Long-term Outcome after Liver Resection for Hepatocellular Carcinoma Larger than 10 cm.

BACKGROUND: The purpose of the present study was to analyze long-term survival and disease-free survival after liver resection for giant hepatocellular carcinoma (HCC) ≥ 10 cm compared to HCC < 10 cm in diameter. The surgical approach in the treatment of giant HCC may achieve long-term survival and disease-free survival comparable to treatment of smaller lesions. METHODS: This retrospective analysis was a monocentric study conducted in a tertiary university center. It included 101 patients from 114 consecutive liver resections for HCC, separated into two groups: those with tumors less than 10 cm in diameter (small HCC; n = 79) and those with tumors larger than 10 cm (giant HCC; n = 22). The main outcome measures were overall five-year survival, five-year disease-free survival, recurrence rate, perioperative mortality at 30 days, surgical complication rate, and re-intervention rate. RESULTS: The two groups were homogeneously distributed, apart from cirrhosis, which was found more frequently in the group with small HCC (77 vs. 41 %; p = 0.0013). Both median survival (24 vs. 27 months; p = 0.0085) and overall 5-year survival (21 vs. 45; p = 0.04) were significantly poorer in the small HCC group compared to the giant HCC group. There were no differences en terms of recurrence rate, pattern, and timing. CONCLUSIONS: Liver resection for HCC larger than 10 cm is a valuable option in selected patients, one that provides overall survival and disease-free survival comparable to smaller lesions. Functional reserves of the liver, more than the size of the lesion, may be important in patient selection for surgical resection.

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

Topographic ERP analyses: a step-by-step tutorial review.

In this tutorial review, we detail both the rationale for as well as the implementation of a set of analyses of surface-recorded event-related potentials (ERPs) that uses the reference-free spatial (i.e. topographic) information available from high-density electrode montages to render statistical information concerning modulations in response strength, latency, and topography both between and within experimental conditions. In these and other ways these topographic analysis methods allow the experimenter to glean additional information and neurophysiologic interpretability beyond what is available from canonical waveform analyses. In this tutorial we present the example of somatosensory evoked potentials (SEPs) in response to stimulation of each hand to illustrate these points. For each step of these analyses, we provide the reader with both a conceptual and mathematical description of how the analysis is carried out, what it yields, and how to interpret its statistical outcome. We show that these topographic analysis methods are intuitive and easy-to-use approaches that can remove much of the guesswork often confronting ERP researchers and also assist in identifying the information contained within high-density ERP datasets.

Are there positive emotions in short-term dynamic psychotherapy or is it all Freude-less ?

Psychodynamic therapists are often suspicious of positive emotions and consider them to be nothing more than a form of denial or of another defense aiming to diminish painful or difficult affects. Positive emotions seem to exist only through the absence of negative emotions or as something that may happen outside of therapy. On the other hand, clinicians also agree that psychoanalytic work could not be successful without such positive emotions as interest, pleasure, surprise and creativity. Contemporary psychoanalytic thinking and new research findings in the area of relationship regulation are likely to give positive emotions an increasingly prominent place in dynamically oriented therapies. With today's emphasis on the therapeutic relationship and intersubjectivity, the time appears right to integrate positive emotions more formally into psychodynamic clinical theories.

Early and Prolonged Antiretroviral Therapy Is Associated with an HIV-1-Specific T-Cell Profile Comparable to That of Long-Term Non-Progressors.

Background: Intervention with antiretroviral treatment (ART) and control of viral replication at the time of HIV-1 seroconversion may curtail cumulative immunological damage. We have therefore hypothesized that ART maintenance over a very prolonged period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 long-term non-progressors (LTNPs).Methodology/Principal Findings: We have investigated a cohort of 20 HIV-1 seroconverters on long-term ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-associated HIV-1 RNA and DNA, respectively, were demonstrated to be similarly low in both cohorts. These two virologically matched cohorts were then comprehensively analysed by polychromatic flow cytometry for HIV-1-specific CD4(+) and CD8(+) T-cell functional profile in terms of cytokine production and cytotoxic capacity using IFN-gamma, IL-2, TNF-alpha production and perforin expression, respectively. Comparable levels of highly polyfunctional HIV-1-specific CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on HIV-1-specific CD8+ T-cells, consistent with a polyfunctional/non-cytotoxic profile in a context of low viral burden.Conclusions: Our results indicate that prolonged ART initiated at the time of HIV-1 seroconversion is associated with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of early treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.

Population pharmacokinetic study of gentamicin in a large cohort of premature and term neonates.

AIM: This study aims to investigate the clinical and demographic factors influencing gentamicin pharmacokinetics in a large cohort of unselected premature and term newborns and to evaluate optimal regimens in this population. METHODS: All gentamicin concentration data, along with clinical and demographic characteristics, were retrieved from medical charts in a Neonatal Intensive Care Unit over 5 years within the frame of a routine therapeutic drug monitoring programme. Data were described using non-linear mixed-effects regression analysis ( nonmem®). RESULTS: A total of 3039 gentamicin concentrations collected in 994 preterm and 455 term newborns were included in the analysis. A two compartment model best characterized gentamicin disposition. The average parameter estimates, for a median body weight of 2170 g, were clearance (CL) 0.089 l h(-1) (CV 28%), central volume of distribution (Vc ) 0.908 l (CV 18%), intercompartmental clearance (Q) 0.157 l h(-1) and peripheral volume of distribution (Vp ) 0.560 l. Body weight, gestational age and post-natal age positively influenced CL. Dopamine co-administration had a significant negative effect on CL, whereas the influence of indomethacin and furosemide was not significant. Both body weight and gestational age significantly influenced Vc . Model-based simulations confirmed that, compared with term neonates, preterm infants need higher doses, superior to 4 mg kg(-1) , at extended intervals to achieve adequate concentrations. CONCLUSIONS: This observational study conducted in a large cohort of newborns confirms the importance of body weight and gestational age for dosage adjustment. The model will serve to set up dosing recommendations and elaborate a Bayesian tool for dosage individualization based on concentration monitoring.

Accompagnement thérapeutique : le chemin du suivi à long terme [Patient education: the way for long-term follow up]

L'éducation thérapeutique du patient est maintenant parfaitement intégrée dans les soins. Son champ d'application se situe essentiellement dans le domaine des maladies chroniques pour l'acquisition de compétences dans la gestion du traitement, en coopération avec les professionnels. En médecine ambulatoire, patients et soignants se heurtent actuellement aux difficultés du suivi avec sa part d'incertitude, lassitude et de pression économique. La médecine fondée sur les preuves (EBM) et les différents modèles en psychologie de la santé ne nous éclairent que partiellement le chemin. Un nouveau type de démarche réflexive est en train d'émerger. Cette réflexion devrait placer en son centre la notion de relation thérapeutique : entre science et existence. Nous résumons ici ce processus réflexif en cours d'une équipe interdisciplinaire regroupant sciences humaines, art et médecine. Therapeutic education is now perfectly integrated in caring and medicine. Its field of application is primarily in chronic diseases for the acquisition of competences in the management of treatments, in co-operation with health professionals. In ambulatory medicine, patients and health professionals are currently running up against the difficulties of the long-term follow-up with its part of uncertainty, lassitude and economic pressure. EBM and the various models of health psychology light us only partially the way. A new type of reflexive step is emerging. This way of thinking should place in its center the concept of therapeutic relation: between science and being. We summarize here our reflexive process in the course of an interdisciplinary team gathering social sciences, art and medicine

Minimization of calcineurin inhibitors to improve long-term outcomes in kidney transplantation.

Long-term outcomes after kidney transplantation remain suboptimal, despite the great achievements observed in recent years with the use of modern immunosuppressive drugs. Currently, the calcineurin inhibitors (CNI) cyclosporine and tacrolimus remain the cornerstones of immunosuppressive regimens in many centers worldwide, regardless of their well described side-effects, including nephrotoxicity. In this article, we review recent CNI-minimization strategies in kidney transplantation, while emphasizing on the importance of long-term follow-up and patient monitoring. Finally, accumulating data indicate that low-dose CNI-based regimens would provide an interesting balance between efficacy and toxicity.

Impaired left ventricular function as a predictive factor for mid-term survival in octogenarians after primary coronary artery bypass surgery.

BACKGROUND: The impact of preoperative impaired left ventricular ejection fraction (EF) in octogenarians following coronary bypass surgery on short-term survival was evaluated in this study. METHODS: A total of 147 octogenarians (mean age 82.1 ± 1.9 years) with coronary artery diseases underwent elective coronary artery bypass graft between January 2000 and December 2009. Patients were stratified into: Group I (n = 59) with EF >50%, Group II (n = 59) with 50% > EF >30% and in Group III (n = 29) with 30% > EF. RESULTS: There was no difference among the three groups regarding incidence of COPD, renal failure, congestive heart failure, diabetes, and preoperative cerebrovascular events. Postoperative atrial fibrillation was the sole independent predictive factor for in-hospital mortality (odds ratio (OR), 18.1); this was 8.5% in Group I, 15.3% in Group II and 10.3% in Group III. Independent predictive factors for mortality during follow up were: decrease of EF during follow-up for more that 5% (OR, 5.2), usage of left internal mammary artery as free graft (OR, 18.1), and EF in follow-up lower than 40% (OR, 4.8). CONCLUSIONS: The results herein suggest acceptable in-hospital as well short-term mortality in octogenarians with impaired EF following coronary artery bypass grafting (CABG) and are comparable to recent literature where the mortality of younger patients was up to 15% and short-term mortality up to 40%, respectively. Accordingly, we can also state that in an octogenarian cohort with impaired EF, CABG is a viable treatment with acceptable mortality.

Surgery for incarcerated hernia: short-term outcome with or without mesh.

BACKGROUND: Incarcerated hernias represent about 5-15 % of all operated hernias. Tension-free mesh is the preferred technique for elective surgery due to low recurrence rates. There is however currently no consensus on the use of mesh for the treatment of incarcerated hernias, especially in case of bowel resection. AIM: The aims of this study were (i) to report our current practice for the treatment of incarcerated hernias, (ii) to identify risk factors for postoperative complications, and (iii) to assess the safety of mesh placement in potentially infected surgical fields. METHODS: This retrospective study included 166 consecutive patients who underwent emergency surgery for incarcerated hernia between January 2007 and January 2012 in two university hospitals. Demographics, surgical details, and short-term outcome were collected. Univariate analysis was employed to identify risk factors for overall, infectious, and major complications. RESULTS: Eighty-four patients (50.6 %) presented inguinal hernias, 43 femoral (25.9 %), 37 umbilical hernias (22.3 %), and 2 mixed hernias (1.2 %), respectively. Mesh was placed in 64 patients (38.5 %), including 5 patients with concomitant bowel resection. Overall morbidity occurred in 56 patients (32.7 %), and 8 patients (4.8 %) developed surgical site infections (SSI). Univariate risk factors for overall complications were ASA grade 3/4 (P = 0.03), diabetes (P = 0.05), cardiopathy (P = 0.001), aspirin use (P = 0.023), and bowel resection (P = 0.001) which was also the only identified risk factor for SSI (P = 0.03). In multivariate analysis, only bowel incarceration was associated with a higher rate of major morbidity (OR = 14.04; P = 0.01). CONCLUSION: Morbidity after surgery for incarcerated hernia remains high and depends on comorbidities and surgical presentation. The use of mesh could become current practice even in case of bowel resection.

Short- and long-term effects of litter size manipulation in a small wild-derived rodent.

Iteroparous organisms maximize their overall fitness by optimizing their reproductive effort over multiple reproductive events. Hence, changes in reproductive effort are expected to have both short- and long-term consequences on parents and their offspring. In laboratory rodents, manipulation of reproductive efforts during lactation has however revealed few short-term reproductive adjustments, suggesting that female laboratory rodents express maximal rather than optimal levels of reproductive investment as observed in semelparous organisms. Using a litter size manipulation (LSM) experiment in a small wild-derived rodent (the common vole; Microtus arvalis), we show that females altered their reproductive efforts in response to LSM, with females having higher metabolic rates and showing alternative body mass dynamics when rearing an enlarged rather than reduced litter. Those differences in female reproductive effort were nonetheless insufficient to fully match their pups' energy demand, pups being lighter at weaning in enlarged litters. Interestingly, female reproductive effort changes had long-term consequences, with females that had previously reared an enlarged litter being lighter at the birth of their subsequent litter and producing lower quality pups. We discuss the significance of using wild-derived animals in studies of reproductive effort optimization.

Long-term outcome of congenital aortic valve stenosis: predictors of reintervention.

OBJECTIVES: To evaluate long-term outcome of initial aortic valve intervention in a paediatric population with congenital aortic stenosis, and to determine risk factors associated with reintervention. PATIENTS AND METHODS: From 1985 to 2009, 77 patients with congenital aortic stenosis and a mean age of 5.8±5.6 years at diagnosis were followed up in our institution for 14.8±9.1 years. RESULTS: First intervention was successful with 86% of patients having a residual peak aortic gradient 1 regurgitation increased by 7%. Long-term survival after the first procedure was excellent, with 91% survival at 25 years. At a mean interval of 7.6±5.3 years, 30 patients required a reintervention (39%), mainly because of a recurrent aortic stenosis. Freedom from reintervention was 97, 89, 75, 53, and 42% at 1, 10, 15, 20, and 25 years, respectively. Predictors of reintervention were residual peak aortic gradient (p=0.0001), aortic regurgitation post-intervention >1 (p=0.02), prior balloon aortic valvuloplasty (p=0.04), and increased left ventricular posterior wall thickness (p=0.1). CONCLUSIONS: Aortic valve intervention is a safe and effective procedure for congenital aortic stenosis with excellent survival results. However, rate of reintervention is high and influenced by increased left ventricular posterior wall thickness pre-intervention, prior balloon valvuloplasty, higher residual peak systolic valve gradient, and more than mild regurgitation post-intervention. The study highlights that long-term follow-up is recommended for these patients.

Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV.

The prognostic relevance of additional cytogenetic findings at diagnosis of chronic myeloid leukemia (CML) is unclear. The impact of additional cytogenetic findings at diagnosis on time to complete cytogenetic (CCR) and major molecular remission (MMR) and progression-free (PFS) and overall survival (OS) was analyzed using data from 1151 Philadelphia chromosome-positive (Ph(+)) CML patients randomized to the German CML Study IV. At diagnosis, 1003 of 1151 patients (87%) had standard t(9;22)(q34;q11) only, 69 patients (6.0%) had variant t(v;22), and 79 (6.9%) additional cytogenetic aberrations (ACAs). Of these, 38 patients (3.3%) lacked the Y chromosome (-Y) and 41 patients (3.6%) had ACAs except -Y; 16 of these (1.4%) were major route (second Philadelphia [Ph] chromosome, trisomy 8, isochromosome 17q, or trisomy 19) and 25 minor route (all other) ACAs. After a median observation time of 5.3 years for patients with t(9;22), t(v;22), -Y, minor- and major-route ACAs, the 5-year PFS was 90%, 81%, 88%, 96%, and 50%, and the 5-year OS was 92%, 87%, 91%, 96%, and 53%, respectively. In patients with major-route ACAs, the times to CCR and MMR were longer and PFS and OS were shorter (P < .001) than in patients with standard t(9;22). We conclude that major-route ACAs at diagnosis are associated with a negative impact on survival and signify progression to the accelerated phase and blast crisis.