ABSTRACT
Epidermal growth factor receptor (EGFR), which is referred to as ErbB1/HER1, is the prototype of the EGFR family of receptor tyrosine kinases which also comprises ErbB2 (Neu, HER2), ErbB3 (HER3), and ErbB4 (HER4). EGFR, along with other ErbBs, is expressed in the kidney tubules and is physiologically involved in nephrogenesis and tissue repair, mainly following acute kidney injury. However, its sustained activation is linked to several kidney pathologies, including diabetic nephropathy, hypertensive nephropathy, glomerulonephritis, chronic kidney disease, and renal fibrosis. This review aims to provide a summary of the recent findings regarding the consequences of EGFR activation in several key renal pathologies. We also discuss the potential interplay between EGFR and the reno-protective angiotensin-(1-7) (Ang-(1-7), a heptapeptide member of the renin-angiotensin-aldosterone system that counter-regulates the actions of angiotensin II. Ang-(1-7)-mediated inhibition of EGFR transactivation might represent a potential mechanism of action for its renoprotection. Our review suggests that there is a significant body of evidence supporting the potential inhibition of EGFR/ErbB, and/or administration of Ang-(1-7), as potential novel therapeutic strategies in the treatment of renal pathologies. Thus, EGFR inhibitors such as Gefitinib and Erlinotib that have an acceptable safety profile and have been clinically used in cancer chemotherapy since their FDA approval in the early 2000s, might be considered for repurposing in the treatment of renal pathologies.
ABSTRACT
Optic perineuritis is an inflammatory condition that presents with reduced visual acuity and painful eye movement. The presentation of optic perineuritis is similar of optic neuritis which results in delayed diagnosis and management. Up to this date, we found a single case of optic neuritis that presented with transient monocular vision loss (TMVL). No cases of optic perineuritis were associated with TMVL. Here, we report a case of a 30-year-old woman who presented with recurrent attacks of painless vision loss in her left eye, reaching up to 30 attacks per day. Ophthalmological examination was otherwise unremarkable. Lab investigations were normal. Magnetic resonance imaging was done, which showed left optic nerve sheath enhancement suggestive of left-sided focal optic perineuritis. Patient was managed with 1 mg IV methylprednisolone for 3 days. We report this case to shed light on the importance of accurate and early diagnosis of optic perineuritis presenting with TMVL. Prompt management of optic perineuritis is crucial in reducing morbidity and risk of relapse.
ABSTRACT
Background: The association between the cycle threshold (Ct) which reflects the SARS-CoV-2 viral load and the severity of COVID-19 is still not clear. We investigated the association between Ct values, symptoms and the risk of ICU admission and mortality from COVID-19 in Qatar. Methods: This case-control study used data of hospitalized individuals with confirmed COVID-19 during the period March to September 2020. Cases were defined as individuals with confirmed COVID-19 who were admitted to the intensive care unit (ICU) or died and controls as those who were not admitted to the ICU. The association between Ct value, symptoms, ICU admission and mortality was investigated using Ct value as a categorical variable (below and above 25) in multivariable regression models and adjusted for relevant confounders. Results: A total of 622 participants with median age 53 (IQR: 53-63), of which 69% were males, were included. There were 236 ICU admissions and 111 deaths. When categorized, Ct value (<25 vs ≥25) had no association with the odds of ICU admission (OR 0.85, 95% CI 0.56 to 1.29) or odds of mortality (OR 1.21, 95% CI 0.71 to 2.08). Respiratory (OR 2.95, 95% CI 1.57 to 5.56) and gastrointestinal symptoms (OR 1.99, 95% CI 1.18 to 3.35) were associated with higher odds of ICU admission. Similarly, respiratory (OR 4.96, 95% CI 1.10 to 22.43) and gastrointestinal symptoms (OR 3.17, 95% CI 1.29 to 7.84) were associated with higher odds of mortality. Conclusion: Although RT-PCR Ct has good diagnostic value, its prognostic value appears to be unreliable. Respiratory and gastrointestinal symptoms are associated with COVID-19 criticality and mortality in this setting.