A Pan-European Review of Good Practices in Early Intervention Safeguarding Practice with Children, Young People and Families: Evidence Gathering to Inform a Multi-disciplinary Training Programme (the ERICA Project) in Preventing Child Abuse and Neglect in Seven European Countries.

Child maltreatment has detrimental social and health effects for individuals, families and communities. The ERICA project is a pan-European training programme that equips non-specialist threshold practitioners with knowledge and skills to prevent and detect child maltreatment. This paper describes and presents the findings of a rapid review of good practice examples across seven participating countries including local services, programmes and risk assessment tools used in the detection and prevention of child maltreatment in the family. Learning was applied to the development of the generic training project. A template for mapping the good practice examples was collaboratively developed by the seven participating partner countries. A descriptive data analysis was undertaken organised by an a priori analysis framework. Examples were organised into three areas: programmes tackling child abuse and neglect, local practices in assessment and referral, risk assessment tools. Key findings were identified using a thematic approach. Seventy-two good practice examples were identified and categorised according to area, subcategory and number. A typology was developed as follows: legislative frameworks, child health promotion programmes, national guidance on child maltreatment, local practice guidance, risk assessment tools, local support services, early intervention programmes, telephone or internet-based support services, COVID-19 related good practices. Improved integration of guidance into practice and professional training in child development were highlighted as overarching needs. The impact of COVID-19 on safeguarding issues was apparent. The ERICA training programme formally responded to the learning identified in this international good practice review.

Contemporary Ross procedure outcomes: medium- to long-term results in 214 patients.

OBJECTIVE: Our goal was to present 2 decades of our experience with the Ross procedure and its sequential modifications, adopted since 2010, to improve the reoperation rate. METHODS: We performed a single-centre, retrospective review of database information and medical notes about the implantation technique: the freestanding root. We compared era 1 (1997-2009) and era 2 (2010-2019). RESULTS: Between 1997 and 2019, a total of 214 Ross procedures were performed (71% men, median age 24 years) [interquartile range (IQR) 15-38]. Of these, 87% had various forms of congenital-dysplastic aortic valves. The median cross-clamping and bypass times were 173 (IQR 148-202) and 202 (IQR 182-244) min. The median postoperative stay was 6 days (2-77). Thirty-day mortality was 0.5%. The median follow-up time was 8.2 years (IQR 3.9-13.2). Survival at 10 and 20 years was 97% and 95%; freedom from greater than moderate aortic regurgitation or aortic valve intervention was 91% and 80%; and 93% of the patients were in New York Heart Association functional class I. Twenty (21%) patients operated on during era 1 and 6 (9%) during era 2 underwent autograft reoperations. The median follow-up time was 14.3 (IQR 11.5-17.4) and 4.8 (IQR 2.5-7) years. Freedom from autograft reoperation was 87% and 69% at 10 and 20 years, with no significant difference between eras. Freedom from homograft reoperation was 96% and 76% at 10 and 20 years. The presence of aortic regurgitation, infective endocarditis and era 1 were predictors of autograft reoperation. Male gender and era 1 were predictors of neoaortic root dilatation. CONCLUSIONS: The contemporary modified Ross procedure continues to deliver excellent results and should remain part of the strategy to treat children and young adults requiring aortic valve replacement.

Hypocomplementemic type II membranoproliferative glomerulonephritis in a male patient with familial lecithin-cholesterol acyltransferase deficiency due to two different allelic mutations.

Patients with familial lecithin-cholesterol acyltransferase (LCAT) deficiency very often show progressive glomerulosclerosis with evolution to end-stage disease. High levels of an abnormal lipoprotein (lipoprotein X) cause glomerular capillary endothelial damage. The ultrastructural study of renal biopsy specimens shows characteristic glomerular deposits of membrane-like, cross-striated structures and vacuole structures. The gene encoding for LCAT has been mapped to chromosome 16q22.1, and several mutations of this gene cause LCAT deficiency which is inherited as an autosomal recessive trait and which is characterized by corneal opacities, normochromic normocytic anemia, and renal dysfunction. Herein we report clinical features and renal histological findings concerning a 24-year-old male patient with classical familial LCAT deficiency due to two different allelic mutations: a nonsense mutation inherited from the father and a missense mutation inherited from the mother. Moreover, the patient showed glomerular histological lesions and an immunofluorescent glomerular pattern typical of hypocomplementemic membranoproliferative type II glomerulonephritis (dense-deposit disease). The nature of electron-dense material that characterizes dense-deposit disease is still unknown, but there are suggestions that some chemical modifications might occur in the renal basement membranes. Therefore, this clinical case might induce to consider possible relations between disorders of the lipoprotein metabolism and renal dense-deposit disease.

Acute renal failure due to idiopathic tubulo-intestinal nephritis and uveitis: "TINU syndrome". Case report and review of the literature.

Acute renal failure due to idiopathic tubulo-interstitial nephritis associated with bilateral uveitis (TINU syndrome) is a rare clinical event, contracted mainly by girls or women. Here we report the clinical follow-up regarding a 22-year-old woman with acute renal failure (creat. clearance 13.5 ml/min) due to idiopathic tubulo-interstitial nephritis documented by renal biopsy, after bilateral uveitis which healed with local prednisone. The clinical history and the clinical follow-up of our patient were typical of the TINU syndrome. We were able to exclude all diseases causing acute tubulo-interstitial nephritis such as systemic infection, hypersensitivity to drugs, Behcet's disease, Sjogren syndrome, sarcoidosis, systemic lupus or vasculitides. The patient recovered after systemic prednisone.

Frequent clonal loss of heterozygosity (LOH) in the chromosomal region 1p32 occurs in childhood T cell acute lymphoblastic leukemia (T-ALL) carrying rearrangements of the TAL1 gene.

Deletions and chromosomal translocations involving the 1p32 region, are frequently observed in T cell acute lymphoblastic leukemia (T-ALL). One of the most common genetic changes is the breakage of the TAL1 gene, which was originally described to be involved in the T-ALL carrying the t(1;14)(p32;q11) translocation. Site-specific deletions in the TAL1 gene are reported to occur in 12-26% of T-ALL with apparently normal karyotype. In order to investigate the presence of other subkaryotypic abnormalities involving the 1p32 chromosomal region, where TAL1 gene is mapped, we assessed losses of heterozygosity (LOH) for microsatellite markers, in a series of 22 children with T-ALL. Microsatellite polymorphic markers flanking the TAL1 gene (D1S211, D1S197, D1S200 and D1S220) were analyzed to detect LOH. Eight patients displayed LOH for at least one of the markers, suggesting the existence of hot spot regions at the short arm of chromosome 1. Two out of 11 with no molecular evidences of TAL1 gene involvement, compared to six out of 11 in the group of TAL1 rearranged gene, showed LOH at 1p32. TAL1 gene rearrangements and clonal LOH may represent two independent events, but could be related to the same causes. For the first time this study provides evidences that LOH at 1p32 region, occurs in T-ALL in the same region known to be involved in chromosomal deletions and translocations. LOH mapping may help to define the location of a new putative tumor-suppressor gene implicated in the transformation and progression of children T-ALL.

[Paraquat-induced acute dermatitis in a child after playing with a discarded container]. / Dermatite acuta da paraquat in bambina che ha utilizzato per gioco un contenitore abbandonato.

The improper use of pesticide waste containers is a significant risk in rural areas, especially where appropriate systems of draining off refuse are lacking. A case is reported of an eight-year-old child who had played with the abandoned Paraquat container. After contamination with the pesticide she showed several II degree caustic lesions on both thighs and knees, associated with a mild erythemato-desquamative cheilitis and a "strawberry tongue". Common laboratory findings did not reveal any kidney, liver and/or red/white cell alterations and the chest X-ray was normal even several months after the accident. No physical consequences ensued, except for hyperchromic pigmentation on the legs. Where empty pesticide containers are not properly collected, they can represent a risk of pesticide exposure for the general population. They can also be a potential source of pollution for superficial water and soil. In the district where the accident was reported it was estimated that empty containers made up 7% of the weight of the 146,330 kg of pesticides sold to local farmers in 1993, of which about 10,400 kg was burned, buried and dispersed in the soil. Within the framework of a global pesticide prevention programme launched by the Regional Government of Lombardy, local health authorities, with the contribution of farmers, are carrying out a project for the proper collection of empty pesticide containers.

Defective platelet aggregation in response to platelet-activating factor in uremia associated with low platelet thromboxane A2 generation.

The bleeding tendency associated with uremia is likely due to a qualitative platelet dysfunction. So far the data available on platelet aggregation are conflicting. Since platelet-activating factor (PAF) plays a role in primary hemostasis, we studied platelet aggregation in response to PAF in 40 patients with chronic uremia on regular hemodialysis and 12 control subjects. Our results showed that in 28 of 40 uremics, platelet aggregation response to PAF was normal, whereas in the remaining 12 it was defective in that no second wave of aggregation was elicited even if the PAF concentrations were increased by a factor of 10,000. This abnormal response was peculiar to PAF and only partially related to factor(s) of plasma origin. The number of platelet PAF receptors and their affinity for the agonist were comparable in controls and "PAF-unresponsive" patients. The defective platelet aggregation in response to PAF was associated with a statistically significant reduction (P less than 0.01) in thromboxane A2 (TxA2) generation in platelet-rich plasma (PRP) challenged with PAF (10 and 100 nmol/L). When PRPs from PAF-unresponsive patients were preincubated with a stable analogue of prostaglandin endoperoxides/TxA2 U-46619, an irreversible platelet aggregation in response to PAF was obtained. Thus in a subpopulation of uremics, platelet aggregation in response to PAF is selectively abnormal as a consequence of a reduced TxA2 generation.

Low levels of the anticoagulant activity of protein C in patients with chronic renal insufficiency: an inhibitor of protein C is present in uremic plasma.

Twenty-nine of 54 uremic patients had low levels of protein C measured as anticoagulant activity, contrasting with normal levels measured as amidolytic activity or antigenic concentration. We demonstrate that this discrepancy is due to the presence of a soluble plasma inhibitor that interferes specifically with the anticoagulant activity of activated protein C. The inhibitor does not interfere with other coagulation assays. It is resistant to diisopropylfluorophosphate, high temperatures and repeated freezing and thawing. It can be dissociated from protein C by anti-protein C antibodies or by dialysis in vitro and in vivo. It binds to positively charged resins and can be eluted with high salt concentrations without losing its inhibitory capacity. The inhibitory effect is correlated with plasma creatinine levels and fluctuates with time.

L-arginine, the precursor of nitric oxide, abolishes the effect of estrogens on bleeding time in experimental uremia.

We have reported previously that conjugated estrogens that are effective in shortening the prolonged bleeding time in uremic patients are also effective on bleeding time in a rat model of uremia. Using such a rat model we have recently demonstrated that nitric oxide (NO), an endothelium-derived vasodilator, is involved in mediating the bleeding tendency of uremia. With the present study we wanted to investigate whether conjugated estrogen mixture or its active component, 17 beta-estradiol, reduce uremic bleeding by interfering with the NO pathway. Our results showed that the shortening effect of conjugated estrogen and 17 beta-estradiol on bleeding time of uremic rats was completely reversed by giving the animals the NO precursor L-arginine, but not D-arginine, which is not a precursor of NO. Dexamethasone which at variance to progesterone inhibits the process of induction of NO-forming enzyme, shortened the prolonged bleeding time of uremic rats within 4 hours from injection. This effect was eliminated by L-arginine but not D-arginine administration. The glucocorticoid receptor antagonist cortexolone prevented the shortening of bleeding time induced by dexamethasone, suggesting that a receptor-mediated mechanism is involved in the hemostatic effect of dexamethasone as previously reported for estrogens. Unlike conjugated estrogens and dexamethasone, progesterone had no effect on bleeding time. All these findings would indicate that the effect of estrogens and dexamethasone on primary hemostasis in uremia might be mediated by changes in NO synthetic pathway.

Changes in pre- and postsynaptic components of noradrenergic transmission in hippocampal kindling in rats.

We investigated whether modifications in noradrenergic neurotransmission occurred during the development of hippocampal kindling in rats. We measured the release of [3H]norepinephrine (NE) induced by field-electrical stimulation, NE-stimulation of inositol phosphates [( 3H]IP) accumulation in the presence of LiCl and isoproterenol-induced accumulation of cAMP in hippocampal slices taken from rats electrically kindled at stages 2 and 5 in the dorsal hippocampus. One week after the last of at least 3 consecutive stage 5 seizures or 48 h after the last stage 2 stimulation, 2 min electrical stimulation of stratum pyramidale CA1-CA3 or dentate gyrus (DG) slices from kindled and contralateral hippocampi induced frequency-dependent NE release (respectively 2, 4 and 8 times spontaneous release measured at 2, 5 and 10 Hz) which did not significantly differ from that observed in shams (implanted with electrodes but not stimulated). Basal release of NE from kindled and sham-treated rats did not differ either. Isoproterenol induced a dose-dependent increase above basal cAMP concentration ranging from 40% at 0.01 microM to 180% at 10 microM (P less than 0.01, Dunnett's test) which did not differ between stages 2 and 5 and sham-hippocampi. NE (1-1000 microM) induced a dose-dependent, prazosin-sensitive increase in [3H]IP accumulation in the hippocampal slices. A significantly higher increase was found at stages 2 (P less than 0.05, Tukey's test) and 5 (P less than 0.05 and P less than 0.01, Tukey's test) compared to shams at all doses studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant human erythropoietin to correct uremic bleeding.

Recombinant human erythropoietin may improve hemostasis of uremic patients by correcting anemia. However, a complete correction of renal anemia carries the risk of hypertension, encephalopathy, thrombosis, and hyperkalemia. Our aim was to establish the minimum level of packed cell volume (PCV) achieved with recombinant human erythropoietin that corrects the prolonged bleeding time in uremia. Twenty patients with chronic renal failure, anemia, and very prolonged bleeding time (greater than or equal to 15 minutes) were randomly allocated to erythropoietin or no specific treatment. The initial dose of erythropoietin was 50 U/kg intravenously (IV) three times a week. Every 4 weeks, the dose was increased by 25 U/kg until a normalization of bleeding time was achieved. Erythropoietin at a dose ranging from 150 to 300 U/kg/wk induced an increase in PCV to a range of 27% to 32% in all patients but one, and normalized bleeding time in all patients. A significant negative correlation (r = 0.898, P less than 0.001) was found between PCV and bleeding time measurements. Erythropoietin also significantly (P less than 0.01) increased values for red blood cell (RBC) distribution width (basal, 11.3 +/- 0.6; 12 weeks, 13.1 +/- 1.3). Platelet count and platelet function parameters did not significantly change. In untreated patients, no changes were recorded in all the parameters considered. These results establish in a controlled fashion that erythropoietin shortens bleeding time of uremic patients and indicate that a partial correction of renal anemia is enough to normalize bleeding time.