Venetoclax and hypomethylating agents in FLT3-mutated acute myeloid leukemia

FMS-like tyrosine kinase 3 (FLT3) mutations are prevalent in acute myeloid leukemia (AML), and their presence confers adverse risk. FLT3-mutated (FLT3m) AML is a challenging leukemia to manage, particularly in older and unfit patients as well as patients with relapsed/refractory (r/r) disease. We retrospectively analyzed the outcomes of 50 FLT3m AML patients (17 treatment-naïve, 33 r/r) treated with venetoclax (VEN) and hypomethylating agents (HMA). The overall CR/CRi rate with VEN-HMA was 60% (94% in treatment-naïve AML and 42% in r/r AML). Early (60-days) treatment related mortality was 2%. The r/r AML setting was an independent predictor of lower complete response (OR: 0.08; 95%CI: 0.00-0.60, P = .03). Cytogenetics-molecular risk, concurrent mutations, the type of FLT3 mutation (ITD vs TKD), the ITD allelic ratio, the type of HMA, age, prior exposure to HMA and receipt of prior allogeneic transplant did not independently impact response or leukemia-free survival (LFS). Concurrent IDH mutations were associated with lower CR/CRi (P = .01), while ASXL1 or TET2 mutations showed a non-significant association toward higher CR/CRi (P = .07, for both). However, none of the concurrent mutations were an independent predictor for response when adjusted to AML setting. In conclusion, VEN-HMA is associated with encouraging efficacy in FLT3m AML among both newly diagnosed unfit and r/r patients.     

Post-transplant cyclophosphamide and bortezomib inhibit dendritic cell maturation and function and alter their IκB and NFκB

Impairing dendritic cell (DC) function to prevent graft versus host disease (GvHD) is an appealing concept. DC antigen presentation is NF-κB pathway-dependent and bortezomib might therefore play a role in preventing alloreactivity. We obtained DC from the blood of patients enrolled in a phase I study using post-transplant cyclophosphamide and bortezomib for prevention of GvHD. Control samples were obtained from patients receiving standard GvHD prevention regimen. Pre-treatment samples were also collected from enrolled patients. DC isolated on days + 1, + 4, and + 7 showed progressive decrease in the expression of maturation markers in comparison to control. In a DC–CD4 + mixed lymphocyte reaction (MLR) where DC isolated from the recipient blood before graft infusion were the stimulator cells, T cell proliferation measured by bromodeoxyuridine (BrdU) integration was decreased in samples obtained on days + 14 and + 21 in comparison to control group. Finally, measured by real-time PCR, the expression of IκB progressively increased while the expression of NF-κB decreased in DC on days + 1, + 4, and + 7, in comparison to pre-treatment paired controls. We conclude that our data further justify exploring the role of bortezomib in GvHD prevention and propose a novel mechanism of action of bortezomib in DC.     

Comparative biomechanical study on three miniplates osteosynthesis systems for stabilisation of low condylar fractures of the mandible

Open reduction and fixation of low condylar fractures of the mandible can be achieved by many osteosynthesis systems that differ in size, shape, and site of placement according to the surgical approach. We investigated the maximum load and rigidity of 4 osteosynthesis systems: the standard double 4-hole straight miniplates, the inverted y-miniplate (with and without self-drilling screws), and the TriLock Delta condyle trauma plate. The standard double 4-hole straight miniplate osteosynthesis achieved the best fixation and resistance in view of a mean (SD) maximum load of 539.8 (100.2) N, followed by the inverted y-miniplate with the self-drilling screws (246.5 (23.8) N), the inverted y-miniplate with standard screws (242.4 (27.2) N), and finally the TriLock Delta plate (167.4 (39.2) N). Analysis of the slope of the force–displacement diagram from 80 N to 100 N in each group showed that the TriLock Delta miniplate had the highest values for rigidity (17.3 (5.1) N/μm), followed by the inverted y-miniplate groups with self-drilling screws (14.1 (6.4) N/μm), and with standard screws (12.6 (2.5) N/μm). The double 4-hole straight miniplate osteosynthesis had the lowest rigidity (8.7 1.4) N/μm). Despite the significant difference in the maximum load between the double 4-hole miniplates and other investigated osteosynthesis patterns, all groups had sufficient load for the fixation of low condylar fractures of the mandible when postoperative bite forces and the slowly increasing voluntary clenching during healing were considered.     

Safety and efficacy of transvenous lead extraction of very old leads

OBJECTIVESTransvenous lead extraction using mechanical rotational- or laser sheaths is an established procedure. Lead dwell time has been recognized as a risk factor for extraction failure and procedure-related complications. We therefore investigated the safety and efficacy of transvenous extraction of leads with an implant duration of more than 10 years.Open in a separate windowMETHODSBetween January 2013 and March 2017, a total of 403 patients underwent lead extraction in 2 high-volume lead extraction centres. One hundred and fifty-four patients with extraction of at least 1 lead aged over 10 years were included in this analysis. Laser lead extraction was the primary extraction method, with additional use of mechanical rotational sheaths or femoral snares, if necessary. All procedural- and patient-based data were collected into a database and retrospectively analysed.RESULTSMean patient’s age was 65.8 ± 15.8 years, 68.2% were male. Three hundred and sixty-two leads had to be extracted. The mean lead dwell time of treated leads was 14.0 ± 6.1 years. Complete procedural success was achieved in 91.6% of cases, while clinical success was achieved in 96.8%. Failure of extraction occurred in 3.2%. Leads that could not be completely removed had a significantly longer lead dwell time (18.2 vs 13.2 years; P = 0.016). Additional mechanical rotational sheaths or femoral snares were used in 26 (16.9%) patients. Overall complication rate was 4.6%, including 5 (3.3%) major and 2 (1.3%) minor complications. There was no procedure-related mortality.CONCLUSIONSTransvenous lead extraction in leads aged over 10 years is safe and effective when performed in specialized centres and with use of multiple tools and techniques. Leads that could not be completely extracted had a statistically significant longer lead dwell time.     

One-year visual outcome of secondary piggyback pinhole device implantation in pseudophakic eyes with irregular corneal astigmatism and iris trauma

PurposeRetrospective case series evaluating the efficacy and safety of implanting XtraFocus^™ pinhole device in pseudophakic patients with irregular corneal astigmatism with concurrent or standalone iris defect.MethodsElectronic case records were searched for: uncorrected distance visual acuities (UDVA) and corrected distance visual acuities (CDVA), automatic or manifest refraction and spherical equivalent (SE). All main outcomes were evaluated preoperatively and postoperatively at 1, 3, 6, 9 and 12 months, along with patients’ satisfactory outcome and complications.ResultsEleven pseudophakic eyes of 11 patients with a mean age of 54 (range 27–81) years were included. Median UDVA improved significantly from logMAR 0.7 (range 0.1–1.22) pre-operatively to 0.4 (range 0–1.3) at 1-month (p = 0.002); median CDVA remained unchanged at logMAR 0.4 (range 0–0.1) pre-operatively and 0.4 (range 0–0.8) at 1-month (p = 0.36). There were no significant statistical differences in both UDVA and CDVA between the post-operative periods. Ten patients (90.9%) had initial UDVA improvement at 1-month post op. Eight (72.7%) patients expressed satisfaction with improved vision or reduction of glare/halos. Three (27.3%) patients had unsatisfactory visual outcome resulting in 2 requested for implant explantation due to worsening of glare and distressing floaters.ConclusionsXtraFocus^™ is effective in improving vision or reducing glare in pseudophakic patients with irregular corneal astigmatism or intragenic iris trauma, with over 70% expressed satisfactory outcome. Disturbing floaters and glare preclude its use in some resulting in implant explantation.Subject terms: Eye manifestations, Corneal diseases     

Elective neck dissection in T1/T2 oral squamous cell carcinoma with N0 neck: essential or not? A systematic review and meta-analysis

European Archives of Oto-Rhino-Laryngology - Oral squamous cell carcinoma (SCC) is characterized by a high risk of cervical lymph node metastasis with a high incidence of occult metastasis. A...