Pulmonary Hypertension and Right Heart Failure in Chronic Kidney Disease: New Challenge for 21st-Century Cardionephrologists.

Pulmonary hypertension is defined as an increased systolic pulmonary pressure of >30 mm Hg, and it shows a 40% prevalence in hemodialysis patients due to vascular access (both central venous catheter and arteriovenous fistula). Secondary pulmonary hypertension in chronic kidney disease patients is strictly related to pulmonary circulation impairment together with chronic volume overload and increased levels of cytokines and growth factors, such as FGF, PDGF, and TGF-ß, leading to fibrosis. Endothelial dysfunction, together with lower activation of NOS, increased levels of serum endothelin and fibrin storages, involves an extensive growth of endothelial cells leading to complete obliteration of pulmonary vessels. Pulmonary hypertension has no pathognomonic and distinctive symptoms and signs; standard transthoracic echocardiography allows easy assessment of compliance of the right heart chambers. The therapeutic approach is based on traditional drugs such as digitalis-derived drugs, vasodilatory agents (calcium channel blockers), and oral anticoagulants. New pharmacological agents are under investigation, such as prostaglandin analogues, endothelin receptor blockers, and phosphodiesterase-5 inhibitors.

Echocardiography and right ventricular function in NKF stage III cronic kidney disease: Ultrasound nephrologists' role.

TAPSE measurement during echocardiography is a well known measure of right heart systo-diastolic function. Low TAPSE means reduced cranio-caudal excursion of tricuspidal annulus, sign of both reduced ejection fraction and reduced distensibility of right ventricle. It is a good prognostic index for cardiac mortality risk in CHF patients, adding significant prognostic information to NYHA stadiation. Nephrologists do not always fully aware of right ventricular function in their patients affected by chronic renal failure (CRF), even if this datum is probably crucial in vascular access policy. Our study was designed to study right ventricle function and TAPSE on 202 patients affected by moderate chronic renal failure, free from overt pulmonary hypertension. TAPSE, PAPs, right chambers diameters, classical Framingham factors, estimated glomerular filtration rate were recorded. TAPSE was reduced (<23 mm) in 43% of patients enrolled, while dilated right chambers were present in 24%. PAPs exceeded 30 mmHg in 29% of patients. Echocardiographic signs of left ventricular hypertrophy were found in 36% of patients. The ejection fraction was normal in all patients. Statistical analysis showed a significant indirect correlation between TAPSE and PAPs and between TAPSE and tele-diastolic diameters and volumes of the right ventricle, while a direct correlation was observed between TAPSE and Framingham score. TAPSE showed a bimodal distribution, with a subpopulation "low TAPSE - high PAPs", next to a population characterized by normal values ??for both parameters. A reduction in compliance and systolic function of the right heart chambers is quite early and frequent in course of CKD, a fact that the nephrologist should take in due consideration, managing blood volume or planning vascular access for hemodialysis.

Spinal infection multidisciplinary management project (SIMP): from diagnosis to treatment guideline.

Spine infections require a multidisciplinary approach to be treated and solved. A guide line to drive physicians in the deep complexity of such a disease is extremely helpful. SIMP suggests a flow-chart built up on clear concepts such as right and well managed antibiotic therapy, sound stability of the spine, correct and smart use of the standard and functional imaging techniques, such as f18 FDG PET/CT. In 16 months a total of 41 patients have been treated for spondylodiscitis, discitis and vertebral osteomyelitis by our team of physicians and 25 patients have been enrolled in a prospective study whose target is the assessment of the SIMP flow-chart and of every single aspect that characterize it.

The extracellular matrix affects axonal regeneration in peripheral neuropathies.

OBJECTIVE: Recent evidence in animal models suggests that components of the extracellular matrix (ECM) play a primary role in peripheral nerve degeneration and regeneration. METHODS: We investigated the expression of several ECM molecules in human sural nerves by immunohistochemistry, Western blot, and reverse transcriptase PCR analysis. To unravel the possible role of these molecules in nerve regeneration, we compared results obtained from nerves with abundant signs of regeneration with those with complete absence of axonal regeneration. The role of some ECM components on neurite extension was further tested in dorsal root ganglion cultures. RESULTS: We observed that the ECM composition significantly differs in regenerating compared with nonregenerating nerves, independently from their etiologic background. Fibronectin was abundantly expressed in regenerating nerves, whereas vitronectin and fibrin(ogen) prevailed in nonregenerating nerves. Whereas fibronectin is secreted by endoneurial cells, in vivo and vitro studies showed that the source of vitronectin and fibrin(ogen) is the bloodstream. CONCLUSIONS: These data indicate that nerve regeneration is impaired in the presence of breaches in the blood-nerve barrier or impaired extracellular matrix (ECM) degradation that leads to accumulation of plasma vitronectin and fibrin(ogen). The transformation into mature, fibronectin-enriched ECM is necessary for efficient nerve regeneration in humans.

Role of quercetin in modulating rat cardiomyocyte gene expression profile.

Despite extensive studies, the fundamental mechanisms responsible for the development and progression of cardiovascular diseases have not yet been fully elucidated. Recent experimental and clinical studies have suggested that reactive oxygen species play a major pathological role. Oxidative stress reduction induced by flavonoids has been regarded by many as the most likely mechanism in the protective effects of these compounds; however, there is an emerging view that flavonoids may also exert modulatory actions on protein kinase and lipid kinase signaling pathways. Quercetin, a major flavonoid present in the human diet, has been widely studied, and its biological properties are consistent with its protective role in the cardiovascular system. However, it remains unknown whether the cardioprotective effects of quercetin may also occur through the modulation of genes involved in cell survival. The main goal of this study was to examine the gene expression profiling of cultured rat primary cardiomyocytes treated with quercetin using DNA microarrays and to relate these data to functional effects. Results showed distinct temporal changes in gene expression induced by quercetin and a strong upregulation of phase 2 enzymes, highlighting quercetin ability to act also with an indirect antioxidant mechanism.

Beneficial effects of r-h-CLU on disease severity in different animal models of peripheral neuropathies.

Clusterin is a protein involved in multiple biological events, including neuronal cytoprotection, membrane recycling and regulation of complement-mediated membrane attack after injury. We investigated the effect of recombinant human clusterin in preclinical models of peripheral neuropathies. Daily treatment with clusterin accelerated the recovery of nerve motor evoked potential parameters after sciatic nerve injury. Prophylactic or therapeutic treatment of experimental autoimmune neuritis rats with clusterin also accelerated the rate of recovery from the disease, associated with remyelination of demyelinated nerve fibers. These data demonstrate that clusterin is capable of ameliorating clinical, neurophysiological and pathological signs in models of peripheral neuropathies.

Radiofrequency thermal ablation of non spinal osteoid osteoma: remarks on method.

Osteoid osteoma is a small benign tumor, with a ''nidus'' that rarely exceeds 15 mm in diameter. It is relatively common in males, especially teenagers and young adults. It involves mainly the appendicular skeleton, the femur in particular, and rarely the axial skeleton. It requires treatment because it causes intense pain. In recent years alternative, less invasive, treatments have been proposed, such as drilling combined with ethanol injections, and thermal ablation with laser or radiofrequency. This study assesses 117 patients affected by osteoid osteoma, treated by radiofrequency thermal ablation between June 2001 and November 2003. We describe the patient recruitment procedure, CT-guided technique, the percutaneous approach, thermal ablation, and the instruments used. Data were analyzed thoroughly, and modifications that have improved the effects of treatment have been highlighted. The results achieved since the method was perfected have been extremely encouraging, confirming that the technique is very effective if performed correctly. For that reason radiofrequency thermal ablation has become the treatment of choice for non-spinal osteoid osteoma at Rizzoli Orthopaedic Institute.

Radiofrequency thermoablation of primary non-spinal osteoid osteoma: optimization of the procedure.

Osteoid osteoma is a small benign tumor that requires treatment due to the intense pain it causes. Surgical therapy has been the ablative technique of choice after a failure of medical therapy. Recently, numerous less invasive, alternative procedures have been proposed: drill trepanation with or without ethanol injections, cryoablation, and thermoablation with laser or radiofrequency. The aim of this review is to retrospectively assess the effect of radiofrequency (RF) thermoablation in the treatment of primary non-spinal osteoid osteoma. From June 2001 to July 2003, we treated 106 patients affected by osteoid osteoma with RF thermoablation. Five patients with spinal osteoid osteoma and four with a previously treated osteoma were excluded from the study. In this paper, we assess the results obtained in a selected group of 97 primary non-spinal osteoid osteoma. The lesions were predominantly in the metaphysics of the femur. Central nidus calcifications were frequent and there was no prevalence for which side they occurred. Primary success was achieved in 82 patients (85%), while we obtained secondary success in 15 patients (15%). In two patients (2%), pain persisted between the two treatments and failed to be resolved, even after the second treatment; therefore, surgical excision was performed and complete resolution was obtained. No complications were reported. In conclusion, our results confirm that the treatment of choice for non-spinal osteoid osteoma is RF thermoablation, offering several advantages over ablative techniques.

Intrapelvic migration of the prosthetic acetabular component.

The authors propose a preoperative evaluation protocol for cases of dislocation of the prosthetic cup complicated by intrapelvic migration, obtained by studying 20 cases of prosthetic loosening with protrusion of the acetabular component in the pelvis, treated by reimplantation or explantation. In all of the patients, accurate preoperative planning was carried out, because of the considerable frequency of dislocation, compression or damage to the vascular and nervous structures deriving from migration inside the pelvis of the acetabular component. The authors suggest that in all cases of acetabular loosening evaluation involve standard X-rays, bone scan with technethium99 and with marked granulocytes, CT scan. When the cup protrudes in the pelvis, prior to surgery, CT scan with contrast medium will be required, and if the risk of vascular involvement exists, angiography should also be carried out.

Vitamin E-bonded cellulose membrane, lipoperoxidation, and anemia in hemodialysis patients.

In hemodialysis patients, oxidative stress results from an imbalance between the production of reactive oxygen species and antioxidant defense mechanisms. Recently, a new dialysis multi-layer membrane has been developed, by modifying the inner surface of regenerated cellulose to support a vitamin E coating. The aim of our study was to investigate the effects of hemodialysis treatment with vitamin E-modified membrane on anemia and erythropoietin requirement in a group of chronic uremic patients. Ten uremic, non diabetic, patients on standard bicarbonate dialysis were treated with vitamin E-bonded dialysis membrane for 12 months. Hematological parameters, erythropoietin requirement, serum vitamin E and serum malonyldialdehyde (MDA) were evaluated before starting the study and monthly. No significant changes in hemoglobin level, RBC count, hematocrit and EPO requirement were observed. Basal vitamin E levels were in the normal range (13.0 +/- 2.88 mg/L vs. 14.79 +/- 3.12 mg/L; NS). On the contrary, basal MDA levels were higher than those observed in the control group (1.87 +/- 0.36 vs. 1.13 +/- 0.18 mmol/mL; p < 0.01) and a significant decrease of MDA levels was found after 1 month of Excebrane treatment (1.39 +/- 0.25 nmol/mL; p < 0.02). In conclusion, the role of the "oxidative hemolysis" in the pathogenesis of anemia in CHD patients is still not clearly defined, but it could be of minor clinical relevance. Although the effectiveness of vitamin E-coated membranes as a scavenger of ROS allows a better control of intradialytic oxidative stress, it doesn't seem to contribute to clinical management of anemia in these patients.

Resection surgery in the treatment of vertebral tumors.

With the purpose of clarifying the limits of resection surgery (en bloc excision) for the treatment of bone tumors of the spine, the authors report the indications and results of 43 operations. This series was homogeneous in terms of oncological and surgical staging, as well as with regard to surgical method used and anaesthesiology. Three different types of surgery were performed: en bloc resection of tumors of the body (sectors 5-9 or 4-8 depending on the WBB staging system), of the posterior arch (sectors 10-3) or characterized by eccentric growth (sectors 2-5 or 8-11). The surgical margins were histologically studied in all of the cases: based on the evaluation and on histological diagnosis further chemo- and/or radiation therapy were decided on. Long-term follow-up was obtained for all of the cases (from 6 to 153 months, mean 30 months; 26 cases followed for more than 24 months). Six of the patients died as a result of the disease from 10 to 28 months after resection. There were 4 local recurrences, 4 pulmonary metastases, and 5 metastatic disseminations to the skeleton and to other tissues observed in 11 patients. At final follow-up 33 patients (77%) were thus disease-free (32 continually), in excellent condition, and capable of living a normal life. Complications and treatment are also reported. A careful study of the neoplasm, an appropriate selection of the patients based on diagnosis and histological staging, a knowledge of the natural progression of bone neoplasms and of the surgical anatomy of the vertebral column, the application of suitable measures of anaesthesiological control, allow for a correct cost/benefit evaluation of this type of surgery as compared to oncological methods that are less effective but more diffused. On the basis of these considerations indications for en bloc resection in tumors of the spine are defined.

Intralesional surgery of primary tumors of the anterior cervical column.

The study involves a series of 10 primary neoplasms of the anterior cervical column (body and transverse processes) surgically treated by intralesional excision and followed-up after 2-10 years. The series included 6 benign and 4 malignant neoplasms. Among the benign tumors 4 cases were classified Enneking stage II (2 osteoid osteomas, 1 fibrous dysplasia, 1 osteoma): after simple excision none of the cases revealed symptoms or signs of recurrence at long-term follow-up. The other 2 benign forms were stage III (giant cell tumor and aneurysmal cyst): both of the cases were treated by extracapsular intralesional excision after selective arterial embolization and reconstruction with anterior fusion; the giant cell tumor was irradiated after surgery: at long-term follow-up the patients were asymptomatic and there were no signs of recurrence. The 4 malignant neoplasms (stage IIB) were 1 osteosarcoma and 3 solitary plasmacytomas with spinal cord compression. The osteosarcoma was treated by intralesional excision in 3 stages and radiation therapy, and there were no signs of disease 6 years after diagnosis. The cases of plasmocytoma were treated by intralesional excision and spinal cord decompression, anterior fusion with iliac graft and plate, radiation therapy, and chemotherapy, and they died after 2, 3 and 4 years with findings of multiple myeloma with no signs of disease at the level of the cervical vertebra treated.

Anterior surgery in trauma of the cervical spine.

The study reports a series of 37 traumatic lesions of the cervical spine treated surgically by anterior approach. The series includes two IInd type fractures of the odontoid, treated by direct screwing, 32 recent fractures or fracture-dislocations of the lower cervical spine treated by decompression and anterior arthrodesis with a plate, 3 inveterate dislocations treated by anterior-posterior osteotomy in 2 cases, and decompression-arthrodesis in the third. One amyelic fracture of the odontoid healed in 4 months, the other patient, with Frankel C spinal cord lesion improved to D, but died 4 months later as a result of bronchial pneumonia ab ingestis. In all of the recent lower cervical lesions fusion was obtained in 3-12 months (mean 4.5 months). Eight incomplete spinal cord lesions improved by 2 Frankel classes in 3 cases and by 1 in 5. Six nerve root lesions healed with complete recovery. Three cases with no neurologic deficit remained unchanged as did 15 complete spinal cord lesions. In the 3 inveterate cases we obtained healing of a slow-developing myelopathy (Frankel D) after osteotomy, no improvement after osteotomy in the second case (Frankel B). In the case submitted to decompression and anterior fusion we obtained recovery from Frankel B to E in three months, but the patient then died as a result of pulmonary complications. Direct screwing of the odontoid allows us to obtain healing of the type II fractures without blocking C1-C2 movement with a posterior fusion. Anterior surgery in traumas of the lower cervical spine allows for anatomical decompression of the spinal cord and bone reconstruction with good results, avoiding the risk of neurologic progression caused by dragging of the disc material in the spinal canal, that may take place at the time of non-surgical reduction or by posterior approach of the dislocations. In our series complications included 2 infections, 1 that healed without sequelae and the other with kyphosis, and a fistula of the hypopharynx caused by fibrobronchoscopy 1 year after osteosynthesis, that healed after primary repair. For this latter complication anterior surgery can, at most, be considered a contributing cause, because of the deep scar.

[Anatomopathology, computerized tomography, and magnetic resonance correlations in soft tissue liposarcoma]. / Correlazioni tra anatomia patologica, Tomografia Computerizzata e Risonanza Magnetica nei liposarcomi dei tessuti molli.

Liposarcomas are one of the most common soft tissue malignant tumors; they can be differentiated in four histologic subtypes: well-differentiated, myxoid, round cell and pleomorphic liposarcomas. The search of differential CT and MR patterns to better classify the lesions in the proper histologic subtype is justified by the different histologic features, clinical course and especially prognosis, of every lesion subtype. From 1990 to 1995, 50 liposarcoma patients were examined preoperatively with CT and MRI in our Institute of Radiology. We found 7 well-differentiated liposarcomas (14%), twenty myxoid liposarcomas (40%), ten round cell liposarcomas (20%) and, finally, 13 pleomorphic liposarcomas (26%). The thigh was the most common tumor site (60%). The following parameters were considered: lesion margins, tissue homogeneity, fat tissue ratio and the presence of calcifications. Well-differentiated liposarcomas presented well-defined and regular margins (72%), mildly heterogeneous appearance (44%) and more than 75% fat tissue (72%). Myxoid liposarcomas presented well-defined and regular margins (65%), heterogeneous appearance (65%) and less than 25% fat tissue (95%). The diagnosis of myxoid liposarcoma can be made in the presence of myxoid tissue, which has very low CT attenuation values and mildly hypointense signal on T1-weighted and progressively hyperintense signal on T2-weighted MR images. Round cell and pleomorphic liposarcomas are high-grade malignancies and they cannot be distinguished from other malignant soft tissue lesions. In these cases, the diagnosis can be made only at histology.

En bloc resections of bone tumors of the thoracolumbar spine. A preliminary report on 29 patients.

STUDY DESIGN: Twenty-nine patients with primary bone tumors and solitary metastases of the thoracolumbar spine treated with en bloc resection are reviewed retrospectively. OBJECTIVE: To demonstrate the possibility to apply in the spine the same principles of surgical oncology adopted for primary bone tumors of the limbs. SUMMARY OF BACKGROUND DATA: The surgical oncologic staging systems currently applied in limb tumor surgery are difficult to apply to spinal tumors. The anatomic conditions make extralesional surgery difficult or impossible, which has restrained a more common use of resection surgery in the spine. Focus is put on a new surgical staging system and en bloc vertebral resection. METHODS: Twenty-five primary malignant and aggressive benign bone tumors and four solitary metastases were treated. The patients were submitted to oncologic and surgical staging for surgical planning. The primary tumors were classified according to Enneking system: three Stage IA, six Stage IB, eight Stage IIB, eight Stage 3 benign. Staging according to the Weinstein-Boriani-Biagini system was also done. Thirteen lesions involved the vertebral body; nine lesions developed in the posterior arch, or part of it, and seven lesions occupied part of the body and part of the arch. A careful anesthesiologic evaluation was performed as well as a continuous intraoperative on-line monitoring of the vital parameters. The en bloc resections (multisegmental in five patients) were performed in 10 thoracic, in 16 lumbar, in two thoracolumbar lesions, and in one lumbosacral lesion. Reconstruction was performed, aiming to replace the resected columns. The specimens were submitted to histologic study of the margins. All the patients were followed, and their status was defined on clinical and imaging studies. RESULTS: In 20 patients, a wide margin was achieved, in eight a marginal margin, in one an intralesional margin. The margin was contaminated in seven patients. Surgical time was 3-21 hours (average, 12 hours). No patient died during surgery or from surgical complications. Three mechanical failures of the implants required additional surgery. One deep infection arose. The only neurologic problems observed were related to the nerve roots sectioned for oncologic purpose. No local recurrence was found at follow-up evaluation after 6-134 months (average, 30 months). CONCLUSIONS: En bloc resection can be performed in selected tumors of the spine; the indication to such major surgery must be based on the oncologic stage, and the procedure must be carefully planned. For this purpose, the Weinstein-Boriani-Biagini system could be a helpful tool. Long-term results must be weighed before a definitive statement of the indications can be made.

Anterior extraoral surgery to the upper cervical spine.

STUDY DESIGN: A series of 10 patients surgically treated with prevascular or retrovascular extraoral retropharyngeal approach to the upper cervical spine is examined. OBJECTIVES: In orthopedic surgery, retropharyngeal approach may replace the transoral surgery, obviating the risks of infection and the uncomfortable postoperative course of cases in which median labiomandibular glossotomy was used to accomplish complex bone reconstruction. SUMMARY OF THE BACKGROUND DATA: The transoral approach is reported in literature as the classical anterior access to the upper cervical spine that provides direct exposure for anterior decompression of the spinal cord. The risks, the surgical limits, and the postoperative difficulties of transmucosal access suggest the use of an anterior extraoral retropharyngeal approach in orthopedic surgery. METHODS: The series includes four neoplastic lesions (osteoma, aneurismal bone cyst, giant cell tumor, solitary metastasis), three retropharyngeal ossifications resulting from diffuse idiopathic skeletal hyperostosis, and a single case of os odontoideum, craniocervical malformation, and postlaminectomy kyphosis. RESULTS: At follow-up evaluation, all patients achieved a satisfactory outcome, with good clinical and radiographic results; nasotracheal intubation obviated the need for tracheostomy. The wide surgical exposure allowed reconstruction with iliac strut bone grafts and internal fixation in six patients, avoiding the need of a halo device. The only complications were four instances of transient palsies of the marginal mandibular branch of the facial nerve. CONCLUSIONS: In the anterior surgery of the upper cervical spine, the prevascular approach allows a wide surgical exposure, with visualization similar to that obtained with median labiomandibular glossotomy. The retrovascular approach is indicated in selected cases, such as tumor adjacent to the vertebral artery and C1-C2 arthrodesis with bilateral transarticular screws according to Barbour.

Dysphagia due to cervical osteophytosis.

Cervical lesions caused by diffused idiopathic skeletal hyperostosis may cause compression of the upper respiratory and digestive paths. Horizontal anterior osteophytes that are not fused can cause dysphagia and dysphonia, large prevertebral ossifications extended or segmental may cause difficulty in breathing. A series of 6 cases with dysphagia, dysphonia, dyspnea due to duffused idiopathic skeletal hyperostosis, with cervical lesions is reported. In 3 cases, affected with moderate dysphagia, conservative treatment with anti-inflammatory drugs and a proper diet allowed for the symptoms to be controlled, and for spontaneous evolution of the lesions to occur, with fusion and remodeling of the compressive osteophytes. These patients continue to be asymptomatic 2-7 years after the first observation. In 3 cases affected with severe respiratory and/or nutrition deficit, the osteophytes and ossifications were surgically removed by prevascular extrapharyngeal approach, and rapid resolution of symptoms ensued. The follow-up 1-2 years after treatment showed that patients were asymptomatic and that radiographically there was no recurrence of lesions.