Robuvit® (French oak wood extract) in the management of functional, temporary hepatic damage. A registry, pilot study.

AIM: The aim of this registry study was to evaluate the evolution of moderate functional hepatic failure (MTHF) using a proprietary new oak wood supplement (Robuvit®) extracted from Quercus Robur. Recent studies have indicated the protective effect of oak wood extracts on liver injury. Quercus wood extracts have shown hepatoprotective effect on initial induced liver-injury. METHODS: This registry included a total of 75 patients with MTHF characterized by: decreased albumin levels; increased total bilirubin, altered hepatic functions enzymes, increased oxidative stress, negative viral hepatitis markers. RESULTS: The two groups (best management in comparison with best management+ Robuvit®) were comparable: 32 Robuvit® patients and 29 comparable controls) completed the 12-week registry. At inclusion, the blood parameter values in the two groups were comparable. At the end of the supplementation period, the increase in albumin levels was significantly (P<0.05 at 12 weeks) faster and higher in the Robuvit® group. The decrease in ALT-SGPT and AST-ASAT was significant in the supplement group (P<0.05 at 4 and 12 weeks); the tests were normalized at 4 and 12 weeks. Controls remained out of the normal range for more than 12 weeks. Alkaline phosphatase was normalized at 4 and 12 weeks in Robuvit® patients; they were decreased, but not normalized in controls at 4 weeks (Robuvit® group's values were significantly better; P<0.05). Values were normalized in controls (significantly higher in comparison with Robuvit®; P<0.05) at 12 weeks. Total bilirubin was normalized in Robuvit® subjects at 4 and 12 weeks. Results were significantly better in comparison with controls (P<0.05). Direct bilirubin values increased more in the Robuvit® group at 4 and 12 weeks (P<0.05). Gamma GT values were normalized at 4 and 12 weeks in the Robuvit® group. There was a less important decrease in controls (P<0.05) without normalization at 12 weeks. Plasma free radicals increased at inclusion showed a significant decrease in Robuvit® subject (at 4 and 12 weeks) with normalization at 12 weeks. Persisting, elevated values in controls were observed even at 12 weeks (P<0.05). ESR and CRP decreased in both groups with a more important decrease in the Robuvit® group (P<0.05). Hepatitis markers were negative when repeated at 4 and 12 weeks. CONCLUSION: Data from this pilot, supplement registry study indicate a significant protective activity of Robuvit®, associated with a very good safety profile, in patients with temporary hepatic failure. The activity of Robuvit® seems to be mediated by its anti-inflammatory activity.

Circulating cytokines present in the serum of peripheral arterial disease patients induce endothelial dysfunction.

Peripheral arterial disease (PAD) is a chronic condition caused by atherosclerosis and is a severe complication of type 2 diabetes (T2D). We hypothesised that chronic condition of arterial disease engenders inflammation and endothelial damage in response to circulating cytokines released in the blood stream of PAD patients. We explored the levels of circulating cytokines in PAD patients with and without diabetes by multiplex cytokine array compared with non-PAD controls. Serum from PAD patients with or without diabetes showed high levels of VEGF, IFN-gamma, TNF-alpha, MCP-1, and EGF. VEGF levels correlated with TNF-alpha and IFN-gamma, significantly. Endothelial cells (ECs) were exposed to the different altered cytokines to evaluate changes in cell growth, migration and tubule-like formation, displaying impairment on proliferation, migration and tubule formation. Our findings demonstrate that a set of cytokines is significantly increased in the serum of PAD patients. These cytokines act to induce endothelial dysfunction synergistically. VEGF strongly correlated with TNF-alpha and IFN-gamma, opening new therapeutic perspectives.

A simple method to treat post-kydney transplantation lymphocele.

OBJECTIVE: To describe our experience with ultrasonic-guided instillation of povidone-iodine to treat post-kidney transplantation lymphocele. Patients and methods. We studied the safety and efficacy of this procedure for treatment of lymphocele in 6 male kidney transplanted recipients in which we assisted a progressive increase of creatinine and urinary proteins levels and color-Doppler ultrasonography demonstrated an increase (25,4%) of index of resistence (IR) Using eco-colorDoppler, the related-graft lymphocele location and the distance to the anterior abdominal wall were determined; then, a radiopaque double-lumen catheter was used to instillate 5% povidone-iodine 10 ml. Results. Percutaneous drainage achieved a resolution rate of 100%. Studying the rate of peripheral and internal vascularization of the kidney before and after treatment, eco-colorDoppler showed a significant decrease of the IR (24,6%). Conclusions. The US-guided povidone-iodine instillation for treatment of lymphocele following renal transplantation may be considered as first choice therapy in such disease.

Abdominal Compartment Syndrome: diagnostic evaluation and possible treatment.

BACKGROUND: Abdominal compartment syndrome (ACS) is a clinical condition caused by an increase in intra-abdominal pressure. The incidence is variable, based on the type of patients taken into consideration, increasing exponentially in critical conditions, such as traumatized, burned patients in shock. The syndrome can also follow surgical procedures like transplantation of abdominal organs, for example configuring rare pictures such as RACS (post-transplant kidney syndrome). In most cases the symptoms are non-specific and varied according to the different etiology of the ACS, therefore the diagnosis may not be immediate. AIM: The aim of this work is to evaluate the best therapeutic approach based on the evidence in the literature. RESULTS: An early diagnosis, which can also identify the stages of intra-abdominal hypertension, is necessary to ensure the survival of the patient, implementing an integrated multidisciplinary treatment, expecially in the early stages of the development of the ACS. CONCLUSIONS: The definitive treatment is surgical and is based on the decompression of the abdomen.

Loup-assisted technique to create arterio-venous fistulas in elderly. A single centre experience.

AIMS: The radio-cephalic arteriovenous fistula (RCAVF) is the first choice treatment in end-stage renal disease patients. In the last few years, the hemodialysis population has shown a high percentage of elderly patients (> 65 year old) with comorbidities, mainly vascular diseases, which may adversely affect their vascular access success. The aim of this study was to evaluate the effectiveness of a loup-assisted technique to create RCAVFs in over 65 patients. PATIENTS AND METHODS: 98 consecutive patients with renal failure were prospectively observed. The patient were divided in relation to their age (> 65 year old; < 65 year old). In both groups, a microsurgical distal RCAVF was created. Statistics included the prevalence of distal RCAVF created, the incidence of immediate failure, the primary and secondary patency rate at one year. RESULTS: Distal RCAVF was created in 82.60% of patients younger than 65 years and in 73.07% of patients older than 65 years, with no statistically significant difference. The incidence of immediate failure, the primary and secondary patency at one year were not statistically significant between the two groups. CONCLUSIONS: Distal RCAVF should be the first choice vascular access even in ESRD elderly patients. The loup-assisted microsurgical fistula creation, allows to perform distal RCAVF with success, even in patients older than 65 years old, achieving similar results to younger patients.

Advantage of eradication therapy for Helicobacter pylori before kidney transplantation in uremic patients.

From January 1999 to February 2007, 61 end-stage renal disease (ESRD) candidates for kidney transplantation underwent an esophagogastroduodenoscopy (EGDS) to detect Helicobacter pylori (HP). We correlated treatment for HP before transplantation and upper digestive tract hemorrhagic complications and possible recurrence of peptic disease posttransplantation. The 32 (52.4%) HP-Positive cases were divided into 2 groups: (1) 17 patients who underwent treatment for the eradication of the infection with 40 mg/d omeprazole for 4 weeks, 500 mg claritromycin twice daily for 7 days, and 2 g/d amoxicillin for 7 days; and (2) 15 untreated patients. No significant differences were found in the hemorrhagic erosive gastritis of patients with regard to the treated HP-Positive and nontreated HP-Positive patients (2 vs 3) and between the HP-negative patients and the nontreated HP-Positive patients (2 vs 3). The presence of gastric or duodenal ulcers was significantly higher in the nontreated patient than in the treated HP-positive patients (5 vs 1; P=.05) and significantly higher in the nontreated HP-Positive patients than in the HP-negative patients (5 vs 0; P=.05). We concluded that HP-positive patients should therefore be treated for the infection to avoid a long-term significant increase of gastric and/or duodenal peptic disease subsequent to renal transplantation in these immunodepressed subjects.

Use of monitoring intraoperative parathyroid hormone during parathyroidectomy in patients on waiting list for renal transplantation.

This report describes the use of intraoperative parathyroid hormone (ioPTH) assay during parathyroidectomy for patients with secondary hyperparathyroidism on the waiting list for renal transplantation. The levels of ioPTH were determined among waiting list patients undergoing subtotal parathyroidectomy and tertiary hyperparathyroidism patients undergoing procedures. The levels of ioPTH were significantly reduced at 10 minutes by 59.7,3% among with secondary hyperparathyroidism and 68.9% among tertiary hyperparathyroidism. A 15 minutes it was 85% in secondary hyperparathyroidism and 89.7% in tertiary hyperparathyroidism. A decrement of 50% in basal values at 10 minutes and 85% decrement or more at 15 minutes was predictive for the success of abnormal parathyroid gland removal. The application of this technique during subtotal parathyroidectomy results was useful to predict a correct excision of abnormal parathyroid glands among patients with secondary hyperparathyroidism on the waiting list and for tertiary hyperparathyroidism patients.

[Risk factors' analysis of transient and permanent hypoparathyroidism after thyroidectomy].

AIMS: This review evaluates those main risk factors that can affect patients undergoing thyroidectomy, to reach a better pre- and post-operative management of transient and permanent hypoparathyroidism. DISCUSSION: The transient hypoparathyroidism is a potentially severe complication of thyroidectomy, including a wide range of signs and symptoms that persists for a few weeks. The definitive hypoparathyroidism occurs when a medical treatment is necessary over 12 months. Risk factors that may influence the onset of this condition after thyroidectomy include: pre- and post-operative biochemical factors, such as serum calcium levels, vitamin D blood concentrations and intact PTH. Other involved factors could be summarized as follow: female sex, Graves' or thyroid neoplastic diseases, surgeon's dexterity and surgical technique. The medical treatment includes the administration of calcium, vitamin D and magnesium sometimes. CONCLUSIONS: Although biological and biochemical factors could be related to iatrogenic hypoparathyroidism, the surgeon's experience and the used surgical technique still maintain a crucial role in the aetiology of this important complication.

The medical and surgical treatment in secondary and tertiary hyperparathyroidism. Review.

INTRODUCTION: Hyperparathyroidism is an alteration of the pathophysiological parathyroid hormone (PTH) secretion due or an independent and abnormal release (primary or tertiary hyperparathyroidism) by the parathyroid or an alteration of calcium homeostasis that stimulates the excessive production of parathyroid hormone (secondary hyperparathyroidism). AIMS: There is not a standard, clinical or surgical, treatment for hyperparathyroidism. We review current diagnostic and therapeutic methods. DISCUSSION: In secondary hyperparathyroidism (2HPT) there is a progressive hyperplasia of the parathyroid glands and an increased production of parathyroid hormone. Several causes are proposed: chronic renal insufficiency, vitamin D deficiency, malabsorption syndrome. The tertiary hyperparathyroidism (3HPT) is considered a state of excessive autonomous secretion of PTH due to long-standing 2HPT and it's usually the result of a lack of suppression in the production of PTH. The pathophysiological implications are both skeletal and extraskeletal: it damages the cardiovascular system, nervous system, immune, hematopoietic and endocrine system. The introduction of new drugs has improved the survival of these patients, allowing the inhibition of the synthesis of PTH. Indication for surgical treatment is unresponsive medical therapy. CONCLUSIONS: There are no large prospective studies that comparing the medical and surgical treatment. The choice is not unique and we have to consider the singolar case and the clinical condition of the patient.

Use of marginal donors in kidney transplantation: our experience.

The use of elderly donors has been advocated to expand the organ donor pool because of increased needs and the organ shortage. The aim of this study was to analyze whether the use of elderly donors and marginal kidneys affected the outcome of renal transplantations. Herein we presented data on 126 kidney transplantations performed from January 1996 to September 2003 using 32 marginal donors (group A) and 94 ideal donors (group B). We analyzed the medical and surgical complications and the graft survivals at a median follow-up of 18 months. Medical and surgical complications occurred in 22% and 5% versus 7% and 4% in groups A and B, respectively. The mean cold ischemia time and the mean age were greater for patients undergoing kidney transplantations from marginal donors. No differences were observed in graft survival in groups A and B. In conclusion, our data suggested that with an appropriate strategy and a correct selection of patients, marginal kidneys can be safely used to decrease the gap between demand and supply.

Intraoperative parathyroid hormone monitoring during parathyroidectomy for hyperparathyroidism in waiting list and kidney transplant patients.

This report describes the use of the intraoperative parathyroid hormone (ioPTH) assay during parathyroidectomy in waiting list and transplanted patients. ioPTH levels were determined in 40 patients on the waiting list for kidney transplantation with secondary hyperparathyroidism who underwent subtotal parathyroidectomy and 9 transplanted patients with tertiary hyperparathyroidism who underwent removal of hyperplasic glands. Rapid PTH levels decreased significantly at each time period; the percentage decrease in rapid PTH levels was 61.3% among patients with IPT II and 70.2% in patients with IPT III at 10 minutes and 86.5% in patients with IPT II and 91% in patients with IPT III at 15 minutes after excision of hypersecreting parathyroid tissue. A decrease of 50% or more from baseline PTH levels at 10 minutes and/or a decrease of 85% or more at 15 minutes predicted successful removal of abnormal parathyroid glands. The application of this technique during subtotal parathyroidectomy has proved useful for correct excision of parathyroid glands among waiting list patients with IPT II, while in kidney transplant patients with IPT III it allowed removal of only the pathological glands with a limited surgical approach.

Successful treatment of gastrointestinal bleeding with recombinant factor VIIa after kidney transplantation in patients with pancytopenia.

Hemostatic disorders can often complicate transplantation procedures. Moreover, antihemmorhagic drugs may not efficiently control bleeding that occurs in such cases. We report on a patient who underwent kidney transplantation complicated by bone marrow aplasia and gastric bleeding who was successfully treated with recombinant activated FVII (Novoseven). In May 2005, a 53-year-old man affected by chronic renal insufficiency underwent kidney transplantation. At the beginning of June, laboratory tests showed progressive reduction in the blood cell count with anemia, granulocytopenia, and thrombocytopenia related to the development of marrow insufficiency. We commenced transfusion therapy and administered hematologic growth factors. On June 3, 2005, the patient underwent surgical procedure to repair the abdominal wall. Two days thereafter, the postsurgical period was complicated by an episode of melena. The patient received additional treatment with packed red cells, platelets, and fresh-frozen plasma. The gastrointestinal bleeding continued until June 9, 2005, when therapy with recombinant activated FVII (Novoseven) was commenced at an initial dose of 90 microgr/kg. The first bolus did not significantly reduce the blood loss; it was therefore administered as a successive bolus at the same dosage that was able to stop bleeding. Endoscopic examination performed the day after showed the absence of the hemorrhagic lesion in the gastric mucosa. In the subsequent days, the need for transfusion was dramatically reduced with no episode of bleeding. At the same time, the laboratory and clinical findings of marrow insufficiency disappeared. Our case report showed that the use of a global antihemorrhagic factor, such as Novoseven, can successfully control gastrointestinal bleeding even in complicated patients despite failure of traditional antihemostatic therapy.

PTFE mesh in renal allograft compartment syndrome.

We report a case of anuria in a 42-year-old female kidney transplant patient that occurred secondary to extrinsic compression from a large kidney being placed extraperitoneally in a small iliac fossa. Prompt reexploration in the immediate postoperative period resulted in salvage of the graft with restoration of kidney function. The abdominal wall was reconstructed using prosthetic mesh, which decreased the compartment pressure within the iliac fossa sufficiently to allow the renal vein patency and the kidney perfusion. We think that this tension-free surgical technique should be applied in those cases in which the retroperitoneal space is less than the size of the kidney to avoid renal allograft compartment syndrome or incisional hernia.

Renal Allograft Compartment Syndrome: Is It Possible to Prevent?

Renal allograft compartment syndrome (RACS) is a complication characterized by increased pressure over 15 to 20 mm Hg of the iliac fossa site of transplanted kidney that can lead to a reduction of the blood supply to the graft, resulting in organ ischemia. This study aims to evaluate, through a review of the literature, the incidence, detection, treatment, and possible prevention of RACS. The incidence of this complication, which appears generally in the immediate post-transplantation period, is currently approximately 1% to 2% and is underestimated because of poor nosography for the presence of symptoms common to other post-transplantation complications. Doppler ultrasound is indispensable to evaluate the graft function in the immediate postoperative period and in the following days. The onset of RACS involves a surgical decompression of the graft and the subsequent closure of the abdominal wall with tension-free technique. Several authors agree that only the immediate surgical decompression following an early diagnosis can ensure a recovery of the graft. Early detection of the RACS is the key to preventing the loss of the graft. It is desirable to prevent this syndrome by reducing the discrepancy in weight between donor and recipient by 17%. However the shortage of organs makes such a selection not easy; therefore, in cases at risk for RACS, a close instrumental and clinical monitoring of the patient during post-transplantation recovery is recommended, so a prompt surgical decompression can be performed if RACS is suspected.

Comparison Between Rapid Intraoperative and Central Laboratory Parathormone Dosage in 12 Kidney Transplant Candidates.

BACKGROUND: The rapid intraoperative parathormone (PTH) and at central laboratory PTH dosage gives similar results. The central laboratory provides results in longer times and higher costs. Intraoperative measurement can reduce time and costs during parathyroidectomy. METHODS: Twelve patients undergoing parathyroidectomy for hyperparathyroidism renal transplant candidates were included. Diagnosis was made by laboratory tests (serum calcium, PTH) and imaging techniques (ultrasonography and scintigraphy). All patients presented PTH levels of >400 pg/mL (the limit value to be maintained in list for kidney transplantation) and resistant to medical therapy. For each patient, 2 blood samples were collected before surgery at anesthesia induction for PTH testing intraoperative (rapid assay) and central laboratory, and 10 minutes after the removal of each gland. The times from collection-processing to communication to the surgeon of the results were compared for both the methods. It was considered successful the abatement of PTH of ≥70% at rapid intraoperative testing and consequently surgical intervention stopped before communication of central laboratory PTH testing. RESULTS: The average time of reporting the test results of the central laboratory was 41.5 minutes (SD ± 9), whereas with the rapid intraoperative PTH (ioPTH) testing the average time was 9.9 minutes (SD ± 2.02). An average of 33.6 minutes of the duration per intervention (SD ± 10.27) were virtually saved with the use of ioPTH testing. The 2 values of the Pearson correlation (ρ) of 0.99 obtained (for baseline) and 0.975 (for the 10-minute) lead us to conclude that there is an excellent correlation between the series of data. CONCLUSIONS: Rapid ioPTH testing, owing to its accuracy, permits a dramatic reduction of operating time for patients with secondary hyperparathyroidism that need to be treated before inclusion on the waiting list.

Renal hydatidosis. Discussion of a clinical case complicated by post acute pancreatitic cyst.

In this paper the authors describes a rare case of renal hydatidosis complicated by post acute pancreatitic cyst. There have been no reports up till now either of any physiopathological between the development of hydatid cysts in the vicinity of the pancreas and subsequent pancreatitis, or of any correlation between long-term albendazole therapy and acute pancreatitis. In our particular case, however, the volumetric increase of the renal cyst caused external compression of the pancreas and the consequent slowing-down of bilio-pancreatic flow, which probably led to the development of acute pancreatitis. Since, in our opinion, the pancreatic pseudocyst required surgical removal, we decided to perform the operation there and then; intraoperative examination of the cystic fluid and the presence of daughter cysts confirmed the suspected diagnosis of hydatidosis, of clear renal origin since it was closely attached to the upper pole and continued along the upper calyces renales; the cyst was easily detached from the lower and posterior edge of the liver, and was completely removed, together with its pericystium, which was detached from the lower surface of the liver and from the inferior subhepatic vein; only a tiny disk of pericystium was left in communication with a calyx, sutured to the rest of the kidney. The pancreatic cyst was drained by means of a mesocolic Roux-loop cysto-jejunostomy.

[Pancreatic harvesting from multiorgan donors for islet transplantation]. / Il prelievo di pancreas da donatore multiorgano per trapianto di insule.

The result of human islet isolation procedures to transplant in type I insulin-dependent diabetic patients is significantly conditioned by the technique used for pancreas procurement from multiorgan donor. In fact, during multiorgan procurement, an improper handling of the gland could result in edema or degranulation of the acinar tissue, detrimental for the islet purification step. The surgical technique used by our surgical team, includes some important refinements to obtain the largest quantity and the best quality of purified endocrine material.

[Harvesting of the rat pancreas with in-situ perfusion. A microsurgical technic]. / Prelievo di pancreas di ratto con perfusione in situ. Tecnica microchirurgica.

One of the principal obstacles to pancreatic islet transplantation is the poor yield of islet from donor pancreas. Many techniques have been designed to increase the yield of islets. The influence of pancreas harvesting technique on islet isolation and function has received little attention. The authors report their experience about pancreas procurement in the rat using a multiorgan harvesting technique according to the original methods of Starzl in the human cadaver donors with in situ liver and pancreas flushing with U.W. solution. Sixty adult male Wistar rats weighting 100 gr. on average entered into our studies and underwent to different techniques of pancreas procurement. Our results demonstrate that the microsurgical multiorgan retrieval technique with in situ U.W. flushing via common iliac artery allows the best islets recovery with a larger number and more vital cells compared with the traditional exanguinatio technique, though it is more expensive and time consuming.

Effect of autologous transplantation of bone marrow cells concentrated with the MarrowXpress system in patients with critical limb ischemia.

Critical limb ischemia (CLI), a vascular disease affecting lower limbs, with high morbidity and mortality, is becoming a challenge due to the aging of the population. Patients without direct revascularization options have the worst outcomes. To date, 25% to 40% of CLI patients are not candidates for surgical or endovascular approaches, facing a major amputation as the ultimate option. This study sought to assess the safety and efficacy of transplantation of autologous bone marrow concentrates in "no-option" patients to restore blood perfusion by collateral flow and limb salvage. We performed a nonrandomized, noncontrolled pilot study for no-option CLI patients using intra-arterial infusion of autologous bone marrow concentrate. Variation of blood perfusion parameters, evaluated by laser doppler flowmetry after 6 and 12 months, was set as primary endpoint. Thirteen enrolled patients showed improvements in objective measurements of perfusion. This uncontrolled study provided evidence that transplantation of autologous bone marrow concentrates was well tolerated by CLI patients without significant adverse effects, demonstrating improved perfusion, confirming the feasibility and safety of the procedure.

Autologous bone marrow cell therapy for peripheral arterial disease.

Inadequate blood supply to tissues caused by obstruction of arterioles and/or capillaries results in ischemic injuries - these injuries can range from mild (eg, leg ischemia) to severe conditions (eg, myocardial infarction, stroke). Surgical and/or endovascular procedures provide cutting-edge treatment for patients with vascular disorders; however, a high percentage of patients are currently not treatable, owing to high operative risk or unfavorable vascular involvement. Therapeutic angiogenesis has recently emerged as a promising new therapy, promoting the formation of new blood vessels by the introduction of bone marrow-derived stem and progenitor cells. These cells participate in the development of new blood vessels, the enlargement of existing blood vessels, and sprouting new capillaries from existing blood vessels, providing evidence of the therapeutic utility of these cells in ischemic tissues. In this review, the authors describe peripheral arterial disease, an ischemic condition affecting the lower extremities, summarizing different aspects of vascular regeneration and discussing which and how stem cells restore the blood flow. The authors also present an overview of encouraging results from early-phase clinical trials using stem cells to treat peripheral arterial disease. The authors believe that additional research initiatives should be undertaken to better identify the nature of stem cells and that an intensive cooperation between laboratory and clinical investigators is needed to optimize the design of cell therapy trials and to maximize their scientific rigor. Only this will allow the results of these investigations to develop best clinical practices. Additionally, although a number of stem cell therapies exist, many treatments are performed outside international and national regulations and many clinical trials have been not registered on databases such as ClinicalTrials.gov or EudraCT. Therefore, more rigorous clinical trials are required to confirm the first hopeful results and to address the challenging issues.