suggests monitoring for at least h in patients with ESC guidelines recommend a for h of Event monitors not ECG is recorded only the a suspected episode or the patient cardiac is an of Holter, ECG and in to an cardiac Holter a to a Holter ECG, using an to the patient of This a The without the The heart rhythm for After this the are and for to a The of the ECG is by and is included in the for the on ECG-monitoring are and often by different monitoring For example, a Holter with 24 h of Holter The detected significantly more the Holter, due to the different monitoring In the 24 h that both devices were in the of the Holter was significantly the Patients the to be more and were less likely affected by randomized trials have used for screening of AF. For example, in the individuals were randomized to of rhythm monitoring with a Holter after or Atrial fibrillation was by in of the in the In the patients with aged years and were randomized to days of Holter monitoring or After AF was detected in in the Holter and in the standard of the AF detected by the were with the is the clinical significance of these asymptomatic AF detected using ECG-monitoring should be and according to the clinical of for example, of a of AF not have the same significance in as in and patients after a Implantable loop are for AF after cryptogenic stroke, AF monitoring after and of AF, and AF detection in patients with are and and have and years of available devices allow and are and are In one of the of patients from the at of the that were been to at the or The most common associated with the were patients patients and or patients at the In cryptogenic stroke, of stroke early detection of AF is for The of anticoagulation to a risk The risk of stroke in patients with cryptogenic stroke is with per Based on a asymptomatic AF was in a of patients with cryptogenic stroke after A was for the with or irregular Holter ECG, with detection of in for conventional Holter ECG over only increased after and for for Holter ECG after results are consistent with the of randomized an external event-triggered with conventional Holter However, this method is to a time and be regarded as to with a potential monitoring of to The of for the detection of SCAF is further by a study in individuals without a of AF who presented at least one risk for years of and of stroke or presence of heart failure. In this subclinical of AF with at least were by in of included In patients AF was anticoagulation was according to current ESC results were in the In individuals with at least one stroke risk stroke, or heart with AF was detected in In in individuals in the control only were with AF. of the anticoagulation due to detected AF resulted in no significant in the incidence of stroke or the and control P The results of the study that anticoagulation was not after any AF detection due to the of be an for these In patients who AF with a of and with patients in conventional This can be by the confidence of the clinical in the of an devices with an atrial or with the of rhythm allow to the cardiac rhythm and detect atrial AF, as and can be stored in for and diagnosis to be from due to or by or Atrial high-rate currently as of at least of atrial with an atrial are asymptomatic and in terms of of the episode or time in atrial tachyarrhythmias a burden, as to The for using the AHRE, or is that the patient no of AF and that AF was with a standard 12-lead ECG or an ECG the criteria for clinical The prevalence of AHRE, often as AF patients with on heart and In AHRE can be detected in of patients and to in and Patients with to be more at risk patients with of are associated with a to increase in stroke risk with patients without these the risk of stroke these patients is the risk of patients with clinical In a AHRE was significantly associated with increased thromboembolic risk and increased incidence of clinical with stroke thus that a a risk for or clinical AF, as shown by the a of of the patients who subclinical atrial tachyarrhythmias asymptomatic clinical monitoring of these patients is thus in patients with longer and a stroke risk The at it is appropriate to anticoagulation for AHRE 24 h is not the risk of stroke is increased the of is longer 24 as shown by the In patients with atrial lasting no increase in stroke risk been and no anticoagulation is In patients with 24 the clinical benefit of anticoagulation is currently in two randomized trials in Supplementary material online, Table Patients with a substantial with from to AF on the AF at detection and The longer the AF at detection, the the probability of a to an AF. The of h been in the to be associated with an increase in the risk of associated At on anticoagulation to of monitoring and clinical on of clinical stroke risk based on If identification of AF could the of appropriate therapy, or have in the A new novel for an AF was using the from million patients without a of AF registered in the these a considered different was as the optimal with an the of for AF with the should be that the and of over time, in allow for in the validity in a to in the nature of risk and for AF and such as algorithm designed to detect AF based on rhythm been The algorithm was using a million stored recorded from more individuals. The on a to and the and it was validated and in two different with at least one ECG with AF were as cases after the rhythm The algorithm showed a of a specificity of a sensitivity of and an of in detecting individuals with documentation of AF after the rhythm ECG using only from the rhythm methods have been to signals from the single-lead ECG or For a been to detect AF from photoplethysmography signals from the Heart or the Heart these results are the clinical of these will be by the of algorithm to a population and by the to diagnostic and in the these AF in of high-risk A of based on individual risk is presented in 1. of of atrial fibrillation screening based on individual risk and need to be these tools can be widely used in clinical the of these not allow and to in the of the of the for ECG based on and and new have potentially significant for detecting and diagnosing AF. us and risk in the In the of a the of AF screening are the clinical of there is the of stroke and heart with a in a of there is the of atrial and progression the other there can be some of screening, to ECG due to a and the associated and risk of screening for atrial fibrillation from effective to reduce the heart Atrial effective to reduce the heart Atrial and risk of screening for atrial fibrillation from effective to reduce the heart Atrial effective to reduce the heart Atrial of clinical and from in screening, some individuals can to be In the of the subjects to with the shown different patients and In some a that patients not to be in it to their been the patient the and management should be a is not patient should be to or to in a screening of the potential or of the screening, the of the screening and the of a or This could be to the general population to increase AF, to or not would be in and frequently the should be from clinical stroke, to patients is a screening As the of the and should be In this an the as to for of and cognitive and to The current AF definition requires recording in classical ECG or Holter ECG at least a episode of AF. 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A single 4 X 4 system matrix is used to represent the para-axial properties of optical systems consisting of separated obliquely crossed spherocylindrical lenses. The 4 X 4 system matrix is a generalization and combination of the 2 X 2 Gaussian system matrix for spherical optical systems, and the 2 X 2 dioptric power matrix for a single spherocylindrical lens or for obliquely crossed spherocylindrical lenses in contact with each other. The 4 X 4 system matrix approach simplifies both the conceptual and numerical analysis of complicated astigmatic systems.

<h3>BACKGROUND AND PURPOSE:</h3> The 2016 revision of the <i>World Health Organization Classification of Tumors of the Central Nervous System</i> mandates codeletion of chromosomes 1p and 19q for the diagnosis of oligodendroglioma. We studied whether conventional MR imaging features could predict 1p/19q status. <h3>MATERIALS AND METHODS:</h3> Patients with previous 1p/19q testing were identified through pathology department records, typically performed on the basis of an oligodendroglial component on routine histology; 69 patients met the inclusion criteria. Preoperative imaging of patients with grade II or III gliomas was retrospectively assessed by 2 neuroradiologists, blinded to the 1p/19q status. Thirteen MR imaging features were first assessed in a small initial cohort (<i>n</i> = 10), after which the criteria were narrowed for the remaining patients as a validation cohort. <h3>RESULTS:</h3> There was 85% agreement between radiologists for the overall prediction of 1p/19q status in the validation cohort, with an accuracy of 84%. The presence of &gt;50% T2-FLAIR mismatch and calcification was found to be the most useful for predicting 1p/19q status. The &gt;50% T2-FLAIR mismatch variable was demonstrated in 14 tumors and had 100% specificity for identifying a noncodeleted tumor (<i>P</i> = .001), with 97% interobserver correlation. Calcification was visualized in 7 tumors, 6 of which were 1p/19q codeleted (specificity, 97%; <i>P</i> = .006), with 100% interobserver correlation. <h3>CONCLUSIONS:</h3> The presence of &gt;50% T2-FLAIR mismatch is highly predictive of a noncodeleted tumor, while calcifications suggest a 1p/19q codeleted tumor. If formal 1p/19q testing is not possible, a combined MR imaging–histologic assessment may improve the diagnostic accuracy over histology alone.

We report a study of the shapes of the tibial and femoral articular surfaces in sagittal, frontal and coronal planes which was performed on cadaver knees using two techniques, MRI and computer interpolation of sections of the articular surfaces acquired by a three-dimensional digitiser. The findings using MRI, confirmed in a previous study by dissection, were the same as those using the digitiser. Thus both methods appear to be valid anatomical tools. The tibial and femoral articular surfaces can be divided into anterior segments, contacting from 0 degrees to 20 +/- 10 degrees of flexion, and posterior segments, contacting from 20 +/- 10 degrees to 120 degrees of flexion. The medial and lateral compartments are asymmetrical, particularly anteriorly. Posteromedially, the femur is spherical and is located in a conforming, but partly deficient, tibial socket. Posterolaterally, it is circular only in the sagittal section and the tibia is flat centrally, sloping downwards both anteriorly and posteriorly to receive the meniscal horns. Anteromedially, the femur is convex with a sagittal radius larger than that posteriorly, while the tibia is flat sloping upwards and forwards. Anterolaterally, both the femoral and tibial surfaces are largely deficient. These shapes suggest that medially the femur can rotate on the tibia through three axes intersecting in the middle of the femoral sphere, but that the sphere can only translate anteroposteriorly and even then to a limited extent. Laterally, the femur can freely translate anteroposteriorly, but can only rotate around a transverse axis for that part of the arc, i.e., near extension, during which it comes into contact with the tibia through its flattened distal/medial surface as against its spherical posterior surface.

BACKGROUND: Raynaud disease (RD) is a common disorder affecting 3% to 5% of the healthy population, and occurs in more than 90% of patients with connective tissue diseases. The therapeutic options remain limited, particularly in patients with secondary RD due to connective tissue disease. Theoretical considerations lead to the expectation that phosphodiesterase type 5 inhibitors may improve clinical symptoms and digital blood flow in patients with RD. METHODS: We conducted an open-label pilot study in 40 patients with RD, 33 (82%) of whom had secondary and 7 (18%) of whom had primary RD. Digital blood flow was measured by laser-Doppler flowmetry at room temperature and during the cold-exposure test before medical treatment, 1 hour after the initial intake, and after 2 weeks of continuous treatment (10 mg twice a day) with the novel phosphodiesterase type 5 inhibitor vardenafil. Clinical symptoms were recorded by a patient questionnaire and summarized as the Raynaud condition score. RESULTS: Laser-Doppler flowmetry revealed that vardenafil improved digital blood flow in 28 (70%) patients, whereas 12 (30%) did not respond. In individuals responding, digital blood flow significantly increased by a mean +/- SEM of 21.0% +/- 4.9% and 30.0% +/- 5.7% at 1 hour and 2 weeks of treatment at room temperature, respectively, and by 18.8% +/- 4.4% and 35.1% +/- 7.5% at 1 hour and 2 weeks during the cold-exposure test, respectively (P < .01 for all). Consistently, clinical symptoms improved in 27 (68%) of the 40 patients, and the Raynaud condition score declined from a mean +/- SEM of 5.05 +/- 0.38 to 3.54 +/- 0.31 (P < .001). CONCLUSION: Our data indicate that phosphodiesterase type 5 inhibition significantly improves peripheral blood flow and clinical symptoms in a large subset of patients with RD and, thus, may provide a novel therapeutic approach in such individuals.

Dr. W. F. Long pointed out that calculations of decentration in spherocylindrical lenses, as well as calculations of combinations of obliquely crossed spherocylindrical lenses, are considerably simplified by the use of matrix methods. In the obliquely crossed lens problem, Long used eigenvalue techniques to obtain the sphere, cylinder, and axis of the equivalent lens. This paper presents an alternative to the eigenvalue method. This alternative method uses the invariance of the trace and determinant of the dioptric power matrix. This alternative is conceptually easier to understand than the eigenvalue method and perhaps will encourage more people to use the matrix methods.

OBJECTIVE: The purpose of this study was to evaluate the incidence, cause, injury patterns, and MRI findings in knee dislocation in patients with normal and increased body mass index and to determine whether obesity interferes with knee MRI examinations. MATERIALS AND METHODS: A retrospective study of the period from 2000 to 2007 (90 months) was performed at a level 1 trauma center, finding a total of 24 patients who had sustained a knee dislocation. RESULTS: Twenty-two of the 24 patients underwent surgery and 19 patients had an MRI examination of diagnostic quality before surgery. Of the 24 patients, 11 had a body mass index greater than 25 and had knee dislocation due to low-energy trauma (nine due to a simple fall, two to a noncontact sport). Two of these 11 patients were morbidly obese (body mass index>40). These patients had no injuries to the popliteal tendon and they had no irreversible peroneal nerve injuries. Otherwise, the patients' injuries were in agreement with previous knee dislocation studies. Obesity did not interfere with knee MRI examinations. On the basis of the population served by our trauma center, the annual incidence of knee dislocation due to low-energy trauma in overweight patients is about 1.0 per million. CONCLUSION: The annual incidence in obese patients of knee dislocation due to low-energy trauma is not insignificant at a level 1 trauma center. As the prevalence of obesity increases, the injury patterns seen in emergency departments may change. The radiologist should be aware that even after a simple fall, overweight patients may have a knee dislocation.

The 4 x 4 system matrix is applied to corrected astigmatic systems including a schematic eye in which each surface is astigmatic at a different axis. In addition to representing the eye, the 4 x 4 system generates 2 x 2 magnification matrices which describe the meridional magnifications that occur in the presence of astigmatism including the magnifications that occur with bitoric eikonic correcting lenses, or other meridional magnifying systems.

Four patients with acute nonlymphoblastic leukemia and one malignant teratoma refractory to conventional chemotherapy were treated with high doses of cytosine arabinoside (HD ARA-C). They received up to 12 cycles of 1.8 to 3 g/m2 every 12 hours applied by 2-hour infusions. A total of 55 HD ARA-C infusions was performed. All leukemic patients responded. A complete clearance of blasts from the bone marrow was observed in two patients following 8-12 cycles of 3 g/m2. However, relapses occurred after three and seven weeks, in one case with resistance to HD ARA-C. The patient with malignant teratoma did not respond. No severe toxicity emerged even after repeated applications. Adverse reactions included moderate nausea and vomiting (4 patients), diarrhea (2 patients), hepatic dysfunction (1 patient), bone pain (1 patient), blurred vision (1 patient), conjunctivitis (1 patient), and exanthema with partial epidermiolysis (1 patient). Granulocytopenia occurring between 3-8 days after having started the therapy, subsided within 4-25 days. Plasma levels of ARA-C and the metabolite uracil arabinoside (ARA-U) were monitored. At steady state plasma concentrations of ARA-C were 32-97 microM (8-24 micrograms/ml). ARA-C disappeared from the plasma mono- or biphasic with a terminal half-life (t50%) of 7.8-12.6 minutes. The total clearance (Cl) of ARA-C varied between 1.7 and 2.9 liters/kg . h, and the distribution volume (Vss) between 0.44 and 0.86 liters/kg. Cerebrospinal fluid (CSF) levels of ARA-C reached 10-15% of steady state concentrations in plasma.

V těhotenstvĂ­ dochĂĄzĂ­ k ovlivněnĂ­ řady systĂŠmĹŻ včetně muskuloskeletĂĄlnĂ­ho, a to zejmĂŠna axiĂĄlnĂ­ho skeletu. ČastĂ˝m nĂĄsledkem je rozvoj bolestĂ­ v oblasti dolnĂ­ části zad a/nebo pĂĄnve (lumbopelvickĂŠ bolesti), kterĂŠ majĂ­ značnĂ˝ dopad na kvalitu Ĺživota těhotnĂ˝ch a jsou častou příčinou pracovnĂ­ neschopnosti. VĂ˝skyt bolestĂ­ pĂĄnve je popisovĂĄn u 20–65 % těhotnĂ˝ch, nejčastěji udĂĄvanĂĄ prevalence bolestĂ­ dolnĂ­ části zad v těhotenstvĂ­ je kolem 50 %. LumbopelvickĂŠ bolesti mĹŻĹžeme rozdělit na tři kategorie: bolesti dolnĂ­ části zad, bolesti pĂĄnve, kombinovanĂŠ bolesti dolnĂ­ části zad a pĂĄnve. CĂ­lem tohoto sdělenĂ­ je shrnout recentnĂ­ informace o klinickĂŠm obrazu, diagnostice a léčbě lumbopelvickĂ˝ch bolestĂ­ v graviditě.

A pathogenic role for Th17 cells in inflammatory renal disease is well established. The mechanisms underlying their counter-regulation are, however, largely unknown. Recently, Th17 lineage-specific regulatory T cells (Treg17) that depend on activation of the transcription factor Stat3 were identified. We studied the function of Treg17 in the nephrotoxic nephritis (NTN) model of crescentic GN. The absence of Treg17 cells in Foxp3(Cre)×Stat3(fl/fl) mice resulted in the aggravation of NTN and skewing of renal and systemic immune responses toward Th17. Detailed analysis of Stat3-deficient Tregs revealed that the survival, activation, proliferation, and suppressive function of these cells remained intact. However, Tregs from Foxp3(Cre)×Stat3(fl/fl) mice lacked surface expression of the chemokine receptor CCR6, which resulted in impaired renal trafficking. Furthermore, aggravation of NTN was reversible in the absence of Th17 responses, as shown in CD4(Cre)×Stat3(fl/fl) mice lacking both Treg17 and Th17 cells, suggesting that Th17 cells are indeed the major target of Treg17 cells. Notably, immunohistochemistry revealed CCR6-bearing Treg17 cells in kidney biopsy specimens of patients with GN. CCR6 expression on human Treg17 cells also appears dependent on STAT3, as shown by analysis of Tregs from patients with dominant-negative STAT3 mutations. Our data indicate the presence and involvement of Stat3/STAT3-dependent Treg17 cells that specifically target Th17 cells in murine and human crescentic GN, and suggest the kidney-specific action of these Treg17 cells is regulated by CCR6-directed migration into areas of Th17 inflammation.