Trajectories of care in congenital heart disease - the long arm of disease in the womb.

Our understanding of the development of congenital heart disease (CHD) across the lifespan has evolved. These include the evidence for the change in demographics of CHD, the observations that lifelong complications of CHD result in CHD as a lifespan disease, and the concept of long windows of exposure to risk that start in foetal life and magnify the expression of risk in adulthood. These observations set the stage for trajectories as an emerging construct to target health-service interventions. The lifelong cardiovascular and systemic complications of CHD make the long-term care of these patients challenging for cardiologists and internists alike. A life-course approach is thus required to facilitate our understanding of the natural history and to orient our clinical efforts. Three specific examples are illustrated: neurocognition; cancer resulting from exposure to low-dose ionizing radiation; and cardiovascular disease acquired in ageing adults. As patients grow, they do not just want to live longer, they want to live well. With the need to move beyond the mortality outcome, a shift in paradigm is needed. A life-course health development framework is developed for CHD. Trajectories are used as a complex construct to illustrate the patient's healthcare journey. There is a need to define disease trajectories, wellness trajectories and ageing trajectories in this population. Disease trajectories for repaired tetralogy of Fallot, transposition of the great arteries and the Fontan operation are hypothetically constructed. For clinicians, the life-course horizon helps to frame the patient's history and plan for the future. For researchers, life-course epidemiology offers a framework that will help increase the relevance of clinical enquiry and improve study design and analyses. A health-service policy framework is proposed for a growing number of conditions that start in the before birth and extend as long as contemporary survival now permits. Ultimately, the goal is the precision delivery of health services that enables lifelong health management, organization of developmental health services, and integration of vertical and horizontal health-service delivery.

Pan-tropical Sentinel-2 cloud-free annual composite datasets.

Sentinel-2 MSI is one of the core missions of the Copernicus Earth Observation programme of the European Union. This mission shows great potential to map the regional high-resolution spatio-temporal dynamics of land use and land cover. In tropical regions, despite the high revisiting time of 5 days including both Sentinel-2A and 2B satellites, the frequent presence of clouds, cloud-shadows, haze and other atmospheric contaminants are precluding the visibility of the Earth surface up to several months. In this paper we present four annual pan-tropical cloud-free composites computed and exported from Google Earth Engine (GEE) by making use of available Sentinel-2 L1C collection for the period spanning from 2015 to 2020. We furthermore propose empirical approaches to reduce the BRDF effect over tropical forest areas by showing pros and cons of image-based versus swath-based methodologies. Additionally, we provide a dedicated web-platform offering a fast and intuitive way to browse and explore the proposed annual composites as well as layers of potential annual changes as a ready-to-use means to visually identify and verify degradation and deforestation activities as well as other land cover changes.

Characterizing the Subcortical Structures in Youth with Congenital Heart Disease.

BACKGROUND AND PURPOSE: Congenital heart disease is a leading cause of neurocognitive impairment. Many subcortical structures are known to play a crucial role in higher-order cognitive processing. However, comprehensive anatomic characterization of these structures is currently lacking in the congenital heart disease population. Therefore, this study aimed to compare the morphometry and volume of the globus pallidus, striatum, and thalamus between youth born with congenital heart disease and healthy peers. MATERIALS AND METHODS: We recruited youth between 16 and 24 years of age born with congenital heart disease who underwent cardiopulmonary bypass surgery before 2 years of age (n = 48) and healthy controls of the same age (n = 48). All participants underwent a brain MR imaging to acquire high-resolution 3D T1-weighted images. RESULTS: Smaller surface area and inward bilateral displacement across the lateral surfaces of the globus pallidus were concentrated anteriorly in the congenital heart disease group compared with controls (q < 0.15). On the lateral surfaces of bilateral thalami, we found regions of both larger and smaller surface areas, as well as inward and outward displacement in the congenital heart disease group compared with controls (q < 0.15). We did not find any morphometric differences between groups for the striatum. For the volumetric analyses, only the right globus pallidus showed a significant volume reduction (q < 0.05) in the congenital heart disease group compared with controls. CONCLUSIONS: This study reports morphometric alterations in youth with congenital heart disease in the absence of volume reductions, suggesting that volume alone is not sufficient to detect and explain subtle neuroanatomic differences in this clinical population.

Effect of gamma-aminobutyric acid on growth hormone and prolactin secretion in man: influence of pimozide and domperidone.

To investigate the possibility that GH release induced by gamma-aminobutyric acid (GABA) in man is mediated by a dopaminergic mechanism(s), we evaluated the effect of two antidopaminergic compounds, pimozide and domperidone, on the plasma GH response to acute GABA administration (5 g, orally). Only the former compound can freely cross the blood-brain barrier. In 9 normal volunteers, GABA caused a significant increase of plasma GH levels (P < 0.0001 vs. GH levels in a group of 14 controls). In these subjects, pimozide (6 mg/day, orally, for 4 days) significantly blunted the GH elevation induced by GABA (P < 0.01). Unlike pimozide, in 8 additional subjects, domperidone (4 mg injected iv immediately before GABA administration) did not influence the GABA-induced GH response. GABA did not alter either baseline or pimozide-stimulated plasma PRL levels. Likewise, it did not significantly modify the brisk PRL rise after domperidone injection. These findings are consistent with the hypothesis that GABA-stimulated GH secretion is mediated via dopamine release at a suprapituitary level. With regard to PRL secretion, no GABA-dopamine interactions are readily apparent.

Antioxidant drugs combined with alpha-interferon in chronic hepatitis C not responsive to alpha-interferon alone: a randomized, multicentre study.

OBJECTIVE: After non-response to the initial course of therapy, retreatment with alpha-interferon is not effective. The aim of this study was to ascertain whether the administration of N-acetyl cysteine and vitamin E could increase the response rate to retreatment with alpha-interferon. DESIGN: Prospective, multicentre clinical trial. SETTING: Twelve hospitals in Lombardy, Italy. PARTICIPANTS: 120 consecutive patients affected by biopsy-proven chronic hepatitis C who had been non-responders to a previous course of alpha-interferon, administered at the dosage of 3-6 million units (MU) three times a week (tiw) for 6 months. INTERVENTIONS: The patients were randomly assigned to one of two groups of treatment: group A, natural interferon-alphaN3, 6 or 9 MU tiw, when the body weight was < 60 kg or > or = 60 kg, respectively; group B, the same dosage of natural interferon-alphaN3 in association with oral administration of N-acetyl cysteine 1200 mg/day and vitamin E 600 mg/day. The period of treatment was 6 months in both groups. RESULTS: Neither end-therapy biochemical response nor sustained biochemical response rates were improved by the combination treatment, and in no case was clearance of the virus from serum observed. CONCLUSIONS: In this randomized study carried out on 120 patients with chronic hepatitis C not responsive to alpha-interferon, oral supplementation with N-acetyl cysteine and vitamin E did not improve the poor efficacy of retreatment with alpha-interferon alone.

Transesophageal echocardiography in congenital heart disease in the adult.

Progress achieved during the last three decades in medical and surgical treatment of infants and children with congenital heart disease has resulted in a significant number of patients surviving to adulthood. The complexity of the basic malformations in addition to the superimposed surgical interventions makes accurate diagnostic imaging essential. The scope of information obtainable from high-quality TEE supports its use in the follow-up of operated and unoperated adult patients, as well as in surgical and interventional procedures. Application of the segmental analysis of anatomy is as important during TEE as it is during TTE. Supplemental transthoracic 2-D and spectral Doppler flow measurements may be needed when poor beam alignment during TEE precludes accurate gradient determinations. Although, to date, most reports of TEE in patients with congenital heart disease have involved children and adolescents, the informational advantage is potentially greater in older adolescents and adults in whom transthoracic windows are frequently limited. In our experience with 125 TEE studies in adult patients with congenital heart disease (the majority using a biplane probe), horizontal plane TEE imaging provided important additional information concerning pulmonary venous connections, atrial baffle function, atrioventricular anatomy and function, left ventricular outflow tract lesions, and great artery positional relationships. Vertical plane TEE enhances imaging of systemic and pulmonary venous connections, atrial situs, venosus atrial septal defects, atrioventricular anatomy and function, and the ventricular septum and outflow tracts and is essential for complete assessment of complex right ventricular outflow tract anatomy, ventriculoarterial alignment, and the sizing of all aortic segments in coarctation of the aorta.

[Prevalence of infections of the ascitic fluid in 81 consecutive cirrhotic patients]. / Prevalenza di infezione del liquido ascitico in 81 cirrotici consecutivamente osservati.

During a period of 30 months the ascites of 81 patients with liver cirrhosis (65 males and 16 females; 25 in Child B class and 56 in Child C class) consecutively admitted to an Internal Medicine Department have been examined. The number of polymorphonuclear leukocytes (PMNs) and the protein content of ascites were evaluated, and cultures for aerobic and anaerobic bacteria were performed. In 46 patients ascites were sterile (SA); bacteriascites (BA) was observed in 3 patients; neutrocytic ascites (NA) in 18 patients; spontaneous bacterial peritonitis (SBP) in the remaining 14 patients. The number of PMNs and total protein content turned out to be significantly higher and lower respectively in SBP compared to the other groups (p < 0.02). In 10 out of the 17 patients with BA and SBP bacteria of enteric origin were isolated. Total mortality was 23.5% (4 cases).

[Nosographic and diagnostic classification of congenital thrombocytopathies. Clinical interpretative notes]. / Inquadramento nosografico e diagnostico delle trombocitopatie congenite. Spunti interpretativi clinici.

Substantial progress has been made in recent years in the understanding of platelets and their functions. This has permitted a more reasonable classification of congenital platelet diseases, primarily thanks to the standardization of haemostasis and platelet function tests. A comparison is made between the pictures best defined in 17 cases studied at the S. Matteo Polyclinic in recent years. This brought out certain contradictions and suggested that further study in greater depth is required.

[Pharmacokinetics of defibrotide in uremic patients undergoing hemodialysis]. / Farmacocinetica di defibrotide in pazienti uremici sottoposti ad emodialisi.

Defibrotide pharmacokinetics were studied in 6 voluntary healthy subjects and in 10 uremic patients undergoing dialysis during which (instead of heparin) defibrotide was administered to prevent fibrino-formation in the circuit. Blood concentrations of the drug were assessed (expressed with reference to the residual glycidic deoxyribose) during a standard dialysis using defibrotide, 3.5, 15, 30, 45, 60 and 90 minutes after the defibrotide bolus (200 mg) had been injected into the arterial channel. The half-lives of the alpha and beta plasmatic phases were found to be equal at 3.79 and 41.4 min in dialysed subjects and at 1.13 and 16.54 in healthy volunteers. These results indicate that in uremic patients undergoing dialysis at intervals using defibrotide, a longer time is required to eliminate the drug from the circulation. This variation does not however appear to be significant in terms of the therapeutic use of the drug during dialysis.

[Vasopressin-sensitive diabetes insipidus. Case histories]. / Diabete insipido vasopressino-sensibile. Contributo casistico.

Twelve patients, aged 16-66 years, affected by cranial diabetes insipidus either idiopathic or secondary (head injuries, histiocytosis X, metastatic tumors, pituitary or hypothalamic surgery) were studied. Diagnosis was made on the basis of both dehydration test and sensitivity to exogenous vasopressin. The relationship between plasma and urine osmolality at the end of the dehydration test was evaluated (and its usefulness for diagnostic purpose confirmed). According to this test two different conditions, namely partial and complete, of cranial diabetes insipidus were defined. All the patients underwent the following diagnostic procedures: skull x-ray, evaluation of visual fields, encephalic CT-scan. Idiopathic central diabetes insipidus incidence was found to be 33.3% of all cases, with a sharp prevalence for male sex; the median age of onset was 12.5 years. In our experience the frequency of idiopathic condition was similar to that reported in most recent literature confirming a decreasing incidence, most likely due to the use of more sophisticated diagnostic procedures.

Metastasis in the chest wall and in the right ventricle from hepatocellular carcinoma. Description of a clinical case.

The ante mortem diagnosis of right ventricular metastasis from hepatocellular carcinoma (HCC) is quite rare. Also the metastatic invasion of the chest wall following a liver biopsy is seldom reported. We describe a 67 year old patient that, 30 months after a liver biopsy showing HCC, developed an isolated metastasis of the chest in the site of the biopsy which was treated by radiotherapy. The same patient, after 8 months, complained of dyspnea on effort and ECG showed signs of ischemia: echocardiogram, CT scan and MRI revealed the presence of a metastatic mass in the right ventricular cavity. Post mortem examination confirmed the diagnosis.

[Spontaneous bacterial peritonitis (SBP): prevalence and characteristics in a population of 314 cirrhotic patients evaluated at hospital admission]. / La peritonite batterica spontanea (PBS): prevalenza e caratteristiche in una popolazione di 314 pazienti cirrotici valutati all'ingresso in ospedale.

BACKGROUND: The aim of this study was to evaluate the incidence and the characteristics of the infections of ascitic fluid in cirrhotic patients at the moment of hospital admission. METHODS: A total of 314 patients consecutively submitted to ascitic fluid tap within 3 days of hospital admission were studied. Each patient was classified according to Child-Plugh classes. Neoplastic ascites were excluded. The ascitic fluid was analyzed for PMN count, protein and albumin content, cultural and cytological examinations. The patients with ascitic fluid PMN > 250/ml were immediately treated with antibiotics. RESULTS: Out of 314 patients 11% had SBP (94% in class C patients according to Child-Plugh classification), 17% CNNA and 3% MNNB. 15% of SBP patients were asymptomatic. Total protein content in ascitic fluid was significantly lower in SBP and MNNB compared to CNNA and sterile ascites. 56% of the isolated bacteria was Gram-negative, and the most frequently found were Streptococcus, Escherichia coli and Staphylococcus. 80% of the patients with ascites infection underwent third generation cephalosporin treatment. SBP mortality (29%) was significantly higher than CNNA (9%), MNNB (10%) and sterile ascites (11%), also taking into account the subgroup without ascites infection and class C group (14%). CONCLUSIONS: In view of the high incidence (even in the absence of invasive procedures), of the possibility of symptom free patients and of the high mortality of SBP, it is advisable to carry out routine tap in all cirrhotics with ascites at hospital admission.

[Comparison between torasemide and furosemide in the treatment of ascites in cirrhotic patients]. / Confronto tra torasemide e furosemide nella terapia dell'ascite in pazienti cirrotici.

Twenty patients with cirrhosis and ascites were randomly divided in two groups to receive 20 mg/die of the new-loop-diuretic torasemide (T), and 50 mg/die of furosemide (F). All patients also received 200 mg/die of potassium canrenoate. Natriuretic and diuretic effects and consequent loss of weight were significantly better in the torasemide-group (T-group). Otherwise, loss of potassium and sodium/potassium ratio in urine were not significantly higher for T-group. Ammonium lowered with T and remained unchanged with F, but the difference was not statistically significant. No change was observed in blood-pressure, pulse-frequency, electrolyte plasmatic levels, azotemia, creatininemia and serum albumin. A significant increase of diuresis was obtained from the fourth day of treatment onwards by replacing F with T in the F-group. The T-group maintained T for eight days just to evaluate its efficacy and tolerability in the middle term: diuresis kept efficient and no side-effects occurred. This trial showed that T was a good and handy drug for cirrhosis with ascites whether as an alternative to F, or as a sequential treatment.

[Intrahepatic cholestasis: clinical and nosological classification. Critical survey of personal experience]. / Colestasi intraepatica: inquadramento nosografico e clinico. Revisione critica di casistica personale.

We reviewed 20 patients (16 females and 4 males) with intrahepatic cholestasis and recognised the following miscellaneous disorders: 12 primary biliary cirrhosis (PBC), 3 primary sclerosing cholangitis (PSC), 1 immune cholangiopathy (IC), 3 liver sarcoidosis and 1 cholestasis with Horton's arteritis. The aim of the study was to identify potentially differetiating clinical and biochemical findings in intrahepatic cholestasis. Sixty females were affected with changes reflecting a cholestatic pattern including an elevated alkaline phosphatasis and gammaglutamyltransferase level. Pruritus was found in 50 percent of PBC patients; fever addressed often, in liver sarcoidosis and Horton's arteritis. A striking increase of unesterified cholesterol was a common feature of PBC. An elevated polyclonal serum IgM in PBC such as in PSC. A circulating IgM antimitochondrial antibody and antinuclear antibodies were found in 90 percent of PBC patients; isolated antinuclear antibodies were detected in immune colangiopathy patients (IC). Liver biopsy was necessary to establish the diagnosis of intrahepatic cholestasis. Overlapping histopathologic features made diagnosis hard in cholestatic disorders, all but in liver sarcoidosis. Treatment with UDCA or TUDCA+/-colchicin, reduced cholestatic enzymes in 85 percent of PBC cohort, while it was unsuccessful in PSC-group. Steroid treatment was successful in sarcoidosis, Horton's arteritis and immune colangiopathy. Cy A did not improve clinical and biochemical features in PBC.

[The neuroleptic malignant syndrome (NMS). A report of a clinical case with a protracted and recurrent course. A review of the literature]. / Sindrome maligna da neurolettici (SMN). Descrizione di un caso clinico a decorso protratto e recidivante. Rassegna della letteratura.

Neuroleptic malignant syndrome (NMS), characterized by catatonic behavior, generalized muscular rigidity, hyperthermia and autonomic dysfunction, can suddenly arise in patients treated with neuroleptic agents and carries a high mortality rate even today. A case of NMS due to i.m. therapy with haloperidol decanoate is reported in this paper, characterized by sustained course and a severe relapse due to a different therapy with another neuroleptic agent. The patient however, after a prolonged remission from the relapse, was able to resume long term therapy with neuroleptic drugs. The importance of monitoring blood levels of CPK during the follow-up and the effectiveness of therapy with bromocriptine and dantrolene in confirmed. Although the patient presented a good clinical response, she developed permanent cerebral and muscular damage. A wide review of the literature on NMS is reported to throw light on this syndrome, whose recognition and prompt diagnosis are necessary to reduce mortality.

[Therapy of chronic hepatitis C with alpha-interferon in 182 patients. Evaluation of results, response predictive factors and side effects]. / Terapia delle epatiti croniche da virus C con alpha-interferone in 182 pazienti. Valutazione di risultati, fattori predittivi la risposta ed effetti collaterali.

BACKGROUND: The aim of this study was to assess the results, predictors of response and side effects of therapy with alpha-interferon (IFN) in chronic C virus (HCV) infection. METHODS: A group of 182 patients (150 chronic hepatitis and 32 cirrhosis) was treated with alpha-interferon--recombinant IFN in 120 cases (66%), and lymphoblastoid IFN in 62 cases (34%)--at a dosage of 3 MU three times weekly for 12 months. All our patients were prospectively followed for at least 6 months, and 133 patients for more than 2 years. RESULTS: A short-term positive response was achieved in 65% of our patients, a sustained response in 34%, and a long-term response in 35%, the responses being similar both for hepatitis and cirrhosis. Liver histology, after 2 years, improved in 73% of long-term responders, whereas it improved only in 34% of relapsers. The predictors of response were: age, duration of disease, baseline levels of gamma-glutamyltranspeptidase (GGT) and serum ferritin. Both types of IFN proved to have the same efficacy. Side effects were observed in 52% of our patients, which were correlated with age and female sex. CONCLUSIONS: Interferon therapy yields good results, if administered for 12 months, in young patients with disease of short duration and low baseline levels of GGT and serum ferritin, even in the presence of cirrhosis, if at early-stage. Patients with normal alanine aminotransferase (ALT) levels after 3 years may be considered fully recovered. The dosage employed was well tolerated.

[The utility of angiography in the diagnosis and localisation of hepatic angiomas (author's transl)]. / L'utilita' dell'angiografia nella diagnosi e nell'inquadramento degli angiomi epatici.

In the study of benign hepatic tumours, angiography of the coeliac tripod is a fundamental step in the diagnostic course, allowing them to be characterised in detail; within the framework of evaluation of the said expansive forms, particular attention has been directed to differential diagnosis in relation to those malignant lesions that can simulate a benign process.

[Portal cavernoma. Observation of a case and clinico-nosographic considerations (author's transl)]. / Cavernoma portale. Osservazione di un caso e considerazioni clinico-nosografiche.

The clinical case of a sixty-two year old woman suffering for about six years from rare episodes of cramplike pains in the right hypochondriac region, radiated to the homolateral scapula, is described. After diagnosis of biliary calculosis, the patient was admitted to hospital and her gallbladder removed. During the operation a number of venous ectasias of the portal system were evidenced at the hepatic hilus, and their biopsy led to a diagnosis of portal cavernoma. The possible part played by the cavernoma in producing the patient's clinical picture is discussed, with reference also to other cases of cavernoma of varying location. This is followed by a review of the literature, in which stress is placed on the different aetiopathogenetic interpretations of angiomas and in particular of portal cavernomas. The possible evolution of angiomas and present treatment trends are also mentioned.

Monitoring the trend of overweight children in Cremona (anni 1990-1998).

AIM: To evaluate the trend of infantile obesity in the school-aged population of Cremona over time. METHODS: The weight and height of all children aged 6, 9 and 11 attending schools within the health district of Cremona were measured for 9 consecutive years (January 1990-March 1998), giving a total of 17,730 measurements. Pupils whose bodyweight was 20% above the mean weight for stature and sex given by NCHS canthimetric classes were defined as obese. In addition, three degrees of obesity were defined: slight obesity (20-29% excess bodyweight), moderate obesity (30-50%) and severe obesity (over 50%). RESULTS: This study showed the trend of the increasing prevalence of infantile obesity in the zone in question: it rose from an overall level of 6.1% to 13.6% in 1998. The increase regarded all age groups; levels were three times higher in older children, but obesity had more than doubled in 6-year-olds. With regard to the three classes of obesity, there was a particularly striking increase in moderate obesity, whereas the cases of severe obesity remained constant. CONCLUSIONS: These data underline the need for more incisive educational and preventive work in the field of infantile obesity to be carried out as soon as possible.