Stand-Alone Percutaneous Pedicle Screw Lumbar Fixation to Indirectly Decompress the Neural Elements in Spinal Stenosis: A Radiographic Assessment Case Series.

BACKGROUND: The ideal surgical treatment of lumbar canal stenosis remains controversial. Although decompressive open surgery has been widely used with good clinical outcome, minimally invasive indirect decompression techniques have been developed to avoid the complications associated with open approaches. The purpose of this study was to evaluate the radiologic outcome and safety of the indirect decompression achieved with stand-alone percutaneous pedicle screw fixation in the surgical treatment of lumbar degenerative pathologies. METHODS: Twenty-eight patients presenting with spinal degenerative diseases including concomitant central and/or lateral stenosis were treated with stand-alone percutaneous pedicle screw fixation. Radiographic measurements were made on axial and sagittal magnetic resonance (MR) images, performed before surgery and after a mean follow-up period of 25.2 months. Measurements included spinal canal and foraminal areas, and anteroposterior canal diameter. RESULTS: Percutaneous screw fixation was performed in 35 spinal levels. Measurements on the follow-up MR images showed statistically significant increase in the cross-sectional area of the spinal canal and the neural foramen, from a mean of 88.22 and 61.05 mm2 preoperatively to 141.52 and 92.18 mm2 at final follow-up, respectively. The sagittal central canal diameter increased from a mean of 4.9 to 9.1 mm at final follow-up. Visual analog scale (VAS) pain score and Oswestry Disability Index (ODI) both improved significantly after surgery (p < 0.0001). CONCLUSION: Stand-alone percutaneous pedicle screw fixation is a safe and effective technique for indirect decompression of the spinal canal and neural foramina in lumbar degenerative diseases. This minimally invasive technique may provide the necessary decompression in cases of common degenerative lumbar disorders with ligamentous stenosis.

MEvA-X: a hybrid multiobjective evolutionary tool using an XGBoost classifier for biomarkers discovery on biomedical datasets.

MOTIVATION: Biomarker discovery is one of the most frequent pursuits in bioinformatics and is crucial for precision medicine, disease prognosis, and drug discovery. A common challenge of biomarker discovery applications is the low ratio of samples over features for the selection of a reliable not-redundant subset of features, but despite the development of efficient tree-based classification methods, such as the extreme gradient boosting (XGBoost), this limitation is still relevant. Moreover, existing approaches for optimizing XGBoost do not deal effectively with the class imbalance nature of the biomarker discovery problems, and the presence of multiple conflicting objectives, since they focus on the training of a single-objective model. In the current work, we introduce MEvA-X, a novel hybrid ensemble for feature selection (FS) and classification, combining a niche-based multiobjective evolutionary algorithm (EA) with the XGBoost classifier. MEvA-X deploys a multiobjective EA to optimize the hyperparameters of the classifier and perform FS, identifying a set of Pareto-optimal solutions and optimizing multiple objectives, including classification and model simplicity metrics. RESULTS: The performance of the MEvA-X tool was benchmarked using one omics dataset coming from a microarray gene expression experiment, and one clinical questionnaire-based dataset combined with demographic information. MEvA-X tool outperformed the state-of-the-art methods in the balanced categorization of classes, creating multiple low-complexity models and identifying important nonredundant biomarkers. The best-performing run of MEvA-X for the prediction of weight loss using gene expression data yields a small set of blood circulatory markers which are sufficient for this precision nutrition application but need further validation. AVAILABILITY AND IMPLEMENTATION: https://github.com/PanKonstantinos/MEvA-X.

GA-Mediated Disruption of RGA/BZR1 Complex Requires HSP90 to Promote Hypocotyl Elongation.

Circuitries of signaling pathways integrate distinct hormonal and environmental signals, and influence development in plants. While a crosstalk between brassinosteroid (BR) and gibberellin (GA) signaling pathways has recently been established, little is known about other components engaged in the integration of the two pathways. Here, we provide supporting evidence for the role of HSP90 (HEAT SHOCK PROTEIN 90) in regulating the interplay of the GA and BR signaling pathways to control hypocotyl elongation of etiolated seedlings in Arabidopsis. Both pharmacological and genetic depletion of HSP90 alter the expression of GA biosynthesis and catabolism genes. Major components of the GA pathway, like RGA (REPRESSOR of ga1-3) and GAI (GA-INSENSITIVE) DELLA proteins, have been identified as physically interacting with HSP90. Interestingly, GA-promoted DELLA degradation depends on the ATPase activity of HSP90, and inhibition of HSP90 function stabilizes the DELLA/BZR1 (BRASSINAZOLE-RESISTANT 1) complex, modifying the expression of downstream transcriptional targets. Our results collectively reveal that HSP90, through physical interactions with DELLA proteins and BZR1, modulates DELLA abundance and regulates the expression of BZR1-dependent transcriptional targets to promote plant growth.

1.36 million years of Mediterranean forest refugium dynamics in response to glacial-interglacial cycle strength.

The sediment record from Lake Ohrid (Southwestern Balkans) represents the longest continuous lake archive in Europe, extending back to 1.36 Ma. We reconstruct the vegetation history based on pollen analysis of the DEEP core to reveal changes in vegetation cover and forest diversity during glacial-interglacial (G-IG) cycles and early basin development. The earliest lake phase saw a significantly different composition rich in relict tree taxa and few herbs. Subsequent establishment of a permanent steppic herb association around 1.2 Ma implies a threshold response to changes in moisture availability and temperature and gradual adjustment of the basin morphology. A change in the character of G-IG cycles during the Early-Middle Pleistocene Transition is reflected in the record by reorganization of the vegetation from obliquity- to eccentricity-paced cycles. Based on a quantitative analysis of tree taxa richness, the first large-scale decline in tree diversity occurred around 0.94 Ma. Subsequent variations in tree richness were largely driven by the amplitude and duration of G-IG cycles. Significant tree richness declines occurred in periods with abundant dry herb associations, pointing to aridity affecting tree population survival. Assessment of long-term legacy effects between global climate and regional vegetation change reveals a significant influence of cool interglacial conditions on subsequent glacial vegetation composition and diversity. This effect is contrary to observations at high latitudes, where glacial intensity is known to control subsequent interglacial vegetation, and the evidence demonstrates that the Lake Ohrid catchment functioned as a refugium for both thermophilous and temperate tree species.

Deep drilling reveals massive shifts in evolutionary dynamics after formation of ancient ecosystem.

The scarcity of high-resolution empirical data directly tracking diversity over time limits our understanding of speciation and extinction dynamics and the drivers of rate changes. Here, we analyze a continuous species-level fossil record of endemic diatoms from ancient Lake Ohrid, along with environmental and climate indicator time series since lake formation 1.36 million years (Ma) ago. We show that speciation and extinction rates nearly simultaneously decreased in the environmentally dynamic phase after ecosystem formation and stabilized after deep-water conditions established in Lake Ohrid. As the lake deepens, we also see a switch in the macroevolutionary trade-off, resulting in a transition from a volatile assemblage of short-lived endemic species to a stable community of long-lived species. Our results emphasize the importance of the interplay between environmental/climate change, ecosystem stability, and environmental limits to diversity for diversification processes. The study also provides a new understanding of evolutionary dynamics in long-lived ecosystems.

Minimally invasive spinal fixation in an aging population with osteoporosis: clinical and radiological outcomes and safety of expandable screws versus fenestrated screws augmented with polymethylmethacrylate.

OBJECTIVE: The goal of this study was to compare the clinical and radiological outcomes between fenestrated pedicle screws augmented with cement and expandable pedicle screws in percutaneous vertebral fixation surgical procedures for the treatment of degenerative and traumatic spinal diseases in aging patients with osteoporosis. METHODS: This was a prospective, single-center study. Twenty patients each in the expandable and cement-augmented screw groups were recruited. Clinical outcomes included visual analog scale (VAS), Oswestry Disability Index (ODI), and satisfaction rates. Radiographic outcomes comprised radiological measurements on the vertebral motion segment of the treated levels. Intraoperative data including complications were collected. All patients completed the clinical and radiological outcomes. Outcomes were compared preoperatively and postoperatively. RESULTS: An average shorter operative time was found in procedures in which expandable screws were used versus those in which cement-augmented screws were used (p < 0.001). No differences resulted in perioperative blood loss between the 2 groups. VAS and ODI scores were significantly improved in both groups after surgery. There was no significant difference between the 2 groups with respect to baseline VAS or ODI scores. The satisfaction rate of both groups was more than 85%. Radiographic outcomes also showed no significant difference in segment stability between the 2 groups. No major complications after surgery were seen. There were 4 cases (20%) of approach-related complications, all in fenestrated screw procedures in which asymptomatic cement extravasations were observed. In 1 case the authors detected a radiologically evident osteolysis around a cement-augmented screw 36 months after surgery. In another case they identified a minor loosening of an expandable screw causing local back discomfort at the 3-year follow-up. CONCLUSIONS: Expandable pedicle screws and polymethylmethacrylate augmentation of fenestrated screws are both safe and effective techniques to increase the pullout strength of screws placed in osteoporotic spine. In this series, clinical and radiological outcomes were equivalent between the 2 groups. To the authors' knowledge, this is the first report comparing the cement augmentation technique versus expandable screws in the treatment of aging patients with osteoporosis.

Mediterranean winter rainfall in phase with African monsoons during the past 1.36 million years.

Mediterranean climates are characterized by strong seasonal contrasts between dry summers and wet winters. Changes in winter rainfall are critical for regional socioeconomic development, but are difficult to simulate accurately1 and reconstruct on Quaternary timescales. This is partly because regional hydroclimate records that cover multiple glacial-interglacial cycles2,3 with different orbital geometries, global ice volume and atmospheric greenhouse gas concentrations are scarce. Moreover, the underlying mechanisms of change and their persistence remain unexplored. Here we show that, over the past 1.36 million years, wet winters in the northcentral Mediterranean tend to occur with high contrasts in local, seasonal insolation and a vigorous African summer monsoon. Our proxy time series from Lake Ohrid on the Balkan Peninsula, together with a 784,000-year transient climate model hindcast, suggest that increased sea surface temperatures amplify local cyclone development and refuel North Atlantic low-pressure systems that enter the Mediterranean during phases of low continental ice volume and high concentrations of atmospheric greenhouse gases. A comparison with modern reanalysis data shows that current drivers of the amount of rainfall in the Mediterranean share some similarities to those that drive the reconstructed increases in precipitation. Our data cover multiple insolation maxima and are therefore an important benchmark for testing climate model performance.

Pseudoaneurysm of a segmental lumbar artery following a full-endoscopic transforaminal lumbar discectomy: a rare approach-related complication.

Full-endoscopic transforaminal lumbar discectomy is based on a puncture technique using a guide needle to reach the target area of the foramen via a percutaneous posterolateral/lateral approach. It may correlate with specific approach-related complications, as exiting nerve root injury. We report the first case of pseudoaneurysm of the lumbar segmental artery secondary to a transforaminal full-endoscopic surgery in the treatment of a lumbar herniated disc. A 39-year-old man underwent left L4-L5 full-endoscopic transforaminal lumbar discectomy for a herniated disc. Three hours after surgery, he experienced acute progressive abdominal pain. An abdomen CT scan showed contrast extravasation in the left paraspinal compartment at L4 vertebral body level. The selective left lumbar angiogram revealed a pseudoaneurysm of a side branch of the left lumbar segmental artery, which was treated by endovascular coiling. The patient made a rapid postoperative recovery without further complications and was discharged 4 days later. This report identifies a rare complication of transforaminal full-endoscopic surgery in the treatment of a herniated lumbar disc. To our knowledge this is the first case of pseudoaneurysm formation of the lumbar artery following a full-endoscopic transforaminal lumbar discectomy.

Spontaneous Spinal Arthrodesis in Stand-Alone Percutaneous Pedicle Screw Fixation Without in Situ Fusion in Patients With Lumbar Segmental Instability: Long-Term Clinical, Radiologic, and Functional Outcomes.

BACKGROUND: No study to date has established how commonly spontaneous fusion occurs after stand-alone percutaneous pedicle screw fixation in adult population. In this retrospective single-center study, we investigated the effectiveness, long-term solidity and safety of stand-alone percutaneous pedicle screw fixation without in situ fusion and the influence of presence or absence of fusion on the clinical outcome of patients with low-grade lumbar segmental instability. METHODS: Eighty-eight patients with symptomatic low-grade spondylolisthesis were treated with posterior stand-alone percutaneous pedicle screw fixation without bone graft. Radiographic evaluation was used to determine if spontaneous fusion or absence of fusion was present. The solid fusion and absence of fusion groups were analyzed clinically (visual analog scale and Oswestry Disability Index) and with a validated self-administered questionnaire. RESULTS: The average duration of follow-up was 70.5 months (range, 48-120 months). Radiologic signs of spontaneous fusion were present in 45.5% of the cohort and absent in 54.5%. Clinical outcome was excellent to good in 73.8% of the cohort (in 70.9% of cases with spontaneous fusion and in 67.5% of cases with absence of fusion). No significant differences in visual analog scale scores for residual back and lower limb pain between the 2 groups were seen at the final follow-up. At the final follow-up, 5 of 88 patients (5.6%) underwent revision surgery. CONCLUSIONS: Percutaneous pedicle screw fixation offers several advantages that help minimize approach-related morbidity, while achieving similar clinical outcome as seen with more traditional invasive procedures. A solid fixation without bone graft provides long-term clinical benefits. In our patients, the appearance of a spontaneous solid fusion and the absence of fusion after stand-alone pedicle screw fixation were correlated with similar improved clinical outcomes at long-term follow-up.

Ambulatory cardiology network in Greece: Clinical and therapeutic implications in the outpatient setting. The TEVE-SSF study.

BACKGROUND: Community based registries are particularly valuable tools to Preventive Cardiology as they summarize epidemiological data of ischemic heart disease risk factors, medications and lifestyle characteristics. METHODS: We enrolled 1191 patients, from an outpatient community based cardiology network, dedicated to cover medically, office based professionals. We recorded demographic and lifestyle characteristics, risk factors for ischemic heart disease, all clinical entities diagnosed and therapies which were prescribed for hypertension and lipid disorders specifically. RESULTS: Our population consisted of 659 males (55%) and 532 females (45%), (mean age 46±14). A sedentary lifestyle was almost universal (92%), followed by smoking (44%) and overweight body composition (38%). Unhealthy lifestyle increased significantly during the third decade of life, while multimorbidity ascended during the fifth. Cardiovascular morbidity was present in 611 patients (51%), while 289 patients (24%) were found negative for cardiovascular disease and positive for a different system diagnosis. Lipid disorders (32%) and hypertension (31%) were the most frequent cardiovascular entities. ß-Blockers and statins were the most frequently prescribed medications for hypertension and lipid disorders respectively. CONCLUSION: Cardiovascular morbidity was frequent in this ambulatory middle aged population, whereas multimorbidity (mainly from gastrointestinal and endocrine system) was a significant coexisting problem, even for a cardiology oriented outpatient population. Unhealthy lifestyle is of major importance because it was present in the majority of our patients early in their life and because it was statistically related to hyperlipidemia and hypertension. Preventive Cardiology must introduce special interventions to deescalate the presence of unhealthy lifestyle in young populations.

Lateral Brow Lift: A Multi-Point Suture Fixation Technique.

BACKGROUND: Descent of the lateral aspect of the brow is one of the earliest signs of aging. The purpose of this study was to describe an open surgical technique for lateral brow lifts, with the goal of achieving reliable, predictable, and long-lasting results. METHODS: An incision was made behind and parallel to the temporal hairline, and then extended deeper through the temporoparietal fascia to the level of the deep temporal fascia. Dissection was continued anteriorly on the surface of the deep temporal fascia and subperiosteally beyond the temporal crest, to the level of the superolateral orbital rim. Fixation of the lateral brow and tightening of the orbicularis oculi muscle was achieved with the placement of sutures that secured the tissue directly to the galea aponeurotica on the lateral aspect of the incision. An additional fixation was made between the temporoparietal fascia and the deep temporal fascia, as well as between the temporoparietal fascia and the galea aponeurotica. The excess skin in the temporal area was excised and the incision was closed. RESULTS: A total of 519 patients were included in the study. Satisfactory lateral brow elevation was obtained in most of the patients (94.41%). The following complications were observed: total relapse (n=8), partial relapse (n=21), neurapraxia of the frontal branch of the facial nerve (n=5), and limited alopecia in the temporal incision (n=9). CONCLUSIONS: We consider this approach to be a safe and effective procedure, with long-lasting results.

Interspinous spacer decompression (X-STOP) for lumbar spinal stenosis and degenerative disk disease: a multicenter study with a minimum 3-year follow-up.

Interspinous distraction devices provide an effective treatment for patients suffering from lumbar spinal stenosis and/or degenerative disk disease. The aim of this multicenter study was the prospective evaluation of patients treated for symptomatic lumbar spinal stenosis with interspinous process decompression (IPD) implants compared with a population of patients managed with conservative treatment. 542 patients affected by symptomatic lumbar spine degenerative disease were enrolled in a controlled trial. 422 patients underwent surgical treatment consisting of X-STOP device implantation, whereas 120 control cases were managed conservatively. Both patient groups underwent follow-up evaluations at 6, 12, 24, and 36 months using the Zurich Claudication Questionnaire, the Visual Analog Scale score and spinal lumbar X-rays, CT scans and MR imaging. One-year follow-up evaluation revealed positive good results in the 83.5% of patients treated with IPD with respect to 50% of the nonoperative group cases. During the first three years, in 38 out of the 120 control cases, a posterior decompression and/or spinal fixation was performed because of unsatisfactory results of the conservative therapy. In 24 of 422 patients, the IPD device had to be removed, and a decompression and/or pedicle screw fixation was performed because of the worsening of neurological symptoms. Our results support the effectiveness of surgery in patients with stenosis. IPD may offer an effective and less invasive alternative to classical microsurgical posterior decompression in selected patients with spinal stenosis and lumbar degenerative disk diseases.

Treatment with oral paricalcitol in daily clinical practice for patients with chronic kidney disease stage 3-4: a preliminary study.

BACKGROUND: Active vitamin D is an effective treatment for secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients often complicated by hypercalcaemia and hyperphosphataemia. Treatment with paricalcitol, a selective vitamin D receptor activator, has shown benefits by adequately reducing parathyroid hormone (PTH) levels with minimal changes in serum calcium (Ca) and phosphorus (P). The purpose of this study is to present data on the use of oral paricalcitol in real-life clinical practice in patients with CKD stage 3-4 and SHPT. METHODS: We studied 43 patients, M/F: 25/18, median age: 74 years (47-87), CKD stage 3/4: 16/27, with SHPT, who were prescribed oral paricalcitol at recommended doses for 6 months. Monthly measurements of serum intact PTH (iPTH), Ca, P, alkaline phosphatase (ALP), haemoglobin, albumin (ALB), lipid profile, proteinuria and 24-h urine creatinine clearance were performed 3 months before and 6 months after treatment initiation. RESULTS: Paricalcitol induced a significant, early and sustained, through the end of follow-up period, decrease in iPTH and ALP levels and an increase in serum ALB. No significant increase in Ca and P levels as well as in Ca × P product was observed during the study period. No significant changes were found in protein excretion, kidney function and the other measured parameters between baseline and last evaluation. Paricalcitol final median dose was 5 µg/week ranging between 3 and 7 µg/week. CONCLUSIONS: In the context of real-life clinical practice, oral paricalcitol for 6 months is an effective, well-tolerated treatment of SHPT in CKD stage 3-4 with minimal effects on calcium and phosphorus metabolism.

Chronic kidney disease epidemiology collaboration equation accuracy in predicting peritoneal dialysis-delivered creatinine clearance.

INTRODUCTION: Measuring total (residual kidney plus peritoneal) creatinine clearance (CrCl) with 24-h urine and dialysate collections is recommended for peritoneal dialysis (PD) adequacy evaluation. Prediction equations applied in this instance could simplify the approach. Cockcroft-Gault and modification of diet in renal disease (MDRD) four (MDRD-4) and six (MDRD-6) variables equations have been tested in this setting, and conflicting results have been reported. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is currently considered to be more sensitive than the established equations for kidney function estimation. However, its performance in PD adequacy evaluation has not been studied. Our aim was to assess CKD-EPI equation's performance in predicting total measured CrCl (MCC) in PD patients. MATERIAL AND METHODS: A group of 23 consecutive PD patients, male/female: 5/18, median age: 66 (32-91) years, median time on PD 32 (2-126) months, were enrolled in the study. All were treated by automated PD (APD). Sixteen out of twenty-three had residual renal function (RRF). MCC was determined from 24-h dialysate and urine collections and also predicted by Cockcroft-Gault, MDRD (4 and 6), and CKD-EPI equations. RESULTS: CKD-EPI and MDRD-6 estimation results were similar to MCC (9.01 ± 3.90 and 9.54 ± 2.98 vs. 8.64 ± 3.75 mL/min/1.73 m(2) p = 0.49 and 0.09, respectively). Neither the presence nor the volume of residual urine affected the accuracy of prediction. Cockcroft-Gault and MDRD-4 equations differed significantly from MCC and were not accurately predictive. CONCLUSION: CKD-EPI equation could be used with accuracy for predicting MCC in PD patients. Only MDRD-6 showed similar accuracy, whereas MDRD-4 and Cockcroft-Gault equations were found to be inappropriate in this setting.

Surgical approach for nevoid hyperkeratosis of the areola.

Nevoid hyperkeratosis of the breast is a rare condition affecting the nipple, the areola or both. It appears in both sexes and it can by lateral or unilateral. It can also accompany other skin diseases or systemic conditions including malignancies. Treatment may not be easy due to aesthetic consequences but surgery seems to be the most preferable therapeutic option. We report such a case successfully managed by surgical intervention.

Intraoperative modification of Pitanguy technique of reduction mammaplasty for elevation of the nipple-areola complex in case of severe breast ptosis.

BACKGROUND: The Pitanguy method of reduction mammaplasty has been shown to be an anatomically safe technique in the management of the ptotic breast. However, the technique, as first described, cannot be applied in gigantomastia or severe breast ptosis cases or cases of dense parenchyma of the breast. The senior surgeon suggested an intraoperative modification of the Pitanguy method of reduction mammaplasty to make it applicable for such cases. METHODS: A retrospective study of 122 patients with severe breast ptosis (70), gigantomastia (45), or dense breast parenchyma (7) who underwent a modification of the Pitanguy method was performed. The current procedure involves all the operating steps of the superior pedicle technique as described by Pitanguy, from the marking technique to the keel resection of the breast. If the nipple-areola complex is elevated inadequately, the surgeon can use the senior surgeon's modification to elevate the complex to the desired height. This modification consists of dissecting the upper pole of the breast vertically to the fascia of the pectoralis major muscle and laterally to the nipple-areola complex. The medial flap is then advanced superiorly, rotated 90°, and sutured to point A, while the lateral flap is placed below the medial one. This maneuver maximizes elevation of the nipple-areola complex to the desired height. RESULTS: The mean change in nipple position was 14 cm (range = 10-16 cm). The mean weight reduction of each breast was 900 g (range = 700-1300 g). The follow-up included 119 patients and the follow-up period ranged from 1 to 3 years (mean follow-up = 2 years). Three patients were operated on less than 3 months ago and were not involved in this study. All patients gained natural shaped breasts and they were pleased with the results. Serious complications, including flap necrosis, were avoided since caution was used to preserve the internal mammary perforators while performing this method. CONCLUSION: This technique provides a versatile, well-vascularized pedicle that allows elevation of the nipple-areola complex at the desired height in cases of severe breast ptosis, gigantomastia, or dense breast parenchyma.

Neurilemoma of the popliteal fossa: report of two cases with long subclinical course and misleading presentation.

The authors report two cases of neurilemoma localised in the popliteal fossa. Both patients experienced non-specific symptoms, such as painful numbness and burning dysaesthesia, involving the lower extremity. Tinel's sign was positive over the popliteal fossa. The patients sought medical advice and underwent conservative treatment without any relief, for a long time before the right diagnosis was made. Magnetic resonance imaging revealed in both patients a well- circumscribed mass posterior to the sciatic nerve, occupying the popliteal fossa. Following surgical excision of the neurilemoma, the patients experienced immediate relief of their chronic symptoms. In similar situations, ultrasound or magnetic resonance imaging of the whole sciatic nerve should be performed if this is indicated by detailed physical examination. Once the diagnosis is made, neurilemomas should be surgically removed, in order to exclude malignancy, prevent neurologic deficits and provide relief of symptoms.

Secondary prognosis after cardioembolic stroke of atrial origin: the role of left atrial and left atrial appendage dysfunction.

BACKGROUND: Secondary prevention studies for cardioembolic strokes show a remarkable variability in stroke recurrence rates. Various reports have raised questions regarding differences in baseline clinical characteristics and in methodology to explain this wide variability. HYPOTHESIS: The purpose of the present study is to examine the 2-year outcome after first cardioembolic stroke of atrial origin and to correlate secondary prognosis with left atrial and left atrial appendage dysfunction. METHODS: Baseline evaluation included computed tomographic and/or magnetic resonance scanning, Doppler scanning, digital subtraction angiography, and transthoracic and transesophageal echocardiography to establish the diagnosis of atrial source of emboli. Twenty-six patients in nonrheumatic atrial fibrillation and 13 in sinus rhythm were followed for recurrent stroke and vascular death as endpoints (event +/-). RESULTS: Patients in sinus rhythm had a total of 23% (standard deviation +/- 12%) recurrence rate. All event (+) patients were on aspirin and died from this second cardioembolic stroke. Of patients in nonrheumatic atrial fibrillation, 50% were event (+) at the end of the first year (death rate 46%). Patients on warfarin therapy had 20% recurrence rate versus 70% on aspirin (relative risk 0, 18, 95% confidence interval, 0.05-0.48, p 0.041). Inward peak velocity of left atrial appendage was the only echocardiographic variable significantly reduced in event (+) patients (21 +/- 7 vs. 31 +/- 17 cm/s, p 0.048). CONCLUSIONS: Patients with nonrheumatic atrial fibrillation and first atrial origin cardioembolic stroke are at increased risk for recurrence if severe dysfunction of the left atrial appendage is present and if they do not receive warfarin treatment. Patients with sinus rhythm and first atrial origin cardioembolic stroke form a small stroke subgroup, in which recurrences are accompanied by a remarkably high death rate.