[Bio-ecological control of chronic liver disease and encephalopathy]. / Controllo bio-ecologico della cirrosi epatica e dell'encefalopatia.

Minimal encephalopathy was originally associated with chronic liver disease but is increasingly associated with most other chronic diseases and particularly with diabetes and also chronic disorders in other organs: kidneys, lungs, thyroid and with obesity. It is increasingly with dramatically increased and more or less permanent increase in systemic inflammation, most likely a result of Western lifestyle. Frequent physical exercise and intake of foods rich in vitamins, antioxidants, fibres, lactic acid bacteria etc in combination with reduction in intake of refined and processed foods is known to reduce systemic inflammation and prevent chronic diseases. Some lactic acid bacteria, especially Lb paracasei, lb plantarum and pediococcus pentosaceus have proven effective to reduce inflammation and eliminate encephalopathy. Significant reduction in blood ammonia levels and endotoxin levels were reported in parallel to improvement of liver disease. Subsequent studies with other lactic acid bacteria seem to demonstrate suppression of inflammation and one study also provides evidence of clinical improvement.

Ab initio calcineurin inhibitor-based monotherapy immunosuppression after liver transplantation reduces the risk for Pneumocystis jirovecii pneumonia.

At the Tor Vergata University of Rome, ab initio calcineurin inhibitor-based monotherapy immunosuppression (IS) is the standard of treatment after liver transplantation (LT). As the net state of IS determines the onset of Pneumocystis jirovecii pneumonia (PCP), we hypothesized that, in the presence of weak impairment of the immune function, as determined by the above-mentioned IS, the host is not overexposed to the risk for PCP and consequently the specific anti-PCP prophylaxis is unnecessary. In a single-cohort descriptive study, we retrospectively investigated the incidence of PCP in 203 LT patients who did not receive anti-PCP prophylaxis because they were under monotherapy IS. The primary endpoint of the study was the incidence of PCP during the first 12 months following LT; secondary endpoints were the incidence of acute rejection requiring additional IS and of CMV infection. No cases of PCP were recorded. The incidence of CMV and acute rejection was 3.9% and 0.9%, respectively. Our data suggest that monotherapy IS after LT may nullify the risk for PCP even in the absence of any specific prophylaxis.

Fatal hemorrhage in two renal graft recipients with multi-drug resistant Pseudomonas aeruginosa infection.

Pseudomonas aeruginosa (PA) infections occurring after renal transplantation (RT) represent a potentially life-threatening complication. We present 2 cases of early death following RT in which PA was transmitted, possibly from the donor to the recipients, despite preoperative cultures that were negative. The donor had developed PA-related bilateral pneumonia while in the intensive care unit. However, after appropriate antibiotic therapy, no signs of infection were present at the time of organ retrieval and cultures were negative. Both recipients received a renal graft from the same donor and developed multi-drug resistant (MDR)-PA infections with bacterial phenotypes and resistances similar to the donor. The first recipient died 9 days after RT from rupture of a false aneurysm of the external iliac artery, caused by a fully thickened PA-related arteritis. The second recipient died postoperatively on day 10 after rupture of an aneurysm in the right vertebral artery. Our experience shows that MDR-PA infection early after RT may be a catastrophic event. Specific anti-PA antibiotic therapy in RT patients during the perioperative period is recommended in the case of PA infection in the donor, even after apparent successful therapy with negative cultures.

Clinical operational tolerance after kidney transplantation: a short literature review.

The clinical era of solid organ transplantation started with a renal transplantation (RT) performed between identical twins in Boston in 1954. The patient did not receive any immunosuppression, thus representing the very first case of operational tolerance (Tol). However, more than half a century later, we must admit the inadequacy of our knowledge regarding such a fundamental aspect of transplant immunology, as demonstrated by the fact that Tol has never been achieved in an intention-to-treat protocol. Herein we aim to shortly review the worldwide experience on clinical operational Tol after RT. Thus far, reports on successful cases of Tol after RT have been anecdotal: the largest series included no more than 10 individuals. We will understand that Tol can develop even in the presence of either HLA mismatches or blood group incompatibility at baseline, in the presence of anti-HLA antibodies during follow-up, as well as in patients having experienced acute rejection. Despite the lack of robust evidence, the fact that Tol is often accidentally discovered by transplant physicians during follow-up in noncompliant patients justifies the hypothesis that the real number of Tol cases might be much higher than currently reported.

Incidence of urinary tract infections caused by germs resistant to antibiotics commonly used after renal transplantation.

BACKGROUND: The inadequate utilization of antibiotics is responsible for the development of urinary tract infections (UTI) after renal transplantation (RT), through the induction of resistance to the antibiotics themselves. The purpose of this study was to evaluate the incidence of resistance to cefotaxime (CEF) and trimethoprim/sulfamethoxazole (TMP-SMX), routinely used for surgical perioperative prophylaxis and prevention of Pneumocystis carinii, respectively. MATERIALS AND METHODS: We enrolled all adult patients having received an RT from 2001 to 2006 and having a minimum follow-up of 6 months. Urine cultures (UC) were routinely performed at every outpatient clinic control and whenever required by the onset of significant clinical signs/symptoms. UTI was diagnosed by the presence of a positive UC. The endpoint of the study was the emergence of bacterial strains resistant to either CEF or TMP/SMX. RESULTS: We recorded 169 UTI in 76 patients (38 men/38 women, 33%) over a mean follow-up of 779.9+/-523.3 days. Thirty-nine patients (51%) developed more than 1 UTI episode. When gram-negative bacteria were considered, 102/144 (70.8%) tests showed resistance to TMP/SMX, while data were available in about only 7 gram-positive infections (5/7, 71%). CEF was tested less frequently with 21/43 (49%) germs resistant to this molecule. CONCLUSIONS: The onset of bacterial resistance to either TMP/SMX or CEF is frequent after RT. A wiser stricter utilization of antibiotics is mandatory. Standard antibiotic protocols should be revised.

De novo autoimmune hepatitis following liver transplantation: a case report.

De novo autoimmune hepatitis (AIH), a rare disorder first described in 1998, appears in patients with liver transplants due to autoimmune and nonautoimmune etiologies. De novo AIH occurs in 2.5% to 3.4% of allografts; children seem to have a predilection for this syndrome. We have present herein a case of a liver allograft recipient who developed chronic hepatitis associated with autoimmune features outlining the clinical course, liver histology, and response to treatment.

Emergency Kidney Transplantation in Recipients With Iliocaval Thrombosis Using Splenic Vessel Anastomosis After Splenectomy: A Case Series.

BACKGROUND: The external iliac vein is the standard site used for venous anastomosis in kidney transplantation. When a pre-transplantation diagnosis of iliocaval thrombosis is established, a different and suitable venous drainage for the renal outflow must be identified for successful transplant. METHODS: We report 4 cases of kidney transplantation, performed from 2004 to 2016, in recipients presenting with thrombosis of the inferior vena cava and iliac system needing, because of the lack of access for dialysis, urgent kidney transplantations. The splenic vessels were used in all cases for the graft's vascular anastomosis after splenectomy. RESULTS: Kidney transplantation after splenectomy, with anastomosis of the renal vessels to the splenic ones, was completed in all 4 patients. All of the cases were technically successful with good renal function on discharge. During the follow-up, no graft losses were registered as due to thrombotic event or inadequate renal venous outflow. A normal vascular inflow and outflow was confirmed by means of follow-up ultrasound. Two grafts were lost at 31 months and 91 months, both to noncompliance with immunosuppressive therapy. The other 2 are currently functioning well. Notably, the kidney's position in the left upper quadrant has not caused technical difficulties in urologic reconstruction. CONCLUSIONS: In our experience, kidney transplantation using splenic vessels for vascular anastomosis is technically feasible and very useful in the setting of complete iliocaval thrombosis.

The role of liver transplantation in the treatment of hereditary hemorrhagic telangiectasia: a short literature review.

The liver is involved in up to 73% of patients suffering from hereditary hemorrhagic telangiectasia (HHT), but only some of them become symptomatic. Although management is often conservative, sometimes a more aggressive approach is required. The role of surgery is still undefined. Open ligation, banding, or closure of the arteriovenous malformation feeding artery have been proposed but rejected, as they are followed by an unacceptably high incidence of complications, derived from ischemia of the biliary tree. Orthotopic liver transplantation (OLT) has been successfully attempted in 28 patients with cardiac, biliary, or portal hypertension as well as mixed clinical presentations. Twenty-four were alive at time of data collection. Cardiovascular and pulmonary functions have improved after the operation in most cases. Intrahepatic relapse of the hallmark lesion of the disease (telangiectasia and arterovenous malformation) has been recently described in two cases. OLT represents a valuable therapeutic option for hepatic-based HHT, provided early diagnosis and referral to a specialized unit.

Cytomegalovirus and gastric cancer after renal transplantation: a possible interplay.

We herein have described a case of de novo gastric cancer in a renal transplant recipient with a concomitant diagnosis of gastrointestinal cytomegalovirus (CMV) disease. We hypothesize that CMV, through causing an imbalance between cell proliferation and cell death, functions as the causative agent for the progression of the gastric tumor in this case after gastric colonization. To the best of our knowledge, this is the second such case ever reported of such kind and may represent a platform for investigations aimed at understanding the possible interplay between CMV and gastric cancer.

Management of kidney transplantation in a factor VII-deficient patient: case report.

Transplantation in patients with congenital bleeding disorders is a challenge requiring an integrated approach of various specialists. Renal transplantation, the most frequent type of solid organ transplantation, is rarely performed in individuals with congenital hemorrhagic disorders. We performed a renal transplantation in a 53-year-old man with end-stage renal disease and congenital coagulation factor VII deficiency, a rare bleeding disorder with a peculiar clinical picture requiring replacement therapy in surgical interventions. Perioperative bleeding was successfully prevented by administration of recombinant activated factor VII. Treatment schedule, administration rate, and long-term follow-up are reported in detail. Our report confirmed the feasibility and safety of recombinant activated factor VII in major surgical procedures like solid organ transplantations. Success requires evaluation of doses and therapeutic schedules as well as a multidisciplinary approach.

A rare case of herpes simplex type 1 bronchopneumonia associated with cardiomegaly in renal transplantation.

INTRODUCTION: We report a rare case of herpes simplex virus (HSV) type 1B in patient with kidney transplant as a possible cause of patient death. CASE REPORT: A 32-year-old renal transplanted Caucasian man was referred for asthenia, fever, anemia, chest pain, cough, dyspnea, myalgias, peripheral edema, acute renal failure, diffuse cutaneus and mucous vesicles, and acute weight gain. The home therapy consisted of tacrolimus, sodic mycophenolate, and steroids. Laboratory data, bronchoscopy, and bronchial mucosal biopsy revealed HSV1B. We administered antiviral and antibiotic agents and reduced tacrolimus with clinical resolution. But after 10 days from discharge, the patient was admitted for acute cardiomegaly. So using ex adiuvantibus criteria we administered antiviral therapy with complete clinical improvement. CONCLUSION: According to the literature, posttransplant HSV1B infection is a rare but severe complication of kidney transplantation associated with poor graft survival and a high mortality. Only an early, accurate diagnosis with efficient treatment permitted resolution of the problem. Our report stresses the difficulty of HSV2B clinical diagnosis and treatment.

Kidney transplantation from older donors.

BACKGROUND: The use of kidneys from older donors has become generally accepted and increasingly common, despite the knowledge that donor age is a well-known risk factor for graft failure. AIM: To review our experience with the utilization of kidneys from donors older than 60 years. PATIENTS AND METHODS: Among two hundred eight patients, 32 (group A) received an organ obtained from a donor older than 60 years. The organs were age-matched with a maximum gap of 20 years between donors and recipients. Organs from older donors were assigned to recipients presenting a body mass index lower than that of the donor. The primary end point was patient and graft survival. Secondary endpoints were incidences of delayed graft function and of acute rejection episodes as well as renal function at 3 months and yearly. RESULTS: The two groups were comparable in terms of demographic features, indications for transplantation, comorbidities, as well as cold and warm ischemia times. The Mean lengths of follow up were 31.4 ± 20.3 months and 30.3 ± 20.1 months, respectively. Graft and patient survivals were comparable. Mean creatinine values at the study intervals were significantly lower among group B who received grafts from younger donors. The incidence of delayed graft function and acute rejection episodes were similar: 15.6% (5/32) versus 20.5% (36/176; P=0.35) and 15.6% (5/32) and 12.1% (21/167; P=0.136) in groups A and B, respectively. CONCLUSIONS: Donor age older than 60 years showed a negative impact on kidney function. Though, given the escalating disparity between organ supply and demand, this precious source of organs cannot be neglected. We need better ways to use the available organs.

Regenerative medicine applied to solid organ transplantation: where do we stand?

The objective of regenerative medicine (RM) and Tissue Engineering (TE) is to create living functional tissues to repair or replace tissues or organ functions. This field holds the promise of regenerating damaged tissues and organs in the body. It has the potential to solve the problems of organ shortage and of toxicities deriving from life-long immunosuppression. In fact, cells in the regenerated organ would match those of the patient, from whom they would normally be derived. In the past decade, RM/TE has achieved striking results which are of interest to the transplant community. However, major roadblocks on the avenue to full success include the need for a deeper understanding of cell biology and of interactions with the extracellular matrix. We are presently not able to grow and expand cells indefinitely and safely in various scenarios where RM/TE may be indicated. The production of adequately vascularized scaffolds to optimize nutrients and oxygen delivery, assessment of the viability and function of the cells in the bioengineered construct, and the costs remain areas of scientific research.

Steroid-free immunosuppression after liver transplantation does not increase the risk of graft fibrosis.

BACKGROUND: Steroid-free immunosuppression after liver transplantation (OLT) is effective and safe in the short and mid terms. However, research has shown a higher risk for late fibrosis among pediatric liver transplant recipients who have steroids withdrawn. Our aim was to test this hypothesis in the adult population. PATIENTS AND METHODS: The study involved 27 adults, 14 of whom were on a regimen of cyclosporine, azathioprine, and steroid (group A) and 13 cyclosporine and azathioprine steroid-free immunosuppression (group B). The main end point of the study was liver graft histology in the late stage after OLT, with emphasis on the evolution of fibrosis, which was scored according to Ishak. The secondary end points were patient and graft survivals, liver and kidney functions, rejection rates, infections, and tumors, as well as the incidences of cardiovascular and metabolic complications. RESULTS: After a mean follow-up of 89.3 +/- 21 months, the mean fibrosis scores did not differ between the 2 groups (2.2 +/- 1.5 vs 1.9 +/- 1.2; P = NS). One group A patient developed a severe acute rejection episode. The 7-year patient and graft survivals, as well as liver and kidney functions, incidence of infections, and cardiovascular and metabolic complications were comparable. Patients receiving steroids showed a trend toward an higher rate of de novo malignancies. CONCLUSION: Steroid-free immunosuppression did not increase the risk of graft fibrosis in the long term.

A rare case of colic thrombotic microangiopathy in renal transplantation.

INTRODUCTION: We report a case of thrombotic microangiopathy (TM) in patient with UC and kidney transplantation. CASE REPORT: A 59-year-old Caucasian may with a renal transplant, with atrial fibrillation and ulcerative colitis (UC), was referred for asthenia, fever (38 degrees C), anemia, colicky pain, and bloody diarrhea. The maintenance therapy consisted of CSA, sodium mycophenolate, steroids, ticlopidine, and mesalazine. Laboratory data, colonscopy, and colic mucosal biopsy revealed de novo colic TM. We administered antibiotics and antishock therapy, reducing CSA, withdrawing ticlopedine and maintaining mesalazine with the resolution of the problem. CONCLUSION: Posttransplantation TM is an uncommon but severe complication of kidney transplantation associated with reduced graft survival and a high risk for death. Only an early, accurate diagnosis with optimal treatment permits resolution of the problem.

Surgical antibiotic prophylaxis after renal transplantation: time to reconsider.

The optimal regimen for perioperative antibiotic prophylaxis after renal transplantation remains to be determined. Worldwide, it seems there is a trend toward decreased use of prophylaxis from the first 48 hours to several days after surgery. However, bacterial strains resistant to common antibiotic agents arise even if only a single dose of a molecule is administered at any time. Inasmuch as infections currently are the primary cause of hospitalization after renal transplantation, it is desirable to not favor selection of resistant strains that may not be treated appropriately in the event of onset of infection. Therefore, antibiotic therapy, whether for therapeutic or prophylactic purposes, should be administered based exclusively on clinical evidence. Because systemic antibiotic prophylaxis is not effective against infections of the urinary tract, the objective of perioperative antibiotic prophylaxis should be to prevent infection of the surgical wound. In this case, administration of a single dose of an antibiotic agent (1-shot regimen) at the induction of anesthesia is effective and safe. For these reasons, it is urgent that new guidelines be defined for perioperative antibiotic prophylaxis. Multicenter prospective randomized trials comparing 1-shot vs multiple-dose regimens should be performed to establish the optimal regimen.

Superior vena cava syndrome due to thrombotic occlusion in a thrombophilic renal transplant recipient: a case report.

The case of a superior vena cava syndrome due to a central venous catheter thrombosis occurring in a second renal transplant patient is described. Imaging revealed thrombosis of the right internal jugular vein with extension along the confluence of the brachiocephalic veins and partial obstruction of the superior vena cava. Anticoagulant therapy with subcutaneous low-molecular-weight heparin was followed by warfarin administration. Despite adequate treatment, the symptomatology worsened because of thrombus organization. A workup revealed a complex prothrombotic underlying condition. Cardiothoracic surgeons were consulted, and an operative reconstruction of the superior vena cava using spiral vein bypass grafting was performed. In this report we describe the clinical presentation, diagnosis, and treatment of this case, with an emphasis on the role of thrombophilia.

Serious renal hemorrhage in Masson tumor.

Intravascular papillary endothelial hyperplasia (IPEH; Masson tumor) is a vascular lesion of blood vessels, first described in 1923 by Masson, who termed it "hemangioendotheliome vegetant Intravasculaire." This lesion consists of an exuberant, usually intravascular, proliferation of normal endothelial cells and is considered to be a reactive vascular proliferation after traumatic vascular stasis. The disease frequently occurs in skin and subcutaneous tissue; occurrence in solid organs is rare. We report a rare case IPEH that recurred as a possible consequence of an acute hypertensive arterial crisis in a patient with chronic kidney failure after kidney transplantectomy. Thirty days after transplantectomy, a 49-year-old white man receiving hemodialysis had pain in the left abdominal flank and acute anemia with serious hypovolemia after a hypertensive arterial crisis. An emergency non-contrast enhanced abdominal computed tomographic scan showed a massive retroperitoneal hemorrhage. A left nephrectomy was performed for evidence of a native kidney breach with toilette of the abdominal cavity. Histologic analysis revealed that the renal lesion had several important distinguishing characteristics that confirmed the diagnosis of IPEH. This lesion is considered to be an usual form of thrombus organization that is marked by excessive papillary endothelial proliferation. In rare cases, it is present in a solid organ of the abdominal cavity especially the kidney. Intravascular papillary endothelial hyperplasia is a benign lesion but can be dangerous. Clinical, radiologic, and histologic diagnosis of IPEH is difficult.

A systematic review of two different trimetoprim-sulfamethoxazole regimens used to prevent Pneumocystis jirovecii and no prophylaxis at all in transplant recipients: appraising the evidence.

BACKGROUND: The aim of this study was to clarify the potential advantages of a low-dose regimen of trimethoprim-sulfamethoxazole prophylaxis to prevent Pneumocystis jirovecii pneumonia (PJP) in transplant recipients (80/400 mg/d every day or 160/800 mg/d every other day) with those obtained from the full-dose prophylaxis (160/800 mg/d every day) or no prophylaxis. METHODS: Prospectively randomized and retrospectively case controlled studies were selected. RESULTS: Four studies matched the inclusion criteria-2 randomized and 2 case controls-for a total of 570 patients. The pneumonia incidence was 0% after full-dose prophylaxis (0/181), 1% after the low-dose regimen (1/105), and 11% with no prophylaxis (31/284). Pneumonia occurrences were significant lower between the full-dose prophylaxis versus the no prophylaxis group (0% vs 11%; P < .001), and between the low-dose and no prophylaxis groups (1% vs 11%; P < .001). There was no difference between patients receiving the full-dose prophylaxis versus the low-dose regimen (0% vs 1%; P = NS). CONCLUSIONS: The low-dose gives similar results as the full-dose regimen for the prevention of PJP and seems a feasible, safe option for transplanted patients.

Clinical operational tolerance after solid organ transplantation.

Clinical operational tolerance (COT) is a clinical condition obtainable with difficulty after solid organ transplantation (SOT). It is characterized by perfectly normal graft function in the total absence of maintenance immunosuppression. Major benefits deriving from the onset of COT are the reduction of risk for immunosuppression-related side effects and the improved quality of life. Currently, COT can be safely achieved in stable liver transplant recipients; it remains a challenge after renal transplantation. Only 1 case of COT has been reported after lung transplantation; no cases have been described after other types of SOT. Overall, mechanisms of COT are unclear and strategies to induce COT cannot be applied on a regular base to a large cohort of SOT recipients. Due to the failure of molecularly based tolerogenic protocols, great hope relies in the adoption of cell-based strategies.