Pharmacological Approaches to Modulate the Scarring Process after Glaucoma Surgery.

Glaucoma is an acquired optic neuropathy that results in a characteristic optic nerve head appearance and visual field loss. Reducing the IOP is the only factor that can be modified, and the progression of the disease can be managed through medication, laser treatment, or surgery. Filtering procedures are used when target pressure cannot be obtained with less invasive methods. Nevertheless, these procedures require accurate control of the fibrotic process, which can hamper filtration, thus, negatively affecting the surgical success. This review explores the available and potential pharmacological treatments that modulate the scarring process after glaucoma surgery, analyzing the most critical evidence available in the literature. The modulation of scarring is based on non-steroidal anti-inflammatory drugs (NSAIDs), mitomycin, and 5-fluorouracil. In the long term, the failure rate of filtering surgery is mainly due to the limitations of the current strategies caused by the complexity of the fibrotic process and the pharmacological and toxicological aspects of the drugs that are currently in use. Considering these limitations, new potential treatments were investigated. This review suggests that a better approach to tackle the fibrotic process may be to hit multiple targets, thus increasing the inhibitory potential against excessive scarring following surgery.

Pediatric Use of Recombinant Human Nerve Growth Factor 20 µg/mL Eye Drops (Cenegermin) for Bilateral Neurotrophic Keratopathy in Congenital Corneal Anesthesia.

PURPOSE: This study aimed to present the efficacy and safety of cenegermin eye drop (Oxervate; Dompè Farmaceutici, Milan, Italy) treatment in a pediatric patient affected by neurotrophic keratopathy (NK) with Goldenhar syndrome. METHODS: This case reports an infant presenting ulceration and a small central opacity in the cornea of the right and left eyes, respectively. The NK bilaterally worsened despite the use of therapeutic contact lenses and temporary partial tarsorrhaphy. Magnetic resonance imaging showed absence and hypoplasia of the right and left trigeminal nerves, respectively. Cenegermin eye drops were administered 1 drop/each eye, 6 times daily for 8 weeks to promote corneal healing. RESULTS: Complete healing was achieved in both eyes after treatment. During the 16-month follow-up period, no epithelial defect, recurrence, or complications were noticed, whereas corneal opacities progressively became clearer, although insignificant improvements in corneal sensitivity or in the reflex tearing were observed. CONCLUSIONS: Cenegermin was effective in treating NK in an infant with Goldenhar syndrome.

Antiplatelet Therapy with Cangrelor in Patients Undergoing Surgery after Coronary Stent Implantation: A Real-World Bridging Protocol Experience.

Objective The aim of the study is to describe the real-world use of the P2Y 12 inhibitor cangrelor as a bridging strategy in patients at high thrombotic risk after percutaneous coronary intervention (PCI) and referred to surgery requiring perioperative withdrawal of dual antiplatelet therapy (DAPT). Materials and Methods We collected data from nine Italian centers on patients with previous PCI who were still on DAPT and undergoing nondeferrable surgery requiring DAPT discontinuation. A perioperative standardized bridging protocol with cangrelor was used. Results Between December 2017 and April 2019, 24 patients (mean age 72 years; male 79%) were enrolled. All patients were at high thrombotic risk after PCI and required nondeferrable intermediate to high bleeding risk surgery requiring DAPT discontinuation (4.6 ± 1.7 days). Cangrelor infusion was started at a bridging dose (0.75 µg/kg/min) 3 days before planned surgery and was discontinued 6.6 ± 1.5 hours prior to surgical incision. In 55% of patients, cangrelor was resumed at 9 ± 6 hours following surgery for a mean of 39 ± 38 hours. One cardiac death was reported after 3 hours of cangrelor discontinuation prior to surgery. No ischemic outcomes occurred after surgery and up to 30-days follow-up. The mean hemoglobin drop was <2 g/dL; nine patients received blood transfusions consistent with the type of surgery, but no life-threatening or fatal bleeding occurred. Conclusion Perioperative bridging therapy with cangrelor is a feasible approach for stented patients at high thrombotic risk and referred to surgery requiring DAPT discontinuation. Larger studies are warranted to support the safety of this strategy.

Activation of immune responses in patients with relapsed-metastatic head and neck cancer (CONFRONT phase I-II trial): Multimodality immunotherapy with avelumab, short-course radiotherapy, and cyclophosphamide.

INTRODUCTION AND BACKGROUND: Second-line treatment of platinum-resistant relapsed/metastatic (R/M) head and neck cancer (HNC) is a currently unmet clinical need. Clinical trials showed improvement in overall survival and quality of life of R/M-HNC patients treated with anti-PD-1 regardless of the number of prior chemotherapy lines; however, the percentage of long-term survivors remains limited.This study aims to test the hypothesis that attacking the tumor microenvironment at multiple levels can increase immunogenicity of R/M-HNC without worsening the safety profile of immune checkpoint inhibitors. METHODS/DESIGN: In this open label, multi-center, single-arm, Phase Ib/II, R/M-HNC patients pretreated with at least one line of therapy containing platinum, fluorouracil, and cetuximab will receive a daily metronomic dose of 50 mg cyclophosphamide without a drug-free break, 10 mg/kg avelumab on day 1 and every other week until progression, and a single fraction of 8 Gy radiotherapy on day 8. DISCUSSION: The treatment protocol aims to reverse immune evasion of the tumor through a radiotherapy-induced self-vaccination effect, suppression of CD4+ CD25+ FoxP3+ regulatory T-cell function by metronomic cyclophosphamide, and effector T-cell reactivation owing to the inhibition of the PD-1-PD-L1 axis by avelumab.The immunologic interplay induced by the proposed combined treatment may theoretically improve the activity of avelumab without increasing its toxicity profile.Finally, an ancillary translational study will be extended to all the patients' population. TRIAL REGISTRATION: EudraCT n. 2017-000353-39.

Dermatan sulfate: an alternative to unfractionated heparin for anticoagulation in hemodialysis patients.

BACKGROUND: Unfractionated heparin (UFH) is the standard anticoagulant in regular dialysis treatments (RDTs), despite the fact that it may induce thrombocytopenia, dyslipidemia, allergy and osteoporosis. Dermatan sulfate (DS) selectively inhibits thrombin, does not inhibit F-Xa and does not interfere with platelets (PLTS). Here we described an original protocol for the use of DS as anticoagulant in RDT and compared its effects with those of UFH. METHODS: In 102 patients, 7,254 RDTs were performed using DS for anticoagulation (DS-phase) and 5,707 with UFH (UFH-phase). DS was supplied as initial bolus (80 ± 12 mg) and continuous infusion (14 ± 7 mg/hour). With UFH, the initial bolus was 1,475 ± 141 IU and continuous infusion 576 ± 349 IU/hour. Activated partial thromboplastin time and its ratio were measured at least monthly, both before (pre-RDT APTT ratio) and after (post-RDT APTT ratio) RDT sessions. With 41 of 102 patients, both DS and UFH doses were not changed during study phases (stable patients). In this subset, the coefficient of variation (CV) of all pre-RDT APTT ratio and post-RDT APTT ratio values was calculated. RESULTS: In DS and UFH phases, post-RDT APTT ratio increased by 61% and 50%, respectively, by comparison with pre-RDT APTT ratio (p<0.001). PLTS count was lower in the UFH than in the DS phase (p<0.01). In stable patients, post-RDT APTT ratio CV was lower in the DS than in the UFH phase (p<0.001), which indicates a more predictable anticoagulant effect of DS compared with UFH. CONCLUSIONS: DS appeared as effective as UFH for anticoagulation in RDT. It can reliably be considered as an alternative approach especially in cases of thrombocytopenia or other adverse effects of UFH.