Radiological Manifestations of Rhino-Orbito-Cranial Mucormycosis in COVID-19 Patients Correlated With Pathological and Clinical Outcomes and Emphasis on Magnetic Resonance Imaging-Based Scoring System.

There was tremendous increase in the number of cases of mucormycosis among patients affected by coronavirus disease 2019 (COVID-19) during the second wave of pandemic in South Asian countries. This invasive fungal infection primarily affects paranasal sinuses and can have orbito-facial and intracranial extension. We are presenting the radiological findings of invasive mucormycosis with pathological and clinical outcome correlation. It is important for radiologists to have the knowledge of various presentations of this opportunistic infection for early diagnosis and helping clinicians in planning the appropriate line of management. The study also emphasizes on the correlation between the extent of involvement with clinical outcome and we proposed a magnetic resonance imaging (MRI) based scoring system to standardize and prognosticate the patients affected with mucormycosis. MATERIALS AND METHODS: We utilized GE 1.5 tesla, 16-channeled MRI machine for scanning the clinically suspected mucormycosis patients and did plain and contrast study of the paranasal sinuses, orbito-facial study and included brain as and when required. Images were acquired in axial, coronal, and sagittal planes using T1, T2, and fat-saturated short tau inversion recovery sequences (STIR), fat-saturated contrast sequences for better evaluation of the extent of the disease. Diffusion-weighted sequence was also acquired to detect ischemic changes in optic nerve or brain parenchyma. Contrast study was used to detect any major vessel occlusion or cavernous sinus thrombosis in the study population. RESULTS: Total number of cases (n) included in the study were 32. The mean age group was 41-50 years with the median age was 47 years. Out of 32 cases (n=32), in 16 cases (50%) the disease was limited only to the paranasal sinuses and in remaining 16 (50%) cases, disease has spread to other regions such as orbits, facial soft tissues, optic nerve, and brain parenchyma. All the 18 cases with Mild score (MRI ROCM score 1-3) survived and all those with severe score (2 cases) (MRI ROCM score 7-10) did not survive. CONCLUSION: During the second wave of COVID-19 pandemic, we observed a significant rise in acute invasive mucormycosis infection primarily involving the paranasal sinuses and spread to orbito-facial, cerebral parenchyma causing related complications and hence increased morbidity and death. Radiologically, using MRI, it was effectively possible to detect early extrasinonasal spread and other fatal complications thereby guiding the physicians and surgeons in the proper early aggressive management of the disease. Here, we have described the radiological characteristics of paranasal sinus mucormycosis and its spread to other regions. We also proposed an MRI-based Scoring System for standardized assessment of the disease severity. We observed in our study that the extent of disease on MRI is directly correlating with mortality.

Copper and Zinc Feud: Is This Myelodysplasia or Myelodysplastic Syndrome?

We report a case of a 59-year-old male who developed pancytopenia and multiorgan failure attributed to copper deficiency from exogenous consumption of zinc tablets. During the six months preceding his presentation, he had experienced increasing shortness of breath, lightheadedness, and fatigue. Laboratory studies revealed pancytopenia with profound anemia (hemoglobin level 2.8 g/dL) along with evidence of acute kidney injury and acute heart failure; the patient was presumed to have multiorgan failure due to profound anemia. Bone marrow biopsy revealed dyspoiesis suggestive of myelodysplastic syndrome (MDS). There were no cytogenetic abnormalities observed. However, the blood workup analysis found low copper and ceruloplasmin levels, whereas zinc levels were excessively elevated (257 mg/dL). Upon inquiry, the patient reported taking an over-the-counter zinc supplement of an unknown quantity for over a year. After two months of copper treatment, his blood count returned to normal. This case highlights a rare presentation of zinc-induced copper deficiency resulting in pancytopenia and severe anemia-related multiorgan failure. A growing number of hematological disorders are being linked to copper deficiency. Copper deficiency pancytopenia is a reversible condition that often goes unnoticed and can be misdiagnosed as MDS because it has similar hematological characteristics.

Elevated COVID19 mortality risk in detroit area hospitals among patients from census tracts with extreme socioeconomic vulnerability.

BACKGROUND: the incidence of novel coronavirus disease (COVID19) is elevated in areas with heightened socioeconomic vulnerability. Early reports from US hospitals also implicated social disadvantage and chronic disease history as COVID19 mortality risk factors. However, the relationship between race and COVID19 mortality remains unclear. METHODS: we examined in-hospital COVID19 mortality risk factors in a multi-hospital tertiary health care system that serves greater Detroit, Michigan, a predominantly African American city with high rates of poverty and chronic disease. Consecutive adult patients who presented to emergency departments and tested positive for COVID19 from 3/11/2020 through 4/18/2020 were included. Using log-binomial regression, we assessed the relationship between in-hospital mortality and residence in census tracts that were flagged for extreme socioeconomic vulnerability, patient-level demographics, and clinical comorbidities. FINDINGS: a total of 1,015 adults tested positive for COVID19 during the study period; 80% identified as Black people, 52% were male and 53% were ≥ 65 years of age. The median body mass index was 30•4 and the median Charlson Comorbidity Index score was 4. Patients from census tracts that were flagged for vulnerability related to socioeconomic status had a higher mortality rate than their peers who resided in less vulnerable census tracts (ß 0.26, standard error (SE) 0.11, degrees of freedom (df) 378, t-value (t) 2.27, exp(ß) 1.29, p-value 0.02). Adjustment for age category, Black race, sex and/or the Charlson Comorbidity Index score category reduced the magnitude of association by less than 10% [exp(ß) 1.29 vs. 1.21]. Black race [p = 0.38] and sex [p = 0.62] were not associated with mortality in this sample. INTERPRETATION: people who lived in areas flagged for extreme socioeconomic vulnerability had elevated mortality risk in our predominantly African-American cohort of COVID19 patients who were able to seek hospital care during the so-called 'first wave' of the pandemic. By contrast, Black race was not associated with mortality in our sample.

A potential peptide therapeutic derived from the juxtamembrane domain of the epidermal growth factor receptor.

The epidermal growth factor receptor (EGFR) is involved in many cancers and EGFR has been heavily pursued as a drug target. Drugs targeting EGFR have shown promising clinical results for several cancer types. However, resistance to EGFR inhibitors often occurs, such as with KRAS mutant cancers, therefore new methods of targeting EGFR are needed. The juxtamembrane (JXM) domain of EGFR is critical for receptor activation and targeting this region could potentially be a new method of inhibiting EGFR. We hypothesized that the structural role of the JXM region could be mimicked by peptides encoding a JXM amino acid sequence, which could interfere with EGFR signaling and consequently could have anti-cancer activity. A peptide encoding EGFR 645-662 conjugated to the Tat sequence (TE-64562) displayed anti-cancer activity in multiple human cancer cell types with diminished activity in non-EGFR expressing cells and non-cancerous cells. In nude mice, TE-64562 delayed MDA-MB-231 tumor growth and prolonged survival, without inducing toxicity. TE-64562 induced non-apoptotic cell death after several hours and caspase-3-mediated apoptotic cell death with longer treatment. Mechanistically, TE-64562 bound to EGFR, inhibited its dimerization and caused its down-regulation. TE-64562 reduced phosphorylated and total EGFR levels but did not inhibit kinase activity and instead prolonged it. Our analysis of patient data from The Cancer Genome Atlas supported the hypothesis that down-regulation of EGFR is a potential therapeutic strategy, since phospho- and total-EGFR levels were strongly correlated in a large majority of patient tumor samples, indicating that lower EGFR levels are associated with lower phospho-EGFR levels and presumably less proliferative signals in breast cancer. Akt and Erk were inhibited by TE-64562 and this inhibition was observed in vivo in tumor tissue upon treatment with TE-64562. These results are the first to indicate that the JXM domain of EGFR is a viable drug target for several cancer types.