Medical management and positive outcome after prolonged recumbency in a case of equine herpesvirus myeloencephalopathy.

A 17-year-old mare presenting with acute fever, weakness and bladder dysfunction was diagnosed with equine herpesvirus myeloencephalopathy (EHM). The mare become transiently recumbent, underwent parenteral fluid therapy, plasma infusion, steroidal/nonsteroidal anti-inflammatory drugs (SAID/NSAIDs) and bladder catheterization. After 10 days the mare was hospitalized. Neurological evaluation revealed ataxia and proprioceptive deficits mainly in the hind limbs. The mare was able to stand but unable to rise from recumbency or walk. Secondary complications included Escherichia coli cystitis, corneal ulcers and pressure sores. A full-body support sling was used for 21 days. Medical treatment included systemic antimicrobials, NSAIDs, gradual discontinuation of SAIDs, parenteral fluid therapy and bladder lavage. The mare tested positive for Varicellovirus equidalpha 1 (EHV-1) DNA in nasal swab and blood samples on day 13 and in urine samples on days 13 and 25 after the onset of fever. Neurological signs improved over a period of 34 days and the mare was discharged with mild hind limb weakness/ataxia. Secondary complications resolved within 2 weeks. At the eight-month follow-up, marked improvement in locomotory function had been achieved.

Predicting early recurrence after resection of initially unresectable colorectal liver metastases: the role of baseline and pre-surgery clinical, radiological and molecular factors in a real-life multicentre experience.

BACKGROUND: Advances in surgical techniques and systemic treatments have increased the likelihood of achieving radical surgery and long-term survival in metastatic colorectal cancer (mCRC) patients with initially unresectable colorectal liver metastases (CRLMs). Nonetheless, roughly half of the patients resected after an upfront systemic therapy experience disease relapse within 6 months from surgery, thus leading to the question whether surgery is actually beneficial for these patients. MATERIALS AND METHODS: A real-world dataset of mCRC patients with initially unresectable liver-limited disease treated with conversion chemotherapy followed by radical resection of CRLMs at three high-volume Italian institutions was retrospectively assessed with the aim of investigating the association of baseline and pre-surgical clinical, radiological and molecular factors with the risk of relapse within 6 or 12 months from surgery. RESULTS: Overall, 268 patients were included in the analysis and 207 (77%) experienced recurrence. Ninety-six (46%) of them had disease relapse within 6 months after CRLM resection and in spite of several variables associated with early recurrence at univariate analyses, only primary tumour resection at diagnosis [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.32-0.89, P = 0.02] remained significant in the multivariable model. Among patients with resected primary tumours, pN+ stage was associated with higher risk of disease relapse within 6 months (OR 3.02, 95% CI 1.23-7.41, P = 0.02). One hundred and forty-nine patients (72%) had disease relapse within 12 months after CRLMs resection but none of the analysed variables was independently associated with outcome. CONCLUSIONS: Clinical, radiological and molecular factors assessed before and after conversion chemotherapy do not reliably predict early recurrence after secondary resection of initially unresectable CRLMs. While novel markers are needed to optimize the cost/efficacy balance of surgical procedures, CRLM resection should be offered as soon as metastases become resectable during first-line chemotherapy to all patients eligible for surgery.

Improvement of diaphragmatic performance through orthotopic application of decellularized extracellular matrix patch.

Muscle tissue engineering can provide support to large congenital skeletal muscle defects using scaffolds able to allow cell migration, proliferation and differentiation. Acellular extracellular matrix (ECM) scaffold can generate a positive inflammatory response through the activation of anti-inflammatory T-cell populations and M2 polarized macrophages that together lead to a local pro-regenerative environment. This immunoregulatory effect is maintained when acellular matrices are transplanted in a xenogeneic setting, but it remains unclear whether it can be therapeutic in a model of muscle diseases. We demonstrated here for the first time that orthotopic transplantation of a decellularized diaphragmatic muscle from wild animals promoted tissue functional recovery in an established atrophic mouse model. In particular, ECM supported a local immunoresponse activating a pro-regenerative environment and stimulating host muscle progenitor cell activation and migration. These results indicate that acellular scaffolds may represent a suitable regenerative medicine option for improving performance of diseased muscles.

Multidisciplinary lifestyle intervention in the obese: its impact on patients' perception of the disease, food and physical exercise.

BACKGROUND AND AIMS: To be successful, lifestyle intervention in obesity must take into account patients' views. The aim of the present study, conducted using a narrative-autobiographical approach, was to report on the perception of disease, food and physical exercise in a group of 80 obese patients during a structured multidisciplinary lifestyle intervention. METHODS AND RESULTS: Patients underwent lifestyle intervention, of three months' duration, structured in the following steps: 1) an initial medical examination; 2) an interview by a psychologist; 3) an assessment by a dietician, 4) a physical examination by a specialist in sports medicine; 5) an individualized program consisting of 24 sessions (two per week) of structured indoor exercise 6) eight sessions of group therapeutic education; 7) Nordic walking activity combined with walking excursions during weekends. All the narrative autobiographic texts obtained during the lifestyle intervention were submitted for content analysis; data were analysed according to the ''grounded theory'' method. According to patients' descriptions at the end of the intervention, lifestyle intervention resulted in enhanced self-efficacy and a reduction in their dependency on food and people; their fear of change was also diminished because, by undergoing intervention, they had experienced change. CONCLUSION: The findings made in the present qualitative analysis suggest that whenever multidisciplinary lifestyle intervention is planned for patients with obesity, it is of the utmost importance to tailor the approach while taking the following key aspects into account: motivation, barriers and/or facilitators in lifestyle change, patients' perceptions of obesity and relationship with food, diet and exercise.

Evaluation of anti-Moraxella bovis pili immunoglobulin-A in tears following intranasal vaccination of cattle.

Infectious bovine keratoconjunctivitis (IBK) is a highly contagious ocular disease of cattle caused by Moraxella bovis (Mb). Parenterally administered immunogens used to prevent the disease do not offer complete protection possibly because they stimulate a poor ocular mucosal secretory response, in which locally secreted immunoglobulin-A (sIgA) is one of the main components. The principal aim of this study was to evaluate by an indirect enzyme linked immunosorbent assay (ELISA), the local ocular mucosal sIgA response against Mb purified pili, produced after intranasal inoculation of experimental vaccines. Pili were adjuvanted by several different adjuvants (QuilA, Marcol Arlacel, Marcol Span, microencapsulated pili with PLGA polymers). Results were compared to sIgA response produced by adjuvant placebo inoculations and by IBK natural infection. Significantly higher anti-pili IgA response (p<0.05) was detected in calves vaccinated intranasally with pili QuilA and pili Marcol Span compared to control calves, although this specific immune response did not seem to be related to protection against Mb infection or typical IBK lesion development.

Dynamics of Moraxella bovis infection and humoral immune response to bovine herpes virus type 1 during a natural outbreak of infectious bovine keratoconjunctivitis in beef calves.

Infectious bovine keratoconjunctivitis (IBK) is an acute disease caused by Moraxella bovis (Mb). Several factors may predispose animals to an IBK outbreak; one commonly observed is infection with bovine herpes virus type 1 (BHV-1). The aim of this study was to investigate the dynamics of BHV-1 virus infection and its relation with clinical cases of IBK in weaned calves from a beef herd with a high prevalence of lesions caused by Mb. Sampling was carried out in six stages and included conjunctival swabs for isolating Mb as well as blood samples for identifying antibodies specific for BHV-1. A score for IBK lesions after observing each eye was determined. The findings of this study showed a high prevalence of BHV-1 virus infection (100% of animals were infected at the end of the trial); 67% of animals were culture-positive for Mb, but low rates of clinical IBK (19% of calves affected) were detected at the end of the trial. These results suggest that infection with BHV-1 did not predispose these animals to IBK, and that Mb infection produced clinical and subclinical disease in the absence of BHV-1 co-infection.

The combination of immunosuppressive drugs with 8-methoxypsoralen and ultraviolet a light modulates the myeloid-derived dendritic cell function.

The functional properties of myeloid dendritic cells (DCs) differ, depending on microenvironmental factors as well as on their stage of maturation. The main approaches for the selective enhancement of the tolerogenic properties of DCs include the induction of a pharmacological arrest of the DCs maturation and the genetical engineering of DCs expressing immunosuppressive molecules. Several immunosuppressive/anti-inflammatory agents have been discovered that potentially inhibit DC maturation and immunogenicity. Photopheresis (ECP) is an immunomodulatory therapy in which leucocytes are exposed to 8-methoxypsoralen (8-MOP) and ultraviolet (UV) A radiation (PUVA). The combination of ECP with immunosuppressive agents has demonstrated efficacy in the management of transplanted patients by reducing either the incidence of organ rejection or the pharmacological toxicity. In particular, we have observed in hepatitis C virus (HCV)-positive patients that the same combination has reduced the immunosuppressive burden and improved sustainability and efficacy of pre-emptive antiviral therapy after liver transplantation. Therefore, in our work we investigated the in vitro effects of PUVA, combined with immunosuppressive drugs (IDs), on both in vitro human DC generation and maturation, in order to contribute to understanding the immunological mechanisms underlying this pharmacological combination. Monocyte PUVA-treatment was performed by using an in vitro experimental protocol that we previously described. PUVA-treated or -untreated highly purified CD14+ cells were incubated with the association of the immunosuppressive drugs, used in the management of liver transplantation, at two different concentrations, in the presence of IL-4 and GM-CSF. The treatment with IDs at the highest concentration (corresponding to that used in clinical practice), alone or in association with PUVA, induced an immunosuppressive effect, by impairing both DC generation and maturation. Neither immunosuppressive drugs at the lowest concentration nor their combination with PUVA affected myeloid DC generation, but modified DC functions, strengthening the induction of a tolerogenic pattern. As this ID concentration was arbitrarily chosen, further experiments could highlight whether lower concentrations than those used in clinical practice would elicit the same effect on DCs and potentially improve their functional properties. This work describes an original experimental approach exploring the in vitro mechanism of action of the combined procedure of PUVA with immunosuppressive drugs, used in liver transplantation, on DCs generation and function. Our results contribute to the knowledge of the mechanisms of action of this combined procedure on DCs, suggesting useful therapeutic implications for the in vivo therapy.

Linezolid treatment for gram-positive infections: a retrospective comparison with teicoplanin.

In randomized studies linezolid, indicated for Gram-positive infections, was as effective as teicoplanin in critical ill patients or was superior to teicoplanin in skin infection, pneumonia and bacteremia. We performed a 2-year comparative, retrospective study of patients treated with linezolid or teicoplanin in a single hospital for the same indications. We collected information about the type of infection, the responsible pathogen, therapy administered before study drugs, antibiotic associated with the study drugs, length of hospital stay (LOS), adverse events and outcome of the infections. The aim of the study was to evaluate the efficacy of linezolid in this retrospective patients series. Overall we identified 169 patients treated with linezolid and 91 with teicoplanin. Response to therapy, (resolution or improvement of infection) was better in patients treated with linezolid compared to teicoplanin (83.9% versus 69.2%, p=0.002). Response to therapy by type of pathogen showed the superior efficacy of linezolid against Staphylococcus aureus (including MRSA) and enterococci; although not statistically significant because of the small number of patients enrolled, they were close to significance (p<0.056 for S. aureus, p<0.055 for MRSA, p<0.061 for enterococci). Overall LOS in linezolid-treated patients was 4.6 days (p<0.041) less. Empirical use of linezolid reduced lOS by 6 days (p<0.038), especially in VAP and bacteremia patients (p<0.05). Mortality due to infection was 9.8% in both groups, and adverse events were most frequently documented in linezolid-treated patients. Linezolid was clinically superior to teicoplanin in the treatment of Gram-positive infections.

Evaluation of an uncalibrated arterial pulse contour cardiac output monitoring system in cirrhotic patients undergoing liver surgery.

BACKGROUND: The pulmonary artery catheter is invasive and may cause serious complications. A safe method of cardiac output (CO) measurement is needed. We have assessed the accuracy and reliability of a recently marketed self-calibrating arterial pulse contour CO monitoring system (FloTrac/Vigileo) in end-stage liver failure patients undergoing liver transplant. The pattern of alterations known as cirrhotic cardiomyopathy, and the transplant procedure itself, provided an evaluation under varying clinical conditions. METHODS: The cardiac index was measured simultaneously by thermodilution (CI(TD): mean of four readings) using a pulmonary artery catheter and pulse contour analysis (CI(V): mean value computed by the FloTrac/Vigileo over the same time period). Readings were made at 10 time-points during liver transplant surgery (T1-T5) and on the intensive care unit (T6-T10). CI(V) was computed using the latest Vigileo software version 01.10. RESULTS: A total of 290 paired readings from 29 patients were collected. Mean (SD) CI(TD) was 5.2 (1.3) and CI(V) was 3.9 (0.9) litre min(-1) m(-2), with a corrected for repeated measures bias between readings of 1.3 (0.2) litre min(-1) m(-2) and 95% limits of agreement of -1.5 (0.2) to 4.1 (0.3) litre min(-1) m(-2). The percentage error (2SD(Bias)/meanCI(TD)) was 54%, which exceeded a 30% limit of acceptance. Low peripheral resistance and increasing bias were related (r=0.69; P<0.001). The Vigileo system failed to reliably trend CI data, with a concordance compared with thermodilution below an acceptable level (at best 68% of sequential readings). CONCLUSIONS: In cirrhotic patients with hyperdynamic circulation, the Vigileo system showed a degree of error and unreliability higher than that considered acceptable for clinical purposes.

Transcranial doppler sonography is useful for the decision-making at the point of care in patients with acute hepatic failure: a single centre's experience.

Acute hepatic failure (ALF) is an uncommon disease characterized by a rapid deterioration of the hepatic function with severe derangements of the mental status in previously healthy subjects due to massive hepatocytes necrosis. Neurological impairment, due to intracranial hypertension and cerebral ischemia, is a key factor because it is a main criterion to decide when to proceed to liver transplantation, which is only treatment for these patients. Therefore, neurological monitoring holds an essential role in the clinical management of ALF patients but it needs to be performed at the point-of-care in the majority of the cases as such critically ill patients cannot be moved away from the ICU because they frequently need continuous hemodynamic, ventilatory and renal support. We herein report and discuss our experience relating to the use of transcranial sonography as a neuro-monitoring tool in ALF patients. In our series this technique allowed a repeatable and reliable non-invasive assessment of cerebral blood flow changes at the bedside thus avoiding the complications associated with the use of an intracranial probe to measure intra-cranial pressure and making it possible to correctly evaluate the timing and feasibility of liver transplantation.

False positive tardus-parvus waveforms after liver transplantation: a case of wide discrepancy between donor and recipient hepatic arteries mimicking anastomotic stenosis.

BACKGROUND: Parvus-tardus waveforms of the hepatic artery after liver transplantation usually indicate an arterial complication and severe impairment of hepatic arterial perfusion with a sensitivity of 91% and a specificity of 99.1%. Thus, it has been emphasized that detection of such waveforms should prompt emergency angiography. MATERIALS AND METHODS: Arterial reconstruction during a liver transplantation was successfully accomplished by an end-to-end anastomosis, performing a "flute-spout" widening of the anastomosis with a 7/0 prolene running suture between a small recipient proper hepatic artery and the donor common hepatic artery. RESULTS: On day 7 posttransplantation color Doppler ultrasonography revealed a parvus-tardus waveform pattern in the hepatic arterial flow. Computed tomographic (CT) angiography showed only a caliber discrepancy between the donor and recipient stumps, excluding an arterial stenosis or thrombosis. Since normal liver function persisted, the patient underwent routine follow-up. After 15 months the patient was alive and well; hepatic artery spectral waveforms were unchanged and liver functions were consistent with a mild hepatitis C virus (HCV) recurrence. CONCLUSIONS: This is a report of false positive tardus-parvus waveforms, due to a discrepancy between the donor and recipient arteries despite a wide anastomosis. Knowledge of technical reconstruction details may be helpful for correct interpretation of color Doppler findings. CT angiography should be considered before more invasive examinations.

Potential applications of extracorporeal photopheresis in liver transplantation.

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy performed through a temporary peripheral venous access with documented efficacy in heart and renal transplantation. We originally reported that ECP represented a valuable alternative to treat graft rejection in selected liver transplant (OLT) recipients. We have investigated potential applications of ECP for prophylaxis of allograft rejection. The first field explored was the use of ECP for delayed introduction of calcineurin inhibitors (CNI) among high-risk OLT recipients seeking to avoid CNI toxicity. In 42 consecutive patients that we assigned to prophylaxis with ECP, we were able to delay CNI introduction after postoperative day 8 in one-third of them. The second field was the use of ECP for prophylaxis of acute cellular rejection among ABO-incompatible OLT recipients. In our experience, none of 11 patients treated with ECP developed a cell-mediated rejection. The third field was ECP application in hepatitis C virus-positive patients seeking to reduce the immunosuppressive burden and improve sustainability and efficacy of preemptive antiviral treatment with interferon and ribavirin. Among 78 consecutive patients, we were able to start preemptive antiviral treatment in 69.2% of them at a median time from OLT of 14 days (range = 7 to 130 days). Thirty-six (66.7%) patients completed the treatment course with an end of treatment virological response of 50.0% and a sustained virological response of 38.9%. These preliminary results await validation in larger prospective studies with longer follow-up periods.

Colistin in combination with rifampin and imipenem for treating a blaVIM-1 metallo-beta-lactamase-producing Enterobacter cloacae disseminated infection in a liver transplant patient.

A case of bla(VIM-1) producing E. cloacae disseminated infection in a patient submitted to orthotopic liver transplantation is described. Synergism between colistin, rifampin and imipenem was studied in vitro and this combination of three drugs was used to treat E. cloacae infection. The synergistic activity of this combination was demonstrated showing an increased activity of the serum bactericidal activity in comparison with the bactericidal activity of the serum taken during the previous therapy.

Liver transplantation due to Herpes Simplex virus-related sepsis causing massive hepatic necrosis after thoracoscopic thymectomy.

Following thorascopic thymectomy performed because of myasthenia gravis, a 25-year-old man was affected by fulminant hepatic failure (FHF) of unknown etiology. He was then transferred to our department, where his clinical situation worsened with the onset of renal failure, shock, coagulopathy and coma. Given the young age of the patient, the immediate availability of a donor, and the absence of a definite diagnosis of sepsis at the time, it was decided to proceed with liver transplantation. The results of a polymerase chain reaction (PCR) test (a technique that was unavailable at the referring hospital), which arrived only a few hours later, indicated the presence of herpes simplex virus (HSV) DNA in several of the patient's samples; this led to the formulation of a diagnosis of FHF due to HSV. It is worth noting that HSV-IgM and HSV-IgG assays had always been negative in this patient. Despite acyclovir therapy with initially encouraging clinical results, the patient died several days later because the viral infection had spread to the graft, lungs, heart, spleen, stomach and kidneys. Since evaluating antibody response is not always useful in diagnosing HSV infection, and particularly if PCR methodology is unavailable, it is worth initiating early empiric antiviral therapy when the etiology of FHF is indeterminate This is because the timeliness of treatment while awaiting virological confirmation may be critical to survival. If a liver transplantation becomes mandatory, careful consideration should be given to the extent of the viral infection and its response to therapy because of the possibility of viral spread to the graft.

Nurses' knowledge and application of evidence-based guidelines for preventing ventilator-associated pneumonia.

AIM: The aim of the study was to evaluate the nurses' knowledge and to highlight the causes that hinder guidelines implementation. EXPERIMENTAL DESIGN: descriptive study. SETTING AND PARTICIPANTS: 106 nurses working in the ICUs of a major Italian hospital of national importance. INTERVENTION: administration of a questionnaire listing 21 non-pharmacological strategies considered the most useful in the literature. RESULTS: Eighty-four nurses responded to the questionnaire. Only 19 (22.6%) declared that their knowledge of ventilation associated pneumonia (VAP) and the strategies used to prevent it were satisfactory, whereas 46 (54.8%) declared that they were poorly informed; 68 nurses (80.9%) said that they applied one or more strategies, and 15 (17.9%) that they applied none. The reasons given for not applying the strategies were: method not foreseen in Department protocols (31.5%), lack of the necessary resources (14.3%), disagreement with the method (3.2%), high costs (2.6%), the possibility of causing discomfort (1%) or side effects (0.6%). CONCLUSIONS: In our experience, VAP preventive strategies are widely applied by nurses, but not in a responsible and informed manner. It is important to ensure that nurses receive continuous training and are involved in drawing up and updating Departmental protocols and guidelines for care and behaviour.

Cost analysis of tumor downsizing for hepatocellular carcinoma liver transplant candidates.

We report the results of a prospective, intent-to-treat (ITT) trial on the costs of selective tumor downsizing (DS) before liver transplantation (LT) for patients affected with hepatocellular carcinoma (HCC). The trial started in January 1997 including adult patients with nodular-type HCC within and beyond the Milan criteria. Patients were downsized with transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI) and/or radiofrequency ablation (RFA) according to clinical predictors. TACE and RFA were performed as inpatient procedures, while PEI was performed on an outpatient basis. Costs of DS were obtained according to the Tuscany Health Reimbursement Fee Catalog adjusted to yearly inflation rates from 1997 through 2005. Data analysis was performed at 1 year after the last enrollment of 198 patients, including 161 (81.3%) who were transplanted: 34 (17.2%) dropped out and 3 (1.5%) were still on the waiting list. One hundred and fifty-two patients (76.7%) underwent DS for a total of 201 procedures: 159 TACE, 39 PEI, and 3 RFA. Overall costs in Euros (euro) of waitlisting were 861,801.24 euro: 548,460 euro (63.7%) for pretransplantation evaluation; 197,994.84 euro (22.9%) for control visits and hospitalizations; and 115.346.4 euro (13.4%) for DS. Mean costs of DS were 758.58 euro +/- 270 euro per downstaged patient (747.53 euro +/- 257.1 euro Milan; 774.01 euro +/- 287.71 euro non-Milan); 582.85 euro +/- 398.87 euro per waitlisted patient (520.28 euro +/- 406.23 euro Milan; 520.28 +/- 364.48 euro non-Milan); and 716.4 euro per transplanted patient (580.67 euro Milan; 1026.76 euro non-Milan; +76.8%). A selective policy of tumor DS increased the costs of LT waitlisting by 13.4%, but due to higher dropout rates among non-Milan patients, the cost utility of DS was 76.8% higher in the Milan group.