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The impact of COVID-19 changed the use and delivery of health care services, requiring an abrupt shift in treatment and staffing models 1,2. This is particularly salient in youth acute and intensive treatment services (AITS), including inpatient psychiatric hospitals (IPH), intensive outpatient programs (IOP), and partial hospitalization programs (PHP), because of challenging issues of maintaining high-quality care and a safe therapeutic milieu during increased demand for acute services,3 all while limiting transmission of COVID-19 on locked units, in close quarters, and for youths traveling back and forth to day-programs. Over the past year, AITS adapted and evolved without the ability to pause services and plan, increase staffing, or allocate additional resources. This article discusses themes of changes made based on more than 20 facilities across the United States through the American Psychological Association Child and Adolescent Psychology Division’s Acute, Intensive, and Residential Service Special Interest Group.4 These facilities include psychiatric inpatient units and day-treatment programs. We discuss lessons learned from these changes, the need for evaluating these changes, and application of these lessons in future crises.

American Indian (AI) and Indigenous peoples utilize traditional medicine/healing (TM/H) for health and well-being. Allopathic health care practitioners (HCPs) receive minimal training and education on TM/H and its application and integration into health care settings. Lack of knowledge and practice guidelines on how to navigate these 2 health care perspectives (allopathic and traditional) creates uncertainties in the treatment of AI and Indigenous peoples. Such conflicts can undermine patient autonomy and result in culturally incongruent practice. This article presents a case study showcasing suggestions for how HCPs can direct clinical decision making when working with AI/Indigenous patients who utilize TM/H. The article argues that health professions education institutions and HCPs must dedicate effort to expanding awareness of and education about TM/H to enhance the delivery of evidence-based and integrated clinical treatment for AI/Indigenous patients.

Background Two prospective studies that were performed before the era of highly sensitive solid-phase assays have shown a lower incidence of acute rejection in highly sensitized kidney-transplant patients given polyclonal antibodies compared with those given anti-CD25 monoclonal antibodies. Methods This prospective pilot randomized French multicenter study aimed to compare anti–T-lymphocyte Ig (ATLG) (n = 32) and basiliximab (n = 27) in highly sensitized kidney-transplant patients without preformed donor-specific antibodies (pDSAs) as assessed by a Luminex Single-Antigen flow bead assay. Only patients with a calculated panel reactive antibody ≥50%, with at least 1 antibody with a mean fluorescence intensity ≥5000 and without a historical pDSA and without a pDSA on the day of transplantation were included. Results Treatment failure as defined by biopsy-proven acute rejection, patient lost to follow-up, graft loss, and death was observed in 18.8% (95% confidence interval [CI], 8.9%–37.1%) and 18.8% (95% CI, 8.9%–37.1%) in patients who received ATLG and 14.8% (95% CI, 5.8%–34.8%) and 28.2% (95% CI, 14.2%–51.2%) of patients who received basiliximab, respectively at 6 (P = 0.66) and 12 (P = 0.62) months post-transplantation. One T cell–mediated rejection was observed in ATLG-treated patients (3.1%). One antibody-mediated rejection due to a de novo donor-specific antibody (DSA) occurred in basiliximab-treated patients (3.7%). Patient survival, graft survival, kidney parameters, and infection rate were similar in the 2 groups. Conclusion This pilot study indicates that in highly sensitized kidney-transplant patients without pDSAs, both ATLG and basiliximab can be used efficiently and safely. However, because of the lack of power, these results should be interpreted with caution., Graphical abstract

International audience; Recently, Akalin et al.1 reported a 28% mortality among kidney‐transplant patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2). Two of the 10 patients who died had been transplanted within the previous 5 weeks. During the coronavirus disease (COVID)‐19 outbreak, kidney transplant programs were suspended in several countries2. Although the pandemic is still ongoing, the stop of lockdown has prompted several transplant centers to restart kidney transplantation programs. It is recommended to consider that donors and recipients are screened for SARS‐CoV‐2 before transplantation by means of nuclear acid tests with or without chest CT scans.

Autobiographical memory studies conducted with narrative methods are onerous, requiring significant resources in time and labor. We have created a semi-automated process that allows autobiographical transcribing and scoring methods to be streamlined. Our paper focuses on the Autobiographical Interview (AI; Levine, Svoboda, Hay, Winocur, & Moscovitch, Psychology and Aging, 17, 677-89, 2002), but this method can be adapted for other narrative protocols. Specifically, here we lay out a procedure that guides researchers through the four main phases of the autobiographical narrative pipeline: (1) data collection, (2) transcribing, (3) scoring, and (4) analysis. First, we provide recommendations for incorporating transcription software to augment human transcribing. We then introduce an electronic scoring procedure for tagging narratives for scoring that incorporates the traditional AI scoring method with basic keyboard shortcuts in Microsoft Word. Finally, we provide a Python script that can be used to automate counting of scored transcripts. This method accelerates the time it takes to conduct a narrative study and reduces the opportunity for error in narrative quantification. Available open access on GitHub ( https://github.com/cMadan/scoreAI ), our pipeline makes narrative methods more accessible for future research.

Introduction Une faible immunogenicite des vaccins a ARN messager a ete rapportee chez les patients transplantes d’organes solides apres deux doses vaccinales. Description L’objectif de cette etude retrospective monocentrique etait d’identifier les facteurs predictifs de reponse vaccinale apres l’administration de deux doses de vaccin a ARN messager. Methodes Au total, 393 patients ont beneficie de deux doses de vaccins a ARN messager a 1 mois d’intervalle (vaccin BNT162b2, Pfizer-BioNTech, n = 391 ; vaccin mRNA 1273, Moderna, n = 2). Resultats A 1 mois de la seconde dose de vaccin a ARN messager, 97 des 288 transplantes renaux ont developpes des anticorps anti-SARS-CoV2 (33,7 %), contre 31 des 65 patients transplantes hepatiques (47,7 %), 5 des 35 patients transplantes thoraciques (14,3 %), et 1 des 5 transplantes du pancreas (20,0 %) (p = 0,005). Les patients ayant developpes une reponse vaccinale etaient plus jeunes, plus souvent des hommes et transplantes depuis plus longtemps que les patients non-repondeurs. Les patients ayant recu un traitement d’induction developpaient moins souvent des anticorps anti-SARS-CoV2 que les patients n’ayant pas recu de traitement d’induction. Les patients recevant de l’acide mycophenolique, des corticoides ou du belatacept developpaient moins souvent une reponse vaccinale. Inversement, les patients recevant des inhibiteurs des mTOR developpaient plus souvent des anticorps anti-SARS-CoV2. Finalement, quel que soit le type d’organe greffe, les patients ayant une reponse vaccinale avaient un DFG estime superieur a celui des patients n’ayant pas developpes d’anticorps. En analyse multivariee, etre un homme, a distance de la greffe et avoir un DFG eleve etaient associes a une reponse vaccinale positive. A l’inverse, etre jeune, receveur d’organe thoracique, sous traitement par acide mycophenolique, corticoides ou belatacept etaient associes a une reponse vaccinale negative. Conclusion La vaccination anti-SARS-CoV2 a ARN messager a deux doses possede une faible immunogenicite chez les receveurs d’organes solides. Le traitement immunosuppresseur serait le seul parametre modifiable permettant d’ameliorer la reponse vaccinale.

Composites are experiencing a new era. The spatial resolution at which is to date possible to build up complex architectured microstructures through additive manufacturing-based and sintering of powder metals 3D printing techniques, as well as the recent improvements in both filament winding and automated fiber deposition processes, are opening new unforeseeable scenarios for applying optimization strategies to the design of high-performance structures and metamaterials that could previously be only theoretically conceived. Motivated by these new possibilities, the present work, by combining computational methods, analytical approaches and experimental analysis, shows how finite element Design Optimization algorithms can be ad hoc rewritten by identifying as design variables the orientation of the reinforcing fibers in each ply of a layered structure for redesigning fiber-reinforced composites exhibiting at the same time high stiffness and toughening, two features generally in competition each other. To highlight the flexibility and the effectiveness of the proposed strategy, after a brief recalling of the essential theoretical remarks and the implemented procedure, selected example applications are finally illustrated on laminated plates under different boundary conditions, cylindrical layered shells with varying curvature subjected to point loads and composite tubes made of carbon fiber-reinforced polymers, recently employed as structural components in advanced aerospace engineering applications.

Background In cardiac amyloidosis the application of Speckle Tracking Echocardiography allows to identify a specific left ventricular (LV) longitudinal strain (LS) pattern characterized by “apical sparing”, with a prominent involvement of basal and middle segments and normal LS of apical cap. The pattern of regional LS has been never investigated in monoclonal gammopathy of undetermined significance (MGUS), a condition which can predispose to cardiac amyloidosis. Purpose To compare LV regional LS patterns and LS base-to-apex behaviour of patients affected by MGUS in comparison with healthy subjects. Methods We enrolled 40 patients affected by MGUS (M/F=20/20; age 62.6±13.8 years), asymptomatic for cardiac symptoms, and a control group of 40 healthy subjects, matched for sex and age. Nineteen (47%) MGUS patients showed prevalent free K light chain and 21 (53%) had prevalent free λ light chain. Participants underwent standard echo-Doppler exam, including Speckle Tracking of the three apical views. Global longitudinal strain (GLS), the average LS of six basal (BLS), six middle (MLS), and six apical (ALS) segments (considered in absolute values) and relative regional strain ratio RRSR [=ALS/(BLS+MLS)] were computed. Exclusion criteria were overt heart failure, LV ejection fraction Results The two groups were comparable for body mass index, blood pressure and heart rate. LV mass index, relative wall thickness, left atrial volume index and Doppler-derived LV diastolic parameters did not differ significantly between the two groups. LV ejection fraction was also similar in MGUS and healthy controls. GLS resulted significantly lower in MGUS group than in controls (20.5±3.0 vs. 22.4±2.0%, p1. The figure depicts a LS bull'eye of a MGUS patient showing the prominent involvement of LV basal segments. Conclusions In presence of a normal LV ejection fraction, MGUS patients show a subclinical LV longitudinal systolic dysfunction. This is testified by a reduction of GLS and of regional LS which involves mainly LV basal segments, without substantial changes of relative regional strain ratio. LV regional longitudinal dysfunction could be useful to monitor LV myocardial mechanics during follow-up of MGUS patients. LS bull's eye in a MGUS patient Funding Acknowledgement Type of funding source: None

Background In non-valvular atrial fibrillation (AF) patients, risk stratification scores such as CHA2DS2VASc and HASBLED allow the prediction of thromboembolic and bleeding risks, respectively. However, no risk score for the prediction of AF recurrence has been yet validated. Purpose To evaluate the mayor anthropometric and echocardiographic determinants of AF recurrence in non-valvular paroxysmal AF patients at 1 year follow-up. Methods Among 395 consecutive adult patients with non valvular AF enrolled in the Neapolitan Atrial Fibrillation (NeAfi) Echo registry, 177 (F/M = 87/90, age = 66.5± 11.9 years) had paroxismal AF and underwent 1-year follow-up. Fifteen patients had AF recurrence. Anthropometric parameters and blood pressure (BP) were recorded and CHA2DS2VASc and HASBLED scores were calculated. At baseline, patients underwent a comprehensive echo-Doppler exam, including quantification of left atrial (LA) size measurements, peak atrial longitudinal strain (PALS) and left ventricular (LV) global longitudinal strain (GLS). Binary logistic regression analysis was used to establish a mathematical model of the relationship between the variables and AF recurrence. The covariates for regression analysis were chosen as potential confounding factors based on their significance in independent T test analyses for continuous variables of chi-square for dichotomous variables, or on their biological plausibility. Results AF recurrence was higher in male than in female patients (14.4 vs 2.3%, p = 0.008). Patients with AF recurrence had similar body mass index, systolic and diastolic BP and heart rate compared to those without. The two groups were similar for LV end-systolic and end-diastolic volumes, ejection fraction, LV mass index, diastolic indexes, pulmonary artery systolic pressure and GLS. LA diameter (p = 0.235) and PALS (p = 0.375) were also similar between the two groups, whereas LA volume index (LAVi) was greater in patients experiencing AF recurrence (45.5 ± 15.7 vs. 36.7 ± 10.4 ml/m², p = 0.003). Binomial multiple regression analysis model explained 25% (Nagelkerke R²) of the variance in AF recurrence and correctly classified 95.0% of cases. Males were 8.9 times more likely to exhibit AF recurrence than females (p = 0.04). Greater LAVi was associated with an increased likelihood of exhibiting AF recurrence (OR = 1.07, p = 0.03), whereas CHA2DS2VASc >1 in men and >2 in women, HASBLED >3 and greater LA diameter or lower PALS did not add significant information to the model. Conclusions Male gender and, with a lower extent, LAVi appear to be major determinants of AF recurrence in non-valvular paroxysmal AF. The quantification of PALS does not seem to add valuable information in the prediction of recurrent AF.

Background Hyperuricemia has been reported to accelerate the occurrence and worsening of cardiovascular disease, being a risk factor for coronary heart disease and cardiac mortality. Elevated uric acid (UA) is also associated with left ventricular (LV) hypertrophy and with LV diastolic dysfunction. The effect of hyperuricemia (HU) on LV systolic function is still unclear. Purpose Aim of our study was to evaluate the impact of elevated UA serum levels on LV systolic function, also evaluating longitudinal deformation, in a population of hypertensive patients. Methods We enrolled 160 treated hypertensive patients (M/F = 104/56, age 58.2 ± 13.3 years, blood pressure = 136.7 ± 16.8/81.3 ± 10.9 mmHg), who underwent standard echo-Doppler exam, including speckle tracking quantification of global longitudinal strain (GLS, considered in absolute value). HU was defined as UA≥7 mg/dL and the study population was divided in two groups: patients with (n = 63) and without (n = 97) HU. Exclusion criteria were coronary artery disease, overt heart failure, hemodynamically significant valve heart disease, primary cardiomyopathies, permanent atrial fibrillation and inadequate echo imaging. Results The two groups were comparable for sex prevalence, blood pressure and heart rate. Patients with HU were older and had higher body mass index (BMI) (both p Conclusions In hypertensive patients with multiple cardiovascular risk factors, the presence of HU is associated with LV diastolic and systolic dysfunction. Serum UA levels and GLS resulted independently associated even after adjusting for several clinical and echo confounders. Acid uric might be considered as an independent marker of early LV dysfunction, able to identify hypertensive patients at increased risk for heart failure. Abstract P658 Figure. Relation between uric acid and GLS

Background Overweight and obesity are related to the risk of new-onset atrial fibrillation (AF). Peak atrial longitudinal strain (PALS) is an advanced echocardiographic parameter of left atrial (LA) function with a recognized diagnostic and prognostic role in both the general population and AF. Purpose To investigate the impact of body mass index (BMI) on LA function by utilizing standard and advanced echocardiography in patients with non-valvular AF. Methods In the NeAfib-Echo registry, 395 consecutive adult patients with non-valvular AF (F/M: 175/220; mean age 70.6 ± 11 years, BMI: 27.8 ± 5.6 kg/m²) were enrolled. 215 patients (54.1%) had permanent/persistent AF (prAF) and 178 (45.9%) had paroxysmal AF (pxAF). Anthropometric parameters and blood pressure (BP) were recorded and CHA2DS2VASc score was calculated. Patients underwent a complete echo-Doppler exam, including determination of PALS and left ventricular (LV) global longitudinal strain (GLS) (both reported in absolute values). The overall population was divided according to BMI tertiles: first tertile 29.3 Kg/m² (n = 130). Results No significant difference of sex prevalence, age, systolic BP and heart rate was found among the three BMI tertiles, whereas diastolic BP was higher in the third tertile (p Conclusions In patients with non valvular AF, overweight and obesity exert a detrimental effect on LA function as testified by the gradual PALS reduction with the increase of BMI tertiles. BMI is associated with PALS independently of several confounders including CHA2DS2VASc. Besides CHA2DS2VASc score, BMI could be considered as an additional factor for evaluating cardiovascular risk in non valvular AF. Abstract P814 Figure. Relation between BMI and PALS

International audience; Little is known about the impact of posttransplant blood transfusion on the sensitization of anti-HLA antibodies and the formation of donor-specific antibodies (DSAs). The aims of our study were to determine the 1-year incidence of DSAs (assessed using a solid-phase assay) and antibody-mediated rejection (AMR) in kidney transplant patients who had or had not received a blood transfusion during the first year after transplantation. Included were 390 non– HLA-sensitized patients who had received an ABOcompatible kidney transplant and had not previously or simultaneously received a nonkidney transplant. Overall, 64% of patients received a red blood cell transfusion within the first year after transplantation, most within the first month. The overall 1-year incidence of DSAs was significantly higher in patients that had undergone transfusion (7.2% vs. 0.7% in patients with no transfusion, p < 0.0001). AMR occurred more often in the transfusion group (n = 15, 6%) compared with the nontransfusion group (n = 2, 1.4%; p = 0.04). Blood transfusion was an independent predictive factor for de novo DSA formation butnot for AMR. Patients who had a transfusion and developed DSAs were more often treated with cyclosporin A (n = 10, 55.5%) rather than tacrolimus (n = 45, 19.4%; p = 0.0001). In conclusion, early posttransplant blood transfusion may increase immunological risk, especially in underimmunosuppressed patients.

Reconstruction after excision of infiltrating basal cell carcinomas (BCCs) of the upper pole of the ear can be achieved with different techniques. The concept of spare-part surgery, which allows the surgeon to perform primary reconstruction of a defect without harvesting tissue from the adjacent areas, has been applied to the ear anatomy. We describe our experience with the use of a fillet flap from the residual external ear in two patients out of a series of six, undergoing reconstruction of ear defects after infiltrating BCC resection between January 2011 and December 2014. Reconstruction with the fillet of pinna flap was proven to be an easy surgical technique with good functional and cosmetic outcomes. Our technique, not previously reported, enhances the versatility of ear reconstruction.

Most bioactive food components show a rapid inactivation or biodegradation that challenge their beneficial effects. Since regulation authorities require efficient food quality and acceptability, edible passive coating has been developed to improve and extend food shelf life while protecting nutritional values. Encapsulation processes in oil and fat structures therefore provide a high protection for fat soluble nutraceuticals, as sustained and controlled delivery systems. Among the various existing systems, nanoorganogels offer unique properties due to their multiplied surface, while preserving the physical properties of bulk materials. Thus, nanoencapsulation currently receives a lot of attention from industrial R&Ds. Screening approaches have been developed to promote food-grade and GRAS-approved organogelators available for the scaled up manufacture of nanoscale organogel delivery systems. Ongoing challenges of the food industry include intensifying the search for viable health-promoting nanomaterials or nanostructured matrices displaying desirable properties in food applications. In these aspects, the nanoorganogel technologies have recently shown tremendous potential in food applications as structured edible oils, dietary supplements with high oral bioavailability or safer preservative agents for consumers.

While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report.

Throughout history, while the example of Muhammad as head of state and Shariah principles have been reference points, diverse and competing models of government and law have existed. Although many changes occurred with the spread of the Islamic Empire and the rise and fall of...

International audience; Pneumocystis pneumonia (PCP) in solid organ transplant (SOT) recipients becomes rare in the immediate posttransplantation period thanks to generalized prophylaxis. We aimed to identify the predictive factors for PCP in the era of universal prophylaxis and to propose a strategy for preventing PCP beyond the first year after transplantation. In a retrospective case-control study, 33 SOT cases with PCP diagnosed between 2004 and 2010 were matched with two controls each to identify risk factors for PCP by uni- and multivariate analysis. All the patients benefited from 6 months of posttransplantation trimethoprim-sulfamethoxazole prophylaxis. Most PCP in SOT patients occurred during the second year posttransplantation (33%). By univariate analysis, age, nonuse of tacrolimus, total and CD4 lymphocyte counts, gamma-globulin concentration and cytomegalovirus (CMV) infection appeared to be PCP risk factors. In the final multivariate analysis, age (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI]: 1.3-10.4), CMV infection (OR: 5.2, 95% CI: 1.8-14.7) and total lymphocyte count (OR: 3.9, 95% CI: 1.4-10.7) were found to be independently associated with PCP. The second year posttransplantation appeared to be the new period of highest risk of PCP. Age, CMV viremia and lymphocytes were the most pertinent predictive criteria to evaluate the risk of PCP in clinical practice.

Thrombotic microangiopathy (TMA) is one of the hallmark vascular lesions of antiphospholipid syndrome nephropathy (APSN). These lesions are at high risk of recurrence after kidney transplantation. The complement pathway is thought to be active in this process. We used eculizumab to treat three consecutive kidney transplant recipients with posttransplant TMA due to APSN recurrence that was resistant to plasmapheresis and explored the complement deposition and apoptotic and vascular cell markers on the sequential transplant biopsies. Treatment with eculizumab resulted in a rapid and dramatic improvement of the graft function in all three patients and in improvement of the TMA lesions within the graft. None of these patients had TMA flares after eculizumab was withdrawn. At the time of TMA diagnosis, immunofluorescence studies revealed intense C5b-9 and C4d depositions at the endothelial cell surface of the injured vessels. Moreover, C5b-9 colocalized with vessels exhibiting a high rate of apoptotic cells. Examination of sequential biopsies during eculizumab therapy showed that TMA lesions, C4d and apoptotic markers were rapidly cleared but the C5b-9 deposits persisted for several months as a footprint of the TMA. Finally, we noticed that complement inhibition did not prevent the development of the chronic vascular changes associated with APSN. Eculizumab seems to be an efficient method for treating severe forms of posttransplant TMA due to APSN recurrence. Terminal complement inhibition does not prevent the development of chronic APSN.

International audience; There is no approved therapy for hepatitis C virus (HCV) infection after kidney transplantation, and no data regarding the use of new‐generation direct antiviral agents (DAAs) have been published so far. The aims of this pilot study were to assess the efficacy and safety of an interferon‐free sofosbuvir‐based regimen to treat chronic HCV infection in kidney transplant recipients. Twenty‐five kidney transplant recipients with chronic HCV infection were given, for 12 (n = 19) or 24 weeks (n = 6), sofosbuvir plus ribavirin (n = 3); sofosbuvir plus daclatasvir (n = 4); sofosbuvir plus simeprevir, with (n = 1) or without ribavirin (n = 6); sofosbuvir plus ledipasvir, with (n = 1) or without ribavirin (n = 9); and sofosbuvir plus pegylated‐interferon plus ribavirin (n = 1). A rapid virological response, defined by undetectable viremia at week 4 after starting DAA therapy, was observed in 22 of the 25 patients (88%). At the end of therapy, HCV RNA was undetectable in all patients. At 4 and 12 weeks after completing DAA therapy, all had a sustained virological response. The tolerance to anti‐HCV therapy was excellent and no adverse event was observed. A significant decrease in calcineurin inhibitor levels was observed after HCV clearance. New‐generation oral DAAs are efficient and safe to treat HCV infection after kidney transplantation.

Background and Purpose: Despite numerous studies suggesting a relationship between paradoxical embolism from a patent foramen ovale (PFO) and stroke, the role of PFO as a risk factor for cerebral ischaemia remains controversial. We therefore sought to determine the association between a RLS detected by contrast-enhanced transcranial Doppler ultrasonography (c-TCD) and recurrent stroke in an unselected population sample. Methods: We analyzed the records of 763 patients with diagnosis of cerebral ischaemia at our institution. All patients had undergone TCD-based detection of RLS. Embolic signals have been measured both under resting conditions and after performing a Valsalva maneuver. For follow-up, all patients were contacted by mail, which included a standardized questionnaire. Endpoints of follow-up were defined as recurrence of cerebral ischaemia, occurrence of myocardial infarction or death from any cause. Results: Follow-up data were available in 639 patients (83.7%). At baseline, a RLS was detected in 140 (28%) men and in 114 (42%) women. Ten shunt-carriers (1.6%) and 32 patients (5.0%) without RLS had suffered a recurrent stroke. After adjustment for age, sex, and atrial fibrillation, the hazard ratio of RLS for stroke recurrence was 0.86 (95% CI 0.41-1.79). The condition of RLS at rest adjusted for age, sex, stroke subtype, and cardiovascular risk factors was not found to increase the risk of stroke substantially (HR 1.16 [95% CI 0.41-3.29]) Conclusion: Our data suggest that the risk of recurrent stroke in subjects with PFO is not significantly increased in comparison with subject without it.

The given and family names of two co-authors were incorrect in the published article. The correct spelling should read as: Sampath Chandra Prasad and Vinagolu K Rajasekhar.

Rituximab off-label use includes organ transplantation. We review the occurrence of infectious disease and its outcome after rituximab therapy. Between April 2004 and August 2008, 77 kidney-transplant patients received rituximab therapy [2-8 courses (median 4) of 375 mg/m2 each] for various reasons. Their results were compared with a control group (n=902) who had received no rituximab. After a median follow-up of 16.5 (1-55) months for rituximab patients and 60.9 (1.25-142.7) months for control patients, the incidence of infectious disease was 45.45% and 53.9% (ns), respectively. The incidence of bacterial infection was similar between the two groups, whereas the viral-infection rate was significantly lower, and the rate of fungal infection was significantly higher in the rituximab group. Nine out of 77 patients (11.68%) died after rituximab therapy, of which seven deaths (9.09%) were related to an infectious disease, compared to 1.55% in the controls (p=0.0007). In the whole population, the independent predictive factors for infection-induced death were the combined use of rituximab and antithymocyte-globulin given for induction or anti-rejection therapy, recipient age, and bacterial and fungal infections. After kidney transplantation, the use of rituximab is associated with a high risk of infectious disease and death related to infectious disease.

Background and purpose: Despite numerous studies, the role of patent foramen ovale (PFO) as a risk factor for stroke due to paradoxical embolism is still controversial. On the assumption that specific lesion patterns, in particular multiple acute ischaemic lesions on diffusion-weighted magnetic resonance imaging, indicate a cardioembolic origin, we compared the MRI findings in stroke patients with right-to-left shunt (RLS) and those without. Methods: The records of 486 patients with diagnosis of cerebral ischaemia were reviewed. For detection of RLS, contrast-enhanced transcranial Doppler (c-TCD) was carried out in all patients. An MRI scan of the brain was performed in all patients. Affected vascular territories were divided into anterior cerebral artery, middle cerebral artery, vertebrobasilar artery system including posterior cerebral artery, brain stem and cerebellar stroke, and strokes occurring in more than one territory. Results: We did not find a specific difference in neuroradiological lesion patterns in patients with RLS compared with patients without RLS. In particular, 23 of 165 patients (13.9%) with RLS showed multiple ischaemic lesions on MRI in comparison with 45 of 321 patients (14.0%) without RLS (P = 0.98). These findings also applied for the subgroup of cryptogenic strokes with and without RLS. Conclusion: We found no association between an ischaemic lesion pattern that is considered as being typical for stroke due to cardiac embolism and the existence of PFO. Therefore, our findings do not provide any support for the common theory of paradoxical embolism as a major cause of stroke in PFO carriers.

BACKGROUND The independent prognostic significance of different indices of blood pressure (BP) variability is not clear. We investigated the prognostic value of BP variability estimated as s.d. or average real variability (ARV) of daytime and night time BP, in hypertensive patients. METHODS The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1,280 sequential hypertensive patients (550 initially untreated and 730 initially treated) aged > or =40 years. Subjects with s.d. or ARV of daytime or night time systolic or diastolic BP below or above the median were classified as having low or high BP variability. RESULTS During the follow-up (4.75 +/- 1.8 years), 104 cardiovascular events occurred. The event rate per 100 patient-years was 1.71 in the global population. After adjustment for other covariates, Cox regression analysis showed that cardiovascular risk was higher in subjects with high ARV of daytime systolic BP in initially untreated, initially treated, and all the subjects (high vs. low ARV, hazard ratio (HR) 2.29 (1.06-4.94), HR 1.90 (1.06-3.39), and HR 2.07 (1.31-3.28), respectively). ARV of daytime diastolic BP and night time BP, and s.d. of daytime and night time BP were not significantly associated with risk or were not independent predictors of outcome. CONCLUSIONS In this study, high ARV of daytime systolic BP resulted in an independent predictor of cardiovascular risk in hypertensive patients, while high s.d. did not. Our data suggest that, in comparison to s.d., ARV could be a more appropriate index of BP variability and a more useful predictor of outcomes.

This prospective study examined the value of serum neurofilament protein levels for detecting peri-operative brain damage following carotid endarterectomy. An ELISA was used for quantification of neurofilament protein heavy chain (NfH(SMI35)) levels from patients undergoing endarterectomy for symptomatic (n = 17) and asymptomatic high-grade internal carotid artery stenosis (n = 30). All patients underwent diffusion-weighted brain imaging before and after the procedure. NfH(SMI35) levels were significantly higher in patients with a symptomatic carotid artery stenosis (0.131 ng/ml) if compared to asymptomatic patients (0.055 ng/ml, P = 0.01). However, serum NfH(SMI35) levels were not related to signs of brain ischemia on routine brain imaging techniques. Our pilot data suggests that raised NfH(SMI35) serum levels in patients with symptomatic carotid artery disease may be a sensitive biomarker for diffuse ischemic damage to the CNS. We conclude that NfH(SMI35) failed to qualify as a biomarker for peri-operative brain injury in CEA and factors that may have compromised the validation of this biomarker are discussed and need to be taken into account for the design of further studies.

AIM To provide data on conversion of kidney transplant patients from sirolimus to everolimus. MATERIALS AND METHODS In this 6-month prospective, open-label pilot study, maintenance renal transplant patients receiving sirolimus, mycophenolic acid and corticosteroids without concomitant calcineurin inhibitor (CNI) therapy were converted to everolimus 8 mg/day (8 - 15 ng/ml), and followed for 6 months. Mycophenolic acid and corticosteroid therapy were continued unchanged. Patients with acute rejection within the previous 3 months were excluded. RESULTS 11 patients were recruited and completed the study (mean 5.1 +/- 1.8 years post transplant). Mean everolimus trough level remained within target throughout the study. Mean GFR remained stable (Day 0, 48.4 +/- 8.4 ml/min/1.73 m2, Month 6, 49.5 +/- 17.3 ml/ min/1.73 m2 (p = 0.966), as did mean renal phosphate threshold (TmPO4/GFR) (Day 0, 0.41 +/- 0.15 mmol/l, Month 6, 0.40 +/- 0.17 mmol/l (p = 0.966)). Serum phosphates increased significantly from 0.71 to 0.77 mmol/l (p = 0.01), but tubular reabsorption of phosphates and 24-h phosphaturia remained unchanged and mean PTH concentration tended to decrease. No patient died, lost their graft or experienced biopsy-proven acute rejection after conversion. There were no cases of CMV infection. Tolerability remained similar post conversion. Hematological and lipid parameters remained stable. Liver enzymes and sex hormones remained within normal ranges. CONCLUSION This pilot study suggests that converting kidney transplant patients receiving CNI-free maintenance immunosuppression from sirolimus to everolimus, at relatively high exposure levels, is safe and easily manageable. There was no consistent evidence for a change in GFR or proximal tubular function.

International audience; Hepatitis E virus (HEV) infection was thought to be responsible for acute hepatitis that did not become chronic. However, we have recently reported that HEV infection can evolve to chronic hepatitis, at least in solid-organ transplant patients. We report on two cases of rapidly progressive of HEV-related cirrhosis that occurred in two organ-transplant patients. Case 1: A kidney-pancreas-transplant patient developed acute HEV hepatitis 60 months after transplantation, which evolved to chronicity as defined by persisting elevated liver-enzyme levels and positive serum HEV RNA. At 22 months after the acute phase, she presented with cirrhosis and portal hypertension, that is ascites and esophagus varices. Case 2: A kidney-transplant patient developed acute hepatitis 36 months after transplantation, which persisted and remained unexplained for 38 months. Then, HEV RNA was searched for in their serum and stools, and was found to be positive in both. Retrospective analysis of available stored serum, mainly the serum obtained at the acute phase, confirmed the diagnosis of chronic hepatitis E. In both cases, a liver biopsy showed cirrhosis. We conclude that HEV infection cannot only evolve to chronic hepatitis, but can also be responsible for rapidly progressing cirrhosis in organ-transplant patients.

The reasons for the increased incidence of de novo anti-human leukocyte antibody (HLA) donor-specific antibodies (DSAs) observed after kidney allograft nephrectomy are not fully understood. One advocated mechanism suggests that at graft loss, DSAs are not detected in the serum because they are fixed on the nonfunctional transplant; removal of the kidney allows DSAs to then appear in the blood circulation. The aim of our study was to compare anti-HLA antibodies present in the serum and in the graft at the time of an allograft nephrectomy. Using solid-phase assays, anti-HLA antibodies were searched for in the sera of 17 kidney transplant patients undergoing allograft nephrectomy. No anti-HLA antibodies were detected in the graft if they were not also detected in the serum. Eleven of the 12 patients who had DSAs detected in their sera also had DSAs detected in the grafts. Epitopic analysis revealed that most anti-HLA antibodies detected in removed grafts were directed against the donor. In summary, our data show that all anti-HLA antibodies that were detected in grafts were also detected in the sera. These intragraft anti-HLA antibodies are mostly directed against the donor at an epitopic level but not always at an antigenic level.

Carotid artery stenosis can be classified by magnetic resonance imaging (MRI) as lesion types I–VIII according to a modified histological scheme based on American Heart Association (AHA) guidelines. Lesion types IV–V and VI are regarded as high-risk plaques.We aimed to evaluate the clinical relevance of this classification for identifying unstable plaques. Eighty-five patients (29 female) with severe carotid artery stenosis (diagnosed by Doppler and duplex ultrasonography) were imaged using a 1.5 T scanner with bilateral phased-array carotid coils. T1-, T2-, time-offlight (TOF) and proton-density (PD)-weighted studies were obtained. The carotid plaques were classified as lesion types III–VIII according to the MRI-modified AHA criteria. Thirty-five patients presented with a recently symptomatic stenosis; 50 patients were asymptomatic. Lesion types IV–V (51.4 % vs. 22 %) and VI (20 % vs. 4%; P < 0.0001) were found significantly more often in symptomatic patients compared to those without a history of cerebral ischemia. The distribution of lesion types differs significantly between symptomatic and asymptomatic carotid artery stenosis. High-risk lesion types IV–V and VI were overrepresented in recently symptomatic patients. MRI according to the modified AHA-criteria may be a suitable tool for detection of unstable carotid lesions.

Background: Several reports indicate a decreased cortisol response to adrenocorticotropic hormone in preterm infants developing chronic lung disease and in preterm infants with refractory hypotension. Low-dose hydrocortisone (HC) may allow for beneficial effects. Objective: Our aim was to assess whether HC is able to increase survival without chronic lung disease. Methods: We performed a double-blind, randomized, placebo-controlled trial. Fifty mechanically ventilated infants (birth weight: 500–1,249 g) were randomized to receive treatment (HC 0.5 mg/kg/12 h for 9 days, then HC 0.5 mg/kg/24 h for 3 days) or placebo. Major outcome was survival without oxygen dependence at 36 weeks of postconceptional age (O2-free survival). Results: The basic characteristics were similar between the two groups. O2-free survival was higher in the HC group (64 vs. 32%). The advantage was particularly evident among infants without antenatal steroids. The mortality rate was 16% in the HC group versus 40% in the control group (difference not significant). Hypotension after recruitment was reduced by HC (0 vs. 30%). The incidence of gastrointestinal perforation and other adverse effects was similar between the two groups. Conclusions: HC prophylaxis improved O2-free survival and early cardiocirculatory function in our population, without important short-term effects. The neurodevelopmental outcome will be assessed at 2 years.

The swine-origin influenza A (H1N1) virus is mainly responsible for flu. No hepatitis attributable to H1N1 virus has been previously documented. Herein, we report on a kidney transplant patient who developed influenza H1N1 virus-induced hepatocellular injury. The patient's body temperature was only somewhat elevated, and pulmonary and flu symptoms were mild. H1N1 virus was detected by polymerase chain reaction assay in nasopharyngeal and bronchoalveolar swabs, as well as in the serum. The hepatocellular injury episode resolved after the patient had been placed on oseltamivir therapy. This observation suggests that acute hepatocellular injury could be linked to the influenza H1N1 virus.

In 1992, the defmition of erectile dysfunction (ED) replaced the old term of impotence that had been used for many centuries, in order to avoid the general confusion existing until today in this field. In the past, the origin of impotence had been attributed to different causes such as psychological diseases, or witches and demons. In 1764, Fusanacci described impotence that can occur in the male as well as in the female, as a defect in reproduction. The main causes responsible for impotence were identified as inability to achieve erection, a very fluid seminal ejaculation, a defective organ, dryness of testicles, and lack of copulative power after many sexual intercourses with healthy women. Some decades later in 1847, Beatty affirmed that one of the most remarkable changes that can be observed in the passage from childhood to maturity is the development of the sexual organs, followed by the appearanee of new sensations. He dis1inguished impotenee that oeeurs only in men from sterility that for him affeets women, and divided the eauses of impotenee into 3 classes: organie, functional and moral (today defmed as psyehologieal). For Beatty, the . progress of knowledge had taken away magie and soreery from the human mind and now it was widespread only ," among the lowest and most ignorant classes of humble people. In this way, he shows the evolution ofmedieal scienee d~ in XIX eentury in aceepting only the rational explanation of the human diseases.

We assessed whether conversion from tacrolimus (TAC) to cyclosporine (CsA) was associated with a reduction in hepatitis C virus (HCV) viral load among HCV-positive liver transplant (OLT) patients. Patients and Methods Nine OLT patients with recurrent HCV have TAC and prednisone immunosuppression. None received any HCV antiviral therapy. After the last intake of TAC, the patients underwent a 12-hour area under the curve (AUC 12 ) measurement of both TAC and HCV viral loads. The next morning (D 0 ) patients were given CsA (4 mg/kg bid). At the first intake of CsA and at 1 month (M 1 ) later, the patients underwent AUC 12 for CsA and HCV viral loads. Biological data, including aspartate (AST) and alanine (ALT) aminotransferase, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), and bilirubin levels, were collected during AUC 12 , and at M 1 and M 3 . Results With respect to liver enzymes (AST, ALT, GGT), there was no significant difference between D 0 , M 1 , and M 3 . Conversely, there was a significant decrease in AP between D 0 and M 3 ( P = .02), and a significant increase in total bilirubin between D 0 and M 1 ( P = .04), and between D 0 and M 3 ( P = .01). HCV viral load significantly increased by M 3 ( P = .01). At no time (D 0 , M 1 ) was there any correlation between the AUC 12 of TAC or CsA, and between AUC 12 HCV viral load. Conclusion This pilot study found no acute or chronic anti-HCV effects from CsA that were evident within 12 hours after CsA administrations or beyond 1 month of CsA therapy, respectively.

International audience; Although large retrospective studies have identified the presence of donor-specific antibodies (DSAs) to be a risk factor for rejection and impaired survival after liver transplantation, the long-term predicted pathogenic potential of individual DSAs after liver transplantation remains unclear. We investigated the incidence, prevalence and consequences of DSAs in maintenance liver transplant (LT) recipients. Two hundred sixty-seven LT recipients, who had undergone transplantation at least 6 months previously and had been screened for DSAs at least twice using single-antigen bead technology, were included and tested annually for the presence of DSAs. At a median of 51 months (min–max: 6–220) after an LT, 13% of patients had DSAs. At a median of 36.5 months (min–max: 2–45) after the first screening, 9% of patients have developed de novo DSAs. The sole predictive factor for the emergence of de novo DSAs was retransplantation (OR 3.75; 95% CI 1.28–11.05, p = 0.025). Five out of 21 patients with de novo DSAs (23.8%) developed an antibody-mediated rejection. Fibrosis score was higher among patients with DSAs. In conclusion, monitoring for the development of DSAs in maintenance LT patients is useful in case of graft dysfunction and to identify patients with a high risk of developing liver fibrosis.

This retrospective study sought to compare two modes of administration of antithymocyte globulin (RATG) after renal transplantation.Before 1993, group I patients (n = 93) received fixed doses of RATG (1 mg/kg per day) for 8 consecutive days. Thereafter, RATG was either continued at the same dose for 15 days, in cases of delayed graft function, or was infused every other day at the same dose until serum creatinine level became150 micromol/L. After 1993, group II patients (n = 66) received RATG at full dose (1 mg/kg per day) during the first 3 days and thereafter the doses were adjusted to target a CD2 T-cell count50/mm3. Both groups received steroids, azathioprine, and cyclosporine. The mean follow-up after transplantation was 117 +/- 31 months in group I and 93 +/- 19 months in group II.The RATG cumulative dose and consequently cost were significantly higher among group I than group II patients. Long-term patient and graft survival were similar in both groups. The rate of acute graft-rejection episodes was significantly higher among group I than group II patients. At 7 years posttransplantation, the serum creatinine level and creatinine clearance were similar in the two groups. The rate of cytomegalovirus infection, as well as the cumulative incidence of severe infections and cancers were also similar in both groups. Among the cancers, skin neoplasms represented 30% in group I and 26% in group II (P = ns).Adjusting RATG doses according to the CD2 lymphocyte count is safe, and a less expensive than using full doses.

Background Expert panels of colorectal surgeons consistently rank anastomotic leak as among the most important quality metrics for colectomies. Nonetheless, most administrative and clinical databases do not collect data on anastomotic leaks and rely on reported organ space surgical site infections (OSI) as a proxy for identifying anastomotic leaks. This study questions the validity of using OSI as a surrogate for anastomotic leak. Methods The Upstate New York Surgical Quality Initiative (UNYSQI) is a collaboration of 12 hospitals that prospectively collects colectomy-specific metrics, including anastomotic leak, in addition to standard National Surgical Quality Improvement Program (NSQIP) data, including OSIs. Cases with an organ space infection and/or anastomotic leak were selected from the 2010–2011 UNYSQI database. Patient characteristics and outcomes were compared for cases with organ space infections and anastomotic leaks. Results Overall, 3% of colectomies had a reported organ space infection and 4% had an anastomotic leak. Among cases having anastomotic leaks, only 25% were also coded as having an organ space infection, leaving 75% of anastomotic leaks not captured by the NSQIP database (κ = 0.272; P ≤ .001). Conclusion Organ space infection is a poor surrogate for anastomotic leak, resulting in grossly underestimated leak rates and seemingly represents different postoperative courses. Procedure-specific quality measures for colorectal surgery should include data collection on anastomotic leaks to provide accurate data for use in improving patient care.

International audience; Ochroconis gallopava is an emerging cause of mycosis in solid organ transplant recipients. Herein, we report a rare case of disseminated O. gallopava infection that involved lung, subcutaneous area, brain and peritoneum in a heart transplant recipient. Despite voriconazole therapy, the patient died 2 months after diagnosis.

Supergrid is a grid that enables to transfer electricity produced by renewable sources from the production places, located in regions, like ocean coasts and Sahara desert, to the consumptions centers. Several projects were developed supported by EU in last years and others will be proposed on such topic in the next future. In this paper the authors propose a method able to evaluate the projects in terms of their compatibility with the EU policy.