Increase in landslide activity after a low-magnitude earthquake as inferred from DInSAR interferometry.

On August 16th, 2018, a Mw 5.1 earthquake struck the Molise region (central Italy), inducing 84 earthquake-triggered landslides that predominantly involved soil covers of clayey materials and flysch on gently dipping slopes. To quantify the spatiotemporal landslide activity in the months immediately after the earthquake, a differential SAR interferometry (DInSAR) analysis was performed for a time span from 2 years before to one year after the earthquake, recognising both first-time and reactivated landslides. The results showed a clear increase in landslide activity following the low-magnitude earthquake with respect to the activities recorded in the same months of the previous years. Several coherent landslides (earth slides and earth flows) were observed following seasonally recurrent rainfall events. Such increases were observed for both reactivated and first-time landslides, showing decreases in inactive periods and activity over longer periods. Furthermore, the spatial density distribution of the landslides was investigated in the postseismic time interval along transects perpendicular and parallel to the direction of the tectonic element responsible for the seismic event. An asymmetrical distribution was deduced parallel to the fault strike with a higher number of landslides located inside the compressional sector according to a strike-slip faulting mechanism.

Frailty Related Factors as Predictors of Functional Recovery in Geriatric Rehabilitation: The Sarcopenia And Function in Aging Rehabilitation (SAFARI) Multi-Centric study.

BACKGROUND: Frailty-related characteristics, such as sarcopenia, malnutrition and cognitive impairment, are often overlooked, both in clinical practice and research, as potential contributors to functional recovery during geriatric rehabilitation. OBJECTIVE: The aim of the study was to identify frailty-related characteristics associated with functional recovery in a cohort of post-orthopedic surgery and post-stroke older adults. DESIGN: Multi-centric cohort study. Participanst and Settings: Patients over 65 years, admitted to three geriatric rehabilitation units, in Spain and Italy, after an orthopedic event or a stroke, from December 2014 to May 2016. MEASUREMENTS: The Absolute Functional Gain (AFG) defined as the difference between Barthel Index score at discharge and at admission, and the Relative Functional Gain (RFG) that represents the percentage of recovery of the function lost due to the event, were selected as outcomes. Both outcomes were analyzed as continuous and dichotomous variables. Analyses were also stratified as diagnostic at admission. RESULTS: We enrolled 459 patients (mean age±SD=80.75±8.21 years), 66.2% women, 69.5% with orthopedic conditions and with a length of stay of 28.8±9.1 days. Admission after a stroke (Odds Ratio=0.36, 95% Confidence Interval=0.22-0.59]) and a better functional status at admission (OR=0.96, 95% CI=0.94-0.97), were associated with a lower likelihood of AFG, while a better pre-event Barthel index (OR=1.03 for each point in score, 95% CI=1.01-1.04), being able to walk (OR=2.07, 95% CI=1.16-3.70), and a better cognitive status at admission (OR=1.05, 95% CI=1.01-1.09), were associated with a higher chance of AFG. Post-stroke patients with delirium at admission had a re-duced chance of AFG (OR=0.25, 95% CI=0.07-0.91]). Patients admitted after an ortho-pedic event with better pre-event functional status (OR=1.04, 95% CI=1.02-1.06) and able to walk at admission (OR=2.79, 95% CI=1.29-6.03]) had an increased chance of AFG. Additionally, in both diagnostics groups, a better handgrip strength increased the chance of RFG. CONCLUSIONS: Among frailty-related variables, physical, cognitive and muscular function at admission could be relevant for functional improvement during geriatric reha-bilitation. If confirmed, this data might orient targeted interventions.

Phase III study in stage IV non-small-cell lung cancer patients treated with two courses of cisplatin/gemcitabine followed by a randomization to three additional courses of the same combination or gemcitabine alone.

BACKGROUND: This randomised phase III study investigated if in responsive and stable disease (SD) stage IV patients after two courses of cisplatin and gemcitabine, single-agent gemcitabine (experimental arm) was not inferior in terms of overall survival (OS) to cisplatin-gemcitabine (standard arm). PATIENTS AND METHODS: Noninferiority was defined as an increase in the hazard of death (HR) < or = 1.33 in the experimental arm. From January 2001 to February 2004, 340 patients were registered and 250 were randomised. Cisplatin was administered on day 1 at 75 mg/m2 and Gemcitabine on days 1 and 8 at 1250 mg/m2 every 3 weeks. RESULTS: Response rate after two courses was 29%. The 1-year progression-free survival was 13% in both arms. One-year survival was 52% in the standard and 42% in the experimental arm for an HR of 1.21 [90% confidence interval (CI) 0.97-1.51]. Postprogression survival was in favour of the standard arm (HR 1.30, 95% CI 0.99-1.70, P = 0.051). Grades 3-4 toxicity favoured in the experimental arm. CONCLUSION: In responsive and SD patients with stage IV non-small-cell lung cancer it was not possible to demonstrate that three courses of gemcitabine alone are not inferior, in terms of OS, to the standard approach of three courses of cisplatin-gemcitabine.

A randomised clinical trial of two docetaxel regimens (weekly vs 3 week) in the second-line treatment of non-small-cell lung cancer. The DISTAL 01 study.

Docetaxel (75 mg m(-2) 3-weekly) is standard second-line treatment in advanced non-small-cell lung cancer (NSCLC) with significant toxicity. To verify whether a weekly schedule (33.3 mg m(-2) for 6 weeks) improved quality of life (QoL), a phase III study was performed with 220 advanced NSCLC patients, < or =75 years, ECOG PS < or =2. QoL was assessed by EORTC questionnaires and the Daily Diary Card (DDC). No difference was found in global QoL scores at 3 weeks. Pain, cough and hair loss significantly favoured the weekly schedule, while diarrhoea was worse. DDC analysis showed that loss of appetite and overall condition were significantly worse in the 3-week arm in the first week, while nausea and loss of appetite were more severe in the weekly arm in the third week. Response rate and survival were similar, hazard ratio of death in the weekly arm being 1.04 (95% CI 0.77-1.39). A 3-weekly docetaxel was more toxic for leukopenia, neutropenia, febrile neutropenia and hair loss; any grade 3-4 haematologic toxicity was significantly more frequent in the standard arm (25 vs 6%). The weekly schedule could be preferred for patients candidate to receive docetaxel as second-line treatment for advanced NSCLC, because of some QoL advantages, lower toxicity and no evidence of strikingly different effect on survival.

Factors predicting docetaxel-related toxicity: experience at a single institution.

We studied factors predicting docetaxel-related toxicity in 113 unselected patients with metastatic cancer treated under routine daily practice. Docetaxel was administered in either a weekly, bi-weekly or tri-weekly schedule. All patients received prophylactic dexamethasone. Twenty-six patients were aged 70 or more, and 28 (24.8%) had an ECOG performance status (PS) score > or = 2. Primary tumors were mainly in breast, lung, and stomach (58, 25, and 14 patients, respectively). Most patients had metastases at two or more sites and were heavily pretreated. NCI-CTC graded toxicities were mild. Grade 3/4 leucopenia and neutropenia occurred in 19.4% and 10.6% of patients, respectively, with febrile neutropenia in 2 patients. Severe nonhematologic toxicities were rare, except for asthenia (8 patients). Complete alopecia occurred in 26.6% of patients. A proportional-odds regression analysis demonstrated that the tri-weekly schedule and older age represented independent risk factors for all-grade leucopenia, whereas a poor PS for anemia. Primary tumor in breast, tri-weekly schedule, an abbreviated and low dose of corticosteroids premedication, and high duration and cumulative dose of docetaxel were factors predicting asthenia. Risk factors for alopecia and vomiting were tri-weekly schedule and high docetaxel cumulative dose, respectively. In conclusion, in daily clinical practice docetaxel toxicity may be correlated with factors related to patient, disease, and treatment characteristics. Taking into account these variables could be a first step toward individualizing treatment.

Mitomycin C, 5fluorouracil and folinic acid in combination with alpha 2b interferon for advanced colorectal cancer.

AIMS AND BACKGROUND: This study was conducted to investigate the activity and toxicity of 5fluorouracil folinic acid+mitomycin C combined with alpha 2b interferon in advanced colorectal cancer based upon recent studies suggesting a possible biochemical modulation of 5fluorouracil by interferon. PATIENTS AND METHODS: Between June 1990 and April 1991 25 previously untreated patients with advanced colorectal carcinoma were treated with mitomycin C 10 mg/m2 iv bolus on day 1, 5fluorouracil 375 mg/m2 on days 1 to 4 and folinic acid 200 mg/m2 on days 1 to 4 every 4 weeks, combined with alpha 2b interferon 3 million U day continuously. RESPONSE: Of the 25 patients entered into the study, 20 were evaluable for response as 5 patients withdrew due to toxicity (grade 3-4 thrombocytopenia in 4 cases and fatigue in 1). No complete response was recorded, 6 patients had partial remission (30%; 95% confidence interval, 10% to 50%), 4 experienced no change and 10 showed progressive disease. The toxicity of this regimen was significant, particularly myelosuppression. CONCLUSIONS: This combination showed a significant toxicity and low response rate compared with other 5fluorouracil based regimens in advanced colorectal cancer.

Accelerated hemopoietic recovery after chemotherapy and autologous bone marrow transplantation in hematological malignancies using recombinant GM-CSF: preliminary results obtained in 14 cases.

Human recombinant granulocyte-macrophage colony-stimulating-factor has been employed, on a compassionate basis, in 14 hematological patients in order to reduce the duration of the neutropenic period after high-dose chemotherapy for the treatment of hematological malignancies (7 traditional CHT courses, 7 autologous bone marrow transplantations). The compound was administered intravenously by 6-hour infusion at a dose of 5 microgram/kg/day until the patient reached at least 1000 PMN in the peripheral blood. Eleven out of the 13 evaluable patients showed a significative improvement in hemopoietic recovery, even though in CHT patients hematological reconstitution was higher in terms of PMN counts. The ABMT patients, however, showed a faster myeloid recovery than that obtained both in a group of 14 NHL and in a series of 8 MM previously submitted to ABMT in our Institution. Moreover the increase in peripheral neutrophils appeared to be stable, since it was maintained throughout one month after the end of rhGM-CSF therapy. We did not observe effects on platelet or erythrocyte recovery. We conclude that rhGM-CSF is active in accelerating the recovery of myelopoiesis, without significant toxic or collateral effects.

Accelerated chemotherapy with or without GM-CSF for small cell lung cancer: a non-randomised pilot study.

Two series of five consecutive patients with small cell lung cancer were treated with an "accelerated" chemotherapy regimen of cyclophosphamide-doxorubicin-vincristine (CAV) and cisplatin-etoposide (PE) alternated possibly every week. In the first group of patients (median age 49 years, range 46-52) recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was given as soon as grade IV leukopenia occurred, while in the second group (median age 59 years, 55-68) no growth factor was administered. The mean interval between chemotherapy courses and the mean duration of chemotherapy were 10 and 57 days, respectively, in the patients supported with GM-CSF compared with 13 and 72 days in the control group. One GM-CSF treated patient was withdrawn after the third cycle because of severe toxicity. The mean white blood cell and platelet nadirs were 600 and 46,000/microliters in the first group vs. 840 and 105,000/microliters in the controls. Overall chemotherapy dose-intensity was increased by two fold in the patients given GM-CSF compared with a 1.5 fold increase in the control patients. In all cases, irrespective of their treatment, there was an impaired colony forming capacity of circulating and marrow haemopoietic progenitor cells when grade IV leukopenia occurred, with recovery after the end of leukopenia. This pilot study suggests that accelerated CAV/PE chemotherapy is feasible both with and without GM-CSF. Different GM-CSF schedules as well as combinations of different haemopoietic growth factors may further improve dose-intensity.

The combined administration of thymomodulin and interleukin 2 reverses T-cell unresponsiveness in mice infected with Mycobacterium bovis-BCG.

Mice infected intravenously with high doses of M. bovis, strain BCG, showed a marked impairment of delayed-type hypersensitivity to PPD evaluated in in vivo skin tests and in vitro as splenocyte blast transformation. However, this state of unresponsiveness could be partially reversed after 1 month of infection by the intraperitoneal injection of a calf thymus acid lysate (thymomodulin). Furthermore, BCG-infected mice treated in vivo simultaneously with both thymomodulin and interleukin 2 immediately developed positive skin reactions and blast transformation to PPD and did not become anergic in the course of infection.

A calf thymus acid lysate improves clinical symptoms and T-cell defects in the early stages of HIV infection: second report.

Thymomodulin is a calf thymus acid lysate capable of inducing T lymphocyte maturation. Fifteen patients with HIV infection at different stages according to the Walter Reed classification were treated with 60 mg/day of thymomodulin syrup for more than 50 days. Two WR6B subjects had clinical and immunological parameters unchanged and died, while the patient suffering from Kaposi's sarcoma presented an evident clinical and laboratory improvement with remission of the neoplasia. The other 12 patients ranging from WR2 to WR5B showed an improvement of clinical symptoms after thymomodulin therapy accompanied by the normalization of CD4/CD8 ratio (P less than 0.001). This helpers/suppressors increase was due to a significant increase of CD4 cells (P less than 0.01) and also to a decrease of the CD8 lymphocytes (P less than 0.05). Thymomodulin administration did not cause an enhancement of the urinary levels of neopterin, a marker of T-cell activation.

[Perennial allergic rhinitis. Prophylaxis of acute episodes using thymomodulin]. / Rinopatia allergica perenne. Profilassi degli episodi acuti mediante l'impiego di timomodulina.

The therapeutical effectiveness of a calf thymic derivative (thymomodulin), orally administrable, in patients suffering from perennial allergic rhinitis is described. The use of thymomodulin for 4 months at the dosage of 120 mg daily in 20 patients significantly reduced (p less than 0.001), if compared with the previous year, the monthly mean frequency of allergic episodes. Also objective symptoms improved (p less than 0.05). The clinical course was associated with the normalization of IgE plasmatic levels (p less than 0.001) and consequently the mean of RAST and PRICK tests scores decreased (p less than 0.001). Eosinophil count was significantly reduced (p less than 0.001), while IgG serum levels were increased (p less than 0.02).

[Prevention of recurrent respiratory infections in adults]. / Prevenzione delle infezioni respiratorie ricorrenti dell'adulto.

The authors compared the results obtained by using antibiotic therapy, vaccine, thymomodulin (a calf thymus acid lysate) and association of vaccine-thymomodulin in order to prevent acute infectious episodes in a group of 85 patients suffering with recurrent respiratory infections. The use of thymomodulin, alone and in association with vaccine, at the dose of 120 mg/die for 20 days/month during the period of observation (4 months), determined a higher reduction, (p less than 0.001) if compared with the other treatments, of the number and the duration of infectious episodes and moreover of the antibiotics' intake. Also the respiratory symptoms, and in particular the fits of coughing, showed an improvement. The pulmonary function indices and the laboratory parameters were unchanged in all groups studied.

Update and future perspectives of a thymic biological response modifier (Thymomodulin).

Thymomodulin (Ellem Industria Farmaceutica spa, Milan, Italy) is a calf thymus acid lysate with immunomodulating activities. It is composed of several peptides with a molecular weight range of 1-10kD. Extensive studies in animal systems showed that Thymomodulin exhibited no, or very little toxicity even when used at high doses. Studies done in vitro and in vivo demonstrated that Thymomodulin is a biologically active compound which regulates the maturation of human and murine pre T lymphocytes, as well as modulate the functions of apparently mature human and animal B and T lymphocytes. It was observed that Thymomodulin can promote myelopoiesis as demonstrated by an increase of granulocyte-macrophage colonies in agar. Although additional studies to examine its target cell lineage are required, it appears that Thymomodulin exhibits specificity toward T cells. Therefore, enhancement of other cell lineage functions by Thymomodulin may be indirect, and mainly due to its effect on T cells. Of major importance is to note that Thymomodulin is prepared in a manner which allows it to maintain its biological activity when administered orally.

Frequency of hydatidiform mole in Lombardy, Northern Italy.

The frequency of hydatidiform mole in Lombardy (a region in Northern Italy with 8.9 million inhabitants) over the period 1979-1982 was estimated using the Regional Hospital Discharge Registration System, where information is collected on all discharges from public and private hospitals. After revision of registrations and clinical records, 347 cases of hydatidiform mole were confirmed. The estimated frequency was 66.22 per 100,000 pregnancies (SE = 3.56), or 1 in 1510 pregnancies. The risk of hydatidiform mole was not elevated in teenage women, but rose markedly above age 40, and was almost 300 times higher for women age 50 or older. The frequency of hydatidiform mole observed in the nine provinces of Lombardy was significantly heterogeneous, and this variation could not be explained in terms of differences in maternal age distribution.