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BACKGROUND The literature on white matter anatomy underlying the human orbitofrontal cortex (OFC) is scarce in spite of its relevance for glioma surgery. OBJECTIVE To describe the anatomy of the OFC and of the underlying white matter fiber anatomy, with a particular focus on the surgical structures relevant for a safe and efficient orbitofrontal glioma resection. Based on anatomical and radiological data, the secondary objective was to describe the growth pattern of OFC gliomas. METHODS The study was performed on 10 brain specimens prepared according to Klingler's protocol and dissected using the fiber microdissection technique modified according to U.T., under the microscope at high magnification. RESULTS A detailed stratigraphy of the OFC was performed, from the cortex up to the frontal horn of the lateral ventricle. The interposed neural structures are described together with relevant neighboring topographic areas and nuclei. Combining anatomical and radiological data, it appears that the anatomical boundaries delimiting and guiding the macroscopical growth of OFC gliomas are as follows: the corpus callosum superiorly, the external capsule laterally, the basal forebrain and lentiform nucleus posteriorly, and the gyrus rectus medially. Thus, OFC gliomas seem to grow ventriculopetally, avoiding the laterally located neocortex. CONCLUSION The findings in our study supplement available anatomical knowledge of the OFC, providing reliable landmarks for a precise topographical diagnosis of OFC lesions and for perioperative orientation. The relationships between deep anatomic structures and glioma formations described in this study are relevant for surgery in this highly interconnected area.

Objective: Nonsteroidal anti-inflammatory drugs (NSAID) are essential in surgeons’ armamentarium for pain relief and antiphlogistic effects. However, spine surgeons are concerned about the drugs’ impact on coagulation, fearing hemodynamic instability due to blood loss and neurological complications due to postoperative hematoma. Furthermore, there are no clear guidelines for the use of these drugs.Materials and methods: In this retrospective subgroup analysis of a prospective observational study, we investigated 181 patients who underwent minimally invasive spinal fusions in degenerative lumbar spine pathologies. 83 patients were given NSAID perioperatively, 54 of which were female and 29 male. Of these patients who took NSAID, 39 were on NSAID until at least one day before surgery or perioperatively, whilst the others discontinued their NSAID medication at least three days before surgery. Differences in perioperative blood loss, as well as complication rates between patients with and without NSAID treatment, were investigated.Results: A significantly higher amount of blood loss during surgery and the monitoring period was encountered in patients whose spine was fused in more than one level, regardless of whether NSAID medication was taken or not and up until what point. Furthermore, it was found that taking NSAID medication had no effect on the incidence of postoperative epidural hematomas.Conclusion: Perioperatively taking NSAID medication does not increase blood loss or the incidence of postoperative hematoma in patients undergoing minimally invasive lumbar spinal fusion surgery.

Background The impact of smoking on spinal surgery has been studied extensively, but few investigations have focused on minimally invasive surgery (MIS) of the spine and the difference between complication rates in smokers and non-smokers. We evaluated whether a history of at least one pack-year preoperatively could be used to predict adverse peri- and postoperative outcomes in patients undergoing minimally invasive fusion procedures of the lumbar spine. In a prospective study, we assessed the clinical effectiveness of MIS in an unselected population of 187 patients. Methods We evaluated perioperative and postoperative complication rates in MIS fusion techniques of the lumbar spine in smoking and non-smoking patients. MIS fusion was performed using interbody fusion procedures and/or posterolateral fusion alone. Results Smokers were significantly younger than non-smokers. We did not encounter infection at the site of surgery or severe wound healing disorder in smokers. We registered no difference between the smoking and non-smoking groups with regard to peri- or postoperative complication rate, blood loss, or length of stay in hospital. We found a significant influence of smoking (p = 0.049) on the overall perioperative complication rate. Conclusion MIS fusion techniques seem to be a suitable tool for treating degenerative spinal disorders in smokers.

Objective Long-term outcomes are rarely reported for patients with pediatric hydrocephalus. Ventriculoperitoneal shunting is the surgical standard; nevertheless, in selected patients, a ventriculoatrial shunt (VAS) remains an important alternative. This study aimed to analyze the causes of VAS revisions and complications. Methods Pediatric patients who underwent their first shunt operation between 1982 and 1992 were included. The timing, cause, and modality of VAS revisions were retrospectively determined. Results Overall, 138 patients were treated for hydrocephalus and 61 patients received a VAS during the follow-up period. A primary VAS was the first shunt type in 42 (68.85%) patients. In 19 (31.15%) patients, conversions to second-line VAS were carried out. The rates of VAS revisions performed for dysfunction or elective lengthening of a short atrial catheter were 52.2% and 22.9%, respectively. There was no difference in the number of VAS revisions between patients with primary VASs and second-line VASs. Age at VAS and etiology of hydrocephalus had no effect on the number of revisions. Specific VAS complications were observed in 2 patients. Deep positioning of the distal catheter led to asymptomatic tricuspid regurgitation that was reversible after shortening of the atrial catheter. Another patient presented with shunt nephritis and completely recovered after the atrial catheter was replaced with a peritoneal catheter. Conclusions VAS remains an appropriate second-line alternative in selected patients. Specific VAS complications were rarely observed and completely reversible after treatment. However, regular and specific follow-up examinations are strongly recommended to avoid cardiopulmonary or renal complications.

Bowel perforation by a peritoneal catheter (BPPC) is a serious complication after ventriculoperitoneal shunting, with high mortality and morbidity rates. This patient presented with scalp ulceration over the shunt valve at the retromastoid region 26 years after shunt placement. During revision, the catheter distal to the valve was divided in the clavicular region. As there was no cerebrospinal fluid drainage, we decided to remove the ventricular catheter and valve. The ulceration was debrided and primarily closed. Distal to the clavicle, the disconnected peritoneal catheter was encased in a fibrous, calcified tunnel. To avoid piecemeal resection with multiple incisions, the catheter was not retrieved. Two years later, the patient presented with an abscess and pus draining from the clavicular wound. Cultures were positive for enteric bacteria. BPPC with retrograde spread of infection was suspected, and abdominal computed tomography confirmed perforation. We removed the disconnected catheter, but the perforation site could not be detected during laparotomy. The patient was treated with intravenous antibiotics and recovered without complications. To minimize complications, abandoned catheters should be avoided. Otherwise, patients unnecessarily have a life-long risk of developing abdominal complications. In patients with abandoned catheters and severe abdominal symptoms, BPPC is an important differential diagnosis.

Very large and giant aneurysms are among the most challenging cerebrovascular pathologies in neurosurgery.The aim of this paper is to review the current literature on the management of very large and giant aneurysms and to describe representative cases illustrating possible treatment strategies.In view of the poor natural history, active management using multiprofessional individualized approaches is required to achieve aneurysm occlusion, relief of mass effect, and obliteration of the embolic source. Both reconstructive (clipping, coiling, stent-assisted coiling, flow diversion [FD]) and deconstructive techniques (parent artery occlusion [PAO], PAO in conjunction with bypass surgery, and strategies of flow modification) are available to achieve definitive treatment with acceptable morbidity.Patients harboring such lesions should be managed at high-volume cerebrovascular centers by multidisciplinary teams trained in all techniques of open and endovascular neurosurgery.

Introduction: Very large and giant aneurysms are among the most challenging cerebrovascular pathologies in neurosurgery.Methods: The aim of this paper is to review the current literature on the management of very large and giant aneurysms and to describe representative cases illustrating possible treatment strategies.Results: In view of the poor natural history, active management using multiprofessional individualized approaches is required to achieve aneurysm occlusion, relief of mass effect, and obliteration of the embolic source. Both reconstructive (clipping, coiling, stent-assisted coiling, flow diversion [FD]) and deconstructive techniques (parent artery occlusion [PAO], PAO in conjunction with bypass surgery, and strategies of flow modification) are available to achieve definitive treatment with acceptable morbidity.Conclusions: Patients harboring such lesions should be managed at high-volume cerebrovascular centers by multidisciplinary teams trained in all techniques of open and endovascular neurosurgery.

BACKGROUND The impact of diabetes on spinal surgery has been studied extensively, but very few studies have focused on minimal access spinal technologies (MAST) and complication rates in patients suffering from type 2 diabetes (T2DM). Diabetes increases the risk of wound healing disorders, complication rate and length of stay in the hospital. We focused on the peri- and postoperative complications of MAST in an unselected consecutive population of 187 patients suffering from degenerative disorders lumbar spine disorders. Since mostly older patients are affected by degenerative lumbar changes, we concentrated on T2DM. METHODS We evaluated perioperative and postoperative complication rates associated with MAST fusion techniques in lumbar spine surgery in patients suffering from T2DM compared to patients without diabetes. Lumbar fusion was performed using interbody and posterolateral fusion. RESULTS Eighteen female and sixteen male patients suffered from T2DM (15.65% and 22.22% respectively). No differences between patients with and without T2DM concerning surgery-related complications including infections, severe wound healing disorders or length of in-hospital stay were noted. Peri- or postoperative complication rates, as well as blood loss volumes, were evenly distributed between the two groups. CONCLUSIONS T2DM is not a risk factor for the occurrence of complications in MAST.

OBJECTIVES: To review the surgical results and to identify possible parameters influencing the clinical outcomes in an unselected patient collective undergoing minimally invasive lumbar interbody fusion in a spinal care unit. METHODS: A total of 229 adult patients who underwent minimally invasive lumbar spinal fusion between 2008 and 2016 were included in this retrospective analysis. Lumbar fusion was performed using transforaminal interbody fusion (TLIF) devices and posterolateral fusion. To eliminate confounding parameters, in all patients interbody fusion was indicated by lumbar degenerative pathologies, and surgery was performed using the same fusion device. Treatment efficacy was evaluated using scores describing pain (visual analogue scale [VAS]) and health impairment (EQ‐5D, Oswestry Disability Index [ODI]). The influence of patient age, obesity, active smoking status, and co‐morbidities on clinical outcome and perioperative complications was analyzed. RESULTS: The patient population reviewed had improved VAS (P ((leg pain)) ≤ 0.0001, P ((back pain)) ≤ 0.0001), ODI (P ≤ 0.0001), EQ‐VAS (P ≤ 0.0001), and EQ‐5D subscales “mobility”, “self‐care”, “pain”, and “anxiety” (P ((mobility)) ≤ 0.0001, P ((self‐care)) = 0.41, P ((pain)) ≤ 0.0001, P ((anxiety)) = 0.011) postoperatively. Neither advanced patient age, nor increased body mass index (BMI), hypertension, or active smoking status had a significantly limiting influence on the success of minimally invasive spinal surgeries (MIS). Duration of surgery strongly correlated with the number of spinal levels treated and with intraoperative blood loss (r = 0.774, P ≤ 0.0001, n = 208). Weak positive correlations were found between patient age and duration of surgery (r = 0.184, P = 0.005, n = 229), intraoperative blood loss (r = 0.165, P = 0.012, n = 229), and duration of hospitalization (r = 0.270, P ≤ 0.0001, n = 228), respectively. When compared to non‐smokers, smokers were younger (P ≤ 0.0001), and had a significantly lower BMI (P = 0.001), shorter durations of surgery (P ≤ 0.0001), decreased intraoperative blood loss (P = 0.022), and shorter hospital stays (P = 0.006), respectively. Complications occurred in 17 patients (7%) and were not affected by patient age, BMI, hypertension, or active smoking status. CONCLUSION: Minimally invasive spinal surgery is a safe and effective treatment option and may be superior to open surgery in subpopulations with significant co‐morbidities and risk factors, such as elderly and obese patients as well as patients with an active smoking status.

Objective Realistic, safe, and efficient modalities for simulation-based training are highly warranted to enhance the quality of surgical education, and they should be incorporated in resident training. The aim of this study was to develop a patient-specific virtual cerebral aneurysm-clipping simulator with haptic force feedback and real-time deformation of the aneurysm and vessels. Methods A prototype simulator was developed from 2012 to 2016. Evaluation of virtual clipping by blood flow simulation was integrated in this software, and the prototype was evaluated by 18 neurosurgeons. In 4 patients with different medial cerebral artery aneurysms, virtual clipping was performed after real-life surgery, and surgical results were compared regarding clip application, surgical trajectory, and blood flow. Results After head positioning and craniotomy, bimanual virtual aneurysm clipping with an original forceps was performed. Blood flow simulation demonstrated residual aneurysm filling or branch stenosis. The simulator improved anatomic understanding for 89% of neurosurgeons. Simulation of head positioning and craniotomy was considered realistic by 89% and 94% of users, respectively. Most participants agreed that this simulator should be integrated into neurosurgical education (94%). Our illustrative cases demonstrated that virtual aneurysm surgery was possible using the same trajectory as in real-life cases. Both virtual clipping and blood flow simulation were realistic in broad-based but not calcified aneurysms. Virtual clipping of a calcified aneurysm could be performed using the same surgical trajectory, but not the same clip type. Conclusions We have successfully developed a virtual aneurysm-clipping simulator. Next, we will prospectively evaluate this device for surgical procedure planning and education.

Objective The impact of obesity on spine surgery has been studied extensively, but only a few investigations have been focused on minimally invasive spinal fusion techniques and complication rates in normal-weight, preobese, or obese patients. Obesity was found to be a risk factor for intraoperative complications. Published data tend to favor minimal access surgery techniques (MAST) for obese patients. In a prospective study, we assessed the perioperative and postoperative complications of MAST in a large population of 187 patients. Methods We evaluated perioperative and postoperative complication rates in minimally invasive surgery (MIS) fusion techniques of the lumbar spine in obese, preobese, and normal-weight patients, classified by body mass index (BMI). Lumbar MIS fusion was performed by interbody fusion procedures and posterolateral fusion. In cases of spinal stenosis, a laminotomy was performed (146 patients). Any harmful event occurring during or after surgery was included in the statistical analysis. Results No infection or severe wound healing disorder was encountered in the series. No significant difference in terms of cerebrospinal fluid leakage, blood loss, drainage, or length of hospital stay between the 3 BMI groups was encountered. More clinically insignificant hematomas were encountered in the preobese and obese groups (P = 0.013) than in the normal-weight patients. No significant difference was registered between the BMI or age groups regarding overall complication rates. Conclusion We conclude that preobese and obese patients are good candidates for MAST because BMI did not affect complication rates or duration of surgery.

Objective: Very long-term outcomes are rarely reported for patients with shunted pediatric hydrocephalus. This study aimed to determine the functional, social, and neurocognitive outcomes of such patients after transition to adulthood. Methods: Adult patients with pediatric hydrocephalus who underwent their first shunt operation between 1982 and 1992 were included. Functional, social, educational, working aspects, and verbal intelligence were evaluated. In patients with average or above average verbal intelligence, detailed neuropsychological testing was performed and memory, executive functioning, selective attention, and concentration were assessed. Results: Overall, 137 patients underwent primary surgery because of pediatric hydrocephalus, 53 (38.7%) of whom died during the follow-up period. Of the 84 long-term survivors, 65 (77.4%) agreed to participate and were included for further analysis. Forty-five patients (69.2%) had completed secondary school, but only 34 (52.3%) were integrated in the open labor market. Although the verbal intelligence of 31 patients (47.7%) was within the normal range, 19 (29.2%) had a severe mental handicap. Shunt infections (P = 0.0025), epilepsy (P < 0.0001), and the number of shunt operations (P = 0.0082) were associated with reduced verbal intelligence. Most patients with average or above average verbal intelligence had deficits in detailed neuropsychological testing. In 23 patients, detailed neuropsychological testing was performed. Conclusions: The overall long-term outcome of patients with shunted pediatric hydrocephalus is poor. These results highlight the importance of lifelong routine controls to avoid later complications. Further, repeated neuropsychological examinations might be important to understand the patient's special needs to optimize professional support.

Objective As a result of continuously increasing life expectancy, the number of requests for surgery to treat degenerative diseases of the spine in the elderly population will increase. Since older age is associated with the occurrence of medical comorbidities, the demand for less extensive surgical approaches is growing. The aim of this study is to establish whether minimally invasive fusion techniques are a safe and adequate tool for use in elderly patients. Patients and methods We analyzed 187 patients who underwent minimally invasive surgery (MIS) in the form of one- to four-level fusion procedures. In 146 patients, additional widening of the spinal canal was performed. The subjects were grouped into four age categories of approximately equal size (33–56, 56–66, 66–74 and 74–85). The effect of age on the incidence of peri- and postoperative complications was investigated and compared between the age groups. Results Older age was not associated with the occurrence of perioperative complications, which include wound healing disorders, hematomas, wound traction-blisters and cerebrospinal fluid leakage. Fourteen patients (7.49%) encountered distinct surgical technique related complications, making surgical revision necessary in eight patients (4.28%). Furthermore, increasing age didn’t elevate the risk of postoperative adverse events, i.e. pulmonary embolism, ischemic heart attack or pneumonia, among others. However, older patients were found to stay in hospital longer than younger patients, especially when more than one level was fused. Conclusions Minimally invasive surgery techniques are safe in elderly patients. The small-scale surgical approach guarantees a low incidence of infections and wound healing disorders. However, a longer hospital stay must be expected in older patients.

Objective An abdominal pseudocyst (APC) is a distal catheter site-specific failure in patients treated with ventriculoperitoneal shunts. Few studies with more than 10 patients have been reported. The aim of this study was to analyze causes of peritoneal catheter revisions with special emphasis on revisions because of an APC. Methods Pediatric patients with first shunt operation between 1982 and 1992 were included, and time, cause, and modality of peritoneal catheter revision were determined retrospectively. Results One hundred thirty-eight patients were treated for hydrocephalus, and 112 patients received a peritoneal catheter during the follow-up. An APC was diagnosed in 14 (12.5%) patients, and 28 revisions were needed for its treatment. The rate of shunt infection in patients with APC was 50%, but bacterial examination of the pseudofluid culture revealed infection in only 3 patients. Age at first surgical procedure, type of first surgical procedure, and etiology of hydrocephalus were not associated with APC diagnosis. APC recurred in 4 patients. These patients had a catheter repositioning directly into the peritoneum as first surgical treatment. No recurrences were observed in patients with shunt externalization or replacement of the peritoneal catheter. Conclusions An APC is a major long-term complication after ventriculoperitoneal shunt treatment. Although a sterile inflammatory response cannot be excluded completely, our results favor the hypothesis of low-level shunt infection. In both cases, the surgical consequences are the same. An infected APC should be treated as a shunt infection. Uninfected patients can be treated with shunt externalization and replacement of only the peritoneal catheter.

Purpose: Very long-term follow-up and outcome are rare for pediatric patients with hydrocephalus and shunt operations. The aim of this study was to determine the long-term mortality rates in these patients. Methods: Pediatric patients with first shunt operation between 1982 and 1992 were included. For each patient, time and cause of death were determined. Further, patients with first operation from 1982 to 1987 were compared to those first operated from 1988 to 1992. Results: One-hundred thirty-seven patients were included. Etiologies of hydrocephalus were intraventricular hemorrhage (31.4 %), meningomyelocele (25.5 %), postinfectious (11.7 %), congenital (10.2 %), posterior fossa cyst (8.8 %), aqueductal stenosis (8 %), and others (4.4 %). Overall, 53 patients (38.7 %) died. The percentage of patients surviving 1, 2, 10, and 20 years after first operation were 82.6, 73.6, 69.4, and 65.3 %, respectively. In 23 patients, the cause of death was related to shunt treatment: shunt infection was diagnosed in 18 and acute shunt dysfunction in 5 patients. Mortality was considerably higher for patients with their first operation in time period 1982–1987 compared to time period 1988–1992 (51 versus 25 %). The reduction of mortality was mainly due to an increased survival after shunt infection. Eighty-seven patients survived more than 20 years after initial shunt operation. Of those long-term survivors, three (3.4 %) patients died 22–24 years after first operation. Conclusion: Mortality in hydrocephalic pediatric patients is high especially in the first postoperative years but is even significant in adult patients with pediatric hydrocephalus. As deaths occur even after 20 years, routine follow-up of long-term survivors remains necessary.

BackgroundTransplant of skeletal myoblasts is an attractive alternative to repair irreversibly damaged myocardium in ischemic heart failure. We investigated whether transplant of myoblasts overexpressing placental growth factor would stimulate angiogenesis and enhance myoblast survival in a rat heart failure model.MethodsThree weeks after myocardial infarction, Sprague–Dawley rats in heart failure received intramyocardial injections of Ringer solution (control) or autologous myoblasts, unmodified or transfected with placental growth factor expression plasmid. Sham-operated animals served as noninfarct controls. Cardiac function was assessed by echocardiography to 86 days after engraftment. Immunocytochemistry and fluorescence imaging were used to investigate vessel formation, grafted myoblast survival, infarct wall thickness, and infarct size. Quantitative real-time reverse transcriptase polymerase chain reaction and Western blotting measured tissue messenger RNA and protein expressions.ResultsLeft ventricular function significantly improved with time, and fractional shortening on day 86 was significantly enhanced in transfected myoblast group relative to control (P

Endomyocardial biopsy (EMB) is the "gold standard" in cardiac allograft acute cellular rejection (ACR) diagnosis, but it is invasive. ACR prediction at organ harvest could reduce EMB frequency in low-risk recipients. ACR is reportedly associated with apoptosis and Apollon inhibits apoptosis and promotes cell survival. It is unknown whether donor myocardial tissue Apollon mRNA could predict ACR.Left ventricular biopsies (LVBs) were obtained from 336 donors before and after aortic cross-clamping (ACC) and at 10, 30 and 60 minutes of reperfusion in recipients. Tissue Apollon messenger RNA (mRNA) expression was examined by real-time reverse transcript-polymerase chain reaction (RT-PCR) and correlated with ACR episodes.Apollon LVB expression was significantly decreased before and after ACC in donors and at 10 minutes of reperfusion (por = 0.0233) in recipients who developed Grade 2R and 3R ACR as compared with those with Grade 1R or no ACR. In addition, Apollon myocardial expression was significantly decreased at 10 minutes of reperfusion in patients who developed Grade 3R ACR compared with all other ACR grades (por = 0.0425). In receiver-operating characteristic curve analysis, at a cut-off level of 75.66 arbitrary units, Apollon mRNA before ACC in donors identified combined Grade 2R and 3R ACR with a sensitivity of 94% and a specificity of 96% (p0.0001; area under the curve [AUC] = 0.965; odds ratio [OR] = 0.958; 95% confidence interval [CI] 0.942 to 0.974).Apollon is a sensitive and specific predictor of ACR in donated cardiac allografts and may have important implications in the choice of surveillance.

Objectives Plasminogen activator inhibitor 1 is the primary regulator of urokinase plasminogen activator and tissue plasminogen activator. Plasminogen activator inhibitor 1 is essential in the control of the thrombotic/fibrinolytic balance and is a marker of endothelial cell injury. Idiopathic dilated cardiomyopathy is reportedly associated with endothelial cell dysfunction. Whether endothelial cell damage plays a role in patients with dilated cardiomyopathy after cardiac transplantation remains unknown. Methods In this study explanted hearts of cardiac transplant recipients with ischemic cardiomyopathy and dilated cardiomyopathy, as well as control myocardial tissue, were investigated for expression of urokinase plasminogen activator, tissue plasminogen activator, urokinase plasminogen activator receptor, and plasminogen activator inhibitor 1 and 2. Furthermore, plasminogen activator inhibitor 1 expression was examined in endomyocardial biopsy specimens and sera of patients with ischemic cardiomyopathy and those with dilated cardiomyopathy during the first posttransplantation year. The effect of the patient's serum on endothelial cells was assessed in vitro to examine the role of circulating endothelial cell damage–related factors. Results Plasminogen activator inhibitor 1 expression was upregulated in ischemic cardiomyopathy and dilated cardiomyopathy myocardial tissue versus that seen in control tissue. After transplantation, plasminogen activator inhibitor 1 expression returned to control levels in patients with ischemic cardiomyopathy. In patients with dilated cardiomyopathy, plasminogen activator inhibitor 1 expression increased at 24 weeks after transplantation in both biopsy specimens and sera versus that seen in control tissue. Sera of patients with dilated cardiomyopathy, but not that of patients with ischemic cardiomyopathy, inhibited vascular endothelial growth factor A–induced proliferation of endothelial cells, although downstream target gene activation of early growth response factor 1 and NGFI-A binding protein 2 was not affected. Conclusions These data suggest for the first time that the endothelial cell damage–related process recurs in patients with dilated cardiomyopathy after transplantation, which, independently of vascular endothelial growth factor, is associated with increased plasminogen activator inhibitor 1 expression, and that this pathology might play a role in allograft remodeling in patients with dilated cardiomyopathy.

Cardiac allograft rejection is currently diagnosed from endomyocardial biopsies (EMB) that are invasive and impractical to repeat. A serological marker could facilitate rejection monitoring and minimize EMB-associated risks. We investigated the relation of serum matrix metalloprotease (MMP)-1 and vascular endothelial growth factor (VEGF)-A concentrations to cardiac allograft rejection, using 1176 EMBs and serum samples obtained from 208 recipients. Acute cellular rejection was diagnosed in 186 EMBs. Mean week 1 and week 2 serum MMP-1 concentrations predicted rejection (p = 0.001, AUC = 0.80). At the optimal cut-off level of ≥7.5 ng/mL, MMP-1 predicted rejection with 82% sensitivity and 72% specificity. Initial serum MMP-1

An accessory to suprascapular nerve (XIN-SSN) transfer is considered in patients with obstetric brachial plexus lesion who fail to recover active shoulder external rotation. The aim of this study was to evaluate the quality of extraplexal suprascapular nerve neurotization and to perform a detailed analysis of the infraspinatus muscle (IM) and shoulder external rotation.A XIN-SSN transfer was performed in 14 patients between 2000 and 2007. Patients had been operated at the age of 3.7 ± 2.8 years. Follow-up examinations were conducted up to 8.5 ± 2.5 years. Magnetic resonance imaging was performed to investigate muscle trophism. Fatty muscle degeneration of the IM was classified according to the Goutallier classification. We conducted nerve conduction velocity studies of the suprascapular nerve and needle electromyography of the IM to assess pathologic spontaneous activity and interference patterns. Active glenohumeral shoulder external rotation and global shoulder function were evaluated using the Mallet score.Postoperatively, growth of the IM increased equally on the affected and unaffected sides, although significant differences of muscle thickness persisted over time. There was only grade 1 or 2 fatty degeneration pre- and postoperatively. Electromyography of the IM revealed a full interference pattern in all except one patient, and there was no pathological spontaneous activity. Glenohumeral external rotation as well as global shoulder function increased significantly.Our results indicate that the anastomosis after XIN-SSN transfer is functional and that successful reinnervation of the infraspinatus muscle may enable true glenohumeral active external rotation.

Objective Azithromycin has become a standard of care in therapy of bronchiolitis obliterans following lung transplantation. Matrix metalloprotease-9 broncho-alveolar lavage levels increase in airway neutrophilia and bronchiolitis obliterans. Interleukin-17 may play a role in lung allograft rejection, and interleukin-12 is downregulated in bronchiolitis obliterans. Whether these mechanisms can be targeted by azithromycin remains unclear. Methods Bronchiolitis obliterans was induced by transplantation of Fischer F344 rat left lungs to Wistar Kyoto rats. Allografts with azithromycin therapy from day 1 to 28 or 56 and mono- or combination therapy with the broad-spectrum matrix metalloprotease inhibitor tanomastat from day 1 to 56 were compared to control allografts and isografts. Graft histology was assessed, and tissue cytokine expression studied using Western blotting and immunofluorescence. Results The chronic airway rejection score in the azithromycin group did not change between 4 and 8 weeks after transplantation, whereas it significantly worsened in control allografts ( P = .041). Azithromycin+tanomastat prevented complete allograft fibrosis, which occurred in 40% of control allografts. Azithromycin reduced interleukin-17 expression ( P = .049) and the number of IL-17 + /CD8 + lymphocytes at 4 weeks, and active matrix metalloprotease-9 at 8 weeks ( P = .017), and increased interleukin-12 expression ( P = .025) at 8 weeks following transplantation versus control allografts. Conclusions The expression of interleukin-17 and matrix metalloprotease-9 in bronchiolitis obliterans may be attenuated by azithromycin, and the decrease in interleukin-12 expression was prevented by azithromycin. Combination of azithromycin with a matrix metalloprotease inhibitor is worth studying further because it prevented complete allograft fibrosis in this study.

Objectives Very few cases of arteriovenous malformations (AVMs) associated with gliomas were reported so far in the literature. Methods Here, we report a rare case of a glioblastoma with an AVM-like lesion and review the existing literature. Results We report an unusual case of a 72-year old woman, who presented with a progressive history of aphasia, memory deficit, and headache. Initial MRI imaging was suggestive of a high-grade glioma for which a pterional craniotomy was performed. Intraoperatively, the lesion resembled a vascular malformation. Total extirpation of the lesion was verified by intraoperative MR imaging. Initial histopathological analysis revealed an AVM. Due to the discrepancy between the radiologic and histopathologic findings, the patient was monitored at close intervals. Two month later, multiple lesions were visible on MRI imaging, thus, supporting the diagnosis of malignant glioma. Therefore, after reinvestigating the histopathological sections and cutting the paraffin block in additional serial sections, in only 5% of the section a glioblastoma was discerned which was surrounded by an AVM-like lesion. Conclusion Gliomas are rarely found in association with AVMs and require accurate diagnostic evaluation and interpretation for adequate therapeutic interventions.

Background Glutathione S-transferase P1 1 (GSTP1) belongs to the multigene isozyme family involved in cellular response to oxidative stress and apoptosis. Our initial retrospective proteomic analysis suggested that GSTP1 is associated with heart failure (HF). Although pro–B-type natriuretic peptide (proBNP) serves currently as a surrogate diagnostic and prognostic parameter in HF patients, its specificity remains uncertain. We hypothesized that GSTP1 might be a useful serum marker in the monitoring of HF patients. Methods and Results Serum GSTP1 and proBNP were prospectively measured in 193 patients subdivided based on their ejection fraction (EF) either in equal-sized quintiles or predefined EF groups >52%, 43%–52%, 33%–42%, 23%–32% and ≤22%. At a cutoff of ≥231 ng/mL, GSTP1 identified HF patients with EF ≤22% with 81% sensitivity and 83% specificity, and at a cutoff of ≥655 pg/mL, proBNP identified the same patient group with 84% sensitivity and 22% specificity. GSTP1 at a ≥126 ng/mL cutoff identified EF ≤42% with 90% sensitivity and 95% specificity, or proBNP at a ≥396 pg/mL cutoff had 97% sensitivity and 20% specificity. In regression analyses, GSTP1, but not proBNP, discriminated between EF ≤42% and EF >42% in HF patients. Conclusions These results suggest that GSTP1 is strongly associated with HF and could serve as a sensitive and specific marker to predict the ventricular function in HF patients.

Background. Endomyocardial biopsy (EMB) remains the gold standard for acute cellular rejection (ACR) diagnosis in cardiac transplantation yet is subject to interobserver variability. A method that could avoid discordant EMB analysis would be desireable. The apoptosis rate in EMB correlates with ACR severity. Apollon inhibits apoptosis, and RNF41 catalyzes its degradation. Whether tissue Apollon/RNF41 could diagnose ACR is not known. This study addressed this issue. Methods. Apollon/RNF41 messenger RNA (mRNA) was measured by real time reverse-transcriptase polymerase chain reaction and apoptosis was quantified with TUNEL assays in EMBs of 268 transplant recipients. EMBs were obtained at 1, 2, 3, 4, 7, 12, 24, and 52 posttransplant weeks. Results. At all time points posttransplant, Apollon mRNA decreased significantly in EMBs with ACR grades 2R/3R combined (P≤0.0010) compared with 0/1R combined, although RNF41 mRNA significantly increased in EMBs with ACR grade 1R (P

Background— Primary graft dysfunction (PGD) is a life-threatening complication in cardiac transplantation. A sensitive, specific, and easily measurable predictor in donors could facilitate PGD prevention. Methods and Results— SMARCAL1 is a matrix-associated regulator of chromatin with helicase and ATPase activities, and its serum concentrations were significantly increased in a targeted protein array in donors whose grafts developed PGD. Therefore, this study analyzed SMARCAL1 serum concentrations by ELISA in 336 heart donors before and after aortic cross-clamping (ACC) and in recipients at 10, 30, and 60 minutes reperfusion. Demographic and hemodynamic parameters of donors and recipients as well as transplant procedure characteristics were documented. PGD (n=68) was defined as ventricular dilation and hypocontractility associated with systolic blood pressure 20 mm Hg, and decreased mixed venous oxygen saturation necessitating mechanical circulatory support. SMARCAL1 serum protein concentration was significantly increased only before and after ACC in donors ( P P Conclusions— Donor serum SMARCAL1 may serve as a specific, sensitive, and noninvasive predictive marker in the assessment of cardiac graft quality.

FUNCTIONAL VASCULAR NETWORK DEVELOPMENT IN INFARCTED RAT HEARTS BY SELECTIVE RECRUITMENT OF VESSEL FORMING MACROPHAGES P. Paulus, M. Gmeiner, N. Sela, R. Schaefer, E. Wolner, M. Grimm, S. Aharinejad, Laboratory for Cardiovascular Research, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria; Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria