Infections occurring in adult patients receiving mechanical circulatory support: the two-year experience of an Italian National Referral Tertiary Care Center.

OBJECTIVE: Infection during mechanical circulatory support is a frequent adverse complication. We analyzed infections occurring in this population in a national tertiary care center, and assessed the differences existing between the setting of extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VADs). DESIGN, SETTING, AND PARTICIPANTS: An observational study was made of patients treated with ECMO or VAD in the San Raffaele Scientific Institute (Italy) between 2009 and 2011. INTERVENTIONS: None. RESULTS: Thirty-nine percent of the 46 patients with ECMO and 69% of the 15 patients with VAD developed infection. We observed a mortality rate of 36.1% during mechanical circulatory support and of 55.7% during the global hospitalization period. Although Gram-negative infections were predominant overall, patients with ECMO were more prone to develop Candida infection (29%), and patients with VAD tended to suffer Staphylococcus infection (18%). Patients with infection had longer ECMO support (p=0.03), VAD support (p=0.01), stay in the intensive care unit (p=0.002), and hospital admission (p=0.03) than patients without infection. Infection (regression coefficient=3.99, 95% CI 0.93-7.05, p=0.02), body mass index (regression coefficient=0.46, 95% CI 0.09-0.83, p=0.02), fungal infection (regression coefficient=4.96, 95% CI 1.42-8.44, p=0.009) and obesity (regression coefficient=10.47, 95% CI 1.77-19.17, p=0.02) were predictors of the duration of ECMO support. Stepwise logistic regression analysis showed the SOFA score at the time of implant (OR=12.33, 95% CI 1.15-132.36, p=0.04) and VAD (OR=1.27, 95% CI 1.04-1.56, p=0.02) to be associated with infection. CONCLUSIONS: Infection is a major challenge during ECMO and VAD support. Each mechanical circulatory support configuration is associated with specific pathogens; fungal infections play a major role.

Clinical use of placental hormones in pregnancy management.

Across human pregnancy, placenta represents a transit of oxygen and nutrients from the mother to the fetus and actively produces a large number of hormones that serve to regulate and balance maternal and fetal physiology. An abnormal secretion of placental hormones may be part of the pathogenesis of the main obstetric syndrome, from early to late pregnancy, in particular chromosomopathies, miscarriage, gestational trophoblastic diseases, preeclampsia, gestational diabetes, and pre-term delivery. The possibility to measure placental hormones represents an important tool not only for the diagnosis and management of gestational disorders, but it is also fundamental in the early identification of women at risk for these pregnancy complications. In the last decades, the use of ultrasound examination has provided additional biophysical markers, improving the early diagnosis of gestational diseases. In conclusion, while few placental hormones have sufficient sensitivity for clinical application, there are promising new biochemical and biophysical markers that, if used in combination, may provide a valid screening tool.

BDNF Val66Met polymorphism and brain volumes in multiple sclerosis.

Brain derived neurotrophic factor (BDNF) regulates several CNS physiological and pathological processes. To investigate in multiple sclerosis (MS) patients, the relationship between the Val66Met polymorphism of BDNF and clinical markers of disease activity and MRI markers of focal and diffuse brain pathologies. 45 MS patients and 34 healthy controls (HCs) were genotyped and subjected to clinical-MRI examination. Global white matter fraction (gWM-f), gray matter-f (GM-f), cerebrospinal fluid-f (CSF-f), and abnormal WM-f were measured. We studied 26 Val/Val and 19 Val/Met patients and 23 Val/Val and 11 Val/Met HCs. We found that Val/Val patients had lower GM-f and higher CSF-f than Val/Val HCs; such differences were not statistically significant comparing Val/Met patients to HCs. The regression analysis showed that both Val/Met genotype and relapse number were associated with lower CSF-f. Our data suggest that Met allele might be a protective factor against MS as it is associated to a lower brain atrophy.

Salvage lymphadenectomy in recurrent ovarian cancer patients: Analysis of clinical outcome and BRCA1/2 gene mutational status.

OBJECTIVE: This study is aimed to analyze the clinical outcome of recurrent ovarian cancer patients bearing isolated lymph-node recurrence (ILNR) who underwent salvage lymphadenectomy (SL). The prognostic role of clinicopathological variables and the mutational status of BRCA1/2 have also been investigated. METHODS: This retrospective, single-institutional study included women with platinum-sensitive lymph node recurrence underwent to SL between June 2008 and June 2018. Univariate and multivariate analysis was performed to evaluate the impact of clinical parameters, and BRCA1/2 mutational status on post salvage lymphadenectomy progression-free survival (PSL-PFS). RESULTS: As of June 2019, the median follow-up after SL was 30 months, and the relapse has been documented in 48 (56.5%) patients. In the whole series, the median PSL-PFS was 21 months, and the 3-year PSL-PFS was 36.7%. The median PSL-PFS, according to patients with ILNR (N = 71) versus patients with lymph-nodes and other sites of disease (N = 14), was 27 months versus 12 months, respectively. Univariate analysis of variables conditioning PSL-PFS showed that platinum-free interval (PFI) ≥12 months, normal Ca125 serum levels, and number of metastatic lymph-nodes ≤3 played a statistically significant favorable role. In multivariate analysis, PFI duration ≥12 months and the number of metastatic lymph nodes ≤3 were shown to keep their favorable, independent prognostic value on PSL-PFS. CONCLUSIONS: In the context of SL, the patients with long PFI and low metastatic lymph node numbers at ILNR diagnosis have the best outcome. The BRCA mutational status seems not associated with clinical variables and PSL-PFS, differently from other sites of disease in ROC patients.

Lessons from two human chromatin diseases, ICF syndrome and Rett syndrome.

Spatial organisation of DNA into chromatin profoundly affects gene expression and function. The recent association of genes controlling chromatin structure to human pathologies resulted in a better comprehension of the interplay between regulation and function. Among many chromatin disorders we will discuss Rett and immunodeficiency, centromeric instability and facial anomalies (ICF) syndromes. Both diseases are caused by defects related to DNA methylation machinery, with Rett syndrome affecting the transduction of the repressive signal from the methyl CpG binding protein prototype, MeCP2, and ICF syndrome affecting the genetic control of DNA methylation, by the DNA methyltransferase DNMT3B. Rather than listing survey data, our aim is to highlight how a deeper comprehension of gene regulatory web may arise from studies of such pathologies. We also maintain that fundamental studies may offer chances for a therapeutic approach focused on these syndromes, which, in turn, may become paradigmatic for this increasing class of diseases.

Influence of concomitant mitral valve dysfunction on survival after aortic valve replacement.

Aortic valve pathology is the most common acquired valvular heart disease in the adults of western countries, and mitral regurgitation (MR) is often clinically present in patients with degenerative aortic stenosis or insufficiency. Many studies report an incidence of MR between 65-75% in patients evaluated for aortic valve replacement. Severe aortic valve disease may be associated with functional mitral regurgitation (FMR) defined as the failure of mitral valve to prevent systolic backward flow in the absence of any significant structural or intrinsic valvular disease. Increased afterload and left ventricular remodeling have been implicated to explain FMR in patients with aortic valve disease. Moreover, organic mitral valve disease can be associated with aortic stenosis and can be rheumatic or degenerative. We have examined the data of the literature to understand the evolution of MR, the impact of mitral regurgitation on the outcome of patients undergoing aortic valve replacement, and to determine clinical predictors of prognosis in patients with concomitant MR at the time of aortic valve replacement.

C-reactive protein is increased in patients with degenerative aortic valvular stenosis.

OBJECTIVES: The goal of this study was to assess the presence of systemic inflammation in degenerative aortic valvular stenosis. BACKGROUND: Local inflammatory changes, resembling those observed in atherosclerosis, have been recently reported in degenerative aortic valvular stenosis. It is presently unknown whether systemic signs of inflammation, similar to those observed in atherosclerosis, may be present in this disorder. METHODS: C-reactive protein (CRP) was measured by enzyme immunoassay in 141 subjects: 62 with trileaflet degenerative valvular aortic stenosis and 79 volunteers with similar demographic and clinical characteristics. IgG antibodies against Helicobacter pylori (enzyme-linked immunosorbant assay) and Chlamydia pneumoniae (microimmunofluorescence assay) were also measured. RESULTS: C-reactive protein levels (mg/dl, mean +/- SD) were 0.848 +/- 1.42 in patients and 0.394 +/- 0.50 in controls (p = 0.0001, Mann-Whitney U test). Seroprevalence of H. pylori was 68.7% in patients and 79.7% in controls (p = NS), whereas seroprevalence of C. pneumoniae infection was higher in patients than it was in controls (59.7% vs. 33%, p = 0.003; chi-square test). After adjustment for various covariates in multiple logistic regression, the odds ratio for degenerative aortic stenosis was 3.41 for C. pneumoniae infection (95% confidence intervals [CI]: 1.60 to 7.30) and 2.76 for CRP (95% CI: 1.08 to 7.05). There was no significant difference in patients or controls in CRP levels according to the serostatus for C. pneumoniae. CONCLUSIONS: Systemic signs of inflammation, similar to those found in atherosclerosis, are present in patients with degenerative aortic valve stenosis. They do not seem to be linked to C. pneumoniae or H. pylori infection.

Placental phagocytic cells infected with herpes simplex type 2 and echovirus type 19: virological and ultrastructural aspects.

Placental macrophage cells were kept in a short-term culture and infected with herpes simplex type 2 virus and echovirus type 19. These were observed under optical and electron microscopy. Immunofluorescence, virus titration and autoradiographic technique were used to determine if the virus was replicating in the system. The results showed that the placental phagocytic cells do not allow virus growth and that the virus particles are destroyed right after virus uptake, within 4 h post-infection. The increase of lipid bodies and other cellular alterations suggested the intensive action of these cells against viruses.

The "clover technique" as a novel approach for correction of post-traumatic tricuspid regurgitation.

OBJECTIVE: To describe a novel technique, named "clover," to correct complex post-traumatic tricuspid valve lesions. METHODS: Five patients with severe post-traumatic tricuspid insufficiency underwent valve reconstruction with the clover technique, a new surgical approach that consists of stitching together the middle point of the free edges of the tricuspid leaflets, producing a clover-shaped valve. The mechanism of tricuspid regurgitation was complex in all patients, and right ventricular function was always moderately to severely depressed. An echocardiographic study was performed after cardiopulmonary bypass, at discharge, and at follow-up. RESULTS: Cardiopulmonary bypass time was 32 +/- 6.3 minutes and crossclamp time was 23 +/- 7.4. There was no hospital mortality or morbidity. Intraoperative transesophageal and predischarge transthoracic echocardiography showed perfect results in all patients. No late deaths occurred. At the latest follow-up, extending to 14.2 months (mean 11.3; median 12.4), all patients were asymptomatic (New York Heart Association class I) with trivial (2 patients) or no residual regurgitation (3 patients) on 2-dimensional echocardiogram. No transvalvular gradient was revealed in any patient. A significant reduction of the right ventricular end-diastolic dimensions was noted as well (from 54 +/- 7.1 mm to 40 +/- 7.5 mm, P <.001). CONCLUSIONS: In this preliminary experience, the clover technique increased the feasibility of tricuspid valve repair in case of severe traumatic tricuspid valve insufficiency, leading to very satisfactory mid-term results even in the presence of complex lesions or dilatation and deterioration of the right ventricle.

The double-orifice technique in mitral valve repair: a simple solution for complex problems.

OBJECTIVE: The aim of this study is to report our results with the central double-orifice technique used for the treatment of complex mitral valve lesions. METHODS: The central double-orifice repair has been used in 260 patients (mean age, 56 +/- 14.3 years) over a period of 7 years. The mechanism responsible for mitral regurgitation was prolapse of both leaflets in 148 patients, prolapse of the anterior leaflet in 68, prolapse of the posterior leaflet with annular calcification or other unfavorable features in 31, and lack of leaflet coaptation for restricted motion or erosion of the free edge in 13. Degenerative disease was the cause of mitral regurgitation in 80.8% of the patients, rheumatic disease was the cause in 9.6%, endocarditis was the cause in 6.1%, and ischemic disease was the cause in 2.3%. RESULTS: Hospital mortality was 0.7%, and the overall survival at 5 years was 94.4% +/- 2.59%. Thirteen patients required a reoperation (2 early postoperatively and 11 late during the follow-up), for an overall freedom from reoperation of 90.0% +/- 3.37% at 5 years. Freedom from reoperation was lower in patients with rheumatic valve disease and in patients who did not undergo an annuloplasty procedure. CONCLUSIONS: The effectiveness and durability of the central double-orifice technique were assessed in this study. This type of repair can be a useful addition to the surgical armamentarium in mitral valve reconstruction.

Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study.

OBJECTIVES: We sought to investigate the effect of topical application of tranexamic acid into the pericardial cavity in reducing postoperative blood loss in coronary artery surgery. METHODS: A prospective, randomized, double-blind investigation with parallel groups was performed. Forty consecutive patients undergoing primary coronary surgery were randomly assigned to group 1 (tranexamic acid group) or group 2 (placebo group). Tranexamic acid (1 g in 100 mL of saline solution) or placebo was poured into the pericardial cavity and over the mediastinal tissues before sternal closure. The drainage of mediastinal blood was measured hourly. RESULTS: Chest tube drainage in the first 24 hours was 485 +/- 166 mL in the tranexamic acid group and 641 +/- 184 mL in the placebo group (P =.01). Total postoperative blood loss was 573 +/- 164 mL and 739 +/- 228 mL, respectively (P =.01). The use of banked donor blood products was not significantly different between the two groups. Tranexamic acid could not be detected in any of the blood samples blindly collected from 24 patients to verify whether any systemic absorption of the drug occurred. There were no deaths in either group. None of the patients required reoperation for bleeding. CONCLUSIONS: Topical application of tranexamic acid into the pericardial cavity after cardiopulmonary bypass in patients undergoing primary coronary bypass operations significantly reduces postoperative bleeding. Further studies must be carried out to clarify whether a more pronounced effect on both bleeding and blood products requirement might be seen in procedures with a higher risk of bleeding.

Measuring the severity of depression through a self-report inventory. A comparison of logistic, factorial and implicit models.

The present study investigates the psychometric adequacy of a self-report inventory of depression (the QD2) with respect to the severity of depressive symptoms, within the framework of a unidimensional model of depressive states. Responses to the 52 QD2 items, by 481 subjects divided into four groups (depressed, psychiatric, somatic and control), were subjected to a Rasch analysis. Results show that 15 items (QSD(R1] display a satisfactory goodness of fit for both items and persons, as defined by the Rasch model. This set of items, solely related to 'pure' depression, gives a measure of the severity of depression, free from anxiety symptoms. The discussion focuses upon the advantages of the Rasch model as compared to traditional tests. The Rasch 15-item solution should provide a parsimonious tool for future studies on the classification of depressive disorders.

Self-concept and mood: a comparative study between depressed patients with and without borderline personality disorder.

Within the framework of Self-Structure Theory, this study investigated the relationship between depressed mood and Borderline Personality Disorder (BPD) on self and others descriptions, with a special emphasis on the self-structure's valence, that is, its affective, negative and/or positive content. Seventeen DSM-III-R unipolar depressed patients with associated BPD (DSM-III-R axis II) and twelve unipolar depressed patients without BPD were compared to eighteen non-psychiatric controls on four measures of evaluation and of affective discrepancy of descriptions of self and others. Subjects were administered the grid repertory technique. The analysis of the resulting two-way valence matrix, with attributions as columns, and self and others as rows, showed that depressed patients with and without BPD differed from the non-psychiatric controls with regard to negativity of the descriptions. As compared with the two other groups, depressed patients with BPD showed a distinctive pattern characterised by the joint presence of a negative view of self and a larger affective discrepancy for others, with others being conjunctively assigned positive and negative attributes. Despite some limitations, the distinctive pattern evidenced corroborates the conflicted interpersonal relationship and is in keeping with clinical theorising on BPD.

Diphasic electrodermal response, heart rate and moods.

The simultaneous recording of spontaneous EDA (mono and diphasic SPR), HR and mood self-rating (Q-sort of adjectives), on 35 normal subjects, for 5 consecutive weeks has shown that: (1) The emission of diphasic SPR is significantly related to an increase in monophasic EDA (in frequency and in amplitude) and to a lesser degree with HR acceleration; (2) Such a physiological pattern is significantly associated with depressive mood, though independent from anxious mood. These results confirm the importance of morphological aspects of SPR in assessing normal mood states.

Electrodermal asymmetry during human sleep.

The bilateral spontaneous electrodermal activity (EDA) of four paid volunteer male students was recorded during three consecutive complete nights (after a habituation night). The results showed that: (a) there was a high proportion of electrodermal asymmetry (80%) during human sleep; (b) there were no significant differences in asymmetry between sleep stages; (c) electrodermal laterality during sleep seems to be under a random effects model; and (d) laterality appears to be an unreliable parameter. These results are discussed in terms of the activation theory.

Sex differences in latencies of bilateral electrodermal responses.

The present study examined sex differences in the latencies of bilateral electrodermal responses to stimuli presented in monocular vision. The stimuli were spatial-emotional, verbal-emotional, spatial-neutral and verbal-neutral slides, presented for either 35 ms or 1 s. Subjects were 15 males and 15 females. Bilateral latencies were not influenced by type of stimulus or by right/left hemisphere stimulation, which is in keeping with the most recent findings of bilateral electrodermal activity studies. However, females gave a faster right hand than left hand response and appeared to be more lateralized than males. Males showed shorter latencies on the left hand than on the right. These results confirm the importance of gender in experiments using the bilateral recordings of electrodermal activity.

Mediastinitis following graft replacement of the ascending aorta: conservative approach by omental transposition.

A 57-year-old patient underwent prosthetic replacement of a previously implanted ascending aorta graft and developed a periprosthetic purulent collection 1 month later. He was successfully treated by debridement of infected tissues, antiseptic irrigation and transposition of an omental flap. The postoperative course was uneventful. A chest computed tomography scan performed 15 months later showed no signs of perigraft infection. Prompt conservative surgical treatment including omental transposition can be effective in the treatment of mediastinitis following graft replacement of the ascending aorta.

Tacrolimus as a rescue immunosuppressant after heart transplantation.

OBJECTIVE: The purpose of this retrospective study is to review our experience with tacrolimus as a rescue immunosuppressant for heart transplant recipients with refractory rejection or cyclosporine intolerance. METHODS: From June 1995 to November 1998, 15 cardiac transplant recipients were converted from our standard cyclosporine-based immunosuppressive regimen to a tacrolimus-based treatment. Each patient had been treated with cyclosporine, azathioprine and steroids. Six were switched to tacrolimus for persistent rejection, four for recurrent acute rejection and five for severe debilitating side-effects attributed to cyclosporine. All ten patients converted to tacrolimus because of rejection had been treated with high-dose methylprednisolone intravenously and four had also received anti-lymphocyte globulin (ALG; one patient) or anti-thymocyte globulin (ATG; three patients) preparations. RESULTS: The time between transplantation and conversion to tacrolimus ranged from 44 to 1866 (median, 380) days. The range of follow-up after conversion was 84-1379 (median, 806) days. Eleven patients are alive with a follow-up period of 764+/-435 (median, 820) days. Four patients died between 90 and 930 (median, 464) days after conversion. The average number of episodes of acute rejection/recipient decreased from 2.1+/-1.6 on the cyclosporine regimen to 0.2+/-0.4 on the tacrolimus regimen (P<0.001). When the incidence of acute rejection was normalized for follow-up times (episodes/100 patient-days), the results were 1.1+/-1.4 and 0.07+/-0.2, respectively (P<0.01). The persistent/recurrent rejection resolved in all ten patients who were converted to tacrolimus. None of the five cyclosporine intolerant patients converted to tacrolimus experienced rejection after the changeover. CONCLUSIONS: In our experience, conversion from a cyclosporine-based to a tacrolimus-based maintenance immunosuppression has been shown to be an effective and safe approach to the management of patients with persistent or recurrent cardiac allograft rejection or those with cyclosporine intolerance.

MECP2 gene mutation analysis in the British and Italian Rett Syndrome patients: hot spot map of the most recurrent mutations and bioinformatic analysis of a new MECP2 conserved region.

Rett syndrome (RTT) is an X-linked dominant neurological disorder, which appears to be the most common genetic cause of profound combined intellectual and physical disability in Caucasian females. This syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of unknown target genes. We report a detailed mutational analysis of a large cohort of RTT patients from the UK and Italy. This study has permitted us to produce a hot spot map of the mutations identified. Bioinformatic analysis of the mutations, taking advantage of structural and evolutionary data, leads us to postulate the existence of a new functional domain in the MeCP2 protein, conserved among brain-specific regulatory factors.

Echovirus type 19 and herpes simplex type 2 infection in human placenta tissue explants.

1. Light and electron microscopy have been used to characterize echovirus 19 and herpes simplex type 2 infection of human placenta tissue in vitro. Immunofluorescence, autoradiography and virus adsorption were used to determine virus replication in this system. 2. Placental tissue was permissive to echovirus 19. Trophoblast cells were lysed with liberation of mature virions. However, during the 48-h period of observation, few cells were damaged and the trophoblastic structure was maintained. 3. HSV-2 infection in placental tissue was aborted although trophoblastic cells allowed virus adsorption, penetration and uncoating. A characteristic cytopathic effect was observed in infected trophoblastic cells in spite of the abortive infection.