Uveal melanoma (UM) is the most prevalent primary intraocular cancer in adults. Up to half the patients develop metastases that are currently incurable, and most patients die within two years following the diagnosis of metastases. Therefore, novel therapeutic approaches are required. It has been established that tumor cells are more resistant to the hypoxia cue than non-malignant cells and can remain viable in hypoxia. Oxygen absence in hypoxic tumor areas means the absence of chemotherapeutics and the absence of the effector for radiotherapy (free oxygen radicals). To overcome this treatment resistance, we constructed MuLV-based replication-competent retroviral (RCR) vectors expressing shRNA targeting the hypoxia-response regulating genes CREB and HIF-1. These RCRs express shRNAs either against a single exon or against an exon and the poly-A signal to minimize the point-mutation resistance. These RCRs that only infect replicating cells will preferentially infect tumor cells. Pre-infected Mel270 UM subcutaneous xenografts in SCID mice were monitored weekly in vivo via bioluminescence. Here, we demonstrate that the knockdown of CREB or HIF-1 in UM cells dramatically decreases UM tumor progression. The reduction of the expression of Glut-1, which is a major glucose transporter in cancer cells, within tumors that are infected with the armed viruses may indicate UM’s dependence on glycolysis for tumor progression.
Purpose: To describe the mechanisms and outcomes of open globe injuries (OGIs) in patients 70 years or older. Methods: A retrospective chart review of patients from two large academic centers in Israel who were underwent surgery for OGI. Data was collected from surgical and clinic charts. Anatomical and functional results were recorded as well any additional surgeries and complications. Results: Thirty-two eyes of 32 patients were included. The mechanism of OGI consisted of blunt trauma with ocular rupture secondary to falls. All eyes underwent immediate primary closure of the corneal and scleral lacerations. Additional surgeries were performed in 34.3% of cases. In 31.2% of cases additional surgery was not required, and in 21.9% of cases the damage was so devastating that additional procedures were not recommended. Four patients (12.5%) chose not to undergo additional surgery. Mean visual acuity at presentation was 2.24 ± 0.72 logMAR and it improved to 1.92 ± 0.89 logMAR at final follow-up ( p = 0.002). VA at presentation was significantly correlated to final VA ( p < 0.001). Conclusions: OGI in the elderly represents a unique group. It is mostly related to falls, with a female predominance and a poor visual prognosis. In this patient population, general health concerns and increased risks of anesthesia require special attention. Care should be taken to educate elderly patients and their caretakers on how to avoid falls.
The emerging COVID-19 pandemic poses many difficulties to medical professionals. One of them is the need to use personal protective equipment (PPE) in order to protect themselves and their families, while not compromising their care. Physical examination is one of the cornerstones of medical assessment but parts of it are nearly impossible to do while wearing protective equipment. In this brief report we demonstrate a novel wireless stethoscope and its use for treating suspected and proven COVID-19 patients, as a representative to other infectious diseases.
Background During the corona virus disease (COVID-19) epidemic, many healthcare workers (HCWs) were exposed to infected persons, leading to suspension from work. We describe a dynamic response to exposures of HCWs at the Hadassah Hospital, Jerusalem, to minimize the need for suspension from work. Methods We performed an epidemiological investigation following each exposure to a newly diagnosed COVID-19 patient or HCW; close contacts were suspended from work. During the course of the epidemic, we adjusted our isolation criteria according to the timing of exposure related to symptoms onset, use of personal protective equipment and duration of exposure. In parallel, we introduced universal masking and performed periodic SARS-CoV-2 screening for all hospital personnel. We analyzed the number of HCWs suspended weekly from work and those who subsequently acquired infection. Results In the 51 investigations conducted during March-May 2020, we interviewed 1095 HCWs and suspended 400 (37%) from work, most of them, 251 (63%), during the first two weeks of the outbreak. The median duration of exposure was 30 minutes (IQR, 15-120). Only 5/400 (1.3%) developed infection, all in the first two weeks of the epidemic. After introduction of universal masking and despite loosening the isolation criteria, none of the exposed HCWs developed COVID-19. Conclusions Relatively short exposures of HCWs, even if only either the worker or the patient wore a mask, probably poses a very low risk for infection. This allows us to perform strict follow-up of exposed HCWs in these exposures, combined with repeated testing, instead of suspension from work.
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