Body mass index, lifestyles, physical performance and cognitive decline: the "Treviso Longeva (TRELONG)" study.

OBJECTIVES: The relative contributions of risk factors, as body mass index (BMI), depression, chronic diseases, smoking, and lifestyles (as physical and performance activity, social contacts and reading habit) to cognitive decline in the elderly are unclear. We explored these variables in relation to 7-year cognitive decline in long-lived Italian elderly. DESIGN: Secondary data analysis of a longitudinal study of a representative, age-stratified, population sample. SETTING: The TREVISO LONGEVA (TRELONG) Study, in Treviso, Italy. PARTICIPANTS: 120 men and 189 women, age 77 years and older (mean age 80.2 ± 6.9 years) survivors after seven years of follow up. MEASUREMENTS: Cognitive decline measured as difference between Mini-Mental State Examination (MMSE) score in 2003 and in 2010; Body mass index (BMI), handgrip, Short Physical Performance Battery (SPPB) score, social contacts, reading habit, sight, hearing, schooling, mediterranean diet and multiple clinical and survey data recorded at baseline in 2003. RESULTS: In separate univariate analyses, age, SPPB score < 5, depressive symptoms (GDS) and more comorbidities (CCI) were associated with greater cognitive decline. Otherwise higher BMI, higher handgrip, reading habit, non-deteriorated sight and hearing, and schooling were protective. In a final multivariate model, age and higher BMI were associated with greater cognitive decline while reading habits was protective. SPPB score < 5 tends, though weakly, to be associated with greater cognitive decline. These associations remained with multivariate adjustment for gender, schooling, Charlson co-morbidity index (CCI) and baseline MMSE. CONCLUSION: Age and higher baseline BMI, independent of gender, and other confounding factors, are risk factors for cognitive decline. Reading habit plays a protective role seven years later among northern Italian adults aged 70 years or older. Low physical performance tends, though weakly, to be associated with greater cognitive decline.

The Treviso Dementia (TREDEM) Study: A Biomedical, Neuroradiological, Neuropsychological and Social Investigation of Dementia in North-Eastern Italy.

BACKGROUND: The incidence of dementia increases exponentially with age but knowledge of real disease-modifying interventions is still limited. OBJECTIVES: To describe the study design and methods of a large prospective cohort study aimed at exploring the complex underlying relationships existing among cognition, frailty, and health-related events in older persons with cognitive impairment. DESIGN: Prospective cohort study of a representative population of outpatients attending the Treviso Cognitive Impairment Center between 2000 and 2010. SETTING: The TREVISO DEMENTIA (TREDEM) Study conducted in Treviso, Italy. PARTICIPANTS: 490 men and 874 women, mean age 79.1 ± 7.8 years (range 40.2-100 years). MEASUREMENTS: Physiological data, biochemical parameters, clinical conditions, neuroradiological parameters (e.g., brain atrophy and cerebral vascular lesions identified by computerized tomography scans), neuropsychological assessment, and physical function markers were measured at baseline. Patients were followed-up to 10 years. RESULTS: The final sample included in the study was predominantly composed of women and characterized by an initial physical function impairment and increased vascular risk profile. Cognitive function of the sample population showed moderate cognitive impairment (Mini Mental State Examination 20.2 ± 6.3; Clinical Dementia Rating 1.2 ± 0.7), and a prevalence of vascular dementia of 26.9%. Cortical, subcortical and hippocampus atrophy were all significantly correlated with age and cognitive function. CONCLUSION: Results obtained from the preliminary analyses conducted in the TREDEM study suggest that the database will support the accomplishment of important goals in understanding the nature of cognitive frailty and neurodegenerative diseases.

La enseñanza clínica: el caso de la recorrida de sala / Clinical teaching: the case of bedside rounds # / Clinical teaching: the case of the ward tour / Clinical teaching: the case of bedside rounds #

Posiblemente la enseñanza al lado de la cama del paciente sea tan antigua como la medicina misma. Grandes maestros de la medicina como F. Silvio o Sir W. Osler abogaron por un uso intenso de la misma destacando sus virtudes. En la era moderna, se le reconoce a la enseñanza en las recorridas múltiples aspectos que no pueden ser enseñados en el aula, como el aprendizaje de las habilidades de la comunicación, de la exploración física, la enseñanza de los aspectos humanísticos, etc., pero también múltiples barreras que dificultan una exitosa implementación. En este artículo, se detallan las barreras que con mayor frecuencia impiden que el docente promueva un aprendizaje significativo y profundo, y una serie de propuestas prácticas que favorecen su adecuada implementación. (AU)

Possibly, bedside teaching in medicine is as old as medicine itself. Through history, well-known professors like F. Silvio and Sir W. Osler considered the strength of this teaching strategy and promoted it extensively. In the modern age, it is recognized that bedside teaching covers a variety of aspects that can not be taught in the classroom, such as learning of communication skills, physical examination, etc.; but at the same time, multiple barriers to its successful implementation have been identified. In this article, we describe the most common barriers that teachers should overcome to promote a meaningful and deep learning; as well as a series of practical proposals that are indicated to favour a proper implementation.(AU)

Effect of conditioning horses every third day at v10 on measures of fitness.

This study examined the effect of exercising horses five times per fortnight with two bouts of 5 min duration at their v(10) with 2 days between consecutive exercise sessions. Five Anglo-Arabian horses were treadmill-conditioned for 6 weeks. A standardized exercise test (SET) was performed at the beginning of the conditioning period (CP) to determine the blood lactate-running speed (BLRS) and the heart rate-running speed (HRRS) relationship and the SET was repeated every 2 weeks. After each SET, the BLRS relation was used to calculate the horse's speed (v = velocity), which produced a blood lactate concentration (LA) of 10 mmol/l (v(10) ) and 4 mmol/l (v(4) ). From the HRRS was calculated the speed at which the horses had a heart rate of 180 b/min (v(180) ). Each horse was then conditioned for the next 2 weeks five times at its individual v(10) for two 5-min bouts. Exercise speed was individually adapted to the new v(10) every 2 weeks. In addition, horses were submitted to another SET prescription to determine the peak oxygen consumption (VO(2 peak) ) before, after 3 weeks and at the end of CP. The v(4) of horses increased during the CP (p < 0.05). v(180) did not change (p > 0.05). VO(2 peak) increased in the first 3 weeks of CP (p < 0.05) and levelled off afterwards (p > 0.05). The conclusion drawn was that exercising horses five times per fortnight at their v(10) for two 5-min bouts with 2 days between consecutive exercise sessions improved v(4) and VO(2 peak) but not v(180).

Factors related to disability: evidence from the "Treviso Longeva (TRELONG) study".

Prolongation of life is an important public health goal as long as there is an emphasis on the quality of life (QoL) and independent living. Diminishing abilities to ambulate and participate in activities of daily living point to a serious decline in functional health, increasing the risk of institutionalization and death. In our work we found a pattern of factors associated with disability, especially cognitive impairment, as well as stroke, physical activity and performance, reading, and the nutritional biomarkers, blood albumin and high-density lipoprotein cholesterol (HDL-C). The attention to this cluster of markers, suggesting multidimensional prevention, may have unexpected good effects against disability.

Total hip arthroplasty offset measurement: is C T scan the most accurate option?

BACKGROUND: Femoral offset is difficult to precisely evaluate with conventional X-ray techniques. Femoral offset characterizes the balance between body weight and the resistance provided by the abductor muscles. Total hip arthroplasties should respect this balance. HYPOTHESIS: Computed tomodensitometry (CT-scan) is more accurate than conventional X-ray to evaluate femoral offset. MATERIALS AND METHODS: Sixty-one patients who received unilateral total hip arthroplasties were prospectively included in the study. Femoral offset was measured by three-dimensional CT-scan reconstruction using the "Hip Plan" (Symbios) software. Offset was also determined with conventional X-ray and results were compared. This software can be used to measure leg length by frontal telemetry. It was developed for preoperative-planning of cementless femoral stem implants with modular necks of various lengths and angles. All pre- and postoperative measurements were made according to the same protocol. RESULTS: Femoral offset values in this study were very similar to anatomical values found in the literature. They were significantly higher than values obtained by conventional X-ray by an average of 8%. Implantation of hip replacements resulted in a significant increase in offset (1.88+/-4.71 mm) with a slight variation in leg length. Pre- and postoperative leg length increased slightly in the operated leg by an average of 1.66+/-5.63 mm. Seventeen percent of these femurs had high offset associated with small or average sized proximal medullary canals. This preoperative planning software made it possible to identify these difficulties and to adapt implant components using modular long 8 degrees varus necks to restore high offset. In most of these cases, only small femoral stems could be implanted because of the small size of the intramedullary femoral canal. These individual differences were identified with 3D CT-scan reconstruction and included in the preoperative planning. Moreover, leg length could also be evaluated with this method and included in the preplanning. DISCUSSION: Compared to conventional X-ray, measurements obtained with this preoperative planning method using 3D CT-scan reconstruction are easy to obtain and not dependent upon test conditions because the frame is placed on the femoral axis. Measurements are not influenced by position inconsistencies or if the hip is fixed in external rotation. The significant number of cases with above average offset confirms the importance of obtaining these measurements and the necessity of adapting the strategy in these cases by using lateralized stems, or, as in our series, modular necks to adjust femoral offset and neck angle. LEVEL OF EVIDENCE: Level III diagnostic prospective study.

Accuracy of reconstruction of the hip using computerised three-dimensional pre-operative planning and a cementless modular neck.

Pre-operative computerised three-dimensional planning was carried out in 223 patients undergoing total hip replacement with a cementless acetabular component and a cementless modular-neck femoral stem. Components were chosen which best restored leg length and femoral offset. The post-operative restoration of the anatomy was assessed by CT and compared with the pre-operative plan. The component implanted was the same as that planned in 86% of the hips for the acetabular implant, 94% for the stem, and 93% for the neck-shaft angle. The rotational centre of the hip was restored with a mean accuracy of 0.73 mm (SD 3.5) craniocaudally and 1.2 mm (SD 2) laterally. Limb length was restored with a mean accuracy of 0.3 mm (SD 3.3) and femoral offset with a mean accuracy of 0.8 mm (SD 3.1). This method appears to offer high accuracy in hip reconstruction as the difficulties likely to be encountered when restoring the anatomy can be anticipated and solved pre-operatively by optimising the selection of implants. Modularity of the femoral neck helped to restore the femoral offset and limb length.

High pathological response rate in locally advanced esophageal cancer after neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy schedule with protracted venous infusion of 5-fluorouracil and dose escalation of cisplatin, docetaxel and concurrent radiotherapy.

BACKGROUND: This phase I study was aimed at defining the toxicity profile and pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, protracted venous infusion (PVI) of 5-FU and concomitant radiotherapy (RT) in locally advanced esophageal cancer. PATIENTS AND METHODS: The schedule consisted of a first phase of chemotherapy alone and a second phase of concurrent chemoradiation. Initial doses were: docetaxel and cisplatin 20 mg/m2 on days 1, 8, 15, 29, 36 and 43 plus 5-FU 150 mg/m2 PVI on days 1-21 and 29-49; RT (40 Gy) started on day 29. In the following steps the doses were escalated up to docetaxel 35 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 29, 36, 43, 50 and 57 plus 5-FU 180 mg/m2 PVI on days 1-21 and 150 mg/m2 PVI on days 29-63 concurrently with RT 50 Gy. RESULTS: Forty-seven patients were enrolled and 46 completed the planned treatment. During the concomitant phase, grade 3-4 hematological toxicities occurred in three patients (6.5%) (or 3/174 cycles) and non-hematological toxicities in six patients (13%) (or 7/179 cycles). A pathological downstaging was obtained in 59.6% of the cases (28/47): complete remission (pCR) in 14 patients, near pCR (residual microfoci on the primary pN0) in eight patients, pT2 pN0 in three patients and partial response on the primary with positive lymph nodes in three patients. Six (13%) and 13 (28%) patients were considered stable and non-responders, respectively. In the last dose level, eight pCR and four near-pCR were obtained out of 15 patients. The maximum tolerable dose was not formally defined because dose escalation was stopped at the last dose level. CONCLUSION: This schedule represents a feasible treatment and the high pathological response rate is extremely encouraging; the doses found in the last dose-level are the basis for an ongoing phase II study at our institution.

Pattern of recurrence after surgery in adenocarcinoma of the gastro-oesophageal junction.

AIMS: This study reports mode, timing and predictive factors of recurrence after curative surgery for cardia cancer. METHODS: A prospective study in a series of 92 curatively (R0) resected patients from 1988 to 2002. RESULTS: The 5-year recurrence rate was 71%. Lymph node involvement was the only predictor of recurrence. No patients with more than 6 metastatic nodes were free from relapse 2 years after surgery. Locoregional, peritoneal and haematogenous relapses showed a similar median recurrence time (12, 10 and 12 months, respectively), 80% occurred within 24 months. CONCLUSIONS: Few patients can be cured by surgery, lymph nodal involvement is the only predictor of recurrence.

Persistent excess mortality from lung cancer in patients with stage I non-small-cell lung cancer, disease-free after 5 years.

Among patients with non-small-cell lung cancer (NSCLC), those with pathological stage I have the best expectation of survival; however, survival is reduced to less than 50% in the long term. At present, it is unclear when patients can be reasonably defined as cured, and if they experience a higher incidence of malignant/nonmalignant diseases and a lower expectation of survival than the general population. A total of 134 stage I NSCLC patients, who had undergone resection at the Thoracic Surgery Unit of the General Hospital of Verona (north-eastern Italy) from October 1987 to December 1993, were still disease-free at 5 years. These subjects were further followed up, and morbidity and mortality rates were compared with those recorded in the general population of the same geographical area. The standardised incidence ratios (SIRs) for all malignancies and for lung cancer were higher than expected (2.39, 95% CI=1.6-3.5, P<0.001; 10.1, 95% CI=6.2-15.6, P<0.0001, respectively). The standardised mortality ratio (SMR) was also significantly increased (1.73, 95% CI=1.1-2.6, P=0.013). The excess mortality could be entirely explained by an increase in mortality from lung cancer (5.7, 95% CI=2.8-10.1, P<0.0001). This study shows that patients, resected for pathological stage I NSCLC and tumour-free after 5 years, have a higher incidence of new lung cancer compared with the general population, which in turn determines an excess in all-cause mortality in the following years.

Independent prognostic value of fascin immunoreactivity in stage I nonsmall cell lung cancer.

Fascin-1, the most expressed form of fascin in vertebrate tissues, is an actin-bundling protein that induces cell membrane protrusions and increases motility of normal and transformed epithelial cells. Very few data are available on the role of this protein in nonsmall cell lung cancer (NSCLC). Two hundred and twenty patients with stage I NSCLC and long-term follow-up were evaluated immunocytochemically for fascin expression. Overall, variable fascin immunoreactivity was detected in 98% of 116 squamous cell carcinomas, in 78% of 96 adenocarcinomas, in 83% of six large cell carcinomas, and in the two adenosquamous carcinomas under study. Neoplastic emboli were commonly decorated by the antifascin antibody (P<0.001), also when the surrounding invasive carcinoma was unreactive. Fascin immunoreactivity correlated with high tumour grade (P=0.017) and, in adenocarcinomas, with high Ki-67 labelling index (P=0.021). Adenocarcinomas with a prevalent bronchiolo-alveolar in situ component were less commonly immunoreactive for fascin than invasive tumours (P=0.005). Contralateral thoracic or distant metastases were associated significantly with diffuse (>60% immunoreactive tumour cells) fascin expression in adenocarcinomas (P=0.043), and marginally with strong fascin immunostaining in squamous cell carcinomas (P=0.13). No associations were noted with any other clinicopathological variables tested. Patients with tumours showing diffuse (>60% immunoreactive neoplastic cells) and/or strong immunoreactivity for fascin had a shorter survival (P=0.006 for adenocarcinomas and P=0.026 for squamous cell carcinomas), even after multivariate analysis (P=0.014 and 0.050, respectively). The current study documents for the first time that fascin is upregulated in invasive and more aggressive NSCLC, being an independent prognostic predictor of unfavourable clinical course of the disease. Targetting the fascin pathway could be a novel therapeutic strategy of NSCLC.

The presence of bone marrow cytokeratin-immunoreactive cells does not predict outcome in gastric cancer patients.

The independent prognostic significance of isolated tumour cells in bone marrow is still a matter of debate. This study evaluated the possible association of bone marrow micrometastases with tumour progression and prognosis in patients affected by gastric cancer. Bone marrow aspirates from both iliac crests were obtained from 114 consecutive patients operated on for gastric cancer. The specimens were stained with monoclonal antibody CAM 5.2 which reacts predominantly with cytokeratin filaments 8 and 19. Among 114 cases analysed, 33 cases (29%) had cytokeratine-positive cells in the bone marrow. There was no significant relationship between the presence of bone marrow micrometastases and site, depth of tumour invasion, lymph node metastases, presence of metastases. Patients with cytokeratine-positive cells had a trend towards a diffuse type histology (P=0.06). Among the 88 curatively resected patients, median survivals were 40 months and 36 months for cytokeratine-negative and cytokeratine-positive subsets respectively (P=0.9). Recurrence of the disease was observed in 39 cases (44.3%); 11 of 24 (45.8%) in the cytokeratine-positive subset and 28 of 64 (43.7%) in the cytokeratine-negative subset. In conclusion in our experience the presence of cytokeratine-positive cells in the bone marrow of curatively resected gastric cancer patients did not affect outcome and its independent prognostic significance remains to be proven before its official acceptance in the TNM classification.

High-dose chemotherapy in small-cell lung cancer.

Small cell lung cancer (SCLC) is highly sensitive both to radiotherapy and chemotherapy. Given its high chemo sensitivity, even two decades ago, SCLC was one of the first malignancies deemed suitable for maximising the dose and dose intensity with the support of autologous bone marrow (ABMT). On the whole, results were disappointing and the procedure was practically abandoned. Nowadays some interest is again emerging due to improvements in supportive care, such as the availability of hematopoietic growth factors and the peripheral blood progenitor cells (PBPC). Data of 505 patients included in 26 studies were reviewed. About two thirds of these patients had LD (limited disease). Late intensification protocols were used in 311 patients who, however, represented only the 30% of the population initially given conventional chemotherapy. Of the patients not achieving complete remission (CR) after induction, high-dose induced a CR in 39% of the cases. The use of early intensification was reported in 8 studies including 194 patients. The CR rate was 51.5%. Overall, the probability of achieving the CR was 2-3 times higher in LD than in ED (extensive disease). Relapses occurred at the site of the primary in more than half of the cases, showing that the course of the disease was not modified by the use of high-dose chemotherapy. Toxic deaths occurred in 7% of the treated patients, without difference in the two treatment methods. Though the schedules were too variable to draw firm conclusions, the ICE (ifosfamide, carboplatin, etoposide) and the CBP (cyclophosphamide, cisplatin, carmustine) regimens apparently provided better results, with a 2-year survival rate of 30-50% in the LD subset. An european multicenter randomized trial is ongoing. At the present time high-dose chemotherapy is still to be considered experimental treatment, since major problems such as the selection of the patients, doses and timing of chemotherapy and radiotherapy remain unsolved.

Primary cultures of human hypertrophic prostate tissue in WAJC 404 medium: a study of cell morphology and kinetics.

222 biopsy fragments of human hypertrophic prostate tissue were cultured in WAJC 404 serum-free medium for three weeks. Growth halos were examined after 7, 14 and 21 days of culture by optical and scanning electron microscopy. Colonies formed of two concentric areas showed in the inner halo elementary pseudo-lobular morphological units similar to the prostate structure. The cell morphological patterns of the halo turned out to be four in number. Every cell pattern was defined morphologically, morphometrically and phenotypically. Results indicate that all morphological differences must be attributed to the various phases of cell life, as all cell types were positive to cytokeratin. The nonconstant display of PSAP and PSA showed a moderate tendency to cell differentiation in WAJC 404 medium. Cell kinetics were also studied and revealed a decrease in proliferation after 14 days of culture. Primary cultures from biopsy fragments of human hypertrophic prostate tissue may be used as an experimental model up to the 14th day of culture.

Clinical and histological comparison of tissue damage and healing following incisions with the CO2-laser and stainless steel surgical blade in dogs.

The tissue damage and subsequent healing of skin, linea alba and intestinal wall incisions made with a CO2-laser and a stainless steel surgical blade were evaluated clinically and histologically in dogs (n = 10). The amount of blood lost in each type of skin incision was measured by taking the pre- and postoperative mass of surgical swabs. The tissues were sutured and the skin incisions examined every day. The animals were subsequently euthanased (Day 12) and all incisions examined histologically. A delay in the healing process was observed in the laser incisions of the skin during the first 4 d, but there was no difference in the healing rate of the intestinal wounds or of the linea alba. The blood loss due to the laser incisions was significantly less than that caused by the surgical blade. It was concluded that the CO2-laser can be used with confidence when incising the skin and intestine and that, due to its precision, the surgical blade is by far a more accurate method to incise the linea alba.

Experimental vermeersiekte (Geigeria ornativa O. Hoffm. poisoning) in sheep. I: An evaluation of diagnostic aids and an assessment of the preventive effect of ethoxyquin.

Dried milled Geigeria ornativa, which had been stored at room temperature for 4 years, was fed in rations to sheep. The usefulness of contrast radiography of the oesophagus, biopsies of oesophageal and skeletal muscles, electrocardiography, and clinical pathological parameters for diagnosing vermeersiekte were evaluated. Ethoxyquin was evaluated as a preventive agent. All the sheep developed signs of vermeersiekte but regurgitation was observed in only one animal. Contrast radiography and the examination of tissue biopsies were of diagnostic value in 8 out of 13 and 6 out of 6 sheep respectively. Electrocardiography did not aid in antemortal diagnosis of the condition and selected chemical parameters were non-specific. The inclusion of ethoxyquin in the diet of experimental animals (n = 3) prior to and during feeding of G. ornativa did not prevent the development of vermeersiekte. This study confirmed that dried stored G. ornativa retains its toxicity and that regurgitation is not a consistent clinical sign in sheep with vermeersiekte. The diagnostic value of contrast radiography of the oesophagus and examination of oesophageal and muscle biopsies is reported for the first time.

Breaking strength of CO2-laser and scalpel blade incisions in the dog.

Incisions were made in the skin, linea alba and intestine of dogs (n = 5) with a CO2-laser and a stainless steel scalpel blade. The procedures were carried out on Day 0, 8, 10 and 11 in order to produce 1, 2, 4 and 12-day old samples. On Day 12 the dogs were euthanized, the incisions harvested and the breaking strength of each sample recorded. No significant difference in the strength developed in the skin and intestinal wounds could be observed, whereas the incisions made with the scalpel blade in the linea alba were significantly stronger.

The carbon dioxide laser scalpel.

The CO2-laser is currently used as a scalpel by a large number of medical surgeons, but in the field of veterinary surgery, relatively little has been published on the subject. A review of the origin of medical lasers, the basic physics of laser energy production and the characteristics of laser light was therefore considered necessary. This review includes a discussion on how the optical radiation generated by the different lasers is absorbed, the cutting power of the CO2-laser, and the effect on healing, tensile strength and haemostasis when used in the skin, linea alba and gastrointestinal tract.

[I.V. ketorolac in the therapy of postoperative pain]. / Ketorolac e.v. nella terapia del dolore post-operatorio.

Forty-one patients suffering from postoperative pain were admitted to an open, noncomparative trial. A dose of 10 mg of Kerotolac was administered i.v. to patients complaining severe pain. The analgesic efficacy of the drug was evaluated at 5, 15, 30 minutes and at 1, 1.5, 2, 3, 4, 6 hours after injection; the patients were asked to score their pain relief on the VRS comparing the pre-injection evaluation to each post-injection period. A significant decrease of pain intensity (less than p 0.01) was observed at 45 minutes after injection. No side effects were observed. These results suggest that Ketorolac can be successfully used in the treatment of postoperative pain.