For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The ...debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.
•Deficit irrigation (DI) has been investigated as a valuable and sustainable production strategy.•DI allowed maximum water saving of %, without yield reduction in the young orange orchard.•Indicators ...of tree water status resulted of key importance in the study.•Canopy temperature results reliable as indicator of plant water stress.
In the study, deficit irrigation (DI) strategies were imposed on a young orange orchard in Sicily (Southern Italy) with the aim to monitor and analyze crop physiological features, first yield and fruit quality data for possible negative effects. The orchard includes trees irrigated with drip and sub-drip irrigation systems. Irrigation strategies, based on DI concepts, including regulated deficit irrigation (RDI) and partial root-zone drying (PRD), were adopted during the irrigation seasons 2011 and 2012, each supplying different percentages of the crop evapotranspiration (ETc). Several physiological indices indicative of plant water status were analyzed during the trial, including, stem water potential, stomatal conductance, canopy temperature, trunk diameter variations, leaf area index (LAI). The imposed DI strategies allowed maximum water saving of 41% (PRD treatment), without conditioning the first yield data. Fruit composition resulted positively affected by water restrictions. The impact of the imposed deficit on trees depends mainly on its degree of severity (i.e. lowering of stem water potential above the threshold of −1.3MPa for citrus orchards). A certain growth reduction was observed in DI treatments causing WUE (plant water use efficiency) increase, in terms of reducing competition between vegetative and reproductive growth. Subsurface drip irrigation system, designed for supplying 75% of ETc allowed plant water status, yield and quality data quite comparable with those obtained in the control treatment, supplying 100% of ETc by surface drip irrigation systems. Overall, the obtained results show that the studied DI strategies were successfully applied in a young orange orchard allowing water saving without significant detrimental effect on trees.
Health-related quality of life (HRQOL) is an important goal of therapy for chronic myeloid leukemia (CML) patients treated with current molecular-targeted therapies. The main objective of this study ...was to investigate factors associated with long-term HRQOL outcomes of CML patients receiving imatinib. Analysis was performed on 422 CML patients recruited in an observational multicenter study. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Key socio-demographic and clinical data were investigated for their association with HRQOL outcomes. Chronic fatigue and social support were also investigated. Univariate and multivariate linear regression analyses were used to identify independent factors associated with HRQOL outcomes. Fatigue was the only variable showing an independent and consistent association across all physical and mental HRQOL outcomes (P<0.01). Differences between patients reporting low versus high fatigue levels were more than eight and seven times the magnitude of a clinically meaningful difference, respectively, for the role physical (Δ=70 points) and emotional scale (Δ=63 points) of the SF-36. Fatigue did not occur as an isolated symptom and was most highly correlated with musculoskeletal pain (r=0.511; P≤0.001) and muscular cramps (r=0.448; P≤0.001). Chronic fatigue is the major factor limiting HRQOL of CML patients receiving imatinib.
Nutritional status in citrus plants, which is used as a guide for fertilisation, is normally determined by chemical analysis of leaves. According to standardised procedures, this is a destructive ...method. Leaf analysis detects symptomless detrimental conditions or confirms the nature of visible toxicity. This study proposes the use of a rapid, non-destructive, cost-effective technique to predict orange leaves nutritional status utilising a Vis–NIR (visible–near infrared) portable spectrophotometer and compares its results with standard chemical analyses. Tree nutritional status was evaluated by foliar analysis performed on 50 leaves. Chemical determinations on leaves detected N, P, K, Ca, Mg, Fe, Zn, Mn. For spectral acquisition, a ‘pen probe’ was used to measure the spectral reflectance response on each leaf. Mean reflectance values of all leaves for each treatment were compared by chemometric multivariate methods (PLS, partial least square) to both: a single reference chemical value and to all chemical parameters used together. The best model for single reference chemicals (coefficient of correlation
r = 0.995) and the tests (
r = 0.991) was obtained for potassium. Results also showed a high efficiency in the determination of nitrogen. For all chemical parameters used together, the analysed elements gave correlations in a range from
r = 0.883 for Mg to
r = 0.481 for P with standard error of prevision ranging from 0.01 for P to 12.418 for Fe.
The introduction and the extended clinical use of nilotinib in the first-line treatment of chronic myeloid leukemia have been based on company-sponsored trials. Independent confirmations are ...extremely important. We report an investigator-sponsored study of nilotinib 300 mg twice daily in 130 chronic myeloid leukemia patients in early chronic phase. A deep molecular response was achieved in 46% (MR
) and 17% (MR
) of patients at 2 years; 58% of the enrolled patients achieved a MR
at least once, with a sustained MR
in 52% of them. With a median observation of 29 months (range 24-37 months), 77% of patients were still on treatment with nilotinib. The reasons for permanent discontinuation were: 3% progression, 5% failure or suboptimal response, 8% adverse events, 1% treatment-free remission, and 5% other reasons. Thirteen thrombotic arterial events were reported in 12 patients. A prospective evaluation of metabolic effects showed an increase of fasting glucose without significant variations of glycated hemoglobin, an increase of total cholesterol (both low density lipoprotein and high density lipoprotein fractions) and a decrease of triglycerides. This study confirms a high and rapid efficacy of nilotinib 300 mg twice daily and provides detailed information on the type and incidence of non-hematologic and metabolic adverse events (clinicaltrials.gov identifier: 01535391).
Summary Defects of the dorsum of the foot can be challenging to reconstruct, none more so than the dorsum of the toe. The reverse Dorsalis Pedis Adipofascial Perforator (DPAP) flap is one possible ...reconstructive option for defects in this region. The aim of this study was to first demonstrate the anatomy of this flap, particularly the consistency of the perforators arising from the dorsalis pedis artery. Second, we present a clinical series based on this flap to demonstrate how it can be used. For the anatomical studies, 22 fresh cadaveric lower extremities were dissected, and injection studies were used to delineate the vascular territories. The presence of the distal perforator, distance to the first metatarso-phalangeal joint and diameter of each perforator were recorded. The cadaveric studies confirmed the presence of distal perforators to the first metatarso-phalangeal joint in 100% of limbs examined. The clinical study demonstrated the feasibility of the use of the adipofascial turn-over perforator flap for dorsal foot reconstruction. These anatomic findings provide an alternative method of reconstruction of great toe defects using the reverse DPAP flap.
Summary Aim The aim of this study is to clearly define the vascularisation of the lateral paratibial septum of the leg, defining the basis for a vertical pedicled adipofascial flap harvested from the ...anterolateral aspect of the leg to cover pretibial soft tissue defects. Materials and methods Twelve cadaver legs (eight fixed with formalin and four fresh) were dissected. The vessels running into the lateral paratibial septum were identified. The number of vessels were noted and evaluated at the lateral border of the proximal, middle and distal thirds of the leg. In addition, an angiographic study was performed on two limbs to confirm the connection between tibialis anterior artery and the overlaying fascia through these septal vessels. Results All the specimens had periosteo-septal vessels running in the lateral aspect of the tibia. The average number was 6.6. The distribution was constant in all the thirds of the leg. Conclusion These data are useful to propose the harvesting technique for adipofascial flap with vertical pedicle as a suitable reconstructive option to cover pretibial soft tissue defects.
Summary Background The management of lagophthalmos in patients with long-standing facial palsy is difficult, since the immobility and scleral show have to be corrected to protect the vision. In this ...article, the authors describe the treatment of paralytic eye with a static technique using a medially based orbicularis oculi muscle flap (OOMF) from the upper eyelid in patients with lagophthalmos. Patients and methods From April 2006 to May 2008, five Caucasian patients with ages ranging from 45 to 71 years (mean, 61 years) were treated at the Plastic Surgery Unit of Messina University. All patients underwent orbicularis oculi muscle (OOM) transposition flap to support the lower orbicularis oculi and create a suspension of the eyelid. To validate the anatomical features of the OOM transposition flap, four fresh cadaver heads (eight eyelids) were dissected to demonstrate flap viability, feasibility and suspension effect. Results We achieved resolution of the lagophthalmos and good cosmetic appearance in all cases. The distance between the upper and lower eyelid points during eye closing (as for sleep) was reduced postoperatively on the paralysed side compared to the contralateral healthy side. Follow-up time ranged from 3 to 25 months (mean, 12 months). All patients healed well with no complications of the flaps. There was no flap contraction, recurrent deformity or significant donor-site morbidity in the follow-up period. The incision scars were almost invisible. Conclusions The authors believe that the switching of upper blepharoplasty technique from the upper eyelid to the paralysed and scarred lower lid can be used as a tool to treat lagophthalmos.
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