Life-threatening reactions to propofol

Journal ArticleTo the Editor: Propofol (2,6-diisopropyl phenol; Diprivan; Stuart Pharmaceuticals, Wilmington, DE) has been advocated as a titratable continuous infusion anesthetic agent associated with fast and smooth recovery (2, 7). The anesthetic properties of a smooth induction, short half-life, and rapid emergence from anesthesia after prolonged operations, with a low incidence of nausea and vomiting and little "hangover' sedation, suggest that this agent may be ideally suited for use in intracranial neurosurgery (6). It also may be given in combination with analgesics, such as sufentanyl and inhalational agents. Accordingly, we have adopted propofol for use in all cranial base, vascular, and functional neurosurgical procedures. We are currently using propofol (50-100 /ig/kg/min infusion, with a burst suppression dosage of approximately 250 jiig/kg/min used during periods of vascular interruption) in a balanced protocol with narcotic (sufentanyl) and low dosage inhalational (isoflurane) anesthesia

Intracranial fusarium fungal abscess in an immunocompetent patient: case report and review of the literature.

Introduction Fusarium spp is an omnipresent fungal species that may lead to fatal infections in immunocompromised populations. Spontaneous intracranial infection by Fusarium spp in immunocompetent individuals is exceedingly rare. Case Report An immunocompetent 33-year-old Hispanic woman presented with persistent headaches and was found to have a contrast-enhancing mass in the left petrous apex and prepontine cistern. She underwent a subsequent craniotomy for biopsy and partial resection that revealed a Fusarium abscess. She had a left transient partial oculomotor palsy following the operation that resolved over the next few weeks. She was treated with long-term intravenous antifungal therapy and remained at her neurologic baseline 18 months following the intervention. Discussion To our knowledge, this is the first reported case of Fusarium spp brain abscess in an immunocompetent patient. Treatment options include surgical intervention and various antifungal medications. Conclusion This case demonstrates the rare potential of intracranial Fusarium infection in the immunocompetent host, as well as its successful treatment with surgical aspiration and antifungal therapy

The Physiopathology of T- Cell Acute Lymphoblastic Leukemia: Focus on Molecular Aspects

T-cell acute lymphoblastic leukemia/lymphoma is an aggressive hematological neoplasm whose classification is still based on immunophenotypic findings. Frontline treatment encompass high intensity combination chemotherapy with good overall survival; however, relapsing/refractory patients have very limited options. In the last years, the understanding of molecular physiopathology of this disease, lead to the identification of a subset of patients with peculiar genetic profile, namely \u201cearly T-cell precursors\u201d lymphoblastic leukemia, characterized by dismal outcome and indication to frontline allogeneic bone marrow transplant. In general, the most common mutations occur in the NOTCH1/FBXW7 pathway (60% of adult patients), with a positive prognostic impact. Other pathogenic steps encompass transcriptional deregulation of oncogenes/oncosuppressors, cell cycle deregulation, kinase signaling (including IL7R-JAK-STAT pathway, PI3K/AKT/mTOR pathway, RAS/MAPK signaling pathway, ABL1 signaling pathway), epigenetic deregulation, ribosomal dysfunction, and altered expression of oncogenic miRNAs or long non-coding RNA. The insight in the genomic landscape of the disease paves the way to the use of novel targeted drugs that might improve the outcome, particularly in relapse/refractory patients. In this review, we analyse available literature on T-ALL pathogenesis, focusing on molecular aspects of clinical, prognostic, and therapeutic significance

Small Paroxysmal Nocturnal Hemoglobinuria Clones in Autoimmune Hemolytic Anemia: Clinical Implications and Different Cytokine Patterns in Positive and Negative Patients

Autoimmune hemolytic anemia (AIHA) is characterized by immune mediated erythrocytes destruction by autoantibodies with or without complement activation. Additional pathologic mechanisms include cellular cytotoxicity, cytokline dysregulation, and inadequate bone marrow compensation with fibrosis/dyserythropoiesis. The latter resembles that of bone marrow failures, namely aplastic anemia and myelodysplastic syndromes. Paroxysmal nocturnal hemoglobinuria (PNH) clones are increasingly recognized in bone marrow failure syndromes, and their selection and expansion are thought to be mediated by immune mechanisms. In this study, we aimed to evaluate the prevalence of PNH clones in 99 patients with primary AIHA, and their correlations with disease features and outcomes. Moreover, in the attempt to disclose the physiopathology of PNH positivity in AIHA, serum levels of several immunomodulatory cytokines were tested. A PNH clone was found in 37 AIHA patients (37,4%), with a median size of 0.2% on granulocytes (range 0.03\u201385). Two patients showed a large clone (16 and 85%) and were therefore considered as AIHA/PNH association and not included in further analysis. Compared to PNH negative, PNH positive cases displayed a higher hemolytic pattern with adequate bone marrow compensation. AIHA type, response to therapy, complications and outcome were comparable between the two groups. Regarding cytokine levels, IFN-\u3b3 and IL-17 were lower in PNH positive vs. PNH negative AIHAs (0.3 \ub1 0.2 vs. 1.33 \ub1 2.5; 0.15 \ub1 0.3 vs. 3,7 \ub1 9.1, respectively, p = 0.07 for both). In PNH positive AIHAs, IFN-\u3b3 positively correlated with reticulocytes (r = 0.52, p = 0.01) and with the bone marrow responsiveness index (r = 0.69, p = 0.002). Conversely, IL-6 and IL-10 showed the same pattern in PNH positive and PNH negative AIHAs. IL-6 levels and TGF-\u3b2 positively correlated with clone size (r = 0.35, p = 0.007, and r = 0.38, p = 0.05, respectively), as well as with LDH values (r = 0.69, p = 0.0003, and r = 0.34, p = 0.07, respectively). These data suggest testing PNH clones in AIHA since their prevalence is not negligible, and may correlate with a prominent hemolytic pattern, a higher thrombotic risk, and a different therapy indication. PNH testing is particularly advisable in complex cases with inadequate response to AIHA-specific therapy. Cytokine patterns of PNH positive and negative AIHAs may give hints about the pathogenesis of highly hemolytic AIHA

The effects of primary elevation of cerebral venous pressure on cerebral hemodynamics and intracranial pressure

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23634/1/0000598.pd

Anti-ganglioside antibodies : experience from the Italian Association of Neuroimmunology external quality assessment scheme

Anti-ganglioside antibodies are currently used in the differential diagnosis of suspected immune-mediated neuropathies. In-house and increasingly used commercial assays seem to perform suboptimally, and comparative information on their analytical performance are essentially lacking. Born within the frame of guidelines and standardization activities by the Italian Association of Neuroimmunology, this external quality assessment scheme (EQAS) is a real-life snapshot of the laboratory diagnostics in this field. The EQAS consisted of five surplus, anonymized serum samples from patients with clinically-defined neuropathies and two serum samples from healthy blood donors. Eight laboratories used commercial line-/dot-blots, seven in-house/commercial ELISAs (in addition, 13 laboratories tested a recently released ELISA by B\ufchlmann). Only high anti-ganglioside antibody reactivities were considered, in accordance with consolidated recommendations. Large variations in anti-ganglioside antibody profiles were observed, even, although to a lesser extent, within homogeneous classes of assays. Concordance between the profiles and clinical phenotypes was also partial. Although conducted on a relatively small, but representative number of Italian laboratories, this EQAS shows a critical between-laboratory disagreement in the test results of anti-ganglioside antibodies. Also considering the trend for using certified assays in generalist laboratories, strong efforts toward standardization and the identification of the best method(s) for their determinations are compellingly needed

Breakthrough SARS-CoV-2 infections in MS patients on disease-modifying therapies

Background: Patients with multiple sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines. Objective: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in pwMS on different disease-modifying therapies (DMTs). Methods: Data on the number of vaccinated patients and the number of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers. We estimated the rate of breakthrough infections and of infection requiring hospitalization per DMT. Results: 19,641 vaccinated pwMS were included in the database. After a median follow-up of 8 months, we observed 137 breakthrough infections. Compared with other DMTs, the rate of breakthrough infections was significantly higher on ocrelizumab (0.57% vs 2.00%, risk ratio (RR) = 3.55, 95% CI = 2.74-4.58, p < 0.001) and fingolimod (0.58% vs 1.62%, RR = 2.65, 95% CI = 1.75-4.00, p < 0.001), while there were no significant differences in any other DMT group. In the ocrelizumab group the hospitalization rate was 16.7% versus 19.4% in the pre-vaccination era (RR = 0.86, p = 0.74) and it was 3.9% in all the other DMT groups versus 11.9% in the pre-vaccination period (RR = 0.33, p = 0.02). Conclusions: The risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the DMTs excluding ocrelizumab