Spectrum of opportunistic fungal lung co-infections in COVID-19: What the radiologist needs to know.

Fungal lung co-infections associated with COVID-19 may occur in severely ill patients or those with underlying co-morbidities, and immunosuppression. The most common invasive fungal infections are caused by aspergillosis, mucormycosis, pneumocystis, cryptococcus, and candida. Radiologists integrate the clinical disease features with the CT pattern-based approach and play a crucial role in identifying these co-infections in COVID-19 to assist clinicians to make a confident diagnosis, initiate treatment and prevent complications.

Espectro de coinfecciones pulmonares fúngicas oportunistas en COVID-19: lo que el radiólogo debe saber / Spectrum of opportunistic fungal lung co-infections in COVID-19: What the radiologist needs to know

Las coinfecciones pulmonares fúngicas asociadas a la COVID-19 pueden ocurrir en pacientes gravemente enfermos o con comorbilidades subyacentes e inmunosupresión. Las infecciones fúngicas invasivas más comunes son causadas por aspergilosis, mucormicosis, y las debidas a Pneumocystis, criptococo y cándida. Los radiólogos integran las características clínicas de la enfermedad con el enfoque basado en patrones de TAC y desempeñan un papel crucial en la identificación de estas coinfecciones en la COVID-19 para ayudar a los médicos a realizar un diagnóstico seguro, iniciar el tratamiento y prevenir complicaciones.(AU)

Fungal lung co-infections associated with COVID-19 may occur in severely ill patients or those with underlying co-morbidities, and immunosuppression. The most common invasive fungal infections are caused by aspergillosis, mucormycosis, pneumocystis, cryptococcus, and candida. Radiologists integrate the clinical disease features with the CT pattern-based approach and play a crucial role in identifying these co-infections in COVID-19 to assist clinicians to make a confident diagnosis, initiate treatment and prevent complications.(AU)

Barriers to artificial intelligence implementation in radiology practice: What the radiologist needs to know.

Artificial Intelligence has the potential to disrupt the way clinical radiology is practiced globally. However, there are barriers that radiologists should be aware of prior to implementing Artificial Intelligence in daily practice. Barriers include regulatory compliance, ethical issues, data privacy, cybersecurity, AI training bias, and safe integration of AI into routine practice. In this article, we summarize the issues and the impact on clinical radiology.

[Spectrum of opportunistic fungal lung co-infections in COVID-19: What the radiologist needs to know]. / Espectro de coinfecciones pulmonares fúngicas oportunistas en COVID-19: lo que el radiólogo debe saber.

Fungal lung co-infections associated with COVID-19 may occur in severely ill patients or those with underlying co-morbidities, and immunosuppression. The most common invasive fungal infections are caused by aspergillosis, mucormycosis, pneumocystis, cryptococcus, and candida. Radiologists integrate the clinical disease features with the CT pattern-based approach and play a crucial role in identifying these co-infections in COVID-19 to assist clinicians to make a confident diagnosis, initiate treatment and prevent complications.

Dificultades en la implantación de la inteligencia artificial en la práctica radiológica: lo que el radiólogo necesita saber / Barriers to Artificial Intelligence implementation in radiology practice: What the Radiologist needs to know

La inteligencia artificial (IA) ofrece la posibilidad de cambiar la práctica de la radiología clínica en todo el mundo. Sin embargo, existen dificultades que los radiólogos deben conocer antes de aplicar la inteligencia artificial en la práctica diaria. Estas dificultades incluyen cuestiones de cumplimiento de la legislación, cuestiones éticas, aspectos relacionados con la privacidad de los datos y la ciberseguridad, el sesgo de aprendizaje automático y la integración segura de la IA en la práctica habitual. En este artículo, resumimos estas cuestiones y su repercusión en la radiología clínica.(AU)

Artificial Intelligence has the potential to disrupt the way clinical radiology is practiced globally. However, there are barriers that radiologists should be aware of prior to implementing Artificial Intelligence in daily practice. Barriers include regulatory compliance, ethical issues, data privacy, cybersecurity, AI training bias, and safe integration of AI into routine practice. In this article, we summarize the issues and the impact on clinical radiology.(AU)

Bilateral vision loss as the initial presentation for central nervous system involvement of mantle cell lymphoma: A case series.

PURPOSE: Mantle cell lymphoma is a rare aggressive subtype of non-Hodgkins B cell lymphoma. It typically presents with asymptomatic monoclonal lymphocytosis, lymphadenopathy or bulky extranodal disease. Mantle cell lymphoma rarely affects the central nervous system. We present two cases in which vision loss was the initial symptom of central nervous system involvement by the malignancy. OBSERVATIONS: Both patients initially received high dose intravenous steroids with notable improvement in their vision. CONCLUSIONS AND IMPORTANCE: Early detection and management of optic nerve infiltration by mantle cell lymphoma is essential as it improves visual outcomes and enables prompt management of the patient's systemic disease.

Treatment of MOG antibody associated disorders: results of an international survey.

INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

Uveitis and optic perineuritis in the context of myelin oligodendrocyte glycoprotein antibody seropositivity.

BACKGROUND AND PURPOSE: Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been identified in both children and adults with demyelination, with a strong association with bilateral or recurrent optic neuritis (ON). However, the full clinical spectrum of this newly described condition is unknown. We sought to describe non-ON inflammatory ophthalmological presentations such as uveitis and optic perineuritis in the context of MOG antibody seropositivity. METHODS: Using a live cell-based assay analysed by flow cytometry, we identified seropositive patients referred for MOG antibody testing in Australasia between 2014 and 2017. We identified four MOG antibody-positive patients with non-ON inflammatory ophthalmological presentations and present their detailed clinical information in this case series. RESULTS: Three patients had uveitis either in association with, or remote from, ON. One patient had optic perineuritis and peripheral ulcerative keratitis. We describe the presentation, examination, investigation findings and clinical course of these four patients. CONCLUSIONS: Recognition of these novel clinical associations may expand the clinical spectrum of MOG antibody-associated presentations. An expedited diagnosis may guide the management of these complex patients.

Coronary Artery Disease-Reporting and Data System (CAD-RADS): strengths and limitations.

A new standardised reporting system was introduced recently for coronary computed tomography (CT) angiography interpretation called CAD-RADS (Coronary Artery Disease-Reporting and Data System). Like any other new reporting platform, CAD-RADS has both advantages and disadvantages. Consistency in reporting, better clarity of communication, and more streamlined clinical recommendations are the major strengths of CAD-RADS. It has many limitations such as misinterpretation of CT angiography findings inherent to any CT angiography examination and unique disadvantages like misclassification of abnormalities, potential to misguide the referring physicians by suggesting management based on a single score. In addition, CAD-RADS does not include the details on location and extent of disease in the coronary arteries, coronary anomalies and other cardiac and extra cardiac findings.

Biofilm inhibitory efficiency of phytol in combination with cefotaxime against nosocomial pathogen Acinetobacter baumannii.

AIMS: This study aimed to evaluate the antibiofilm potential of phytol and cefotaxime combinations (PCCs) against Acinetobacter baumannii and to elucidate the molecular mechanism of their antibiofilm potential through the transcriptomic approach. METHODS AND RESULTS: Phytol and cefotaxime combination(s) (PCC(s) [160 µg ml-1  + 8 µg ml-1 for microbial type culture collection (MTCC) strain and 160 µg ml-1  + 0.5 µg ml-1 for clinical isolate] effectively inhibited the A. baumannii biofilm formation. Additionally, light, confocal laser scanning and scanning electron microscopic analyses validated the antibiofilm potential of PCCs. Furthermore, PCCs treated A. baumannii cells showed a decreased level of hydrophobicity index compared to their respective controls. Fourier-transform infrared (FT-IR) spectra of exopolysaccharide matrix extracted from PCCs-treated A. baumannii cells showed a visible decrease in absorbance of polysaccharides, nucleic acids and protein regions compared to the spectra of untreated controls. In the blood sensitivity assay, the PCCs-treated A. baumannii plates showed reduced a number of bacterial colonies compared to their control plates. Reduced level of catalase production was also observed in the PCCs treatment compared to their controls. Transcriptomic analysis revealed the downregulation of bfmR, bap, csuA/B, ompA, pgaA, pgaC and katE biofilm virulence genes in both the A. baumannii strains on treatment with PCCs. CONCLUSION: The obtained results of this study indicate that PCCs have potent antibiofilm activity and downregulate the biofilm-related virulence genes expression in A. baumannii. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this is the pioneering study, which shows the antibiofilm effect of PCCs against A. baumannii along with their molecular mechanism. The antibiofilm effect of PCCs could be a successful strategy for eradicating infections related to A. baumannii biofilms in nosocomial settings.

Phytosynthesized silver nanoparticles as antiquorum sensing and antibiofilm agent against the nosocomial pathogen Serratia marcescens: an in vitro study.

AIM: Serratia marcescens is an important multidrug-resistant human pathogen. The pathogenicity of S. marcescens mainly depends on the quorum sensing (QS) mechanism, which regulates the virulence factors production and biofilm formation. Hence, targeting QS mechanism in S. marcescens will ultimately pave the way to combat its pathogenicity. Thus, the present study is intended to evaluate the efficacy of Vetiveria zizanioides root extract-mediated silver nanoparticles (AgNPs) as a potent anti-QS and antibiofilm agent against S. marcescens. METHODS AND RESULTS: The AgNPs were synthesized using V. zizanioides aqueous root extract and the physiochemical properties of V. zizanioides-based AgNPs (VzAgNPs) were evaluated using analytical techniques such as ultraviolet-visible absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, dynamic light scattering and scanning and transmission electron microscopic techniques. VzAgNPs were found to attenuate the QS-dependent virulence factors, namely prodigiosin, protease, lipase, exopolysaccharide productions and biofilm formation of S. marcescens, without inhibiting its growth. Further, the transcriptomic analysis confirmed the down-regulation of QS-dependent genes, which encode for the production of virulence factors and biofilm formation. CONCLUSION: The current study confirms VzAgNPs as an ideal anti-QS and antibiofilm agent against S. marcescens. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first approach that validates the anti-QS and antibiofilm potential of phytosynthesized VzAgNPs against the nosocomial pathogen, S. marcescens. As VzAgNPs exhibits potent antivirulent activities, it could be used to treat hospital-acquired S. marcescens infections.

Familial transient financial difficulties during infancy and long-term developmental concerns.

BACKGROUND: Socioeconomic difficulties affect the cognitive and emotional development of children. However, the focus of prior studies has largely been on poverty and material hardship. This study expands on the existing literature by examining the impact of familial transient financial difficulties during infancy on long-term cognitive and behavioral outcomes. METHODS: The National Longitudinal Surveys of Youth (79) were used to assess the association between a transient drop in family income by 50% or more (called transient income decline or TID) during the first 3 years of life and later-life Peabody Individual Achievement Math and Reading scores and behavior problem index (BPI) scores (N = 8272-17 348; median assessment age = 9 years). A subsample of matched siblings (N = 2049-4238) was examined to tease out maternal and intra-familial effects. RESULTS: Exposure to TID predicted increased total and externalizing BPI scores (std. coefficients of 0.10 and 0.09, respectively, p < 0.01) in the overall sample. Among matched siblings, exposure to TID predicted increased total, externalizing, and internalizing BPI scores (std. coefficients of 0.27, 0.25, and 0.23, respectively, p < 0.01). CONCLUSION: Familial transient financial difficulties can have long-lasting behavioral effects for infants. The study identifies an early risk factor and at-risk children, thus providing insight into developing early intervention measures for infants to avoid long-term behavioral problems.

Risk factors for community-associated multidrug-resistant Pseudomonas aeruginosa in veterans with spinal cord injury and disorder: a retrospective cohort study.

STUDY DESIGN: Retrospective cohort studyObjectives:To identify independent risk factors associated with community-associated multidrug-resistant Psedomonas aeruginosa (MDRPA) in a population of veterans with spinal cord injury and disorders (SCI/D). SETTING: A total of 127 Veterans Affairs healthcare facilities. METHODS: Laboratory results from 1 January 2012 to 31 December 2013 were collected, and MDRPA cultures were compared with non-MDRPA cultures. RESULTS: One thousand four hundred forty-one cultures were collected from Veterans with SCI/D, including 227 cultures with MDRPA isolates. Characteristics associated with an increased odds of MDRPA include age 50-64 (adjusted odds ratio (aOR)=1.80, 95% confidence interval (CI)=1.13-2.87), MDRPA culture in the past 365 days (aOR=9.12, 95% CI=5.88-14.15) and carbapenem exposure in the past 90 days (aOR=2.56, 95% CI=1.35-4.87). In contrast, paraplegia was associated with a 53% decreased odds of MDRPA compared with those with tetraplegia (aOR=0.47, 95% CI=0.32-0.69). CONCLUSIONS: Risk factors for community-associated MDRPA include prior history of MDRPA and exposure to carbapenems. Awareness of these factors is important for targeted prevention and treatment of MDRPA in patients with SCI/D.

SOCS1 inhibits migration and invasion of prostate cancer cells, attenuates tumor growth and modulates the tumor stroma.

BACKGROUND: The suppressor of cytokine signaling 1 (SOCS1) gene is repressed in prostate cancer (PCa) by epigenetic silencing and microRNA miR30d. Increased expression of the SOCS1-targeting miR30d correlates with higher biochemical recurrence, suggesting a tumor suppressor role of SOCS1 in PCa, but the underlying mechanisms are unclear. We have shown that SOCS1 inhibits MET receptor kinase signaling, a key oncogenic pathway in cancer progression. Here we evaluated the role of SOCS1 in attenuating MET signaling in PCa cells and tumor growth in vivo. METHODS: MET-overexpressing human DU145 and PC3 PCa cell lines were stably transduced with SOCS1, and their growth, migration and invasion of collagen matrix were evaluated in vitro. Cells expressing SOCS1 or the control vector were evaluated for tumor growth in NOD.scid.gamma mice as xenograft or orthotopic tumors. RESULTS: HGF-induced MET signaling was attenuated in SOCS1-expressing DU145 and PC3 cells. Compared with vector control cells, SOCS1-expressing cells showed reduced proliferation and impaired migration following HGF stimulation. DU145 and PC3 cells showed marked ability to invade the collagen matrix following HGF stimulation and this was attenuated by SOCS1. As xenografts, SOCS1-expressing PCa cells showed significantly reduced tumor growth compared with vector control cells. In the orthotopic tumor model, SOCS1 reduced the growth of primary tumors and metastatic spread. Intriguingly, the SOCS1-expressing DU145 and PC3 tumors showed increased collagen deposition, associated with increased frequency of myofibroblasts. CONCLUSIONS: Our findings support the tumor suppressor role of SOCS1 in PCa and suggest that attenuation of MET signaling is one of the underlying mechanisms. SOCS1 in PCa cells also appears to prevent the tumor-promoting functions of cancer-associated fibroblasts.

Bacterial susceptibility patterns in patients with spinal cord injury and disorder (SCI/D): an opportunity for customized stewardship tools.

STUDY DESIGN: Retrospective observational study of bacterial susceptibilities in Veterans with SCI/D as compared to a general patient population. OBJECTIVES: The purpose of this project was to evaluate the prevalence and susceptibility of bacteria isolated from spinal cord injury and disorder (SCI/D) patients as compared with a general patient population and determine whether a SCI/D-specific antibiogram, a report of bacterial susceptibilities used to guide empiric antibiotic selection, would be a useful stewardship tool. SETTING: Veterans Affairs Medical Center located in Cook county, IL, USA. METHODS: Microbiology reports from 1 October 2012 to 30 September 2013 were compiled into a SCI/D-specific antibiogram and compared to a non-SCI/D antibiogram. RESULTS: Persons with positive cultures and SCI/D were younger and had a higher Charlson Index as compared to non-SCI/D patients (P<0.0001 for both). Five thousand one hundred and thirty-one unique isolate cultures were evaluated (SCI/D=23.0%). Frequencies of pathogens isolated in SCI/D and non-SCI/D differed. Methicillin-resistant Staphylococcus aureus occurred more frequently in SCI/D (27.8% vs 55.4%; P<0.0001). Gram-negatives had generally lower susceptibilities in SCI/D and a higher frequency of organisms producing extended-spectrum Beta-lactamases (17.6% vs 5.0%; P<0.0001), carbapenem-resistant Enterobacteriaceae (2.4% vs 0.5%; P<0.0001), carbapenem resistance (7.6% vs 2.4%; P<0.0001) and isolates resistant to ⩾3 antibiotic classes (60.7% vs 28.0%; P=0.0001). CONCLUSION: Different pathogens with poorer susceptibilities are isolated in SCI/D. Thus an SCI/D-specific antibiogram reflective of resistance patterns in these patients may increase the appropriateness of empiric antibiotic selection. The frequency of multi-drug resistant organisms in cultures obtained from patients with SCI/D is worrisome.

Suppressor of cytokine signaling 1-dependent regulation of the expression and oncogenic functions of p21(CIP1/WAF1) in the liver.

The SOCS1 gene coding for suppressor of cytokine signaling 1 is frequently repressed in hepatocellular carcinoma (HCC), and hence SOCS1 is considered a tumor suppressor in the liver. However, the tumor-suppressor mechanisms of SOCS1 are not yet well understood. SOCS1 is known to inhibit pro-inflammatory cytokine production and signaling and to promote activation of the p53 tumor suppressor. However, we observed that SOCS1-deficient mice developed numerous and large liver tumor nodules following treatment with the hepatocarcinogen diethylnitrosamine (DEN) without showing increased interleukin-6 production or activation of p53. On the other hand, the livers of DEN-treated Socs1-null mice showed elevated levels of p21(CIP1/WAF1) protein (p21). Even though p21 generally functions as a tumor suppressor, paradoxically many cancers, including HCC, are known to express elevated levels of p21 that correlate with poor prognosis. We observed elevated p21 expression also in the regenerating livers of SOCS1-deficient mice and in cisplatin-treated Socs1-null hepatocytes, wherein the p21 protein showed increased stability. We show that SOCS1 interacts with p21 and promotes its ubiquitination and proteasomal degradation. Besides, the DEN-treated livers of Socs1-null mice showed increased nuclear and cytosolic p21 staining, and the latter was associated with growth factor-induced, phosphatidylinositol 3-kinase-dependent phosphorylation of p21 in SOCS1-deficient hepatocytes. Cytosolic p21 is often associated with malignancy and chemo-resistance in many cancers. Accordingly, SOCS1-deficient hepatocytes showed increased resistance to apoptosis that was reversed by shRNA-mediated p21 knockdown. In the regenerating livers of Socs1-null mice, increased p21 expression coincided with elevated cyclinD levels. Correspondingly, SOCS1-deficient hepatocytes showed increased proliferation to growth factor stimulation that was reversed by p21 knockdown. Overall, our findings indicate that the tumor-suppressor functions of SOCS1 in the liver could be mediated, at least partly, via regulation of the expression, stability and subcellular distribution of p21 and its paradoxical oncogenic functions, namely, resistance to apoptosis and increased proliferation.