Progressive thrombosis of cervical and intracranial arteries related to Ponatinib treatment for Chronic Myeloid Leukemia.

Ponatinib is a third-generation Tyrosine Kinase Inhibitor (TKI), approved as first-line treatment for Chronic Myeloid Leukaemia (CML) chronic phase. Here we describe a CML patient with a history of subsequent TIAs and an ischemic stroke during Ponatinib treatment. Patient was admitted for a 3-day history of sudden onset left hemiparesis due to an acute ischemic stroke. MRI showed bilaterally the almost total absence of signal in the intracranial tract of anterior circulation and low signal of cerebral posterior circulation. Digital Subtraction Angiography showed multiple steno-occlusions of both anterior and posterior circulation large vessels. The association between cerebrovascular events and TKIs of second and third-generation has been widely described. So Ponatinib was stopped. To our knowledge, this is the first case of multiple ischemic strokes and recurrent TIAs during treatment with Ponatinib, pointing out the importance of accurate quantification of cardiovascular risk before starting Ponatinib.

A standardized protocol for the perioperative management of myasthenia gravis patients. Experience with 110 patients.

BACKGROUND: Video-assisted thoracoscopic extended thymectomy (VATET) is well established in the treatment of myasthenia gravis; however, patient selection remains controversial. Perioperative management protocol is lacking, and concerns regarding post-operative myasthenic crisis still remain. We performed a retrospective observational study evaluating the impact of the introduction of a protocol in the perioperative management of patients with myasthenia gravis who underwent VATET. METHODS: The perioperative management protocol was developed by a team of neurologists and anesthesiologists who reviewed the literature and their previous experience on myasthenia gravis patients. Respiratory, clinical, and neurological patient features were included in the protocol evaluation. A retrospective review of patients who underwent VATET before and after introduction to the protocol was finally performed. RESULTS: The medical records of 66 patients (pre-protocol group) and 44 patients (protocol group) were available for the study. In the pre-protocol group, 17 patients (26%) were admitted to intensive care unit (ICU) during the post-operative period, while three patients (6.8%) of the protocol group met the criteria for ICU post-operative admission. This resulted in a reduction of 73.5% of patients admitted to ICU (P = 0.023) and in an 80% (P = 0.002) reduction of the use neuromuscular blocking agents. Two post-operative myasthenic crises preceded by bulbar symptoms (1.8%) were identified in the pre-protocol group patients. CONCLUSIONS: Although the application of our protocol results in a substantial reduction in the recovery of patients in the ICU and in hospital costs, there was no substantial difference in mortality and morbidity between patients admitted to the surgical ward or to ICU.

The use of desflurane or propofol in combination with remifentanil in myasthenic patients undergoing a video-assisted thoracoscopic-extended thymectomy.

BACKGROUND: Although several studies of the use of desflurane in anesthesia have revealed many desirable qualities, there are no data on the use and effects especially on the neuromuscular function of desflurane on myasthenia gravis (MG) patients. The purpose of this study was to evaluate the use of either desflurane or propofol, both combined with remifentanil, in patients with MG undergoing a video-assisted thoracoscopic-extended thymectomy (VATET). METHODS: Thirty-six MG patients who underwent VATET were enrolled. Nineteen patients were anesthetized with remifentanil and propofol infused with a target-controlled infusion plasma model, and 17 patients with desflurane and remifentanil. No muscle relaxant was used. The intubating conditions, hemodynamic and respiratory changes, neuromuscular transmission and post-operative complications were evaluated. RESULTS: Neuromuscular transmission was significantly decreased in the desflurane group (6.7%, from 3% to 9% during anesthesia P=or<0.05). The intubating conditions were good in all 36 patients and 35 patients were successfully extubated in the operating room. The time-to-awakening, post-operatory pH and base excess were significantly different in the two groups, with a decreasing mean arterial pressure in the group administered with desflurane. No patients required reintubation due to myasthenic or cholinergic crisis, or respiratory failure. No other significant differences between the two groups studied were observed. CONCLUSION: Our experience indicates that anesthesia with desflurane plus remifentanil in patients with MG could determine a reversible muscle relaxation effect, but with no clinical implication, allowing a faster recovery with no difference in extubation time and post-operative complications in the two groups.

Meta-analysis of APOE genotype and subarachnoid hemorrhage: clinical outcome and delayed ischemia.

BACKGROUND: Emerging evidence suggests that the APOE4 allele may increase the risk of a negative outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), but the results are conflicting. A genetic variable predicting the individual clinical course is currently lacking. OBJECTIVE: To examine the association between the APOE4 allele and a negative outcome. A secondary objective was to investigate the association between the APOE4 allele and delayed ischemia, a major complication of SAH. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, CINHAL, LILACS, and www.google.it through March 2006. We hand-searched journals, international conference proceedings, and reference lists of retrieved articles. Individual patient data were requested from the corresponding authors of the original articles. Information on study design, participant characteristics, clinical outcome, delayed ischemia, and confounder distribution were independently abstracted by two investigators. RESULTS: We included eight observational studies (696 patients for the clinical outcome and 600 for the delayed ischemia analyses). The corresponding authors of all the retrieved publications but one gave their original data. Summary odds ratios (ORs) were calculated by means of the random-effect model. The risk of a negative outcome (OR = 2.558; 95% CI 1.610 to 4.065) and delayed ischemia (OR = 2.044; 95% CI 1.269 to 3.291) were increased in the E4 carriers. CONCLUSIONS: In patients with subarachnoid hemorrhage, the expression of the E4 allele is associated with a higher risk of a negative outcome and delayed ischemia.

APOE influences vasospasm and cognition of noncomatose patients with subarachnoid hemorrhage.

OBJECTIVE: To determine the influence of the APOE genotype on functional and cognitive outcome and on the incidence and prognosis of clinical vasospasm (delayed ischemic neurologic deficit [DIND]) in noncomatose patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: The authors reviewed the data of patients admitted for SAH to the Neurosurgical Departments of the San Gerardo Hospital of Monza (January 1996 to December 2001) and the Ospedali Riuniti of Bergamo (January 2002 to September 2003). The authors considered only noncomatose patients and evaluated outcome by means of the Rankin Disability Index and the Mini-Mental State Examination at least 6 months after the SAH. STATISTICAL ANALYSIS: Uni- and multivariate logistic regression. RESULTS: The authors included 101 patients. They found the epsilon4 allele in 26 patients (25.7%). The presence of the epsilon4 allele negatively affected the overall outcome (functional morbidity or cognitive morbidity, or both) (p = 0.0087) and, particularly, cognitive morbidity (p = 0.0028). Those with an epsilon4 allele had delayed ischemic neurologic deficit DINDs more frequently (p = 0.024) and, in the presence of DIND, they were more likely to show permanent neurologic deficits (p = 0.0051). CONCLUSIONS: ApoE4 negatively affects cognitive morbidity and delayed ischemic neurologic deficit recovery. The presence of an epsilon4 allele increases the risk of delayed ischemic neurologic deficit.