Role of CD40 ligand-mediated endothelial cell-monocyte interaction at atherosclerosis predilection sites.

BACKGROUND: Monocyte recruitment into the vessel wall at atherosclerosis predilection sites is essential for lesion development in the early phase of atherosclerosis. Platelets interacting with ultra-large von Willebrand Factor (ULVWF) multimers deposited after CD40 receptor ligation on the endothelial surface form adhesive bridges and facilitate monocyte diapedesis. We hypothesise that enhanced endothelial CD40 expression at arterial bifurcations is responsible for monocyte recruitment and that its absence reduces susceptibility to atherosclerosis. METHODS: Y-shaped channel slides covered with endothelial cells (HUVEC) and isolated perfused carotid artery bifurcations from different mouse lines were used for adhesion studies with isolated fluorescent dye-labelled platelets and monocytes. Monocyte adherence was quantified via fluorescence imaging. Oil Red O staining visualised aortic atherosclerotic plaques, and mRNA expression was determined by qRT-PCR. RESULTS: In response to soluble CD40 ligand (sCD40L) stimulated ULVWF release, the number of monocytes bound distal to the bifurcation of the Y-slide was 1.8-fold greater than without stimulation. The number of adherent monocytes in sCD40L-treated carotid artery bifurcations was 6 to 12.3-fold greater in ApoE knockout mice as compared to bifurcations derived from CD40/ApoE-deficient or control mice. CD40 mRNA expression was 2-fold higher in carotid artery bifurcations of ApoE knockout mice as compared to the proximal unbranched segment. Introduction of the CD40 knockout into the ApoE-/- background reduced the atherosclerosis burden along the entire aorta of these mice by 60 %. CONCLUSIONS: Our data demonstrate the importance of endothelial CD40 expression at atherosclerosis predilection sites for endothelial cell-platelet-monocyte interaction in the early phase of atherosclerosis.

Short-term rapamycin treatment increases life span and attenuates aortic aneurysm in a murine model of Marfan-Syndrome.

BACKGROUND: Marfan syndrome (MFS) is a genetic disorder leading to medial aortic degeneration and life-limiting dissections. To date, there is no causal prevention or therapy. Rapamycin is a potent and selective inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, regulating cell growth and metabolism. The mgR/mgR mice represent an accepted MFS model for studying aortic pathologies to understand the underlying molecular pathomechanisms. This study investigated whether rapamycin inhibits the development of thoracic aortic aneurysms and dissections in mgR/mgR mice. METHODS: Isolated primary aortic smooth muscle cells (mAoSMCs) from mgR/mgR mice were used for in vitro studies. Two mg kg/BW rapamycin was injected intraperitoneally daily for two weeks, beginning at 7-8 weeks of age. Mice were sacrificed 30 days post-treatment. Histopathological and immunofluorescence analyses were performed using adequate tissue specimens and techniques. Animal survival was evaluated accompanied by periodic echocardiographic examinations of the aorta. RESULTS: The protein level of the phosphorylated ribosomal protein S6 (p-RPS6), a downstream target of mTOR, was significantly increased in the aortic tissue of mgR/mgR mice. In mAoSMCs isolated from these animals, expression of mTOR, p-RPS6, tumour necrosis factor α, matrix metalloproteinase-2 and -9 was significantly suppressed by rapamycin, demonstrating its anti-inflammatory capacity. Short-term rapamycin treatment of Marfan mice was associated with delayed aneurysm formation, medial aortic elastolysis and improved survival. CONCLUSIONS: Short-term rapamycin-mediated mTOR inhibition significantly reduces aortic aneurysm formation and thus increases survival in mgR/mgR mice. Our results may offer the first causal treatment option to prevent aortic complications in MFS patients.

Ganglioglioma of the Right Cerebrothalamus in a 7-Year-Old Quarter Horse Cross Gelding.

Intracranial neoplasia in horses is rare compared to other species. Detailed information such as neurological, electroencephalographic, and histopathological examination of horses with intracranial neoplasia associated with seizures is scarce in the literature. Furthermore, ganglioglioma has not been reported in the horse. A 7-year-old Quarter horse cross Paint gelding was examined due to recurrent seizure-like episodes of 1-year duration. The seizures had been increasing in frequency and length, occurring up to 20 times a day at the time of presentation. Neurological examination revealed intermittent obtundation and multiple left sided abnormalities consisting of upper motor facial and tongue hemiparesis, facial hyperesthesia and cervical hypoesthesia, proprioceptive deficits, thoracic limb hypermetria upon head elevation; and intermittent paroxysmal activity consistent with seizures. Cranial nerve reflexes were normal. Vocalization, conjugate vertical nystagmus, intermittent blindness, left sided head tilt and flexion of neck, and lack of response to environmental stimuli were observed during seizure activity. A right sided cerebrothalamic disease was suspected. An electroencephalogram confirmed seizure activity with main focus on the right side at the central, parietal, and occipital regions further supporting neuroanatomical localization. Additionally, subclinical paroxysmal activity was noted on the electroencephalogram. A ganglioglioma was identified in the right cerebrothalamic area, and other cranial parts of the brainstem based on immunohistochemical examination. To the authors' knowledge this is the first report of intracranial ganglioglioma in the horse. This intracranial neoplasia should be added to the possible causes of intracranial masses and seizures in horses.

Clinical, histopathologic, cystoscopic, and fluorescence in situ hybridization analysis of proliferative urethritis in 22 dogs.

BACKGROUND: Proliferative urethritis (PU) is a lower urinary tract disease of dogs characterized by frond-like lesions in the urethra. The etiology of PU is unknown, although an association with bacterial cystitis is reported. OBJECTIVES: Deep-seated bacterial cystitis is associated with PU, particularly in dogs with neutrophilic or granulomatous inflammation. ANIMALS: Twenty-two client-owned dogs with PU and 5 control dogs euthanized for non-urinary disease. METHODS: In retrospective analysis, medical records of dogs with PU from 1986 to 2016 were reviewed. Signalment, clinical signs, cystoscopic findings, antimicrobial use, and results of urine, bladder, or urethral tissue cultures, if available, were recorded. Histopathology was reviewed and classified as lymphocytic-plasmacytic (LP), neutrophilic, LP-neutrophilic (LPN), granulomatous, or pleocellular. Eubacterial fluorescence in situ hybridization (FISH) was performed on 18 tissue samples (13 cases, 5 controls), with subsequent evaluation of bacterial species. RESULTS: Of the 22 dogs, 9 had LP urethritis, 6 had LPN, 4 had pleocellular, and 3 had neutrophilic urethritis. Of note, 7 of 13 PU samples were FISH+ for adherent or invasive bacteria; 1 of 5 controls were FISH+ for adherent bacteria. Five dogs had negative urine and tissue cultures when FISH was positive. There was no association detected between the type of urethral inflammation and the results of urine and tissue culture or FISH. CONCLUSIONS AND CLINICAL IMPORTANCE: The type of inflammation varied widely in these 22 PU cases. Deep-seated bacterial urethritis could be contributing to the inflammatory process in some dogs, regardless of the inflammation type. Urine and tissue cultures likely underestimate bacterial colonization of the urethra in dogs.

Antifungal activity, yield, and composition of Ocimum gratissimum essential oil.

Ocimum gratissimum L. or clove basil, belongs to the Lamiaceae family, has various desirable uses and applications. Beyond its aromatic, seasoning, and medicinal applications, this plant also has antimicrobial activity. This study was aimed at assessing the antifungal activity, yield, and composition of the essential oil (EO) of O. gratissimum. The species was cultivated in garden beds with dystrophic red latosol soil type containing high organic-matter content. The EO was obtained by hydrodistillation of dried leaves in a modified Clevenger apparatus, followed by determination of its content. Chemical characterization was carried out by gas chromatography-mass spectrometry (GC-MS). Microbial activity was assessed using the broth microdilution method, by determining the minimum inhibitory concentration (MIC), in order to compare the antimicrobial effect of EO in 10 isolates-Fusarium oxysporum f. sp tracheiphilum (CMM-0033), F. oxysporum f. sp. cubense (CMM-0813 and CMM-2819), F. oxysporum f. sp lycopersici (CMM-1104), F. solani (CMM-3828), Rhizoctonia solani (CMM-3274), and Macrophomina phaseolina (CMM-2715, CMM-3875, CMM-3615, and CMM-3650). The EO was a highly effective inhibitor of the studied phytopathogenic fungi, with MICs varying from 31.25 to 125 µg/mL. F. oxysporum f. sp lycopersici and R. solani were the most sensitive; both were inhibited at an MIC of 31.25 µg/mL. The EO content in the plant extract was 0.18%. Thirty chemical compounds were detected via GC-MS, with linalool (32.9%) being the major compound followed by 1,8-cineole (21.9%), both oxygenated monoterpenes. It can be concluded that clove basil EO is a highly effective antifungal agent, and therefore, a potential alternative for the control of plant pathogenic diseases.

Partial gastrectomy for resection of a gastric leiomyoma in a guinea pig (Cavia porcellus).

CASE DESCRIPTION A 4-year-old sexually intact male pet guinea pig (Cavia porcellus) was evaluated for a routine wellness examination. CLINICAL FINDINGS During physical examination, a small mass was palpated in the cranial aspect of the abdomen. Abdominal radiographic and ultrasonographic findings were suggestive of a gastric mass. Cytologic evaluation of a fine-needle aspirate of the mass was indicative of spindle cell proliferation most consistent with a sarcoma. TREATMENT AND OUTCOME The patient was anesthetized, and an exploratory laparotomy and partial gastrectomy were performed to resect the gastric mass. Histologic and immunohistochemical examinations of the mass revealed that it was a gastric leiomyoma. The patient recovered from surgery without complications. No evidence of mass recurrence was observed during an abdominal ultrasonographic examination performed approximately 19 months after surgery. CLINICAL RELEVANCE To our knowledge, this was the first report of the clinical diagnosis and successful surgical treatment of a gastric neoplasm in a guinea pig. Gastric leiomyomas are not uncommon in guinea pigs, and although benign, they can cause clinical signs if they become large enough to impair gastric function. Gastrointestinal surgery should be considered as a treatment option for guinea pigs with similar gastric neoplasms.

Clinicopathologic and Histopathologic Renal Abnormalities in Dogs with Coccidioidomycosis.

BACKGROUND: We observed evidence of protein-losing nephropathy in some dogs with coccidioidomycosis, suggestive of immune complex glomerulonephritis (ICGN). The goal of this study was to understand the prevalence of renal histopathologic lesions and proteinuria in dogs with coccidioidomycosis. HYPOTHESIS: Biochemical and histopathological evidence of glomerular lesions is present in dogs with coccidioidomycosis. ANIMALS: Hundred and fifty-six dogs with naturally occurring coccidioidomycosis. METHODS: Retrospective case series. Clinical information and results of clinicopathologic testing were retrieved from the University of California, Davis Veterinary Medical Teaching Hospital (VMTH). Microscopic sections of renal tissue procured from necropsy of dogs with coccidioidomycosis were examined to evaluate the nature and distribution of lesions. RESULTS: A total of 156 dogs with coccidioidomycosis were identified; 87 dogs had serum biochemistry and a urinalysis performed, 17 had urine protein:creatinine ratios (UPCs), and 24 had renal tissue available for histopathology. Eleven (13%) of the 87 dogs were azotemic, 55 (63%) were proteinuric (of which 14 [25%] had clinically relevant proteinuria defined as ≥3+ or ≥500 mg/dL), and 14 dogs had UPC ≥0.5 (range, 0.5-21.5, median 4.2). Thirteen (54%) of 24 dogs had renal histopathologic lesions suggestive of ICGN. Seven of these dogs had urinalyses performed; 5 (71%) had clinically relevant proteinuria as described above. Two dogs (33%) with normal glomeruli had granulomatous nephritis, 1 of which had intralesional Coccidioides spherules. CONCLUSIONS AND CLINICAL IMPORTANCE: Coccidioidomycosis should be considered as a possible contributor to glomerular disease in dogs. Whether similar lesions occur in other mammalian hosts, including humans, warrants further investigation.

[Surgical techniques in mitral valve diseases. Reconstruction and/or replacement]. / Operative Techniken bei Mitralklappenerkrankungen. Rekonstruktion und/oder Ersatz.

Mitral valve (MV) disease is one of the most common heart valve diseases. The surgical and interventional treatment for MV disease requires a multidisciplinary approach. For primary mitral valve regurgitation (MVR) surgical MV repair is the treatment of choice, which can be performed with an excellent outcome and long-term survival in reference centers. The surgical technique used for MV repair depends on the pathological mechanism, the morphological dimensions of the MV, the operative risk and the expertise of the cardiac surgeon. The surgical and interventional treatment of secondary MVVR is the subject of on-going discussions. In patients with moderate secondary MVR undergoing coronary artery bypass grafting, concomitant MV repair should be performed. In the presence of severe secondary MR with risk factors for failure of MV repair, patients should consider having MV replacement. In the rare cases of patients presenting with mitral valve stenosis (MVS) MV repair can be considered in young patients and who are most often treated with MV replacement. The choice between biological or mechanical MV replacement depends on the pathophysiology, the comorbidities, the amount of anticoagulation necessary and the age of the patient. New percutaneous techniques for MV replacement offer new treatment options for reoperation in high-risk patients.

World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs.

Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex-mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed.

DNA Sequence Variants in the Five Prime Untranslated Region of the Cyclooxygenase-2 Gene Are Commonly Found in Healthy Dogs and Gray Wolves.

The aim of this study was to investigate the frequency of regional DNA variants upstream to the translation initiation site of the canine Cyclooxygenase-2 (Cox-2) gene in healthy dogs. Cox-2 plays a role in various disease conditions such as acute and chronic inflammation, osteoarthritis and malignancy. A role for Cox-2 DNA variants in genetic predisposition to canine renal dysplasia has been proposed and dog breeders have been encouraged to select against these DNA variants. We sequenced 272-422 bases in 152 dogs unaffected by renal dysplasia and found 19 different haplotypes including 11 genetic variants which had not been described previously. We genotyped 7 gray wolves to ascertain the wildtype variant and found that the wolves we analyzed had predominantly the second most common DNA variant found in dogs. Our results demonstrate an elevated level of regional polymorphism that appears to be a feature of healthy domesticated dogs.

Spinal cord protection in open- and endovascular thoracoabdominal aortic aneurysm repair: critical review of current concepts and future perspectives.

Unresolved for over half a century now since the beginning of aortic surgery spinal cord injury (SCI) remains the most devastating complication after extensive open and endovascular thoracoabdominal aortic aneurysm (TAA/A) repair. Over the past decade extensive research on spinal cord perfusion lead to a better understanding of previously unknown physiologic mechanisms involved in the suspension of the cord's arterial supply and the consecutive development of SCI underscoring the need for new concepts in treatment strategy and monitoring methods during and after TAA/A repair. Based on this knowledge, new treatment strategies in particular the staged-repair were developed. The first-in-man translation of this idea has just been published introducing the new concept: minimally invasive selective segmental artery coil-embolization. Another approach to overcome the most critical initial period after segmental artery occlusion due to stent graft deployment in the descending or thoracoabdominal aorta is temporary aneurysm sac perfusion, which also has recently been clinically trialed. Furthermore, the new non-invasive real-time monitoring method to record spinal cord viability by means of near-infrared spectroscopy of the paraspinal collateral network by means of near-infrared spectroscopy has also been suggested and successfully introduced in a pilot series to a clinical setting. This review addresses problems, unsolved questions and future perspectives regarding these three new concepts.

[Complication management after interventions on thoracic organs : deep sternal wound infections]. / Komplikationsmanagement nach Eingriffen an Thoraxorganen : Tiefe sternale Wundinfektionen.

With an incidence rate of 0.5-4 % and a mortality of up to 50 %, deep sternal wound infections are a rare but devastating complication after median sternotomy for cardiac surgery. Currently, no standard operating procedures exist. Long-term drainage with continuous lavage or negative pressure wound therapy should be used to condition the wound. After restabilization of the sternum and primary closure, the infection often reoccurs presenting deep cavities with an open, unstable thorax and an uncovered mediastinum. This article gives an overview of the different options for deep sternal wound infections in plastic reconstructive surgery. The key point for successful treatment is still the extent of debridement. Primary coverage with a pedicled flap can be made only if the wound debridement was performed radically enough. In the clinic of the author, in which over 120 patients with deep sternal wound infections were treated in 2.5 years, latissimus dorsi muscle flaps have been established as the gold standard.

Fate of patients with extracorporeal lung assist as a bridge to lung transplantation versus patients without--a single-center experience.

OBJECTIVES: Mechanical lung assist (MLA; extracorporeal membrane oxygenation (ECMO) or extracorporeal lung assist (ECLA)) is increasingly used as a temporary bridge to lung transplantation (LTx). This study was designed to evaluate the impact of preoperative MLA on the operative outcome, including longer-term survival, in comparison to patients undergoing LTx without preoperative MLA. METHODS: A total of 143 patients underwent LTx at our institution from 2002 to 2011. Forty-three percent (n=62) of patients presented with idiopathic pulmonary fibrosis and 71% (n=102) presented with severely elevated pulmonary artery pressure. RESULTS: Thirteen patients (9.1%) required pre-LTx MLA support (age 44 ±13 years, double LTx 73.3%, female gender 53%) whereas 130 patients did not (age 52 ±11 years, double LTx 41.5%, female gender 36.9%). In one patient, MLA was successfully weaned and the patient underwent subsequent LTx. All patients in the MLA group were intraoperatively supported with continuous ECMO. One patient had to be supported with MLA after LTx for a period of 8 days. The short-term and mid-term postoperative survival of the MLA patient group was not significantly different from the non-MLA group (LogRank p=0.28). The 30-day, 90-day and 1-year survivals were 95%, 90% and 71%, respectively, in the patients without MLA compared to 85%, 77% and 68% in the MLA group. CONCLUSIONS: MLA has no impact on long-term survival rate in LTx patients, but has an influence in postoperative survival. MLA support is a valuable tool to bridge unstable patients to LTx.

The effect of stent graft oversizing on radial forces considering nitinol wire behavior and vessel characteristics.

Stent graft fixation in the vessel affects the success of endovascular aneurysm repair. Thereby the radial forces of the stent, which are dependent on several factors, play a significant role. In the presented work, a finite element sensitivity study was performed. The radial forces are 29% lower when using the hyperelastic approach for the vessel compared with linear elastic assumptions. Without the linear elastic modeled plaque, the difference increases to 35%. Modeling plaque with linear elastic material approach results in 8% higher forces than with a hyperelastic characteristic. The significant differences resulting from the investigated simplifications of the material lead to the conclusion that it is important to apply an anisotropic nonlinear approach for the vessel. The oversizing study shows that radial forces increase by 64% (0.54 N) when raising the oversize from 10 to 22%, and no further increase in force can be observed beyond these values (vessel diameter D=12 mm). Starting from an oversize of 24%, the radial force steadily decreases. The findings of the investigation show that besides the oversizing the material properties, the ring design and the vessel characteristics have an influence on radial forces.

[Aneurysms of the ascending aorta and aortic arch]. / Aneurysmen der Aorta ascendens und des Aortenbogens.

BACKGROUND: The treatment of patients with aneurysms of the ascending aorta and aortic arch often represents a challenge due to their complexity. The clinical picture is characterized by further progression of the disease and severe complications, such as acute aortic dissection or even aortic rupture are not uncommon. OBJECTIVES: This article gives a review of definitions, etiology and indications for operative treatment of patients with aneurysms of the ascending aorta and aortic arch. RESULTS AND DISCUSSION: An aortic aneurysm of the ascending aorta is defined as a dilatation of all wall layers of the aorta of more than 50 % in comparison to the normal diameter. This is dependent on age, sex, body surface area and the underlying diseases. In most cases the cause is the presence of atherosclerosis. Connective tissue diseases, bicuspid or monocuspid aortic valves and aortitis represent additional risk factors. Surgical treatment of the ascending aorta, aortic root and aortic arch is carried out in patients without connective tissue diseases and a diameter of ≥ 55 mm and for patients with Marfan syndrome and bicuspid aortic valves with a diameter of ≥ 50 mm. Earlier indications for surgery are present with an aortic diameter of ≥ 45 mm in patients with the following risk factors: familial disposition for aortic dissection (often unrecognized as sudden cardiac death), annual growth rate of the aortic diameter of > 2 mm, comorbid severe aortic valve or mitral valve insufficiency and female patients with a desire to have children. The standard surgical procedures include aortic root replacement, aortic valve reconstruction with aortic root or ascending aorta replacement and partial or total aortic arch replacement depending on the extent of the aneurysm. The so-called hybrid procedures for aortic arch surgery include frozen elephant trunk (ET) techniques and debranching procedures. Good perioperative and postoperative results can be achieved by early diagnostics and an assessment of the indications depending on the individual etiology. Individual and valve-preserving treatment strategies have a favorable influence on the operative outcome.

Invasive cardiac aspergillosis after orthotopic liver transplantation.

Invasive aspergillus infection occurs in 5 - 42 % of liver-transplanted recipients and is a dangerous complication, associated with high mortality if untreated. However, the early diagnosis of invasive aspergillosis can be elusive, as clinical signs are unspecific and the pathogenic agent is difficult to demonstrate. We here report about a 58-year-old man with acute liver failure caused by newly diagnosed chronic hepatitis B infection who underwent liver transplantation. The postoperative course was uneventful, and the patient was discharged after 30 days. After 105 days the patient was readmitted because of fever, recurrent chest and abdominal pain. Computed tomography revealed a cardiac lesion; other diagnostic steps including bone-marrow and endomycordial biopsy, virological and microbiological investigations gave no clear findings. To exclude a malignant process, thoracotomy with mass and simultaneous lower left lobe resection were performed. Histopathological findings revealed an invasive perimyocardial aspergillosis. Immediate intravenous therapy with voriconazole and caspofungin was initiated and monitoring of the mass was performed with transesophageal echocardiography and Cardio-MRI. Due to slightly increase of the lesion, medication was switched to posaconazole and caspofungin. Under this dual fungal treatment the lesion regressed and the patient could be discharged after two months in good clinical condition. Frequent Cardio-MRI scan after discharge showed further mass-regression. Therefore antifungal treatment was switched to oral posaconazole mono-therapy. After one year, complete reduction of the mass was achieved and antifungal therapy was discontinued. Recent diagnostic imaging follow-up showed no pathological finding.

Odontogenic keratocyst in a cat.

Odontogenic cysts are derived from odontogenic epithelium, can be locally invasive and destructive and have been reported rarely in cats. A 16-year-old, male domestic shorthair cat had a 3-year history of a slowly progressive, right mandibular swelling. Intraoral dental radiographs revealed a multilocular, radiolucent, cystic mass within the right mandible that extended from the distal aspect of the canine tooth to the mesial aspect of the fourth premolar tooth. Radiographically, the mass was associated with distortion and regional destruction of the right mandibular bone and resorption of regional tooth roots. Histological examination of an incisional biopsy sample revealed multiple ruptured cysts lined by stratified squamous epithelium of odontogenic origin with luminal parakeratinization and a prominent palisading basal cell layer. The cyst contained abundant orthokeratotic and parakeratotic keratin. The clinical, radiographical and histological features were consistent with a diagnosis of odontogenic keratocyst, as seen in man. This is the first report of an odontogenic keratocyst in a cat.

Spinal cord ischemia in open and endovascular thoracoabdominal aortic aneurysm repair: new concepts.

For more than half a century ischemic spinal cord injury (SCI) and consecutively permanent paraplegia remained the most devastating complication after open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Various neuroprotective strategies (e.g., motor-/somatosensory evoked potential monitoring and cerebrospinal fluid drainage) used as adjuncts have lowered the SCI; maybe most importantly, the modern collateral network (CN) has begun to replace the classic understanding of spinal cord blood supply implying several consequences. Reliable non-invasive tools to monitor cord perfusion to detect imminent spinal cord malperfusion, ischemia and forthcoming neurologic injury (particularly early postoperatively) is not available, neither is a reliable strategy to prevent ischemic injury during distal circulatory arrest and after segmental artery occlusion. Currently, two promising new concepts--potentially advancing spinal protection in open and endovascular TAAA repair--address these issues: 1) non-invasive real-time monitoring of the paraspinous CN-oxygenation via near-infrared spectroscopy (NIRS) as an alternative to the demanding direct neuromonitoring; and 2) preconditioning of the CN as minimally invasive, endovascular "first stage" to increase the resilience of spinal cord perfusion prior to definite aortic repair. This article illustrates both concepts discussing: 1) the clinical application of thoracic and lumbar collateral NIRS monitoring to indirectly detect spinal cord hypoperfusion; and 2) minimally invasive selective segmental artery coil-embolization (MISACE) for (arteriogenic) preconditioning of the CN prior to extensive open or endovascular staged TAAA repair.

Weight loss surgery improves the metabolic status in an obese rat model but does not affect bladder fibrosis associated with high fat diet feeding.

BACKGROUND: Bladder dysfunction has one of the highest prevalences as a comorbidity of obesity in industrialized countries. The aetiopathogenesis of obesity-associated bladder dysfunction is still obscure, but there is growing evidence that general metabolic changes in obese patients may be in part responsible. As demonstrated recently, high fat diet (HFD) significantly alters the protein expression in the urinary bladder, activates multiple signalling pathways associated with cell survival and inflammation and ultimately provokes bladder fibrosis in an obese rat model. The study aimed to elucidate the role of matrix metalloproteases (MMPs) and their specific tissue inhibitors of metalloproteases (TIMPs) in obesity-related bladder extracellular matrix (ECM) remodelling and the effect of weight loss surgery via sleeve gastrectomy (SG) on phenotype and molecular parameters. METHODS: Twenty-four male Sprague-Dawley rats were used for (i) characterization of the HFD phenotype and (ii) evaluation of alterations following SG. Metabolic status, the degree of bladder fibrosis and tissue expression and activity of MMP2, MMP9, MMP14, TIMP1 and TIMP2 were analysed by immunohistochemistry, enzyme-linked immunosorbent assay and activity assays. Statistical differences were calculated by analysis of variance or independent Student's t-test. A P-value <0.05 was considered statistically significant. RESULTS: In HFD rats, we found significant alterations in lipid metabolism, fat mass, free fatty acid profile, insulin resistance and inflammatory markers. Voided volume was significantly decreased, and bladder showed marked fibrosis. MMPs and TIMPs were differentially regulated depending on animal status (controls, chow diet, HFD, and SG- and sham-operated animals) in both urothelium and detrusor smooth muscle. Although animal weight and most metabolic parameters were positively affected by SG, bladder fibrosis persisted. The limitations of this study were 1 month follow-up and lack of direct measurement of bladder function. CONCLUSIONS: Early diagnosis of the bladder dysfunction associated with obesity is essential to allow targeted early intervention, that is, before manifestation of potentially irreversible ECM fibrotic alterations.