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.

The use of recombinant interferon alfa-2b in elderly patients with anti-HCV-positive chronic active hepatitis.

OBJECTIVE: To compare efficacy and tolerance of recombinant interferon alfa-2b in the treatment of anti-HCV-positive chronic active hepatitis (CAH) in subjects aged 65 years and above with those less than 65. DESIGN: A randomized controlled trial. SETTING: Outpatients in two hospitals. PATIENTS: 65 consecutive outpatients with anti-HCV-positive CAH for 1 to 30 years, having basal aminotransferase levels at least twice the normal value. Those 65 and over were randomized to an interferon group (A, n = 22) or a no-treatment group (B, n = 22). All those under 65 received interferon (group C, n = 21). INTERVENTION: Interferon at a dose of 3 mU 3 times a week for a 6-month period. A normalization of serum aminotransferase levels was considered a positive response to therapy. RESULTS: Response to therapy was positive in 62% of the treated elderly compared to 57% of the adults (P = 0.85). The two groups of responders showed a common highly significant reduction of aminotransferase (P < 0.001). Side effects were similar in elderly and young. Two untreated elderly showed spontaneous normalization of aminotransferase. CONCLUSION: Interferon in anti-HCV-positive CAH is useful in the elderly, allowing normalization of aminotransferase, improvement of the histology and remission of the disease in 62% of the cases. Side effects seem to be independent of age. Further studies are required to assess both duration of remission and usefulness of cyclic therapy in previous responders.

Serum thyroid hormone concentrations and recovery of TSH secretion after excision of autonomously functioning thyroid nodules.

Serum concentrations of TSH, TT4, TT3 and rT3 were monitored for one month after excision of ten autonomous thyroid adenomas which had suppressed TSH secretion. Basal serum TSH levels start to increase between 30 hr and 20 days after surgery reaching normal and steady levels by the 24 day. Serum TT3 concentrations rapidly decrease in the first 20 hr to values near the lower limit of the normal range. Thereafter TT3 levels change little until pituitary TSH secretion recovers. Serum TT4 levels also fall, but much more slowly than TT3. Rising TSH levels stimulate residual extranodular thyroid tissue secretion of both TT3 and TT4. However, serum TT3 levels rise more rapidly than TT4 levels. Preoperative serum concentrations of both TT4 and TT3 are related directly to the time required until the beginning of the postoperative rise in TSH levels, and inversely with the maximal postoperative serum TSH concentration achieved. Throughout the study period, for all patients, serum TSH concentrations were inversely related to serum TT4 concentrations. These data suggest that, although the time required until the onset of recovery of TSH secretion is directly related to preoperative levels of TT4 and TT3, the regulation of postoperative TSH levels is dependent upon serum TT4 levels. Also, the serum TT3 levels constant at the lower limit of the normal range before recovery of TSH secretion, and the preferential rise in serum TT3 concentrations associated with rising TSH secretion, may prevent or abbreviate temporary postoperative hypothyroidism.

Triiodothyronine turnover studies in euthyroid patients with autonomous thyroid nodules.

Triiodothyronine (T3) kinetic studies were carried out using 126I-T3 and the single injection technique in eight clinically euthyroid patients with autonomous thyroid nodules and the metabolic results were compared to those obtained in a group of 12 healthy control subjects. Plasma labeled T3 concentration was measured by a chromatographic method based on the extraction of the hormone on Sephadex G-25 columns, followed by its elution with a specific anti-T3 antiserum. The analysis of the experimental plasma disappearance curves of the labeled hormone was performed using the noncompartmental method. The results obtained showed a significantly increased metabolic clearance rate of T3 in the patients with autonomous thyroid nodules, as compared to the control group. On the average, the T3 production rates were increased more significantly than the corresponding circulating levels of the hormone, therefore, suggesting that the significant TSH inhibition observed in the euthyroid patients with autonomous thyroid nodules could be related with an increased peripheral utilization of triiodothyronine.

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.

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.

Bilateral perinephric fluid accumulation: an unusual manifestation of pulmonary hypertension--a case report.

This is the case report of a forty-seven-year-old man with an ostium secundum atrial septal defect and a very high grade of pulmonary hypertension, associated with a large bilateral perinephric fluid accumulation. The fluid accumulation was remarkably reduced after eleven phlebotomies over a twelve-month period. A pathogenetic relation with the Eisenmenger's syndrome is discussed. No previous report of this association has been found in a survey of the literature.

Takayasu's arteritis: low corticosteroid dosage and pregnancy--a case report.

The authors describe a case of Takayasu's arteritis in a twenty-five-year-old Italian woman, characterized by nonspecific symptoms (weakness, arthralgias, fever) and elevated erythrocyte sedimentation rate early onset of these symptoms at the age of about twenty-three years early diagnosis, only eighteen months after the onset of symptomatology absence of progression of the disease under corticosteroid therapy with a follow-up of three years uneventful pregnancy ending in cesarean section and birth of a baby without maternal and neonatal complications.

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.

[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.

[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.

[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.

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.

[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.

[Clinical evaluation of anemia in the aged]. / Valutazione clinica dell'anziano anemico.

Of 533 patients over 65 years old (153 males and 380 females), admitted to geriatric units for various medical diseases, 111 (20.8%) were anemic. Among males the prevalence of anemia was 30.1%, among females 17.1%. Three principal causes of anemia were revealed. The most frequent (42.3%) was microcytic, hypochromic anemia, with low levels of serum iron concentrations, related to gastrointestinal diseases (with chronic occult blood loss). 38.7% of anemic elderly people was affected by chronic diseases. In 19.0% a folate (16 case) and iron (5 cases) deficiency was revealed. These results suggest that anemia in the elderly is always pathological; hemoglobin values lower than 12 g/dl should be considered abnormal and investigated.

[Complete endocardial cushion defect and bone malformations of the hands. Holt-Oram syndrome]. / Difetto completo dei cuscinetti endocardici e malformazioni scheletriche delle mani. Sindrome di Holt-Oram.

A 44 year old woman with upper limb skeletal malformations and endocardial cushion defect is described. This congenital heart disease was rarely reported in association with Holt-Oram syndrome.

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.