Сombined (anti-VEGF and laser) treatment for operated secondary refractory neovascular glaucoma

Purpose. To develop an optimal algorithm for the management of patients with operated neovascular uncompensated glaucoma. Material and methods. 2 patients with operated secondary neovascular glaucoma of stage III-c. In the combined sequential therapy, the anti-VEGF medication Ranibizumab (0.5 mg) was used, laser coagulation of residual newly formed vessels, laser reconstruction in the surgical area, contact transcleral cyclolazercoagulation, and laser coagulation of the peripheral parts of the retina were performed. Results. The combined sequential treatment, combined with the appointment of antihypertensive drugs in drops, allowed to stabilize the level of IOP. IOP indicators remained at the level of normal values during 1 year of follow-up. Conclusion. The use of combined laser technologies and anti-VEGF therapy makes it possible to potentiate and prolong the hypotensive effect in the treatment of patients with operated secondary refractory neovascular glaucoma. Key words: operated neovascular glaucoma, anti-VEGF, combined laser treatment.

Our Experience in Applying the National Polymer Microshunt in Refractory Glaucoma Surgery

Purpose. To analyze the outcomes of the national polymer microshunt implantation in refractory glaucoma surgery and to show its efficacy and safety. Patients and methods. We analyzed the results of treatment of 90 patients (90 eyes) with refractory glaucoma. All patients were divided into two groups: main group and comparison group. The patients in the main group (44 eyes) were implanted with the national polymer microshunt (Reper-NN). The patients in the comparison group (46 eyes) were implanted with Ex-PRESS. Control criteria in the postoperative period included visometry, tonometry by Maklakov, computed perimetry. The examinations were performed preoperatively, at discharge, in a month, in six months and later postoperatively.Results. When implanting the national polymer microshunt we reached the significant decrease in the intraocular pressure in the postoperative period in comparison with the preoperative level. The implantation outcomes of the national polymer microshunt and Ex-PRESS were comparable in efficacy and safety. The easy implantation and special construction of the national polymer microshunt provided with the sufficient efficacy and safety in refractory glaucoma surgery and allowed recommending its further application in the clinical practice.Conclusion. The use of Reper-NN microshunt is effective and safe method of treating refractory glaucoma. The implantation of this shunt may be the method of choice both in primary and secondary refractory glaucoma surgery. The least price of Reper-NN microshunt in comparison with the foreign analogue allows this surgery to be more available for patients with refractory glaucoma.

Assessment of Scleral and Conjunctival Thickness of the Eye after Ultrasound Ciliary Plasty

Purpose. This study aims to assess scleral and conjunctival thickness using optical coherence tomography after ultrasound ciliary plasty (UCP) procedure with reference to scleral marks appearing in the area where the ultrasound energy was applied. Materials and Methods. Seventy-eight patients with primary and secondary refractory glaucoma participated in this study. Complete ophthalmic examinations including measurements of scleral and conjunctival thickness were performed preoperatively and at 1 week, and 1, 3, 6, 12, 18, and 24 months postoperatively. The parameters were determined using the Swept Source OCT with anterior attachment. Thirty-eight patients (58 scleral marks—23 superior and 35 inferior) fulfilled the inclusion criteria and completed the follow-up period of 24 months. Results. The mean ± SD scleral and conjunctival thickness in superior scleral mark before the procedure and at 1 week, and 1, 3, 6, 12, 18, and 24 months after the procedure was 684.57 ± 83.58 μm, 771.78 ± 112.03 μm (p<0.001), 771.74 ± 100.12 μm (p<0.001), 731.38 ± 83.92 μm (p=0.012), 719.52 ± 73.20 μm (p=0.037), 702.91 ± 66.50 μm (p=0.247), 694.13 ± 72.22 μm (p=0.482), and 699.35 ± 70.68 μm (p=0.200), respectively. The mean ± SD scleral and conjunctival thickness in inferior scleral mark before the procedure and at 1 week, and 1, 3, 6, 12, 18, and 24 months after the procedure was 816.86 ± 79.30 μm, 936.37 ± 107.33 μm (p<0.001), 946.00 ± 130.40 μm (p<0.001), 896.63 ± 123.40 μm (p<0.001), 877.69 ± 114.38 μm (p=0.003), 843.03 ± 71.55 μm (p=0.021), 811.86 ± 68.91 μm (p=0.731), and 805.03 ± 69.52 μm (p=0.248), respectively. The transient thickening of the sclera was observed after the procedure; however, after 12 months postoperatively, the parameters returned to the initial value and no significant difference was noted. Conclusion. The sclera thickness increases after UCP. However, with time the thickness reduces to its initial value with no significant difference. Clinical implication of the scleral changes lasts shorter than the measured significant difference in scleral thickness.

Pars plana Ex-Press mini shunt for management of persistent glaucoma in vitrectomized eyes: A novel technique

Purpose: To evaluate the safety and efficacy of a novel approach to implant Ex-Press mini shunt via the pars plana under a scleral flap in pseudophakic or aphakic, vitrectomized patients with secondary refractory glaucoma. Methods: A prospective interventional case series of three patients with secondary glaucoma after pars plana vitrectomy. Intraocular pressure was not controlled by silicone oil removal, if the patient was siliconized, nor the maximum medical treatment. Ex-Press mini shunt via the pars plana was implanted. We evaluated the control of intraocular pressure and the development of intraoperative and postoperative complications. Results: During 1-year follow-up, control of intraocular pressure was achieved; 14, 15, and 15 mmHg at the 3 months, and 15, 15, and 16 mmHg at the 6 months in our three cases without antiglaucoma treatment and 16, 16, and 18 with single antiglaucoma medication at 1 year. Blebs were posterior and diffuse. No complications were encountered intraoperatively or postoperatively. Ultrasound biomicroscopy showed suprachoroidal posterior lake of fluid as an additional filtration route without any choroidal or retinal complication. Conclusion: Implantation of Ex-Press mini shunt via the pars plana in aphakic or pseudophakic, vitrectomized eyes is a promising, safe, and effective technique in patients with secondary glaucoma.

Fatal Hypocalcaemia Due to Hungry Bone Syndrome with Secondary Refractory HyperParathyroidism after Parathyroidectomy: A Case Report

Introduction Hungry bone syndrome (HBS) refers to the rapid, profound, and prolonged hypocalcaemia associated with hypophosphatemia and hypomagnesaemia, and is exacerbated by suppressed parathyroid hormone (PTH) levels, which follows parathyroidectomy in patients with severe primary hyperparathyroidism (PHPT) and preoperative high bone turnover. [1] Case report This report concerns a dialysed patient who underwent surgical treatment for secondary refractory hyperparathyroidism. Haemodialysis was carried out pre-operatively, and subsequently, a total parathyroidectomy with auto-transplantation of parathyroid tissue in the sternocleidomastoid muscle (SCM) was performed. Rapid and progressive hypocalcaemia symptoms developed during the second day postoperatively. Acute cardiac symptoms with tachyarrhythmia, haemodynamic instability and finally asystole occurred, which required cardiopulmonary resuscitation (CPR). The ionic calcium level was 2.2 mg/dL being consistent with a diagnosis of HBS. A second cardiac arrest unresponsive to CPR followed an initial period of normal sinus rhythm. Death ensued shortly after. Before death, the ionic calcium was 3.1 mg/dL. Conclusion HBS, after parathyroidectomy in patients with secondary hyperparathyroidism (SHPT), may be severe, prolonged and sometimes fatal. Generally, HBS symptomatology is that of a mild hypocalcaemia. It can, however, include heart rhythm disturbances with haemodynamic alterations requiring intensive care measurements and even cardiopulmonary resuscitation. A close clinical and laboratory post-parathyroidectomy monitoring of dialysed patients is of the utmost importance.

THE USE OF ALUMINUM SLAG RECYCLING PRODUCTS IN INVESTMENT CASTING TECHNOLOGIES

The studies of fractional, chemical and phase compositions of aluminum-containing slags of different origin found that slags are multi-component systems consisting of metal and non-metal parts. The non-metal part contains water-soluble and water-insoluble components. A practical scheme for recycling aluminum-containing slags was proposed in order to isolate the water-insoluble component to be further used a secondary refractory dusting material. It was found that the secondary refractory dusting material has a positive effect on the quality of refractory ceramic molds in investment casting and the surface finish of experimental aluminum castings. This material improves the strength of refractory ceramic molds by 9 times in comparison with silica sand molds and increases gas permeability by 15 % to 33 % in comparison with fused alumina and silica sand molds, respectively. The study covers the processes used to produce refractory ceramic molds based on the secondary refractory dusting material. The mechanism of interaction between dusting material particles and suspension is theoretically justified in terms of colloid chemistry. Negatively charged aluminum hydroxide micelles appear when ceramic mold layers are formed using the secondary refractory dusting material. Interaction between differently charged Al(OH)3 and SiO2 micelles makes secondary refractory dusting material particles come in close contact with each other. The theoretically justified processes of ceramic mold layer formation with the secondary refractory dusting material make it possible to explain the reduction in the surface roughness of castings made of AK9ch aluminum casting alloy using investment casting by 3.7 times compared with standard production processes.

Gene Mutations Identified in Chemorefractory Acute Myeloid Leukemia

Introduction: Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Recently, multiple recurrently mutated genes have been identified in AML and implicated in various mechanisms of leukemogenesis. However, knowledge regarding the association of gene mutations with primary or secondary resistance to chemotherapy is incomplete. Methods: We analyzed a discovery cohort of 45 patients with chemorefractory AML that were enrolled in a phase 2 clinical trial of a novel conditioning regimen prior to allogeneic stem cell transplant for patients with non-remission AML. DNA was extracted from FACS-purified leukemic cells procured from patients after failure to achieve complete remission (CR) after ≥2 cycles of induction chemotherapy after initial diagnosis ("primary refractory", N=22) or after rapid relapse (<6 months) or failure to achieve CR after ≥1 cycle of induction chemotherapy after relapse ("secondary refractory", N=23). Since TP53 mutations have been previously associated with refractory disease, we selected 29 TP53 wild-type cases from the discovery cohort and performed whole exome sequencing (WES) with a mean read depth of 72X (range 30-140). All somatically acquired gene variants identified by WES in protein-coding genes were verified by Sanger sequencing. In addition, we performed Sanger re-sequencing of 11 recurrently mutated genes in AML (TP53, RUNX1, DNMT3A, TET2, FLT3, NPM1, IDH1, IDH2, ASXL1, NRAS and KRAS) in all 45 cases. Given lack of published WES data in refractory AML, we then compared these mutation frequencies to a cohort of 151 AML patients enrolled consecutively at one center (the "university cohort") with known responses to chemotherapy or The Cancer Genome Atlas (TCGA) data which comprises de novo AML only. Results: WES of 29 TP53 wild-type refractory AML cases revealed a total of 351 confirmed somatic mutations with a median of 13 protein-coding mutations per case (range 5-22). Genes mutated in 7% (2 of 29 cases), and excluding the 11 known recurrently mutated genes listed above, that were not previously described in AML (COSMIC review) included ADAM23, CPNE7, and SIX5. We also identified mutations in NOMO3 and OAS2 in 7% (2 of 29 cases), which have been previously described in AML but at lower frequencies (1.7% [6 of 347; COSMIC] and 0.2% [1 of 347] respectively) based on review of the literature. The genes SRSF2, NOMO3 and OAS2, which were all identified in 7% (2 of 29 cases) in our discovery cohort, had no reported mutations found in the TCGA (p=0.02). Additional genes, which were found in our discovery cohort in 7% (2 of 29 cases) respectively, and were also found in the TCGA, include BCOR, FOXP1, FRYL, PHF6, STAG2, PTPN11 and SETD2. Mutational profiling of the 11 recurrently mutated genes in AML revealed a striking paucity of NPM1 mutations in primary refractory AML (range 0% [discovery cohort] - 3% [university cohort]) compared with chemosensitive AML (31% [university cohort]; p<0.001). TP53 mutations, however, were enriched in primary refractory AML (range 23% [discovery cohort] - 38% [university cohort]) compared with chemosensitive AML (4% [university cohort]; p<0.001). Of note, while FLT3 -ITD mutations were infrequently observed in primary refractory AML (range 0% [discovery cohort] - 14% [university cohort]) compared to chemosensitive AML (27% [university cohort]; p<0.01), they were highly enriched in secondary refractory AML (61% [discovery cohort] - 30% [university cohort]; p=0.03). Conclusions: 1) Whole exome sequencing of 29 TP53 wild-type refractory AML revealed recurrent mutations in ADAM23, CPNE7, NOMO3, OAS2 and SIX5. The function and prevalence of these gene mutations are not well-characterized in AML, including refractory AML and should be determined in a larger cohort of patients; 2) TP53 mutations were significantly enriched in primary refractory disease; 3) Conversely, FLT3 -ITD mutations were significantly enriched in secondary but not primary refractory disease, suggesting the frequent emergence of a chemorefractory FLT3-ITD mutated clone following treatment with conventional chemotherapy; and, 4) NPM1 mutations were significantly under-represented in primary refractory AML. While larger sequencing studies of refractory AML cases are needed, these data do not support gene mutations other than in TP53 as frequent causes of primary refractoriness to chemotherapy in AML. Disclosures Malek: Gilead Sciences: Equity Ownership; Abbvie: Equity Ownership; Janssen Pharmaceuticals: Research Funding.

Early Molecular Response of Marrow Disease to Biologic Therapy Is Highly Prognostic in Neuroblastoma

Purpose: A promising treatment strategy for stage 4 neuroblastoma patients is the repeated application of anti-GD2 immunotherapy after activating myeloid effectors with granulocyte-macrophage colony-stimulating factor (GM-CSF). To use early marrow response as a prognostic marker is particularly relevant for patients not likely to benefit from this therapy. Patients and Methods: Eighty-six stage 4 neuroblastoma patients older than 1 year at diagnosis were classified in four clinical groups on protocol entry: complete remission or very good partial remission (n = 33), primary refractory (n = 33), secondary refractory (n = 10), and progressive disease (n = 10). Bone marrow samples collected before and following treatment were assayed for GD2 synthase mRNA by real-time reverse transcriptase polymerase chain reaction. Response and survival analyses were performed on posttreatment samples before the third cycle at 1.8 months from protocol entry. Results: GD2 synthase mRNA was evident in pretreatment marrow samples of the four clinical groups (42%, 52%, 60%, and 80% of samples, respectively), with median transcript level of 10.0, 16.6, 26.5, and 87.2, respectively. This marker became negative following antibody plus GM-CSF in 77% of complete remission or very good partial remission, 45% of primary refractory, 25% of secondary refractory, and 0% of progressive disease group. Progression-free survival was statistically different between responder and nonresponder groups (P < .0001). Among patients with minimal residual disease, molecular responders had a significantly lower risk of disease progression at a median follow-up of 29.8 months (P = .0001). Conclusion: GD2 synthase mRNA is a sensitive response marker of neuroblastoma in the bone marrow. It is particularly useful for minimal residual disease evaluation and may potentially be useful as an early predictor of resistance to antibody plus GM-CSF immunotherapy.