Outcome of EGFR inhibitors treatment in advanced NSCLC patients, not enrolled in clinical trials.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become a treatment after first-line chemotherapy in patients with advanced NSCLC. We assessed the predictive and prognostic role of EGFR and Kras mutations in NSCLC patients treated with TKIs after progression, not included in clinical trials. Gefitinib 250 mg or Erlotinib 150 mg per os were administered to 70 patients. Radiological assessment was performed every six weeks. EGFR and Kras mutations were found in 21.4% and 24.3% of patients, respectively. At multivariate analysis, Kras mutation was positively associated with progression-free survival (PFS; HR=0.71, 95% CI: 0.53-0.96; p=0.027) and, less clearly, with response (OR=1.84, 95% CI: 0.98-3.45; p=0.057) and survival (HR=0.74, 95% CI:0.54-1.02; p=0.066). EGFR mutation influenced positively PFS (HR=0.69, 95% CI: 0.47-1.02; p=0.06), but not survival. In conclusion, in our unselected patients mutation of Kras correlated with a better outcome. The small number of patients may explain some discrepancies with data in literature.

Age and comorbidities deeply impact on clinical outcome of patients with myelodysplastic syndromes.

BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders, with very different prognosis in given individuals; age and comorbidities are emerging as relevant patient-related factors influencing clinical outcome in MDS. Our aim was to evaluate the impact of age, comorbidities and disease severity (IPSS and IPSS-R prognostic scores) in a "real-life" series of MDS patients. METHODS: 318 patients with available assessment of comorbidities at diagnosis and consecutively registered into the Registro Ligure delle Mielodisplasie were analyzed. Comorbidities were evaluated according to HCT-CI and MDS-CI comorbidity indexes. Overall survival (OS) and the probability of death among patients who did not develop acute myeloid leukemia (NLD cumulative incidence) were analyzed. RESULTS: Comorbidities were seen in 177 (55.7%) patients. An older age (>75 y) had a significant negative impact on OS (p=0.008). HCT-CI was not associated with OS. MDS-CI was of prognostic significance (p=0.001), but the association was limited to pts with IPSS or IPSS-R "lower-risk". In multivariate analysis, MDS-CI remained an independent factor associated with OS and with an increased risk of NLD both when controlling for IPSS (p=0.019 and p=0.001, respectively) and for IPSS-R (p=0.048 and p=0.002, respectively). CONCLUSIONS: Evaluation of age and comorbidities according to a tailored tool such is MDS-CI helps to predict survival in patients with MDS and should be incorporated to current prognostic scores.

Blood reduced glutathione (GSH) concentrations in healthy and ill subjects.

BACKGROUND: Recently blood reduced glutathione (GSH), an important cellular antioxidant, has been proposed as an indicator of health, particularly in the elderly. To date, a gold standard unit for the expression of GSH concentrations is not known. The aim of the study is to define the most sensitive laboratory expression of GSH. EXPERIMENTAL DESIGN: a comparative study among some laboratory expressions of GSH. SETTING: Geriatric and Internal Medicine Units; General Community. PATIENTS AND PARTICIPANTS: forty-eight inpatients from Geriatric and Internal Medicine Units and 82 healthy subjects recruited among medical students and residents, people from preventive medicine services and from local senior centres. EXCLUSION CRITERIA FOR HEALTHY SUBJECTS: use of drugs in the year prior to the study. INTERVENTIONS: neither treatment nor interventions. MEASURES: the laboratory expression of GSH, compared in this study, were mg/dl, packed cell volume (PCV), mg/1010 RBC, mM/gHb. RESULTS: We noted statistically significant differences only if GSH was calculated as mg/1010 RBC; higher values were found in healthy subjects than in inpatients, apart from age. This modality of expression is minimally affected by haematological parameters; the low sensibility of the other modalities may be due to variations of MCV and Hb. Instead, the ratio GSH mg/1010 RBC expresses the true GSH concentrations inside each erythrocyte. This modality of expression is minimally affected by haematological parameters; the low sensibility of the other modalities may be due to variations of MCV and Hb.

New hematological indices in the healthy elderly.

BACKGROUND: Recently, new indices related to erythrocytes and platelet counts have been provided by hematological analysers. The purpose of the study is to investigate these new parameters in the elderly to define their normal values and to compare them with the range provided by the manufacturer. EXPERIMENTAL DESIGN: a comparative study. SETTING: general community, geriatric and internal medicine ambulatories. PATIENTS: sixty healthy free-living elderly (cut-off: 65 years) and 66 healthy young-adults, as a control group. MEASURES: we measured the common and the new hematological parameters by H.1 Bayer technology. The new hematological parameters are red diameter width-RDW, hemoglobin distribution width-HDW, mean platelet volume-MPV, platelet diameter width-PDW, platelet hematocrit-Pct. We then compared the values of our population with the Bayer range. RESULTS: The confidence interval width of the new indices define very faster limits than the Bayer range. Statistical differences were significant only in male groups: young-adults (Y) versus elderly (E) with higher values in Y than E in RBC p=0.002, in Platelet count p=0.050 and in MPV p=0.026; and higher values in E in MCV p=0.008, MCH p=0.006 and PDW p=0.004. CONCLUSIONS: In the literature a wide range of common hematological parameters are reported in the elderly, while the new hematological values have not been discussed till now. Our results may contribute to define the laboratory limits of the new hematological values in the healthy elderly.

Blood zinc, copper and magnesium in aging. A study in healthy home-living elderly.

BACKGROUND: Blood concentrations of copper, zinc and magnesium were determined in healthy elderly to assess whether aging interferes with mineral and micronutrient status. EXPERIMENTAL DESIGN: case series. SETTING: Internal Medicine and Geriatrics ambulatories in a University Hospital in Pisa, a city of Central Italy. PARTICIPANTS: 143 healthy outpatients of both sexes, who underwent a cardiological examination. INTERVENTION: no treatment and intervention were performed. MEASURES: copper (Cu), zinc (Zn) and magnesium--both intraerythrocytic (iMg) and extracellular (eMg)--were measured. RESULTS: The concentrations of Cu and eMg were found significantly higher in the elderly: Cu 117.5 +/- 17.0 micrograms/dl in the elderly vs 102.5 +/- 19.6 micrograms/dl in the younger (p < 0.001); eMg 1.8 +/- 0.2 in the elderly vs 1.7 +/- 0.2 mEq/l in the younger (p < 0.05). On the other hand, the levels of Zn and iMg did not differ in the two groups: Zn 113.3 +/- 14.9 micrograms/dl in the elderly vs 118.0 +/- 17.3 micrograms/dl in the younger, p = n.s.; iMg 4.3 +/- 0.4 mEq/l in the elderly vs 4.2 +/- 0.4 mEq/l in the younger, p = n.s. No correlation was found between age and single elements. CONCLUSIONS: These results suggest that the healthy free-living elderly have an adequate mineral intake. Nutrient supplements may by useful in the elderly with chronic diseases, comorbidities, and polypharmacy to prevent further age dysfunctions.

Congenital hypopituitarism in a 48-year old adult. Natural course, hormonal study and MRI evidence.

A case of Congenital Hypopituitarism (CH) in an untreated 48 yr-old-man is reported. The hormonal studies demonstrated a panhypopituitarism and MR imaging revealed absence of pituitary stalk, small anterior pituitary remnant on the sella floor and ectopic neurohypophysis at the tuber cinereum. The pattern of hormonal responsiveness suggests that CH encompasses findings typical of primary anterior pituitary disease and those of hypothalamic dysfunction.

Congenital hypopituitarism in a 48-year old adult. Natural course, hormonal study and MRI evidence.

A case of Congenital Hypopituitarism (CH) in an untreated 48 yr-old-man is reported. The hormonal studies demonstrated a panhypopituitarism and MR imaging revealed absence of pituitary stalk, small anterior pituitary remnant on the sella floor and ectopic neurohypophysis at the tuber cinereum. The pattern of hormonal responsiveness suggests that CH encompasses findings typical of primary anterior pituitary disease and those of hypothalamic dysfunction.

Takayasu's arteritis on steroid therapy. Seven years follow-up.

The authors report a 7 year follow-up of Takayasu's arteritis (TA) type III, group 1, in a young Italian woman. At diagnosis, at the age of 25, the echotomographic and angiographic studies showed narrow subclavian arteries, narrow abdominal aorta (diameter of 0.6-0.8 cm) below the renal arteries, stenotic left common carotid and renal arteries, and occluded upper mesenteric artery. With steroid therapy, (prednisone 50 mg/day per os), the erythrocyte sedimentation rate (ESR) normalized within 12 days. With a maintenance dosage of 7.5 mg/day per os, the patient achieved remission as documented by the absence of symptoms, the persistent normalization of ESR, and the improving of the diameter of the abdominal aorta (1.3-1.4 cm). On steroid therapy, the patient had a normal pregnancy and delivered a healthy baby girl. The disease has been stable for seven years. Recently, diabetes mellitus occurred and it has been treated with insulin therapy. The rising of ESR after tapering of steroid therapy (prednisone 5 mg per os on alternate days) suggests an alternative treatment with a cytotoxic agent.

[Occult stromal tumour of the small intestine: a cause of chronic intestinal blood loss in a 70 year-old woman]. / Tumore stromale occulto del tenue causa di sanguinamento intestinale cronico in 70enne.

The case of a 70 year-old woman with a chronic gastrointestinal blood loss due to a stromal tumor located in the middle third of the small intestine is reported. The peculiarities of the case are the characteristic immunohistochemistry of the neoplasm and, particularly, the mimetic clinical presentation, a kind of ''phantom tumor'' confirmed only with celiotomy and surgical excision.

[Why regular physical activity favors longevity]. / Perché l'attività fisica abitudinaria favorisce la longevità.

Regular physical exercise is useful at all ages. In the elderly, even a gentle exercise programme consisting of walking, bicycling, playing golf if performed constantly increases longevity by preventing the onset of the main diseases or alleviating the handicaps they may have caused. Cardiovascular diseases, which represent the main cause of death in the elderly, and osteoporosis, a disabling disease potentially capable of shortening life expectancy, benefit from physical exercise which if performed regularly well before the start of old age may help to prevent them. Over the past few years there has been growing evidence of the concrete protection offered against neoplasia and even the ageing process itself.

Tortuosity, kinking, and coiling of the carotid artery: expression of atherosclerosis or aging?

The etiology of carotid abnormalities is both congenital than acquired. The aim of this study was to clarify the role of aging and atherosclerosis in the acquired cases, and the role of these abnormalities in hemodynamic alterations and neurologic symptoms. Over a 1-year period the authors studied all the subjects undergoing carotid examination by continuous-wave and color-coded Doppler sonography at an Angiology Unit. They evaluated neurologic symptoms; risk factors for atherosclerosis; number, sites, and kinds of carotid abnormalities; atherosclerotic lesions; stenosis; hemodynamic alterations of the carotid; and other localizations of atherosclerotic diseases. There were 469 subjects: 272 (58%) with abnormalities (group 1) and 197 (42%) without abnormalities (group 2). The total number of abnormalities was 479 (104 tortuosities, 262 kinkings, and 113 coilings). The abnormalities were more prevalent in the elderly (P<0.001) and in women (P<0.001). In group 1 they found significant prevalences of hyperlipemia (P<0.001), hypertension (P<0.01), chronic cigarette smoking (P<0.01), and ischemic heart disease (P<0.05). Carotid atherosclerotic lesions were more prevalent in group 1 than in group 2 (P<0.001); among the patients with atherosclerotic carotid lesions, those in group 1 were older than those in group 2 (P<0.001). Tortuosity seemed to be associated with fewer hemodynamic alterations. The authors conclude that atherosclerosis, hypertension, and aging may play an important role in producing carotid abnormalities. The aging seemed more important than atherosclerosis. Only a prospective study of patients with carotid abnormalities and no atherosclerotic lesion will clarify the role of hemodynamics and neurologic symptomatology.

[Fever of unknown origin in the elderly of the 90's]. / La febbre di origine sconosciuta nell'anziano degli anni '90.

MATERIALS AND METHODS: Eighteen elderly patients (mean age 76.3 +/- 6.9 years) with fever of unknown origin (FUO) are studied sequentially and prospectively from January 1994 to December 1996. The classic Petersdori's criteria of FUO are no more valid for the elderly. The fever of more than 3-4 weeks duration is the only criterion to be considered, the fever is frequently under 38.5 degrees C and the elderly patient is often studied for more than 1 week outside the hospital. RESULTS: The most frequent underlying conditions were: malignancies in particular haematological diseases, followed by multisystem diseases and infections, tuberculosis "in primis". CONCLUSIONS: Selected investigations directed to the most frequent underlying conditions of FUO in the aged individuals overcome the financial cost and the patient discomfort of the tests since an identified curable disease can improve the life expectancy and quality.

[Cardiac myxoma in the elderly. Clinical study]. / I mixomi cardiaci nell'anziano. Studio clinico.

Cardiac mixoma in the elderly. A clinical study. The clinical features of 13 cardiac myxomas surgically resected are presented. The mean age at presentation was 68 years. Ten were in the left atrium, 5 near the fossa ovalis, 3 at the base of the atrial septum, 1 at the inferior wall and 1 on the anterior leaflet of mitral valve, 3 were in the right atrium, 1 of these was accompanied with a myxoma at the apex of left ventricle. The ECG and the chest X-ray were normal in 9 and in 8 patients, respectively. In 3 patients, the diagnosis was occasionally made by routine 2-dimensional echocardiography. 5 patients presented with fever of unknown origin, arthralgias, weakness, weight loss. None had intracardiac or extracardiac recurrence in the 73 months follow-up. The presentation with constitutional symptoms only like fever of UO, may mimic collagen and neoplastic diseases, vasculitis, lymphomas: the 2-dimensional echocardiography is mandatory to esclude a cardiac myxoma in the elderly.

Age-related modifications in the regulation of the hypothalamic-pituitary-thyroid axis.

We studied the hypothalamic-pituitary-thyroid function in two groups of healthy elderly subjects: group A (n = 23, age range 65-80 years), and group B (n = 11, age range 81-92 years), and in 32 controls, aged 20-60. A TRH test for TSH and prolactin was performed in all subjects, while the TSH circadian modulation was evaluated in elderly subjects only. Group B showed significantly lower fT3 and TSH, and higher fT4 levels with respect to controls (fT3: 4.4 +/- 0.2 vs. 5.2 +/- 0.2 pmol/l, p < 0.05; fT4: 13.1 +/- 0.9 vs. 11.4 +/- 0.4 pmol/l, p < 0.05; TSH: 1.07 +/- 0.21 vs. 1.46 +/- 0.13 mIU/l, p < 0.05). Morning TSH showed an inverse correlation with age (r = -0.42; p < 0.02) among the 34 elderly subjects, but not among controls. Evidence for TSH circadian modulation was found only in group A (nighttime TSH: 1.60 +/- 0.17, vs. daytime: 1.25 +/- 0.13 mIU/l, p < 0.001). The TRH-stimulated TSH peak was reduced among all elderly subjects with respect to controls (A: 6.26 +/- 0.64 mIU/l, p = 0.01; B: 5.02 +/- 0.58 mIU/l, p < 0.01). The maximal PRL response was also blunted (A: 25.7 +/- 2.6 micrograms/l, B: 27.7 +/- 5.2 micrograms/l, p < 0.0005). In conclusion, a resetting of the pituitary threshold of the TSH feedback suppression, along with complex alterations in peripheral thyroid hormone levels, may progressively develop in older people, becoming apparent only with extreme senescence. Moreover, the TSH nocturnal surge may be lost with increasing age, thus providing evidence also for hypothalamic dysfunction.

[5-Aminosalicylic acid in the prevention of recurrences of Crohn's disease]. / 5-Aminosalicylsäure in der Rezidivprophylaxe des Morbus Crohn.

AIM OF STUDY: To evaluate the efficacy of 5-aminosalicylic acid (5-ASA) in preventing recurrences of Crohn's disease. PATIENTS AND METHODS: Between January 1988 and December 1989 a total of 60 patients (37 men, 23 women, mean age 34.8 years) were selected in whom the diagnosis of Crohn's disease had been known for at least 2 years. A further criterion for inclusion was remission for at least one year in patients who had been operated or for one month in the nonoperated ones. Furthermore, the latter must have had at least one recurrence during the last year. They were in turn assigned to be treated with 5-ASA (2.4 g daily by mouth) or not treated (control). The activity and localization of Crohn's disease were defined according to the "Crohn's disease activity index" (CDAI) and the "laboratory index" (LI), as well as by endoscopy and (or) radiology. The patients were examined every 6 months for 4 years. A recurrence was diagnosed if the CDAI was more than 150 or had increased to at least 60 points above the initial value and the LI was above 100. RESULTS: 29 recurrences were noted, 72.4% within the first 2 years. 15 recurrences (46.9%) were in the treated patients and 14 (58.3%) among the untreated controls. The Kaplan-Meier curve (statistical comparison of the probability of recurrence) showed no significant difference between the two groups (P = 0.23): the recurrence rate was the same in the two groups, among the patients with or without previous operation and for different primary localizations. There were no notable side effects. CONCLUSION: Treatment with 5-ASA was not found to influence the likelihood of recurrence. Age, duration of the disease, primary localization and previous operation were not prognostic factors.

[Malignant peritoneal mesothelioma: its relation to asbestos]. / Il mesotelioma maligno peritoneale: la relazione con l'asbesto.

Chronic exposure to asbestos can induce malignant peritoneal mesothelioma (PMM) without pulmonary or pleural involvement (PIMM). The localization to the peritoneum depends on the different susceptibility of the two mesotheliums and, perhaps, on the length of asbestos fibers which can facilitate their direct translocation.

[Vitamin E in the aged]. / La vitamina E nell'anziano.

Aging is a multifactorial process still incompletely known. The role of oxidative damage to cell membranes, as an important phase of the process, is underlined by the recent literature. We emphasize the value of vitamin E as an antioxidant agent supplied by suitable diets in middle age and by cheap tablets in the aged.

[Falls and fractures in the elderly. Causes and consequences]. / Cadute e fratture nell'anziano. Cause e consequenze.

OBJECTIVE: To evaluate the causes of non-pathologic traumatic fractures in the elderly and their consequences on quality of life. DESIGN: A prospective trial. FOLLOW-UP: 12 months for the inpatients and 3 months for the outpatients. SETTING: Basal assessment in orthopaedic hospital; follow-up in geriatric unit. PATIENTS: Both inpatients and outpatients, 65 years and over, both sexes, both living in a nursing home and in their own home, admitted to an orthopaedic hospital because of a fall, with diagnosis of a subsequent fracture. Criteria of exclusion: patients with pathologic fracture. 121 patients were enrolled, 108 had a complete follow-up. SURVEYS: Health and functional status prior to the fracture, causes and concomitant causes of the fall, site of the fracture, complications and functional disabilities. RESULTS: The most frequent cause of fracture is an accidental fall, especially in younger elderly, other causes being acute cardiovascular and neurological diseases. Fractures occur more frequently in females. The most serious injuries affect frailer subjects, with advanced age, neurologic and multiple chronic diseases. Fracture of femur is the most frequent fracture and it has the highest risk complications, functional disabilities and death. CONCLUSIONS: Because of the high frequency of accidental falls, the authors emphasize the necessity of primary prevention, especially the removal of architectural barriers both at home and in public environment.

[Male impotence in old age]. / L'impotenza maschile nella terza età.

Normal aging does not induce impotence, but only modifies the physiology of the erection which, however, allows good sexual intercourse. Impotence, found in 55.0% of the over 75 men, is due to organic or psychogenic causes: above all, penile arterial insufficiency and the collateral effects of drugs for the diseases which often affect the elderly, are the main factors.