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Global spread of severe acute respiratory syndrome coronavirus 2 continues unabated. Binding of severe acute respiratory syndrome coronavirus 2's spike protein to host angiotensin-converting enzyme 2 triggers viral entry, but other proteins may participate, including the neuropilin-1 receptor (NRP-1). Because both spike protein and vascular endothelial growth factor-A (VEGF-A)-a pronociceptive and angiogenic factor, bind NRP-1, we tested whether spike could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuron firing was blocked by spike protein and NRP-1 inhibitor EG00229. Pronociceptive behaviors of VEGF-A were similarly blocked through suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A "silencing" of pain through subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals.

Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues unabated. Binding of SARS-CoV-2's Spike protein to host angiotensin converting enzyme 2 triggers viral entry, but other proteins may participate, including neuropilin-1 receptor (NRP-1). As both Spike protein and vascular endothelial growth factor-A (VEGF-A) - a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuronal firing was blocked by Spike protein and NRP-1 inhibitor EG00229. Pro-nociceptive behaviors of VEGF-A were similarly blocked via suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A 'silencing' of pain via subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals., Competing Interests: CONFLICT OF INTERESTS STATEMENT R. Khanna is the co-founder of Regulonix LLC, a company developing non-opioids drugs for chronic pain. In addition, R. Khanna has patents US10287334 and US10441586 issued to Regulonix LLC. R. The other authors declare no competing financial interest.

Angiosarcoma is a rare soft tissue neoplasm, which accounts for <1% of all soft tissue tumours. It has been previously reported that the incidence rate of angiosarcomas increases following radiotherapy. The present study reports two cases of intra-abdominal angiosarcoma associated with previous radiotherapy treatment. To the best of our knowledge, these associations have not been previously described in English literature. The patients aged 71 and 83 years were admitted to the center for abdominal pain and diarrhea. Each patient had previously had treatment with radiotherapy for prostate adenocarcinoma. During their hospitalization, biopsies were obtained and the diagnosis of angiosarcoma was reached. In each patient the tumors had irregular proliferating vascular channels, lined by atypical endothelial cells, which varied from elongated and spindle-shaped to large and plump. Immunocytochemistry revealed that the tumor cells were positive for the cytoplasmic endothelial markers cluster of differentiation (CD)31 and CD34. The recognition of these associations is important and their occurrence in this rare type of neoplasm should not mislead the pathologist and cause a misdiagnosis of the sarcoma.

Purpose: To report a case of choroidal melanoma in which the absence of 18FDG-positron emission tomography (PET)/computed tomography (CT) uptake in the whole body scan excluded the presence of any foci of metastases. Additionally, the PET/CT study correctly diagnosed the necrotic character of the lesion., Methods: A 76-year-old woman with neovascular glaucoma, and without vitreous or retina visualization, was studied by our ophthalmology service., Results: Ocular ultrasound showed an 18 × 16 mm vitreous exophytic image compatible with choroidal melanoma; magnetic resonance gave a 17 × 15 mm exophytic image, highly intense at T1 and hypointense at T2, with cystic and necrotic images after a contrast injection. An 18FDG-PET/CT study revealed a clearly hypometabolic lesion, representing absence of cell viability and excluding active melanoma cells. No other uptake lesions were detected at the whole-body PET/CT scan, assuming the absence of extraocular metastases. The eye was enucleated, and the pathology study showed a 16 × 15 mm necrotic choroidal melanoma., Conclusions: The 18FDG-PET/CT study correctly depicted the necrotic character of the choroidal melanoma and was able to exclude other foci of metastases.

Background: The safety of combined hepatic artery infusion chemotherapy (HAI) and radiofrequency ablation (RFA) for liver metastases has not been assessed. We conducted a study to determine the feasibility of using HAI after RFA for colorectal cancer (CRC) liver metastases., Methods: Between 1996 and 2001, patients with hepatic metastases from CRC were enrolled onto a prospective study of RFA plus HAI consisting of continuous-infusion floxuridine and bolus fluorouracil. Surgical complications, treatment-related toxicities, and patient outcomes were recorded., Results: Fifty patients were treated with RFA and HAI with or without resection. A median of two lesions per patient, with a median greatest diameter of 2.0 cm, were treated with RFA. Postoperative complications, including 1 death, occurred in 11 of 50 patients. Toxicity from HAI was relatively mild. At 20 months' median follow-up, 32% of patients remained disease free. Ten percent of patients had recurrences at the site of RFA, 30% developed new liver metastases, and 48% developed extrahepatic disease., Conclusions: RFA of CRC liver metastases followed by HAI is feasible and is associated with acceptable complication and toxicity rates. The high rate of disease recurrence in our patients indicates that novel combinations of regional and systemic therapies are needed to improve patient outcomes.

Hepatocellular carcinoma is one of the most common and lethal cancers worldwide. Survival rates generally are poor because of late diagnosis, tumor volume, and location. Early detection combined with surgical treatment advances, however, can provide longer disease-free survival.