A 44-Year-Old Woman With Prolonged Fever and Mediastinal "Lymphadenopathy".

CASE PRESENTATION: A 44-year-old woman with a history of dyslipidemia and chronic anemia from uterine fibroids was admitted to the general medicine department of a tertiary hospital for a prolonged fever of 2 months' duration. The patient reported multiple visits to her local general practitioner, with tympanic temperatures up to 38.2 °C, where she was treated with 2 courses of broad-spectrum antibiotics in view of associated sore throat, nonproductive cough, and generalized lethargy. Although her respiratory symptoms abated within a few days of her initial presentation, her fever and lethargy persisted. Initial chest radiograph was unremarkable. Subsequent CT scan of the thorax, abdomen, and pelvis detected an enlarged subcarinal lymph node measuring 3.7 cm × 1.7 cm and a mildly enlarged pre-carinal lymph node measuring 2.0 × 1.5 cm, with a mean attenuation of 66-77 Hounsfield Units (HU), and no central necrosis or calcification. No significant abnormalities were detected in the abdomen or pelvis. The patient was then referred to the respiratory department for further evaluation.

A Tale of Two Organ Systems: Imaging Review of Diseases Affecting the Thoracic and Neurological Systems. Part 2.

In an era of rapidly expanding knowledge and sub-specialization, it is becoming increasingly common to focus on one organ system. However, the human body is intimately linked, and disease processes affecting one region of the body not uncommonly affect the other organ systems as well. Understanding diseases from a macroscopic perspective, rather than a narrow vantage point, enables efficient and accurate diagnosis. This tenet holds true for diseases affecting both the thoracic and neurologic systems; in isolation, the radiologic appearance of disease in one organ system may be nonspecific, but viewing the pathophysiologic process in both organ systems may markedly narrow the differential considerations, and potentially lead to a definitive diagnosis. In this article, we discuss a variety of disease entities known to affect both the thoracic and neurological systems, either manifesting simultaneously or at different periods of time. Some of these conditions may show neither thoracic nor neurological manifestations. These diseases have been systematically classified into infectious, immune-mediated/ inflammatory, vascular, syndromic/ hereditary and neoplastic disorders. The underlying pathophysiological mechanisms linking both regions and radiologic appearances in both organ systems are discussed. When appropriate, brief clinical and diagnostic information is provided. Ultimately, accurate diagnosis will lead to expedited triage and prompt institution of potentially life-saving treatment for these groups of complex disorders.

A Tale of Two Organ Systems: Imaging review of diseases affecting the thoracic and neurological systems. Part 1.

In an era of rapidly expanding knowledge and sub-specialization, it is becoming increasingly common to focus on one organ system. However, the human body is intimately linked, and disease processes affecting one region of the body not uncommonly affect the other organ systems as well. Understanding diseases from a macroscopic perspective, rather than a narrow vantage point, enables efficient and accurate diagnosis. This tenet holds true for diseases affecting both the thoracic and neurological systems; in isolation, the radiologic appearance of disease in one organ system may be nonspecific, but viewing the pathophysiologic process in both organ systems may markedly narrow the differential considerations, and potentially lead to a definitive diagnosis. In this article, we discuss a variety of disease entities known to affect both the thoracic and neurological systems, either manifesting simultaneously or at different periods of time. Some of these conditions may show neither thoracic nor neurological manifestations. These diseases have been systematically classified into infectious, immune-mediated / inflammatory, vascular, syndromic / hereditary and neoplastic disorders. The underlying pathophysiological mechanisms linking both regions and radiologic appearances in both organ systems are discussed. When appropriate, brief clinical and diagnostic information is provided. Ultimately, accurate diagnosis will lead to expedited triage and prompt institution of potentially life-saving treatment for these groups of complex disorders.

Heterogeneity of non-cystic-fibrosis bronchiectasis in multiethnic Singapore: A prospective cohort study at a tertiary pulmonology centre.

INTRODUCTION: Non-cystic fibrosis bronchiectasis (NCFB) is a highly heterogenous disease. We describe the clinical characteristics of NCFB patients and evaluate the performance of Bronchiectasis Severity Index (BSI) in predicting mortality. METHODS: Patients attending the bronchiectasis clinic between August 2015 and April 2020 with radiologically proven bronchiectasis on computed tomography were recruited. Clinical characteristics, spirometry, radiology, microbiology and clinical course over a median period of 2.4 years is presented. RESULTS: A total of 168 patients were enrolled in this prospective cohort study. They were predominantly women (67.8%), Chinese (87.5%) and never-smokers (76.9%). Median age of diagnosis was 64 years (interquartile range 56-71) and the most common aetiology was "idiopathic" bronchiectasis (44.6%). Thirty-nine percent had normal spirometries. Compared to female patients, there were more smokers among the male patients (53.8% versus 8.5%, P<0.001) and a significantly larger proportion with post-tuberculous bronchiectasis (37.0% vs 15.8%, P=0.002). Fifty-five percent of our cohort had a history of haemoptysis. Lower body mass index, presence of chronic obstructive pulmonary disease, ever-smoker status, modified Reiff score, radiological severity and history of exacerbations were risk factors for mortality. Survival was significantly shorter in patients with severe bronchiectasis (BSI>9) compared to those with mild or moderate disease (BSI<9). The hazard ratio for severe disease (BSI>9) compared to mild disease (BSI 0-4) was 14.8 (confidence interval 1.929-114.235, P=0.01). CONCLUSION: The NCFB cohort in Singapore has unique characteristics with sex differences. Over half the patients had a history of haemoptysis. The BSI score is a useful predictor of mortality in our population.

Chronic Cough With Non-Resolving Mass-like Consolidation.

CASE PRESENTATION: A 72-year-old Chinese man presented with a 5-month history of chronic dry cough, weight loss, and progressive dyspnea. There was no associated hemoptysis, hoarseness, epistaxis, or fever on systemic review. He was a nonsmoker and had no family history of malignancy. He was treated for pulmonary TB 40 years ago. A chest radiograph (Fig 1) showed mass-like consolidation in the right midzone with loss of the right hilar border, a small right pleural effusion, and bi-apical scarring. On physical examination, he was afebrile and normotensive, and he had pulse oxygen saturation of 97%. Examination of the chest was remarkable only for reduced breath sounds over the right chest. He did not have digital clubbing, distended neck veins, or cervical lymphadenopathy.

High-risk chest radiographic features associated with COVID-19 disease severity.

OBJECTIVES: High-risk CXR features in COVID-19 are not clearly defined. We aimed to identify CXR features that correlate with severe COVID-19. METHODS: All confirmed COVID-19 patients admitted within the study period were screened. Those with suboptimal baseline CXR were excluded. CXRs were reviewed by three independent radiologists and opacities recorded according to zones and laterality. The primary endpoint was defined as hypoxia requiring supplemental oxygen, and CXR features were assessed for association with this endpoint to identify high-risk features. These features were then used to define criteria for a high-risk CXR, and clinical features and outcomes of patients with and without baseline high-risk CXR were compared using logistic regression analysis. RESULTS: 109 patients were included. In the initial analysis of 40 patients (36.7%) with abnormal baseline CXR, presence of bilateral opacities, multifocal opacities, or any upper or middle zone opacity were associated with supplemental oxygen requirement. Of the entire cohort, 29 patients (26.6%) had a baseline CXR with at least one of these features. Having a high-risk baseline CXR was significantly associated with requiring supplemental oxygen in univariate (odds ratio 14.0, 95% confidence interval 3.90-55.60) and multivariate (adjusted odds ratio 8.38, 95% CI 2.43-28.97, P = 0.001) analyses. CONCLUSION: We identified several high-risk CXR features that are significantly associated with severe illness. The association of upper or middle zone opacities with severe illness has not been previously emphasized. Recognition of these specific high-risk CXR features is important to prioritize limited healthcare resources for sicker patients.

Radiographic features of COVID-19 based on an initial cohort of 96 patients in Singapore.

INTRODUCTION: Chest radiographs (CXRs) are widely used for the screening and management of COVID-19. This article describes the radiographic features of COVID-19 based on an initial national cohort of patients. METHODS: This is a retrospective review of swab-positive patients with COVID-19 who were admitted to four different hospitals in Singapore between 22 January and 9 March 2020. Initial and follow-up CXRs were reviewed by three experienced radiologists to identify the predominant pattern and distribution of lung parenchymal abnormalities. RESULTS: In total, 347 CXRs of 96 patients were reviewed. Initial CXRs were abnormal in 41 (42.7%) out of 96 patients. The mean time from onset of symptoms to CXR abnormality was 5.3 ± 4.7 days. The predominant pattern of lung abnormality was ground-glass opacity on initial CXRs (51.2%) and consolidation on follow-up CXRs (51.0%). Multifocal bilateral abnormalities in mixed central and peripheral distribution were observed in 63.4% and 59.2% of abnormal initial and follow-up CXRs, respectively. The lower zones were involved in 90.2% of initial CXRs and 93.9% of follow-up CXRs. CONCLUSION: In a cohort of swab-positive patients, including those identified from contact tracing, we found a lower incidence of CXR abnormalities than was previously reported. The most common pattern was ground-glass opacity or consolidation, but mixed central and peripheral involvement was more common than peripheral involvement alone.

Heterogeneity of non-cystic-fibrosis bronchiectasis in multiethnic Singapore: A prospective cohort study at a tertiary pulmonology centre

INTRODUCTION@#Non-cystic fibrosis bronchiectasis (NCFB) is a highly heterogenous disease. We describe the clinical characteristics of NCFB patients and evaluate the performance of Bronchiectasis Severity Index (BSI) in predicting mortality.@*METHODS@#Patients attending the bronchiectasis clinic between August 2015 and April 2020 with radiologically proven bronchiectasis on computed tomography were recruited. Clinical characteristics, spirometry, radiology, microbiology and clinical course over a median period of 2.4 years is presented.@*RESULTS@#A total of 168 patients were enrolled in this prospective cohort study. They were predominantly women (67.8%), Chinese (87.5%) and never-smokers (76.9%). Median age of diagnosis was 64 years (interquartile range 56-71) and the most common aetiology was "idiopathic" bronchiectasis (44.6%). Thirty-nine percent had normal spirometries. Compared to female patients, there were more smokers among the male patients (53.8% versus 8.5%, @*CONCLUSION@#The NCFB cohort in Singapore has unique characteristics with sex differences. Over half the patients had a history of haemoptysis. The BSI score is a useful predictor of mortality in our population.

Radiographic features of COVID-19 based on an initial cohort of 96 patients in Singapore

INTRODUCTION@#Chest radiographs (CXRs) are widely used for the screening and management of COVID-19. This article describes the radiographic features of COVID-19 based on an initial national cohort of patients.@*METHODS@#This is a retrospective review of swab-positive patients with COVID-19 who were admitted to four different hospitals in Singapore between 22 January and 9 March 2020. Initial and follow-up CXRs were reviewed by three experienced radiologists to identify the predominant pattern and distribution of lung parenchymal abnormalities.@*RESULTS@#In total, 347 CXRs of 96 patients were reviewed. Initial CXRs were abnormal in 41 (42.7%) out of 96 patients. The mean time from onset of symptoms to CXR abnormality was 5.3 ± 4.7 days. The predominant pattern of lung abnormality was ground-glass opacity on initial CXRs (51.2%) and consolidation on follow-up CXRs (51.0%). Multifocal bilateral abnormalities in mixed central and peripheral distribution were observed in 63.4% and 59.2% of abnormal initial and follow-up CXRs, respectively. The lower zones were involved in 90.2% of initial CXRs and 93.9% of follow-up CXRs.@*CONCLUSION@#In a cohort of swab-positive patients, including those identified from contact tracing, we found a lower incidence of CXR abnormalities than was previously reported. The most common pattern was ground-glass opacity or consolidation, but mixed central and peripheral involvement was more common than peripheral involvement alone.

Clinical utility of chest radiography for severe COVID-19.

BACKGROUND: Chest radiography (CXR) is performed more widely and readily than CT for the management of coronavirus disease (COVID-19), but there remains little data on its clinical utility. This study aims to assess the diagnostic performance of CXR, with emphasis on its predictive value, for severe COVID-19 disease. METHODS: A retrospective cohort study was conducted, 358 chest radiographs were performed on 109 COVID-19 patients (median age 44.4 years, 58 males and 30 with comorbidities) admitted between 22 January 2020 and 15 March 2020. Each CXR was reviewed and scored by three radiologists in consensus using a 72-point COVID-19 Radiographic Score (CRS). Disease severity was determined by the need for supplemental oxygen and mechanical ventilation. RESULTS: Patients who needed supplemental oxygen (n=19, 17.4%) were significantly older (P<0.001) and significantly more of them had co-morbidities (P=0.011). They also had higher C-reactive protein (CRP) (P<0.001), higher lactate dehydrogenase (LDH) (P<0.001), lower lymphocyte count (P<0.001) and lower hemoglobin (Hb) (P=0.001). Their initial (CRSinitial) and maximal CRS (CRSmax) were higher (P<0.001). Adjusting for age and baseline hemoglobin, the AUROC of CRSmax (0.983) was as high as CRPmax (0.987) and higher than the AUROC for lymphocyte countmin (0.897), and LDHmax (0.900). The AUROC for CRSinitial was slightly lower (0.930). CRSinitial ≥5 had a sensitivity of 63% and specificity of 92% in predicting the need for oxygen, and 73% sensitivity and 88% specificity in predicting the need for mechanical ventilation. CRS between the 6th and 10th day from the onset of symptoms (CRSD6-10) ≥5 had a sensitivity of 89% and specificity of 95% in predicting the need for oxygen, and 100% sensitivity and 86% specificity in predicting the need for mechanical ventilation. CONCLUSIONS: Adjusting for key confounders of age and baseline Hb, CRSmax performed comparable to or better than laboratory markers in the diagnosis of severe disease. CXR performed between the 6th and 10th days from symptom onset was a better predictor of severe disease than CXR performed earlier at presentation. A benign clinical course was seen in CXR that were normal or had very mild abnormalities.

A Dynamic Immune Response Shapes COVID-19 Progression.

The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.

A generalised porous medium approach to study thermo-fluid dynamics in human eyes.

The present work describes the application of the generalised porous medium model to study heat and fluid flow in healthy and glaucomatous eyes of different subject specimens, considering the presence of ocular cavities and porous tissues. The 2D computational model, implemented into the open-source software OpenFOAM, has been verified against benchmark data for mixed convection in domains partially filled with a porous medium. The verified model has been employed to simulate the thermo-fluid dynamic phenomena occurring in the anterior section of four patient-specific human eyes, considering the presence of anterior chamber (AC), trabecular meshwork (TM), Schlemm's canal (SC), and collector channels (CC). The computational domains of the eye are extracted from tomographic images. The dependence of TM porosity and permeability on intraocular pressure (IOP) has been analysed in detail, and the differences between healthy and glaucomatous eye conditions have been highlighted, proving that the different physiological conditions of patients have a significant influence on the thermo-fluid dynamic phenomena. The influence of different eye positions (supine and standing) on thermo-fluid dynamic variables has been also investigated: results are presented in terms of velocity, pressure, temperature, friction coefficient and local Nusselt number. The results clearly indicate that porosity and permeability of TM are two important parameters that affect eye pressure distribution. Graphical abstract Velocity contours and vectors for healthy eyes (top) and glaucomatous eyes (bottom) for standing position.

Temperature Effect on Rheological Behavior of Silicone Oils. A Model for the Viscous Heating.

The rheological behavior of silicone oils, (CH3)3SiO-[Si(CH3)2O]n-Si(CH3)3, and their mixtures is studied. Shear-stress measurements, in the temperature range of 293-313 K, reveal that this polymer family is a group of shear-thinning liquids with a yield stress below which no flow occurs. Experimental diagrams, i.e., shear stress versus shear rate, are satisfactorily described by the Casson fluid model over a wide range of shear rates. In order to monitor the effect of temperature on fluid properties, Casson's rheological model is reformulated using the fictitious shear rate, γ̇f, and the infinite-shear viscosity, η∞, as constitutive parameters. Due to low intermolecular forces and high chain flexibility, γ̇f varies very little when the temperature increases. For this reason, the apparent material viscosity depends on temperature only through η∞, which exponentially decreases until high shear rates are reached, and there is more alignment possible. Interestingly, the temperature sensitivity of this pseudoplastic behavior is the same for all of the silicone oils investigated; therefore, they can be classified according to their tendency to emulsify. Experimental results are then used to model the flow of silicone oils in a cylindrical pipe and estimate the temperature increase due to viscous heating. Numerical results show that the normalized temperature, i.e., ratio of fluid temperature to wall temperature, increases approximately 23%, and the apparent viscosity decreases drastically, going toward the center of the tube. The non-Newtonian nature of fluid is reflected in the presence of a critical region. In this region, the velocity and temperature gradients vanish. Since silicon oil is a surgical tool, we hope that the acquired physicochemical information can provide help to facilitate the removal of this material during surgical procedures.