Abstract Introduction/Objective Invasive fungal sinusitis is a serious condition requiring early diagnosis and treatment. It has been classified into acute, chronic and granulomatous forms. This study aims to investigate clinical pathologic aspects such as a) Frequency of mass forming lesions, b) Frequency of granulomatous reaction, c) Frequency of acute inflammatory reaction and d) Frequency of angioinvasion, perineural invasion and necrosis, to determine if these factors allow a more meaningful clinical-pathologic classification. Methods/Case Report Cases of invasive fungal sinusitis with surgical pathology specimens available in our laboratory since January 1, 2006 to date were gathered. Electronic medical records, histopathologic diagnostic material and laboratory fungal identification results were reviewed. Results (if a Case Study enter NA) Thirty-one cases of invasive fungal sinusitis were found: Twenty-two were acute (< 4wk duration) and 9 chronic. Patient comorbidities in acute cases were malignancies: 45%, diabetes mellitus: 26% and solid organ transplant: 10%. Among patients with malignancies, 5 cases had relapsed/refractory acute myeloid leukemia with neutropenia < 1000/uL. Patients with diabetes mellitus exhibited an average HbA1c of 10.0%. Two out of 3 transplant patients had graft versus host disease. The most common causative fungi were species of Aspergillus, Candida and mucormycetes. By contrast, a third of the chronic cases had a history of recreational drug use and six presented with space occupying lesions seen on imaging studies. Upon histologic review, four of these showed granulomas and the majority of cases exhibited extensive necrosis. Among necrotic cases, perineural and vascular invasion by fungal organisms was identified. Conclusion We report the contrasting clinical pathologic characteristics of acute and chronic invasive fungal sinusitis in a series of cases treated at University affiliated tertiary/quaternary-care Hospitals. Acute invasive sinusitis is usually a complication of severe systemic diseases. Chronic cases are caused by various medical conditions including the use of recreational drug and may mimic neoplasms on imaging.
From the onset of the COVID-19 pandemic, the demand for SARS-CoV-2 testing has resulted in an explosion of analytical tests with very different approaches and designs. The variability in testing modalities, compounded by the lack of available commercial reference materials for standardization early in the pandemic, has led to several challenges regarding data harmonization for viral quantitation.
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a variety of clinical symptoms ranging from no or mild to severe disease. Currently, there are multiple postulated mechanisms that may push a moderate to severe disease into a critical state. Human serum contains abundant evidence of the immune status following infection. Cytokines, chemokines, and antibodies can be assayed to determine the extent to which a patient responded to a pathogen. We examined serum and plasma from a cohort of patients infected with SARS-CoV-2 early in the pandemic and compared them to negative-control sera. Cytokine and chemokine concentrations varied depending on the severity of infection, and antibody responses were significantly increased in severe cases compared to mild to moderate infections. Neutralization data revealed that patients with high titers against an early 2020 isolate had detectable but limited neutralizing antibodies against newly circulating SARS-CoV-2 variants of concern. This study highlights the potential of re-infection for recovered COVID-19 patients.
Harmful algal blooms are increasing globally and pose serious health concerns releasing cyanotoxins. Microcystin-LR (MC-LR), one of the most frequently produced cyanotoxins, has recently been detected in aerosols generated by the normal motions of affected bodies of water. MC-LR aerosol exposure has been linked to a pro-inflammatory influence on the airways of mice, however little is understood about the underlying mechanism or the potential consequences. This study aimed to investigate the pro-inflammatory effects of aerosolized MC-LR on murine airways. C57BL/6 and BALB/c mice were exposed to MC-LR aerosols, as these strains are predisposed to type 1/type 17 and type 2 immune responses, respectively. Exposure to MC-LR induced granulocytic inflammation in C57BL/6 but not BALB/c mice, as observed by increased expression of cytokines MIP-1α, CXCL1, CCL2, and GM-CSF compared with their respective vehicle controls. Furthermore, the upregulation of interleukins IL-17A and IL-12 is consistent with Th1 and Th17 driven type 1/type 17 inflammation. Histological analysis confirmed inflammation in the C57BL/6 lungs, with elevated neutrophils and macrophages in the bronchoalveolar lavage fluid and increased pro-inflammatory oxidized lipids. In contrast, BALB/c mice showed no significant airway inflammation. These results highlight the ability of aerosolized MC-LR to trigger harmful airway inflammation, requiring further research.
Abstract Introduction/Objective The initial months of the SARS-CoV-2 pandemic entailed unprecedented changes to the way lives are lived worldwide, resulting in new means of social and economic engagement. For instance, stay-at-home orders led to youths (and staff) attending school virtually. Likewise, entire sectors of the workforce were blocked from their offices and jobs went online. The aim of these public health policies was to reduce the transmission of SARS- CoV-2; however, less attention has been given to how these policies have impacted the spread of other communicable illnesses. As such, we hypothesized that stay-at-home orders, in conjunction with increased hygiene surveillance and other public health guidelines, altered the transmission cycles of communicable gastrointestinal parasites. We anticipated that when plotted against time, a decrease in positive cases would occur concomitantly with known periods of lockdown; similarly, an increase in positive cases would follow efforts to re-open society. Methods/Case Report To probe this hypothesis, the laboratory information system was queried for positive and negative cases of Giardia and Cryptosporidium identified within the Indiana University Health System based on the Surve-Vue Signature™ Crypto/Giardia assay (Fisher Healthcare, Waltham, MA). Results (if a Case Study enter NA) Results were categorized by patient age: 0 to 18-years-old and 19-110-years-old. Initial review of the pediatric data set reflected that pandemic-related public health measures did not meaningfully alter the incidence of positive test results for these two parasites, though notable observations suggested patterns buried more deeply within the data. Conclusion The findings of this study have broad implications regarding the perceived and actual communicability of Giardia and Cryptosporidium (as well as other gastrointestinal parasites) in both normal and pandemic-times.
Harmful algal blooms are increasing globally and pose serious health concerns releasing cyanotoxins. Microcystin-LR (MC-LR), one of the most frequently produced cyanotoxins, has recently been detected in aerosols generated by the normal motions of affected bodies of water. MC-LR aerosol exposure has been linked to a pro-inflammatory influence on the airways of mice; however, little is understood about the underlying mechanism or the potential consequences. This study aimed to investigate the pro-inflammatory effects of aerosolized MC-LR on murine airways. C57BL/6 and BALB/c mice were exposed to MC-LR aerosols, as these strains are predisposed to type 1/type 17 and type 2 immune responses, respectively. Exposure to MC-LR induced granulocytic inflammation in C57BL/6 but not BALB/c mice, as observed by increased expression of cytokines MIP-1α, CXCL1, CCL2, and GM-CSF compared with their respective vehicle controls. Furthermore, the upregulation of interleukins IL-17A and IL-12 is consistent with Th1- and Th17-driven type 1/type 17 inflammation. Histological analysis confirmed inflammation in the C57BL/6 lungs, with elevated neutrophils and macrophages in the bronchoalveolar lavage fluid and increased pro-inflammatory and pro-resolving oxidized lipids. In contrast, BALB/c mice showed no significant airway inflammation. These results highlight the ability of aerosolized MC-LR to trigger harmful airway inflammation, requiring further research, particularly into populations with predispositions to type 1/type 17 inflammation.
Abstract After tick transmission, the spirochete, Borrelia burgdorferi (Bb), remains at the skin inoculation site for up to 48 hours before spreading and causing Lyme disease. Bb surface agonists should elicit potent inflammation and clearance in skin. However, the ID50 is <50 Bb, indicating efficient immunoevasion and suggesting that traditional in vitro models are inadequate for accurately characterizing Bb pathogenesis (i.e. most models display efficient Bb clearance by phagocytes). Thus, we have devised a confocal microscopy method for visualizing infectious fluorescent Bb in situ and in real-time. Here, we inject Bb into ear skin of anesthetized mice and collect four-dimensional data regarding Bb motility during natural infection. This data is complemented by quantitative PCR and histological analyses of the temporal fall and rise of spirochete numbers in vivo. By 4h, the majority of Bb at the injection site are immobile, while Bb adjacent to the site are highly motile. Two movement types are seen: 1) a back and forth shift that may aid Bb in finding an optimal migration path and 2) a directed run that navigates dermal structures. Analysis indicates an average Bb velocity of ≥100 um per minute in skin, which is >10x faster than any immune cell velocities observed in our model. This suggests that Bb motility is a primary mechanism for host cell evasion and indicates our imaging techniques will allow true delineation of host-Bb interactions critical for Lyme disease development.
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