Current treatment approaches in CML.

Take home messages Five tyrosine kinase inhibitors are available, the treatment strategy is still challenging. Baseline risk, comorbidities, and patient and physician expectations play a pivotal role. Treatment-free remission is a new opportunity

An investigation of performance limits of conventional and tunneling graphene-based transistors

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Nilotinib: a novel encouraging therapeutic option for chronic myeloid leukemia patients with imatinib resistance or intolerance

Although high rates of complete hematologic and cytogenetic remission have been observed in patients with chronic phase chronic myeloid leukemia (CML) treated with imatinib, a short duration of response with eventual emergence of imatinib resistance has also been reported in a subset of CML patients. The most frequent clinically relevant mechanisms that change imatinib sensitivity in BCR-ABL-transformed cells are mutations within the Abl kinase domain, affecting several of its properties. Crystal structure analysis of the Abl-imatinib complex has proven helpful in identifying potential critical residues that hinder interactions of imatinib with mutated Abl. This has led to the development of a second generation of targeted therapies such as nilotinib and dasatinib, already in phase II clinical trials or SKI-606 and MK-0457 in phase I trials. In this review, we discuss the activity of nilotinib, developed by Novartis using a rational drug design strategy in which imatinib served as the lead compound. Preliminary studies demonstrated that nilotinib has more efficacy than imatinib in inhibiting proliferation of BCR-ABL-dependent cells, a relatively safety profile and clinical efficacy in all phases of CML

Necrobiosis Lipoidica Affecting the Leg: What Is the Best Treatment in a Patient with Very High Aesthetic Demand?

Summary: Necrobiosis Lipoidica (NL) is a rare necrotising disorder of the skin characterized by collagen degeneration, thickening of blood vessels, and granulomatous inflammatory process. Its main clinical features are brownish-red papules and yellowish plaques with atrophic central areas. NL affects 0.3% -1.2% of the diabetic population, mostly women (female/male ratio is 3:1). Management of NL is challenging, especially for large lesions refractory to medical therapy, thus requiring surgical excision as an alternative option. Due to the rare occurrence of this condition no treatment guidelines exist and individualized treatment mostly depends on the severity of the lesion, location and patient's expectations. A case of a 30-year-old diabetic woman with very high aesthetic expectations was succesfully treated with staged resections of a giant NL to the leg and reconstruction with dermal template and full thickness skin grafts. Grafts were taken from the groin region bilaterally and from the lower abdomen after a cosmetic mini-abdominoplasty procedure. This approach allowed for a stable and very satisfactory aesthetic result with no donor site exposed scars

Obturator nerve split for gracilis free-flap double reinnervation in facial paralysis

The use of a double-powered free muscle transfer for facial reanimation has been reported by several authors with different types of nerve coaptation. A new nerve coaptation strategy is presented herein. We performed a 1-stage double-powered free gracilis muscle flap transfer in a patient with long-standing facial paralysis by splitting the obturator nerve and anastomosing the 2 free ends to the contralateral facial nerve (through a sural graft) and to the masseteric nerve. Voluntary movement of the transferred muscle with teeth clenching was observed at 6 months after the operation and a symmetric smile with bilateral elevation of the mouth angle at 10 months. Our limited experience suggests that in case of a large cross-section of the obturator nerve, the latter can be split and sutured to the ipsilateral masseteric nerve and to the contralateral facial nerve with a sural graft by double end-to-end anastomosis

Improved effective mobility extraction in MOSFETs

The standard method of extracting carrier effective mobility from electrical measurements on MOSFETs is reviewed and the assumptions implicit in this method are discussed. A novel technique is suggested that corrects for the difference in drain bias during IV and CV measurements. It is further shown that the lateral field and diffusion corrections, which are both commonly neglected, in fact cancel. The effectiveness of the proposed technique is demonstrated by application to data measured on a quasi-planar SOI finFET at 300 K and 4 K

Molecular Monitoring of BCR-ABL Transcripts after Allogeneic Stem Cell Transplantation for Chronic Myeloid Leukemia

AbstractThe monitoring of minimal residual disease (MRD) through low sensitivity real-time (RT) polymerase chain reaction (PCR) analysis of BCR-ABL transcripts allows early detection of chronic myeloid leukemia (CML) relapse after allogeneic hematopoietic stem cell transplantation (HSCT). The introduction of more sensitive techniques, such as RT quantitative (Q)-PCR, may lead to an overestimation of the risk of CML relapse. In this study, we reviewed the results of peripheral blood RT Q-PCR in CML patients who underwent allogeneic HSCT from 1983 to 2007. In our laboratory, RT Q-PCR analysis was routinely performed since 2002. Eighty-seven of 189 patients had available RT Q-PCR data; 63 patients had at least 3 RT Q-PCR analyses assessable. Fifty-two of 63 patients (83%) had, at least once, detectable transcript levels, but with an BCR-ABL/ABL ratio <.1% defined as .1% confirmed by the finding of Ph+ cells in bone marrow. No patients with persistent undetectable transcripts relapsed (P = .19). Relapse did not correlate with the number of occurrences o

Questions concerning tyrosine kinase-inhibitor therapy and transplants in chronic phase chronic myeloid leukaemia

In this provocative commentary, we consider several questions posed by the late chronic myeloid leukaemia (CML) expert Prof. Michele Baccarani, which he challenged us to address after his death. He noted only a small proportion of people with chronic phase CML receiving tyrosine kinase-inhibitor (TKI)-therapy are likely to achieve sustained therapy-free remission (TFR) and even fewer are likely to be cured. Persons most likely to fail TKItherapy can be identified at diagnosis or soon after starting TKI-therapy. These persons are likely to need lifetime TKI-therapy with attendant risks of adverse events, cost and psychological consequences. Allogeneic transplants achieve much higher rates of leukaemia-free survival compared with TKI-therapy but are associated with transplant-related adverse events including an almost 20 percent risk of transplant-related deaths within 1 year post-transplant and a compromised quality-of-life because of complications such as chronic graft-versus-host disease. Subject-, disease- and transplant-related co-variates associated with transplant outcomes are known with reasonable accuracy. Not everyone likely to fail TKI-therapy is a transplant candidate. However, in those who candidates are physicians and patients need to weigh benefits and risks of TKI-therapy versus a transplant. We suggest transplants should be more often considered in the metric when counseling people with chronic phase CML unlikely to achieve TFR with TKI-therapy. We question whether we are discounting a possible important therapy intervention; we think so

Laparoscopically assisted transperineal approach in the management of a giant pelvic lipoma

Giant lipomas affecting the retroperitoneum and pelvis are quite rare. The surgical management of these lesions may be technically demanding and controversies exist with respect to diagnosis, competences being involved, type of surgical approach, radicality, and timing. A unique case presentation of a giant lipoma occupying the whole pelvis and the gluteal region is presented. Due to its size, many anatomical areas are involved, requiring the expertise of multiple specialists to treat. After multidisciplinary counseling, the lesion is radically resected in one stage by using a new videolaparoscopically assisted transperineal access to the pelvis. This type of surgical approach may be of interest for resecting pelvic tumors in women and men