Anti-epider mal growth factor receptor (EGFR)-targeted therapy has been intensely researched in the last years, motivated by the favorable results obtained with monoclonal antibodies in HER2-enriched breast cancer (BC) patients. Most researched alternatives of anti-EGFR agents were tyrosine kinase inhibitors (TKIs) and monoclonal antibodies. However, excluding monoclonal antibodies trastuzumab and pertuzumab, the remaining anti-EGFR molecules have exhibited disappointing results, due to the lack of specificity and frequent adverse side effects. TKIs have several advantages, including reduced cardiotoxicity, oral administration and favorable penetration of blood-brain barrier for brain metastatic BC. Lapatinib and neratinib and recently pyrotinib (approved only in China) are the only TKIs from dozens of molecules researched over the years that were approved to be used in clinical practice with limited indications, in a subset of BC patients, single or in combination with other chemotherapy or hormonal therapeutic agents. Improved identification of BC subtypes and improved characterization of aggressive forms (triple negative BC or inflammatory BC) should lead to advancements in shaping of targeted agents to improve the outcome of patients. Contents 1. Introduction 2. Tyrosine kinase inhibitors (TKIs) used in breast cancer (BC) therapy 3. Limitations and challenges of TKI use in BC chemotherapy 4. Conclusions

The majority of studies concerning Helicobacter pylori ( H. pylori ) are oriented towards the implication of infection with H. pylori in processes that end in the formation of neoplasia, without assessing the impact of the bacterium in triggering acute gastroduodenal hemorrhagic episodes. The present study includes 166 patients with upper digestive hemorrhage, admitted to the ATI Clinic, the Gastroenterology Clinic or to the Surgery II Clinic of the County Emergency Clinical Hospital in Craiova, Romania between 2017 and 2019. All patients were monitored for evolution and received treatment according to current guidelines, and hemorrhagic lesions were biopsied. In the study group, 56.8% of the patients with upper gastrointestinal bleeding (UGIB) were positive for H. pylori and 43.2% were negative. In patients less than 50 years of age, non-steroidal anti-inflammatory drug (NSAID) use and H. pylori infection had a cumulative effect in causing bleeding lesions, but in patients older than 50 years of age, the use of NSAIDs was replaced by therapies with oral antiplatelet or anticoagulant agents. The need for hemostasis surgery was more common in patients who exhibited H. pylori -positive UGIB compared to H. pylori -negative (16 vs. 9.7%). In patients with H. pylori -positive hemorrhagic lesions, gastric resection was frequently required to obtain hemostasis. Persistence of H. pylori infection in patients with a history of gastric resection (4.1%) still predisposes to a hemorrhagic or neoplastic complication.

Background: Recent evidence on the role of vascular endothelial growth factor (VEGF) in the pathogenesis of ischemia and microvascular hyperpermeability leading to macular edema has brought anti-VEGF intravitreal therapy into the limelight. Objective: We performed a systematic literature review focusing on the outcomes and safety of the intravitreal use of aflibercept in diabetic macular edema. Methods: The studies documented cases with at least three consecutive intravitreal injections of aflibercept (IVA) repeated monthly with a follow-up period of at least one year. The outcomes were evaluated in terms of reported functional and anatomical improvement of the macula, as reflected by changes in visual acuity and macular thickness measured by Optical Coherence Tomography (OCT). In addition, for safety assessment, all reported local and general adverse effects were analyzed. Results: All studies showed an overall significant anatomical and functional improvement. In patients with the 5 IVA monthly at the beginning of the therapy, the visual gain at 52 weeks varied widely between 5 and 18.9 EDRS letters, with a mean value of 9.48 letters. The higher gain was obtained in treatment naïve patients, with worse VA and increased CST at baseline. The lower gain was obtained in patients previously treated with anti-VEGF. Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events were not statistically different between the aflibercept group and the laser group. Conclusions: Intravitreal aflibercept therapy provides significant improvement in visual acuity and a good safety profile. Randomized studies are needed to document the optimal frequency of intravitreal injections for optimal treatment.

Neurotoxic warfare chemical agents (CWA/NA) induce major toxicological effects to the affected personnel. Their increased toxicity justifies the necessity of developing analytical methods for diagnosis and specific medical counter measures. CWA/NA are extremely toxic agents which are subject to international regulations (The Geneva Protocol regarding the prohibition of chemical weapons). Taking into account the ban on human experimenting due to high toxicity, simulators of neurotoxic chemical agents are being used in laboratories. These are analogue chemical compounds which possess the same relevant physical, chemical and pharmacodynamical properties of the corresponding agents, but with lower intrinsical toxicity. The synthesis and toxicological characterization of these simulators of neurotoxic chemical agents allow the laboratory research of these extremely toxic compounds and the unfolding of risk-free antidote studies. This paper proposes the synthesis and toxicological testing of chemical compounds which simulate sarin (4-nitrophenyl isopropyl methylphosphonate - NIMP) and VX (4-nitrophenyl ethyl methylphosphonate - NEMP).

Neurotoxic warfare chemical agents (CWA/NA) induce major toxicological effects to the affected personnel. Their increased toxicity justifies the necessity of developing analytical methods for diagnosis and specific medical counter measures. CWA/NA are extremely toxic agents which are subject to international regulations (The Geneva Protocol regarding the prohibition of chemical weapons). Taking into account the ban on human experimenting due to high toxicity, simulators of neurotoxic chemical agents are being used in laboratories. These are analogue chemical compounds which possess the same relevant physical, chemical and pharmacodynamical properties of the corresponding agents, but with lower intrinsical toxicity. The synthesis and toxicological characterization of these simulators of neurotoxic chemical agents allow the laboratory research of these extremely toxic compounds and the unfolding of risk-free antidote studies. This paper proposes the synthesis and toxicological testing of chemical compounds which simulate sarin (4-nitrophenyl isopropyl methylphosphonate - NIMP) and VX (4-nitrophenyl ethyl methylphosphonate - NEMP).