A longitudinal-torsional mode ultrasonic needle for deep penetration into bone.

This work presents a longitudinal-torsional (L-T) composite mode ultrasonic needle device for deep bone penetration. The L-T needle is a geometrically modified version of an L-mode needle whose efficacy as a prototype ultrasonic bone biopsy device has been previously demonstrated by the authors. Finite element analysis (FEA) aided in the design of the L-T needle, with the aim of maximising the achievable torsional displacement while matching the longitudinal displacement achieved by the L-mode needle. Experimental modal analysis (EMA) of the fabricated ultrasonic device was used to identify the modal parameters and validate the FEA model. Harmonic analysis then provided an insight into how the inherent nonlinearities of the high-power transducer are affected by incorporating the geometrical features that degenerate the L mode into an L-T mode. High power characterisation shows that the longitudinal displacement amplitude of the L-T mode needle is larger than that of the L-mode needle. Comparative penetration tests in fresh Wistar rat skull were evaluated by investigating cell death and cell survival. The region of statistically significant cell death was small for both devices, with the combined axial and shear motion of the L-T device causing increased osteocyte necrosis within this region. Nevertheless, the results suggest a promising environment for post-operative healing. It is shown how this technology offers a potential technique for a surgical approach to the petrous apex, an application that requires a deep penetration into bone.

The natural history of vascular and other complications in patients treated with nilotinib for chronic myeloid leukemia.

Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions. Overall, AEs of any grade were reported in 95 patients (43%) and prompted nilotinib cessation in 46 (21%). VAEs occurred in 26 patients (12%), with an incidence of 4.1 events per 100 patient-years. Multivariate analysis identified age (P = .022) and dyslipidemia (P = .007) as independent variables for their development. There was 1 fatal first VAE, whereas the remaining patients either continued nilotinib (14 patients) or stopped it immediately (11 patients). Recurrent VAEs were associated with ongoing therapy in 7 of 14 who continued (with 2 fatal VAEs) vs 1 of 11 who discontinued (P = .04). Nineteen of the 23 evaluable patients surviving a VAE ultimately stopped nilotinib, of whom 14 received an alternative TKI. Dose reduction or cessation because of VAEs did not adversely affect maintenance of major molecular response. These findings demonstrate that in contrast to other AEs, VAEs are ideally managed with nilotinib cessation because of the increased risk of additional events with its ongoing use.

Ultrasonic Needles for Bone Biopsy.

Bone biopsy is an invasive clinical procedure, where a bone sample is recovered for analysis during the diagnosis of a medical condition. When the architecture of the bone tissue is required to be preserved, a core-needle biopsy is taken. Although this procedure is performed while the patient is under local anaesthesia, the patient can still experience significant discomfort. Additionally, large haematoma can be induced in the soft tissue surrounding the biopsy site due to the large axial and rotational forces, which are applied through the needle to penetrate bone. It is well documented that power ultrasonic surgical devices offer the advantages of low cutting force, high accuracy, and preservation of soft tissues. This paper reports a study of the design, analysis, and test of two novel power ultrasonic needles for bone biopsy that operate using different configurations to penetrate bone. The first utilizes micrometric vibrations generated at the distil tip of a full-wavelength resonant ultrasonic device, while the second utilizes an ultrasonic-sonic approach, where vibrational energy generated by a resonant ultrasonic horn is transferred to a needle via the chaotic motion of a free-mass. It is shown that the dynamic behavior of the devices identified through experimental techniques closely match the behavior calculated through numerical and finite-element analysis methods, demonstrating that they are effective design tools for these devices. Both devices were able to recover trabecular bone from the metaphysis of an ovine femur, and the biopsy samples were found to be comparable to a sample extracted using a conventional biopsy needle. Furthermore, the resonant needle device was also able to extract a cortical bone sample from the central diaphysis, which is the strongest part of the bone, and the biopsy was found to be superior to the sample recovered by a conventional bone biopsy needle.

The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia.

Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions. Adverse events were reported in 116 patients (55%), most commonly pleural effusions (53 patients, 25%), which was the predominant cause of permanent drug cessation. Age and dose were risk factors for pleural effusion (P < .01 and .047, respectively). Recurrence rates were higher in those who remained on 100 mg compared with those who dose reduced (P = .041); however, recurrence still occurred at 50 mg. Patients who developed pleural effusions were more likely to have achieved MR4.5 after 6 months of dasatinib than those without effusions (P = .008). Pulmonary hypertension occurred in 5% of patients, frequently in association with pleural effusion, and was reversible upon dasatinib cessation in 6 of 7 patients. Dose reductions and temporary cessations had minimal impact on MR rates. Our observations suggest that by using the lowest effective dose in older patients to minimize the effusion risk, dose modification for cytopenias, and care with concomitant antiplatelet therapy, the necessity for permanent dasatinib cessation due to toxicity is likely to be minimal in immunologically competent patients.

Postictal psychosis in temporal lobe epilepsy: risk factors and postsurgical outcome?

PURPOSE: Postictal psychosis (PIP) occurs in ∼7% of patients with temporal lobe epilepsy (TLE). The aims of this study were to identify risk factors that may predispose patients to developing PIP and determine whether the severity of PIP predicts postsurgical outcome. METHODS: We compared 20 patients with a history of TLE+PIP to 60 age-matched TLE patients without any psychiatric history (TLE-only), with respect to pre-surgical clinical and neuropsychological variables. Group differences in postsurgical psychiatric, histopathological, cognitive and seizure outcomes were also examined. KEY FINDINGS: TLE+PIP patients were significantly less likely to have localised ictal epileptiform activity than the TLE controls (p=0.05) and were significantly more likely to have a positive family psychiatric history than TLE controls (p=0.04). Other pre-surgical clinical and neuropsychological variables did not distinguish between the groups. Patients with two or more PIP episodes had significantly increased odds of developing de novo psychopathology within 4 years of surgery, after controlling for comorbid pre-surgical psychiatric status and a history of SGTCS (OR: 9.11, 95% CI: 1.53-54.10, p=0.02). A history of PIP did not significantly predict other postsurgical outcomes (seizure freedom (ILAE=1) or cognitive outcome). SIGNIFICANCE: Our results suggest that more widespread or diffuse brain abnormalities as reflected by pre-surgical EEG findings and positive genetic determinants may contribute to the development of PIP. Furthermore, patients with recurrent PIP episodes who undergo TLE surgery are at increased risk of developing de novo psychiatric disorders, particularly mood disorders. This has implications for pre-operative counselling and highlights a need for postsurgical psychiatric monitoring for these patients.

Predicting and preventing psychopathology following temporal lobe epilepsy surgery.

Less than 3% of temporal lobe epilepsy (TLE) surgical outcome studies have investigated the psychiatric sequelae and morbidity associated with surgery. This is disproportionate to the extent of the problem. Variable prevalence rates have been reported for post-surgical depression, anxiety, and interictal psychosis. Until recently, very few studies distinguished de novo postoperative presentations from pre-existing conditions, making it difficult to accurately assess the impact of TLE surgery on psychiatric morbidity. Predictors of de novo postoperative presentations have proved elusive. This current review summarizes the findings from a systematic literature review of the psychiatric morbidity associated with TLE surgery including newly published follow-up data from our own series of 280 surgical patients. A framework for future research, possible pathophysiological mechanisms, and translational models are also discussed.

Predictors of psychiatric and seizure outcome following temporal lobe epilepsy surgery.

PURPOSE: Neurosurgery is an effective therapy for selected individuals with medically refractory temporal lobe epilepsy (TLE). De novo psychopathology may complicate the postsurgical outcome. Our aims were to identify predictors of de novo psychiatric and seizure outcome following TLE surgery. METHODS: Medical records of 280 patients who underwent TLE surgery were reviewed. Preoperative and postoperative psychiatric diagnoses were identified, in addition to information on seizure recurrence and neuropsychological status. Logistic regression analysis was used to identify predictors of having a de novo psychiatric diagnosis and remaining seizure-free within 4 years following surgery. KEY FINDINGS: One hundred five patients (38%) had significant psychiatric problems within 4 years following TLE surgery. Fifty-one patients (18%) developed de novo psychopathology; half of cases presented within 6 months and 90% of psychopathologies persisted 6 months or longer. A preoperative history of secondary generalized tonic-clonic seizure(s) (SGTCS) was an independent predictor of de novo psychopathology (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.14-6.59, p = 0.02). From patients with available seizure data, 49% (127 of 258) remained seizure-free for 4 years after surgery. Patients with a history of SGTCS (OR 0.47, 95% CI 0.25-0.90, p = 0.02) and those with a preoperative psychiatric diagnosis (OR 0.53, 95% CI 0.28-0.98, p = 0.04) were significantly less likely to remain seizure-free. SIGNIFICANCE: De novo psychopathology is a significant complication of TLE surgery. Inclusion of neuropsychiatric assessments in the presurgical evaluation may lead to increase in the power of prognostic models used to predict the neurologic outcome of TLE surgery.