Clinical implications of discordant early molecular responses in CML patients treated with imatinib

A reduction in BCR-ABL1/ABL1IS transcript levels to <10% after 3 months or <1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR4; 71.5% vs. 16.1%) compared to individuals with BCR-ABL1/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3-and 6-month time points. Among these patients, those with BCR-ABL1/ABL1IS values >10% at 3 months but <1% at 6 months fared significantly better than individuals with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (event-free survival 68.2% vs. 32.7%; p < 0.001). Likewise, subjects with BCR-ABL1/ABL1IS at 3 months >10% but <1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (75% vs. 18.2%; p < 0.001). Finally, lower BCR-ABL1/GUSIS transcripts at diagnosis were associated with BCR-ABL1/ABL1IS values <1% at 6 months (p < 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points

Storia naturale degli angiomi epatici.

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On the architectural and energy classification of existing buildings: a case study of a district in the city of Palermo

Town Administrations are increasingly facing the challenge to identify smart planning actions to reduce the cities' energy demand by improving the efficiency of the urban energy systems. Buildings play an important role in this regarding both the demand and supply energy. In this scenario, the neighborhood or district scale seems to be the most appropriate to implement a multi-disciplinary approach on which smart planning relies. This paper shows the application, to a district of the city of Palermo (Sicily, Italy), of a methodology for architectural-energy classification of existing buildings. Such methodology provides, regarding the building sector, an easy tool that can support smart planning at district scale using data available to the municipalities. The work also shows a first experimental approach for the neighborhoods' characterization. The basic idea guiding this work is to identify possible features and subsequent intervention actions for energy refurbishment in neighborhoods clusters

[The role of echo-guided percutaneous cholecystectomy in acute cholecystitis].

Personal experience in the treatment of acute cholecystitis with percutaneous cholecystostomy in high risk patients and in elderly patients is reported. Between January 1989 and November 1990, 28 patients affected by acute cholecystitis were treated with percutaneous cholecystostomy at Emergency Surgery Department, Verona University Hospital. The patients treated included 13 men and 15 women; 8 of them were under 70 years old, 5 between 70th and 75th and the remaining patients over 75 years old. The suspected clinical diagnosis of acute cholecystitis was confirmed in all cases by ultrasonography (accuracy 95.4\%). The percutaneous cholecystostomy was successful in 26 over 28 cases. In all these cases patients had a sudden improvement of their clinical conditions. In one case we failed because the guide-wire slipped out of the gallbladder and we couldn't perform a second attempt for the patient's refuse; in an other case there was the dislodgment of the catheter after less than 12 hours from the cholecystostomy and the patient was operated on. Twenty-two of 26 patients whose conditions were improved by percutaneous cholecystostomy, subsequently underwent elective cholecystectomy. In 2 cases of acalculous cholecystitis the patients did not undergo the operation; in 2 cases because of the elderly age of the patients and their bad cardiorespiratory conditions we preferred not to perform the operation. We had not major complications; 6 patients complained pain irradiating to right shoulder which disappeared within 30-60 minutes from the end of the procedure.(ABSTRACT TRUNCATED AT 250 WORDS

Ruolo della colecistostomia percutanea ecoguidata nella colecistite acuta

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Rotture di esofago: inquadramento clinico e trattamento chirurgico.

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Utilizzazione del maltosio come substrato nutrizionale in corso di alimentazione parenterale.

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[The therapy of symptomatic and/or complicated dysontogenetic liver cysts].

Congenital hepatic cysts are a frequent disease, symptomatic in the 16-18\% of the cases. The authors report a review of the literature of the last 20 years about 135 treated surgically patients with symptomatic and/or complicated hepatic cysts. They analyse the different models of treatment both surgical and conservative, referring in special way about the alcoholization of the cysts. The authors finally report their personal experience about eight cases

Apoptotic effects of thiazolobenzimidazole derivatives on sensitive and multidrug resistant leukaemic cells

We investigated the cytotoxic activity of eight thiazolobenzimidazole derivatives on sensitive HL60 and multidrug-resistant(MDR) (HL60R) leukaemia cell lines. The antitumour effects of these compounds were compared with those of RS-TBZ, a thiazolobenzimidazole derivative, previously described in our reports, that was able to induce apoptosis more markedly in MDR cells than in the parental sensitive cell lines. Only two compounds in this study proved to have interesting effects: (a) the S-enantiomer of TBZ, that was able to induce apoptosis in MDR cells in a slightly more selective manner than TBZ (racemic form); and (b) TBZ-4-OCH3 (TBZ-4-OCH3), that showed cytotoxic and apoptotic effects on sensitive and resistant leukaemia cells greater than TBZ, without cytotoxic effects on normal haemopoietic progenitor cells. Moreover, we observed that TBZ-4-OCH3 was also active in cells expressing Bcr-Abl, an oncogene that confers resistance to apoptosis induced by several stimuli, including cytotoxic agents. The inhibition of caspase-9 and caspase-3 by speci®c polypeptide inhibitors decreased the apoptotic e ects of TBZ-4-OCH3 in HL60 cells indicating that apoptosis induced by this compound was, at least partly, caspase-mediated. On the contrary, the blocking of FL-associated cell surface antigen (Fas) using a speci®c Fas-blocking monoclonal antibody did not a ect the level of apoptosis induced by TBZ-4-OCH3 suggesting that the Fas pathway was not involved. In addition, the caspase 8 inhibitor was unable to inhibit the apoptotic activity of TBZ-4-OCH3. The very low toxicity shown by TBZ-4-OCH3 in normal haemopoietic progenitor cells and its high activity in sensitive and MDR neoplastic cells suggest a possible clinical use for this new compound

Semeiotica ecografica degli angiomi epatici a silenzio clinico.

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