Clinical profile and predictors of in-hospital outcome in patients with heart failure: the FADOI "CONFINE" Study.

BACKGROUND: Heart failure (HF) is a major health and social problem. Internal Medicine (IM) wards admit a high proportion of patients with HF, frequently with advanced age and comorbidities. Few recent data are available in this setting, especially on predictors of in-hospital outcome. METHODS: In this observational study, we recruited patients admitted with diagnosis of HF and present in five index days, in 91 units of IM in Italy. Characteristics and management of HF, comorbidities, functional and cognitive status, and quality of life, were analyzed. RESULTS: We observed 1411 patients, with a mean age of 78.7 ± 9.6 years. At admission, 81.7% of the patients were in NYHA classes III-IV. Ninety percent of the patients had at least one comorbidity. Dementia or severely impaired functional status were registered in 21.5% and 22.8% of the patients. In 89 patients (6,3%) a negative outcome (death or clinical worsening) occurred during hospitalization. A number of variables were significantly related to negative outcome by means of univariate analysis (systolic blood pressure <100 mm Hg, pulse pressure ≥ 55 mm Hg, anaemia, brain deficit, permanent bed rest, Barthel Index ≤ 30). At multivariable analysis, significant correlation was retained by anaemia and Barthel Index ≤ 30, the latter being the strongest predictor. CONCLUSIONS: Real-world patients with HF and hospitalized in IM are frequently very old, frail and with multiple comorbidities. Functional and cognitive status significantly influence patients' outcome, and this could lead to a rethinking of the overall (in-hospital but also home-based) management of HF.

Pancreatic cancer: diagnosis and endoscopic staging.

Early diagnosis and appropriate staging of pancreatic adenocarcinoma is of vital importance to possibly detect this otherwise lethal disease at a curable phase and to stratify patients who would benefit the most from surgical resection. The availability of endoscopic ultrasound (EUS) with its unique capability of obtaining refine images of the pancreas has represented a major breakthrough in the management of these difficult tasks. Furthermore, the ability to perform fine needle aspiration (FNA) under real time EUS guidance has offered the possibility to reach a definite diagnosis which has a major impact on the decision making process in the care of patients with both resectable and unresecectable pancreatic cancer. In parallel to the widespread importance of diagnostic EUS, the therapeutic applications of EUS are increasing and may further expand the role of this procedure in the management of pancreatic cancer. This article focuses on the current role of EUS and EUS-FNA in the diagnosis and staging of solid pancreatic lesions in different clinical scenarios, including those individuals at a high risk of developing pancreatic cancer and who may be candidates for a EUS-based screening and surveillance program. Data on the emerging therapeutic role of EUS for pancreatic cancer treatment will also be reviewed.

Endoscopic ultrasound in the evaluation of pancreaticobiliary disorders.

The close proximity of the endoscopic ultrasound probe to the pancreas coupled with the ability to perform fine needle aspiration has made endoscopic ultrasound an extremely important technique for the evaluation of both benign and malignant pancreaticobiliary disorders. In parallel to the widespread importance of diagnostic endoscopic ultrasound, the therapeutic and interventional applications of this procedure are expanding and may become a major breakthrough in the management of pancreaticobiliary diseases. This article focuses on the utility and recent advances of endoscopic ultrasound in the diagnostic evaluation pancreaticobiliary disorders and analyses the data of well established interventional procedures such as celiac plexus neurolysis and pseudocyst drainage. Moreover, the more innovative procedures, such endoscopic ultrasound-guided biliary and pancreatic ducts access and drainage and the experimental use of direct endoscopic ultrasound-guided therapy of both solid and cystic pancreatic lesions will also be reviewed.

Concomitant intraductal papillary mucinous neoplasm and pancreatic endocrine tumour: Report of two cases and review of the literature.

It has been suggested that the occurrence of intraductal papillary mucinous neoplasms in association with pancreatic endocrine tumours is more frequent than expected [Goh BK, Ooi LL, Kumarasinghe MP, Tan YM, Cheow PC, Chow PK, et al. Clinicopathological features of patients with concomitant intraductal papillary mucinous neoplasm of the pancreas and pancreatic endocrine neoplasm. Pancreatology 2006;6:520-6]. Up to now, 10 patients with concomitant intraductal papillary mucinous neoplasms and pancreatic endocrine tumours have been reported [Goh BK, Ooi LL, Kumarasinghe MP, Tan YM, Cheow PC, Chow PK, et al. Clinicopathological features of patients with concomitant intraductal papillary mucinous neoplasm of the pancreas and pancreatic endocrine neoplasm. Pancreatology 2006;6:520-6; Zhao X, Stabile BE, Mo J, Wang J, French SW. Nesidioblastosis coexisting with islet cell tumor and intraductal papillary mucinous hyperplasia. Arch Pathol Lab Med 2001;125:1344-7; Marrache F, Cazals-Hatem D, Kianmanesh R, Palazzo L, Couvelard A, O'Toole D, et al. Endocrine tumor and intraductal papillary mucinous neoplasm of the pancreas: a fortuitous association? Pancreas 2005;31:79-83]. In most cases the synchronous existence of both tumours was incidentally discovered after the examination of the surgical specimen. We report two additional patients with intraductal papillary mucinous neoplasms and pancreatic endocrine tumours, in whom both tumours were diagnosed before surgery.

[Evaluation of thyroid function in a group of over-eighty year-old people]. / Valutazione della funzionalità tiroidea in un gruppo di ultraottantenni.

AIM: A number of studies has shown that during aging thyroid presents some structural changes, whilst no data agree about secretory activity. The aim of the present study was to evaluate thyroid function in a group of healthy over-80 years old people vs a group of young subjects. METHODS: This study was performed on 48 old people, 33 women (68.75%) and 15 men (31.25%), mean age 86.38+/-5.20 years old and 43 young subjects, mean age 33.35+/-3.75 years old; all of them were euthyroid and were not affected with any acute or chronic diseases and did not take any drugs which could interfere with thyroid function. A blood sample was taken from each patient, for dosing TT3, TT4, FT3, FT4, TSH, TgAb, TPOAb. RESULTS: The results of the present study show low serum levels of TT3 in healthy over-80 year old people compared to young people, even if serum levels of TT4, FT3, FT4, TSH have no significant changes. CONCLUSIONS: Functional reduction in thyroid activity during aging has not to be considered responsible for senile involution; it is more appropriate to define it as the expression of a metabolic slow down in the elderly.

[Falls in the elderly]. / Le cadute nell'anziano.

Falls are the main causes of accidental death and disability in elderly people, since they may especially cause hip fractures and a number of related complications. Available incidence estimates are surely in defect, because falls are often omitted both by patients, their family and caregivers. Risk factors may be classified in intrinsic and extrinsic; the former include muscular and osteoarticular diseases or other favouring conditions, whilst the latter include environmental or iatrogenic factors, such as drugs or alcohol consumption. Extrinsic factors may be rapidly modified in the elderly and thus prevented. In fact, prevention of falls is the main intervention of geriatrist, both at patient's home and if patient is hospitalized. In order to reduce the risk of falls, it is sometimes sufficient to stop a treatment or to reduce the doses of drugs causing sedation or orthostatic hypotension, to avoid if possible, the use of sedative-hypnotics, to use non-pharmacological methods for treating insomnia. The introduction of the necessary changes in the environment, the promotion of physical activity, the individuation of the subjects with a high risk of falls and the use of hip protectors are useful means for preventing falls and avoiding their harmful consequences.

A coiled-coil oligomerization domain of Bcr is essential for the transforming function of Bcr-Abl oncoproteins.

In Philadelphia chromosome-positive human leukemias, the c-abl proto-oncogene on chromosome 9 becomes fused to the bcr gene on chromosome 22, and chimeric Bcr-Abl proteins are produced. The fused Bcr sequences activate the tyrosine kinase, actin-binding, and transforming functions of Abl. Activation of the Abl transforming function has been shown to require two distinct domains of Bcr: domain 1 (Bcr amino acids 1 to 63) and domain 2 (Bcr amino acids 176 to 242). The amino acid sequence of domain 1 indicates that it may be a coiled-coil oligomerization domain. We show here that domain 1 of Bcr forms a homotetramer. Tetramerization of Bcr-Abl through Bcr domain 1 correlates with activation of the tyrosine kinase and F-actin-binding functions of Abl. Disruption of the coiled coil by insertional mutagenesis inactivates the oligomerization function as well as the ability of Bcr-Abl to transform Rat-1 fibroblasts or to abrogate interleukin-3 dependence in lymphoid cells. These results strongly suggest that Bcr-Abl oligomers are the active entities in transformation.

Down-regulation of SPARC/osteonectin/BM-40 expression in methylcholanthrene-induced fibrosarcomas and in Kirsten-MSV transformed fibroblasts.

SPARC (secreted protein acid and rich in cysteine), also known as osteonectin or BM-40, is a glycoprotein associated with the extracellular matrix of bone as well as with many soft tissues that produce extracellular matrix, including matrix-producing tumours. Northern and slot-blot analyses were used to study SPARC expression in tumours induced in vivo by methylcholanthrene (MCA) and in transformed cells induced in vitro by Kirsten-MSV and SV-40 infection. MCA-induced tumours expressed SPARC mRNA at quantitatively different levels. Fibroblasts transformed in vitro by Kirsten-MSV, and, to a lesser extent, by SV-40, showed reduced levels of SPARC mRNA expression compared with normal fibroblasts. Run-on assay indicated that transcription of SPARC was lower in the Kirsten-MSV transformed cells than in the normal parental fibroblast culture. However, SPARC mRNA in the transformed culture was as stable as that in normal culture. The difference, therefore, between levels of SPARC mRNA in transformed and normal culture was mainly due to different rates of transcription. Cloned cell lines derived from the Kirsten-MSV transformed culture also showed heterogeneous expression of SPARC: two lines had high and two had low expression of the gene. The level of mRNA correlated with that of the protein secreted. The SPARC expression might contribute to the malignant phenotype.

Effect of adrenergic and Ca2+ antagonists on increased ornithine decarboxylase expression in regenerating rat liver.

Partial hepatectomy (PH) (70% resection) causes within 4 hr an accumulation of ornithine decarboxylase (EC 4.1.1.17, ODC) mRNAs concomitant with an increase in ODC activity, maximum values being observed at 8 and 16 hr, respectively. In the early hours of hepatic regeneration, enhancement of transcriptional-rate of ODC gene, demonstrated by nuclear run-on analysis, can account for the accumulation of ODC mRNAs. The involvement of catecholamines in these processes is demonstrated by using prazosin and propranolol, specific antagonists of alpha 1 and beta adrenoceptors, respectively. Prazosin reduces almost completely the rise of ODC activity at 4 hr, without affecting mRNA levels. At 16 hr, enzyme activity and mRNAs increase, however, over the values observed in regenerating liver of prazosin-untreated animals. These findings suggest that alpha 1-receptor activation triggers positive control signals for ODC gene expression at the early time of liver regeneration and, on the contrary, negative signals at later times by mainly post-transcriptional and transcriptional mechanisms, respectively. Propranolol reduces similarly the initial 4 hr-rise of ODC activity. These results indicate that activation of both alpha 1- and beta-adrenoceptors causes the large increase in ODC activity. Pharmacological manipulation of intracellular Ca2+ levels by verapamil, a Ca2(+)-channel blocker, or neomycin, an inhibitor of Ca2+ release from endogenous stores, diminishes ODC activity at 4 and 16 hr after PH. ODC mRNA levels, which are not modified at 4 hr, increase over the values of partially hepatectomized rat liver at 16 hr. Trifluoperazine inhibits both ODC activity and mRNA accumulation at the times studied. As a working hypothesis it is proposed that Ca2(+)-mediated processes induced by catecholamines are involved in ODC gene expression during the prereplicative phase of liver regeneration.

Osteonectin transcript and metastatic behavior in v-Ki-ras transformed fibroblasts.

Osteonectin is one of the major non-collagenous proteins of bone. However, its transcript has been found in many soft, extracellular matrix-producing tissues; an osteonectin-related protein was detected in tumor basement membrane. We have investigated the expression of osteonectin gene in fresh BALB/c fibroblasts transformed by v-Ki-ras. Transformed cells exhibited lower levels of RNA as compared with normal fibroblasts. The transformed cells were cloned after in vivo tumorigenic assay, and 4 clones were analyzed for osteonectin expression by Northern blots. Two of them were selected for high or low osteonectin expression and tested in vivo in spontaneous and artificial metastasis assays. High osteonectin expression was correlated with high lung colonization. When 10(5) cells were injected i.v., median colony value was 55 and 20 in higher expressor vs. lower expressor respectively (p less than 0.005). Spontaneous metastasis indicates a possible reverse correlation. Our data align osteonectin with other matrix-components and adhesion molecules in affecting potential metastatic spreading of transformed cells.

Cardiac pacing practices in the United States in 1985.

Physicians active in pacemaker implantation and follow-up were surveyed to obtain a profile of permanent cardiac pacing practices in the United States during 1985. Questionnaires were sent to 628 physicians, mainly in New Jersey; 145 responses were received and analyzed. A separate questionnaire was sent to 9 pacemaker manufacturers to solicit information concerning the volume of pacemaker sales and their opinions on a variety of subjects. The rate of permanent pacemaker implantation declined for the first time: it dropped from 518 devices per million population in 1981 to 374 in 1985. Sinus node dysfunction was the chief indication for permanent pacing in 52% of primary implantations; conduction disorders of the atrioventricular node and His-Purkinje system accounted for 41% and ventricular tachyarrhythmias for 2%. Dual-chamber pacing modes were used less frequently than was predicted in 1981, accounting for 30% of primary and 19% of replacement pacemakers. More than 43% of programmable pulse generators were never reprogrammed after implantation. Surveys such as this continue to provide useful information despite obstacles encountered in the use of questionnaires. Important differences in practice patterns and outcomes were identified between surgeons and nonsurgeons, and between frequent and infrequent implanters. These differences reinforce the suggestion that implanters should work at a volume sufficient to maintain their expertise, and that cooperation between surgeons and nonsurgeons would lead to improvements in patient selection, surgical results and optimal pacemaker programming and follow-up care. Better results could be achieved by adopting the continent-wide system of a pacemaker registry now used in Eastern Europe and Great Britain.

A special outpatient clinic for following patients with implanted tachyarrhythmia devices.

Implantable anti-tachycardia devices have become an additional therapeutic option for those patients afflicted with life-threatening tachyarrhythmias. Follow-up of these complex devices are time-consuming and, if mismanaged, may be dangerous to the patient. For these reasons, a special anti-tachycardia device clinic was started at Newark Beth Israel Medical Center in July 1984. From the inception of the clinic to September 1985, 24 patients were followed. Seventy-five percent had antitachycardia devices (ATDs) implanted for treatment of ventricular tachyarrhythmias (VT/VF) with the remaining 25% for supraventricular tachycardias. All patients were seen every 3 months or more often if clinically required. Of 112 clinic examinations, 102 (91%) were scheduled appointments (group I) while the remaining 10 visits (group II) were unscheduled and preceded by symptomatic episodes. The problems detected in clinic (groups I and II) ranged from sudden failure of an AICD to apprehension. Appropriate nonoperative treatment was given during clinic evaluation for 60% of the problems detected in group II, while the remaining 40% required eventual surgical intervention. Compliance throughout the 15-month follow-up period was 100%. Major benefits of the clinic cited by patients and their families were continuity of care, the time allotted to meet the individual needs, and management of most problems on an out-patient basis.

Guidelines for developing multidisciplinary treatment plans.

The formulation of a multidisciplinary treatment plan is important not only because it is required by federal and accreditation agencies but because it increases communication, consistency, and direction among members of the treatment team. Input from all disciplines is most effectively obtained through the multidisciplinary treatment planning conference. The author provides guidelines for formulating a plan in each of four major steps: assessment, problem identification, planning (including priorities, long- and short-term goals, and interventions), and evaluation.