Prevalence, treatment and outcome of patellar luxation in dogs in Italy. A retrospective multicentric study (2009-2014).

OBJECTIVE: To determine the prevalence of patellar luxation in dogs in Italy and its relation to signalment, the frequency and the type of postoperative complications and the outcome of treatment, and to compare the findings with those of other studies. MATERIALS AND METHODS: The medical records from four referral clinics were searched for dogs with orthopaedic disorders referred from 2009 to 2014. From these data, the records of dogs with patellar luxation were identified, and the signalment, age and body weight, grade, side and direction of patellar luxation, treatment, postoperative complications, and outcome were retrieved. Univariate and multivariate statistical analyses were used to evaluate the data. RESULTS: Of 8,694 canine orthopaedic cases, fractures not included, patellar luxation was diagnosed in 559 dogs (801 stifles). Mixed breed dogs were most commonly affected (18%), 85% of the luxations were medial, and 52% of the dogs were female. Of the 559 dogs examined, 400 (574 stifles) met the inclusion criteria for treatment evaluation. Minor complications occurred in five percent of the dogs, and major complications in 16%, including recurrence of patellar luxation in seven percent of the dogs. The outcome was good in 88% of stifles, fair in two percent, and poor in 10%. CLINICAL SIGNIFICANCE: Although patellar luxation was more common in small breed dogs, it also was diagnosed in a significant number of large breed dogs, which included medial patellar luxation in 73% and lateral patellar luxation in 27% of stifles. Body weight and grade of luxation were the only variables statistically correlated with surgical complications.

Mesenchymal stromal cells reset the scatter factor system and cytokine network in experimental kidney transplantation.

BACKGROUND: In former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft. In this study we investigated whether MSC operate by resetting cytokine network and Scatter Factor systems, i.e. Hepatocyte Growth Factor (HGF), Macrophage Stimulating Protein (MSP) and their receptors Met and RON, respectively. METHODS: MSC were injected into the renal artery soon after reperfusion. Controls were grafted untreated and normal rats. Rats were sacrificed 7 days after grafting. Serum and renal tissue levels of IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, MSP/RON, HGF/Met systems, Treg lymphocytes were investigated. RESULTS: In grafted untreated rats IFN-γ increased in serum and renal tissue and IL-6 rose in serum. MSC prevented both the phenomena, increased IL-10 serum levels and Treg number in the graft. Furthermore MSC increased serum and tissue HGF levels, Met tubular expression and prevented the suppression of tubular MSP/RON expression. CONCLUSIONS: Our results demonstrate that MSC modify cytokine network to a tolerogenic setting, they suppress Th1 cells, inactivate monocytes/macrophage, recruit Tregs. In addition, MSC sustain the expression of the Scatter Factor systems expression, i.e. systems that are committed to defend survival and stimulate regeneration of tubular cells.

Antineutrophil cytoplasmic antibody-associated renal vasculitis treated with autologous mesenchymal stromal cells: evaluation of the contribution of immune-mediated mechanisms.

We report the first case of renal antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis treated with autologous mesenchymal stromal cells (MSCs). A 73-year-old man was admitted to the hospital for malaise, weight loss, and oliguria. His serum creatinine level was 2.7 mg/dL but it rapidly increased to 7.8 mg/dL; urinalysis showed proteinuria and hematuria, and the ANCA to myeloperoxidase with a perinuclear pattern (pANCA) titer was high (132 IU/mL). Renal biopsy showed necrotizing crescentic glomerulonephritis. Standard immunosuppressive therapy (cyclophosphamide and corticosteroids) was ineffective. Rituximab therapy was started, but it was discontinued after the third dose to minimize the risk of systemic spread of a severe oral Candida infection and to prevent superinfections that were facilitated by leukopenia. The patient received autologous MSCs, 1.5 × 10(6) cells/kg body weight, intravenously. After 7 days, his serum creatinine level decreased to 2.2 mg/dL, pANCA titer decreased to 75 IU/mL, and urinalysis findings normalized. Eight months later, he received a second MSC infusion because his serum creatinine level increased. In 1 week, his creatinine level decreased to 1.9 mg/dL and his pANCA titer decreased to 14 IU/mL. Immunosuppressive therapy was subsequently withdrawn. At the last follow-up visit, 12 months after the second MSC infusion, the patient remained in clinical remission without any therapy. Infusion of MSCs induced expansion of the T-lymphocyte subset expressing a regulatory T-cell phenotype (CD4(+)CD25(+)Foxp3(+)) and a notable reduction in interferon-γ, interleukin 6, and tumor necrosis factor serum levels.

Multiple electrolyte disorders in a neurosurgical patient: solving the rebus.

BACKGROUND: It is important to ensure an adequate sodium and volume balance in neurosurgical patients in order to avoid the worsening of brain injury.Indeed, hyponatremia and polyuria, that are frequent in this patient population, are potentially harmful, especially if not promptly recognized.Differential diagnosis is often challenging, including disorders, which, in view of similar clinical pictures, present very different pathophysiological bases, such as syndrome of inappropriate antidiuresis, cerebral/renal salt wasting syndrome and diabetes insipidus. CASE PRESENTATION: Here we present the clinical report of a 67-year-old man with a recent episode of acute subarachnoid haemorrhage, admitted to our ward because of severe hyponatremia, hypokalemia and huge polyuria.We performed a complete workup to identify the underlying causes of these alterations and found a complex picture of salt wasting syndrome associated to primary polydipsia. The appropriate diagnosis allowed us to correct the patient hydro-electrolyte balance. CONCLUSION: The comprehension of the pathophysiological mechanisms is essential to adequately recognize and treat hydro-electrolyte disorders, also solving the most complex clinical problems.

A retrospective analysis of dermatological lesions in kidney transplant patients.

BACKGROUND & OBJECTIVES: Kidney transplantation is the best option for patients with end-stage renal disease (ESRD) failure. Prolonged use of immunosuppressive drugs often causes opportunistic infections and malignancies of skin and mucosae, but due to lack of a careful dermatological screening in several transplantation centers the diagnosis and the treatment of dermatological lesions in kidney transplant patients are underestimated. In addition after the introduction of interleukin (IL)-2 -receptor antagonists (basiliximab/daclizumab), mTOR inhibitors and mycophenolate mofetil (MMF)/mycophenolic acid (MPA) in new immunosuppressive protocols only a few studies have analyzed the skin and mucosal lesions in kidney transplant patients. This study was undertaken to evaluate the cutaneous and mucosal diseases after kidney transplantation, and to investigate the association between these and different immunosuppressive protocols and/or demographic features. METHODS: A retrospective analysis was done using medical records of kidney transplantation between 2000 and 2009 at the Transplant Unit of Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. The study included 183 patients (M 57.3%, F 42.7%) aged 51.5 ± 11.8 yr) with transplant age 52.3 ± 34.9 months. Induction therapy was basiliximab and steroids based; maintenance therapy included combination-regimes from cyclosporine, tacrolimus, steroids, mycophenolate mofetil (MM), mycophenolic acid (MPA), rapamycin, everolimus. Anti-rejection therapy was steroid and/or thymoglobulines based. Diagnosis of cutaneous disease was made through examination of skin, mucous membranes, nails and hair evaluation. Skin biopsies, specific cultures and serological tests were done when required. RESULTS: Skin and mucosal diseases were reported in 173 (95.7%) of patients; 88 (50.81%) showed viral lesions; 92 (53.01%) immunosuppression-related lesions; 28 (16.39%) benign tumours; 26 (15.3%) precancers /neoplastic lesions; 24 (14.21%) mycosis; 16 (9.29%) cutaneous xerosis, 15 (8.74%) dermatitis, while absence of cutaneous disease was evident only in 8 (4.37%) cases. An association between drug side effects and anti-rejection treatment ( P ≤ 0.01) and/or calcineurin-inhibitors (CNI) exposure ( P ≤ 0.01) was found. Longer exposure to immunosuppressive drugs (>60 months) was associated with pre-malignancy and malignancy lesions. INTERPRETATION & CONCLUSIONS: Cutaneous diseases are frequent in kidney transplanted patients. Continuous skin monitoring is necessary to make an early diagnosis and to start appropriate treatment.

The role of therapeutic drug monitoring in the treatment of cytomegalovirus disease in kidney transplantation.

Cytomegalovirus (CMV) infection is a common complication following solid organ transplantation that may severely affect the outcome of transplantation. Ganciclovir (GCV) and its prodrug valganciclovir are successfully used to prevent and treat CMV infection; however, in a small percentage of patients, CMV gene mutations may lead to drug resistance. GCV resistance is defined as increasing CMV viremia or progressive clinical disease during prolonged antiviral therapy, due to CMV gene mutation. This has emerged as a new challenge, especially because alternative drugs such as cidofovir and foscarnet have a number of important side effects. Here we report the case of a kidney transplanted patient who experienced life-threatening CMV disease, which initially appeared to be GCV-resistant, but was instead found to be associated with inadequate antiviral drug levels. The patient was then successfully treated by monitoring plasma GCV levels. We suggest using plasma GCV monitoring in the management of all cases of critical CMV disease, in which GCV resistance is suspected.

GM-CSF contributes to prompt healing of ecthyma gangrenosum lesions in kidney transplant recipient.

BACKGROUND: Ecthyma gangrenosum (EG) is an unusual, potentially fatal cutaneous disease, commonly associated with Pseudomonas aeruginosa septicemia. CASE REPORT: We report the case of a 61-year-old man admitted to the Nephrology Department for fever, leukopenia and inguinal and scrotal painful lesions. Physical examination revealed inguinal and scrotal macules, nodules, blisters and ulcers with central necrosis. P. aeruginosa was isolated from an ulcer. EG was diagnosed. Because of the severe leukopenia, granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered until the white blood cell count significantly increased. Based on antibiogram, intravenous ceftazidime and teicoplanin were given for 11 days. Cutaneous manifestations were completely healed in about 2 months. CONCLUSION: We suggest that the combination of GM-CSF with appropriate antibiotics can resolve EG and avoid or minimize the risk of septicemia in immunosuppressed patients.

Mesenchymal stromal cells improve renal injury in anti-Thy 1 nephritis by modulating inflammatory cytokines and scatter factors.

MSC (mesenchymal stromal cells) can differentiate into renal adult cells, and have anti-inflammatory and immune-modulating activity. In the present study, we investigated whether MSC have protective/reparative effects in anti-Thy1 disease, an Ab (antibody)-induced mesangiolysis resulting in mesangioproliferative nephritis. We studied five groups of rats: (i) rats injected with anti-Thy1.1 Ab on day 0 (group A); (ii) rats injected with anti-Thy1.1 Ab on day 0+MSC on day 3 (group B); (iii) rats injected with anti-Thy1.1 Ab on day 0+mesangial cells on day 3 (group C); (iv) rats injected with saline on day 0+MSC on day 3 (group D); and (v) rats injected with saline on day 0 (group E). Rats were killed on days 1, 3, 7 and 14. MSC prevented the increase in serum creatinine, proteinuria, glomerular monocyte influx and glomerular histopathological injury. Furthermore, MSC suppressed the release of IL-6 (interleukin-6) and TGF-ß (transforming growth factor-ß), modulated glomerular PDGF-ß (platelet-derived growth factor-ß), and reset the scatter factors and their receptors, potentiating HGF (hepatocyte growth factor)/Met and inactivating MSP (macrophage-stimulating protein)/Ron (receptor origin nantaise). Few MSC were found in the kidney. These results indicate that MSC improve anti-Thy 1 disease not by replacing injured cells, but by preventing cytokine-driven inflammation and modulating PDGF-ß and the scatter factors, i.e. systems that regulate movement and proliferation of monocytes and mesangial cells.

[Non-heart-beating-donor transplant: the first experience in Italy]. / Trapianto di rene da donatore a cuore non battente: la prima esperienza in Italia.

A promising way to increase the number of kidneys for transplantation is to expand the donor pool by including non-heart-beating donors (NHBDs). The centers involved in NHBD transplantation programs have reported a 16-40% increase in kidney transplants. A key issue with NHBD is the significantly higher rate of delayed graft function (DGF) and primary non-function (PNF) compared with that associated with heart-beating donor (HBD) transplants. However, although transplants from NHBD are associated with a greater incidence of early adverse events, long-term graft survival appears to be similar to that observed after transplants from HBDs. In addition, the use of extracorporeal membrane oxygenation and mechanical perfusion, the careful selection of recipients and donors, and an adequate therapeutic strategy may at least partially reduce the risk of PNF and DGF and improve transplant outcome.