Comparison of clinical characteristics and outcomes of hospitalized patients with seasonal coronavirus infection and COVID-19: a retrospective cohort study.

BACKGROUND: Unlike SARS-CoV and MERS-C0V, SARS-CoV-2 has the potential to become a recurrent seasonal infection; hence, it is essential to compare the clinical spectrum of COVID-19 to the existent endemic coronaviruses. We conducted a retrospective cohort study of hospitalized patients with seasonal coronavirus (sCoV) infection and COVID-19 to compare their clinical characteristics and outcomes. METHODS: A total of 190 patients hospitalized with any documented respiratory tract infection and a positive respiratory viral panel for sCoV from January 1, 2011, to March 31, 2020, were included. Those patients were compared with 190 hospitalized adult patients with molecularly confirmed symptomatic COVID-19 admitted from March 1, 2020, to May 25, 2020. RESULTS: Among 190 patients with sCoV infection, the Human Coronavirus-OC93 was the most common coronavirus with 47.4% of the cases. When comparing demographics and baseline characteristics, both groups were of similar age (sCoV: 74 years vs. COVID-19: 69 years) and presented similar proportions of two or more comorbidities (sCoV: 85.8% vs. COVID-19: 81.6%). More patients with COVID-19 presented with severe disease (78.4% vs. 67.9%), sepsis (36.3% vs. 20.5%), and developed ARDS (15.8% vs. 2.6%) compared to patients with sCoV infection. Patients with COVID-19 had an almost fourfold increased risk of in-hospital death than patients with sCoV infection (OR 3.86, CI 1.99-7.49; p < .001). CONCLUSION: Hospitalized patients with COVID-19 had similar demographics and baseline characteristics to hospitalized patients with sCoV infection; however, patients with COVID-19 presented with higher disease severity, had a higher case-fatality rate, and increased risk of death than patients with sCoV. Clinical findings alone may not help confirm or exclude the diagnosis of COVID-19 during high acute respiratory illness seasons. The respiratory multiplex panel by PCR that includes SARS-CoV-2 in conjunction with local epidemiological data may be a valuable tool to assist clinicians with management decisions.

Determination of the Predictors with the Greatest Influence on Walking in the Elderly.

Background and Objectives: Previous studies have revealed that independent variables (lower extremity strength, postural control ability, and body composition) influence gait performance and variability, but the difference in the relative influence between these variables is unclear. Hence, this study determines the variable that is the most influential predictor of gait performance and variability among potential independent variables in the elderly. Materials and Methods: Seventy-eight subjects aged ≥60 years participated. For each subject, the gait variables and lower extremity muscle strength were measured using an accelerometer worn on both feet during a 6-minute walk and a manual force sensor, respectively. The static balance ability was measured through two force plates, and the body composition was measured by applying bioelectrical impedance analysis. Linear regression analyses were performed stepwise to determine whether these variables affect gait performance and variability. Results: After adjusting for sex and gait performance, the ankle strength, body fat mass, mean velocity in the medial-lateral direction, ankle plantar flexion strength, and girth were predictors of gait speed dorsiflexion, gait performance, swing width of the gait performance, walking speed, and gait variability, respectively. Conclusions: Overall, gait performance in the elderly is related to muscle strength, postural control, and body composition in a complex manner, but gait variability appears to be more closely related to ankle muscle strength. This study provides further evidence that muscle strength is important in motor function and stability.

Secondarily estimated cure fraction and five-year recurrence-free conditional survival probabilities among patients undergoing surgical resection for hepatocellular carcinoma presenting with minor gross vascular invasion.

BACKGROUND: Surgical resection (SR) has been selectively applied in hepatocellular carcinoma (HCC) presenting with minor gross vascular invasion (mGVI) which is defined when tumor invasion is confined to second-order portal branches or segmental branches of hepatic vein. However, little data of long-term outcomes are available for supporting the role of SR as a potentially curable therapeutic option for HCC presenting with mGVI. This study is aimed to estimate a statistical cure fraction and the improvement of recurrence-free conditional survival (RFCS) over time among patients undergoing SR for HCC presenting with mGVI. METHODS: The literature search was conducted focusing on previous studies that investigated the long-term survival rates of patients after SR for HCC presenting with mGVI. The reference cohort was extracted from a study including patients undergoing SR for HCC without vascular invasion. A non-mixture cure model was adopted to estimate the statistical cure fraction. The 5-year RFCS probabilities were also calculated. RESULTS: Three retrospective studies were secondarily analyzed. The probability of being statistically cured after SR for HCC presenting with mGVI was 7.3% (95% confidence interval, 4.4%-11.2%) in the mGVI group, lower than that of the reference cohort (hazard ratio, 1.81; 95% confidence interval, 1.59-2.05). The estimated 5-year RFCS probabilities improved with each additional year of survival. Moreover, 1 year after SR, the 5-year RFCS probabilities of patients with HCC presenting with mGVI was essentially the same as that of the reference cohort. CONCLUSIONS: This study shows that a cure can be expected in around seven percent of patients undergoing SR for HCC presenting with mGVI. Furthermore, recurrence-free survival expectancy improves dramatically over time among those patients who do not have recurrence. Overall, these findings suggest that SR should be considered as a potentially curable treatment for patients with HCC presenting with mGVI.

A Retrospective Study of Coinfection of SARS-CoV-2 and Streptococcus pneumoniae in 11 Hospitalized Patients with Severe COVID-19 Pneumonia at a Single Center.

BACKGROUND A lethal synergism between the influenza virus and Streptococcus pneumoniae has been identified. However, bacterial coinfection is considered relatively infrequent in hospitalized patients with COVID-19, and the co-prevalence of Streptococcus pneumoniae is low. MATERIAL AND METHODS We retrospectively analyzed the clinical characteristics and outcomes of patients subsequently admitted to AMITA Health Saint Francis Hospital between March 1 and June 30, 2020, with documented SARS-CoV-2 and S. pneumoniae coinfection. RESULTS We identified 11 patients with S. pneumoniae coinfection. The median age was 77 years (interquartile range [IQR], 74-82 years), 45.5% (5/11) were males, 54.5% (6/11) were white, and 90.9% (10/11) were long-term care facility (LTCF) residents. The median length of stay was 7 days (IQR, 6-8 days). Among 11 patients, 4 were discharged in stable condition and 7 had died, resulting in an inpatient mortality rate of 64%. CONCLUSIONS At our center, 11 patients with COVID-19 pneumonia who had confirmed infection with SARS-CoV-2 were diagnosed with Streptococcus pneumoniae infection while in hospital. All patients had pneumonia confirmed on imaging and a nonspecific increase in markers of inflammation. The in-hospital mortality rate of 64% (7 patients) was higher in this group than in previous reports. This study highlights the importance of monitoring bacterial coinfection in patients with viral lung infection due to SARS-CoV-2.

Ankle Fracture Detection Utilizing a Convolutional Neural Network Ensemble Implemented with a Small Sample, De Novo Training, and Multiview Incorporation.

To determine whether we could train convolutional neural network (CNN) models de novo with a small dataset, a total of 596 normal and abnormal ankle cases were collected and processed. Single- and multiview models were created to determine the effect of multiple views. Data augmentation was performed during training. The Inception V3, Resnet, and Xception convolutional neural networks were constructed utilizing the Python programming language with Tensorflow as the framework. Training was performed using single radiographic views. Measured output metrics were accuracy, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity. Model outputs were evaluated using both one and three radiographic views. Ensembles were created from a combination of CNNs after training. A voting method was implemented to consolidate the output from the three views and model ensemble. For single radiographic views, the ensemble of all 5 models produced the best accuracy at 76%. When all three views for a single case were utilized, the ensemble of all models resulted in the best output metrics with an accuracy of 81%. Despite our small dataset size, by utilizing an ensemble of models and 3 views for each case, we achieved an accuracy of 81%, which was in line with the accuracy of other models using a much higher number of cases with pre-trained models and models which implemented manual feature extraction.

A natural compound, aristoyagonine, is identified as a potent bromodomain inhibitor by mid-throughput screening.

Bromodomain-containing protein 4 (Brd4) is known to play a key role in tumorigenesis. It binds acetylated histones to regulate the expression of numerous genes. Because of the importance of brd4 in tumorigenesis, much research has been undertaken to develop brd4 inhibitors with therapeutic potential. As a result, various scaffolds for bromodomain inhibitors have been identified. To discover new scaffolds, we performed mid-throughput screening using two different enzyme assays, alpha-screen and ELISA. We found a novel bromodomain inhibitor with a unique scaffold, aristoyagonine. This natural compound showed inhibitory activity in vitro and tumor growth inhibition in a Ty82-xenograft mouse model. In addition, we tested Brd4 inhibitors in gastric cancer cell lines, and found that aristoyagonine exerted cytotoxicity not only in I-BET-762-sensitive cancer cells, but also in I-BET-762-resistant cancer cells. This is the first paper to describe a natural compound as a Brd4 bromodomain inhibitor.

From imaging to reimbursement: what the pediatric radiologist needs to know about health care payers, documentation, coding and billing.

Medical coding and billing processes in the United States are complex, cumbersome and poorly understood by radiologists. Despite the direct implications of radiology documentation on reimbursement, trainees and practicing radiologists typically receive limited relevant training. This article summarizes the payer structure including the state-based Children's Health Insurance Programs, discusses the essential processes by which radiologists request and receive reimbursement, details the mechanisms of coding diagnoses using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes and imaging services using Current Procedural Terminology (CPT) and Healthcare Common Procedure Coding System (HCPCS) codes, and explores reimbursement and coding-related issues specific to pediatric radiology. Appropriate documentation, informed by knowledge of coding, billing and reimbursement fundamentals, facilitates appropriate payment for clinically relevant services provided by pediatric radiologists.

Arabian Sea tropical cyclones intensified by emissions of black carbon and other aerosols.

Throughout the year, average sea surface temperatures in the Arabian Sea are warm enough to support the development of tropical cyclones, but the atmospheric monsoon circulation and associated strong vertical wind shear limits cyclone development and intensification, only permitting a pre-monsoon and post-monsoon period for cyclogenesis. Thus a recent increase in the intensity of tropical cyclones over the northern Indian Ocean is thought to be related to the weakening of the climatological vertical wind shear. At the same time, anthropogenic emissions of aerosols have increased sixfold since the 1930s, leading to a weakening of the southwesterly lower-level and easterly upper-level winds that define the monsoonal circulation over the Arabian Sea. In principle, this aerosol-driven circulation modification could affect tropical cyclone intensity over the Arabian Sea, but so far no such linkage has been shown. Here we report an increase in the intensity of pre-monsoon Arabian Sea tropical cyclones during the period 1979-2010, and show that this change in storm strength is a consequence of a simultaneous upward trend in anthropogenic black carbon and sulphate emissions. We use a combination of observational, reanalysis and model data to demonstrate that the anomalous circulation, which is radiatively forced by these anthropogenic aerosols, reduces the basin-wide vertical wind shear, creating an environment more favourable for tropical cyclone intensification. Because most Arabian Sea tropical cyclones make landfall, our results suggest an additional impact on human health from regional air pollution.

Prognostic significance of microvascular invasion in tumor stage for hepatocellular carcinoma.

BACKGROUND: The presence of microvascular invasion (McVI) in hepatocellular carcinoma (HCC) has been proposed as a cause of recurrence and poor survival, although this has not been officially emphasized in staging systems. Thus, we conducted a retrospective study to investigate the prognostic importance of McVI in tumor staging in patients with HCC who underwent hepatic resection. METHODS: A retrospective analysis was performed of patients who underwent hepatic resection for HCC at our center from 1994 to 2012. Patients with HCC were classified into four groups based on the presence of McVI and extent of gross vascular invasion (VI). RESULTS: The 5-year overall and recurrence-free survival rates of 676 patients were 63.3 and 42.6%, respectively. There was no difference in tumor recurrence or survival rate between patients with HCC and McVI without gross VI and those with gross VI confined to segmental/sectional branches. Multivariate analysis revealed that the extent of VI based on the presence of McVI and gross VI was independently associated with tumor recurrence and overall survival. CONCLUSIONS: McVI was revealed to be an important risk factor similar to gross VI confined to a segmental/sectional branch in patients with HCC who underwent hepatic resection. This finding should be considered when estimating the stage for prognosis.

Mucosa-associated lymphoid tissue (MALT) lymphoma as an unusual cause of malignant hilar biliary stricture: a case report with literature review.

BACKGROUND: Biliary strictures at the hilum of the liver arise from heterogeneous etiologies. The majority is malignant entities, but some may have benign etiologies. It is difficult to distinguish between malignant and benign biliary strictures preoperatively. It has been reported that 5~15 % of preoperative diagnoses of hilar cholangiocarcinoma turn out to be benign lesions or even other types of malignancies. Primary non-Hodgkin's lymphoma of the extrahepatic bile duct is very rare, with only a few cases reported as mucosa-associated lymphoid tissue (MALT) lymphoma arising from the hepatic duct bifurcation. We herein report a case of a female patient presenting with perihilar bile ducts obstructed by primary MALT lymphoma resembling hilar cholangiocarcinoma, along with a review of the literature. CASE PRESENTATION: An 86-year-old female was referred to our hospital manifesting obstructive jaundice and abdominal pain. The reported imaging studies revealed distended intrahepatic bile duct with the stricture of common hepatic duct including bifurcation, which was suspicious of cholangiocarcinoma of the bile duct. The initial laboratory-confirmed cholestasis with a total bilirubin of 8.6 mg/dL, aspartate amino transferase (AST) 178 U/L, alanine transferase (ALT) 105 U/L, and the tumor marker CA 19-9 was elevated with a value of 167 U/mL. Viral markers for hepatitis B and C viruses were negative. She underwent extrahepatic bile duct resection and hepaticojejunostomy. Histological examination of the resected specimen revealed MALT lymphoma. Postoperative follow-up of 1 year has been completely uneventful, without any symptoms or disease recurrence. CONCLUSIONS: In exceptional cases, in which radiologic and clinical features point to cholangiocarcinoma, the actual reason for obstructive jaundice and abdominal pain can be a non-Hodgkin's lymphoma. In the case of a MALT lymphoma, it can be cured with complete resection.

Observationally constrained estimates of carbonaceous aerosol radiative forcing.

Carbonaceous aerosols (CA) emitted by fossil and biomass fuels consist of black carbon (BC), a strong absorber of solar radiation, and organic matter (OM). OM scatters as well as absorbs solar radiation. The absorbing component of OM, which is ignored in most climate models, is referred to as brown carbon (BrC). Model estimates of the global CA radiative forcing range from 0 to 0.7 Wm(-2), to be compared with the Intergovernmental Panel on Climate Change's estimate for the pre-Industrial to the present net radiative forcing of about 1.6 Wm(-2). This study provides a model-independent, observationally based estimate of the CA direct radiative forcing. Ground-based aerosol network data is integrated with field data and satellite-based aerosol observations to provide a decadal (2001 through 2009) global view of the CA optical properties and direct radiative forcing. The estimated global CA direct radiative effect is about 0.75 Wm(-2) (0.5 to 1.0). This study identifies the global importance of BrC, which is shown to contribute about 20% to 550-nm CA solar absorption globally. Because of the inclusion of BrC, the net effect of OM is close to zero and the CA forcing is nearly equal to that of BC. The CA direct radiative forcing is estimated to be about 0.65 (0.5 to about 0.8) Wm(-2), thus comparable to or exceeding that by methane. Caused in part by BrC absorption, CAs have a net warming effect even over open biomass-burning regions in Africa and the Amazon.

Enzymatic prenylation and oxime ligation for the synthesis of stable and homogeneous protein-drug conjugates for targeted therapy.

Targeted therapy based on protein-drug conjugates has attracted significant attention owing to its high efficacy and low side effects. However, efficient and stable drug conjugation to a protein binder remains a challenge. Herein, a chemoenzymatic method to generate highly stable and homogenous drug conjugates with high efficiency is presented. The approach comprises the insertion of the CaaX sequence at the C-terminal end of the protein binder, prenylation using farnesyltransferase, and drug conjugation through an oxime ligation reaction. MMAF and an EGFR-specific repebody are used as the antitumor agent and protein binder, respectively. The method enables the precisely controlled synthesis of repebody-drug conjugates with high yield and homogeneity. The utility of this approach is illustrated by the notable stability of the repebody-drug conjugates in human plasma, negligible off-target effects, and a remarkable antitumor activity in vivo. The present method can be widely used for generating highly homogeneous and stable PDCs for targeted therapy.

IRE1 plays an essential role in ER stress-mediated aggregation of mutant huntingtin via the inhibition of autophagy flux.

Huntington's disease (HD), an inherited neurodegenerative disorder, is caused by an expansion of cytosine-adenine-guanine repeats in the huntingtin gene. The aggregation of mutant huntingtin (mtHTT) and striatal cell loss are representative features to cause uncontrolled movement and cognitive defect in HD. However, underlying mechanism of mtHTT aggregation and cell toxicity remains still elusive. Here, to find new genes modulating mtHTT aggregation, we performed cell-based functional screening using the cDNA expression library and isolated IRE1 gene, one of endoplasmic reticulum (ER) stress sensors. Ectopic expression of IRE1 led to its self-activation and accumulated detergent-resistant mtHTT aggregates. Treatment of neuronal cells with ER stress insults, tunicamycin and thapsigargin, increased mtHTT aggregation via IRE1 activation. The kinase activity of IRE1, but not the endoribonuclease activity, was necessary to stimulate mtHTT aggregation and increased death of neuronal cells, including SH-SY5Y and STHdhQ111/111 huntingtin knock-in striatal cells. Interestingly, ER stress impaired autophagy flux via IRE1-TRAF2 pathway, thus enhancing cellular accumulation of mtHTT. Atg5 deficiency in M5-7 cells increased mtHTT aggregation but blocked ER stress-induced mtHTT aggregation. Further, ER stress markers including p-IRE1 and autophagy markers such as p62 were up-regulated exclusively in the striatal tissues of HD mouse models and in HD patients. Moreover, down-regulation of IRE1 expression rescues the rough-eye phenotype by mtHTT in a HD fly model. These results suggest that IRE1 plays an essential role in ER stress-mediated aggregation of mtHTT via the inhibition of autophagy flux and thus neuronal toxicity of mtHTT aggregates in HD.

Biomedical applications of graphene and graphene oxide.

Graphene has unique mechanical, electronic, and optical properties, which researchers have used to develop novel electronic materials including transparent conductors and ultrafast transistors. Recently, the understanding of various chemical properties of graphene has facilitated its application in high-performance devices that generate and store energy. Graphene is now expanding its territory beyond electronic and chemical applications toward biomedical areas such as precise biosensing through graphene-quenched fluorescence, graphene-enhanced cell differentiation and growth, and graphene-assisted laser desorption/ionization for mass spectrometry. In this Account, we review recent efforts to apply graphene and graphene oxides (GO) to biomedical research and a few different approaches to prepare graphene materials designed for biomedical applications. Because of its excellent aqueous processability, amphiphilicity, surface functionalizability, surface enhanced Raman scattering (SERS), and fluorescence quenching ability, GO chemically exfoliated from oxidized graphite is considered a promising material for biological applications. In addition, the hydrophobicity and flexibility of large-area graphene synthesized by chemical vapor deposition (CVD) allow this material to play an important role in cell growth and differentiation. The lack of acceptable classification standards of graphene derivatives based on chemical and physical properties has hindered the biological application of graphene derivatives. The development of an efficient graphene-based biosensor requires stable biofunctionalization of graphene derivatives under physiological conditions with minimal loss of their unique properties. For the development graphene-based therapeutics, researchers will need to build on the standardization of graphene derivatives and study the biofunctionalization of graphene to clearly understand how cells respond to exposure to graphene derivatives. Although several challenging issues remain, initial promising results in these areas point toward significant potential for graphene derivatives in biomedical research.

Intraosseous vascular malformation of the skull: a case report and literature review.

A 59-year-old woman presented to our clinic with a 3.5× 3-cm protruding mass on her forehead. A skull X-ray revealed a radiolucent osteolytic lesion on the left side of the frontal bone. Additionally, computed tomography showed a 3.1× 1.7× 3.6-cm mass exhibiting a "sunburst" pattern situated between the outer and inner tables of the skull, just superior and lateral to the left frontal sinus. This pattern suggested the presence of an intraosseous vascular malformation (IVM). The lesion was approached via a bicoronal incision. En-bloc resection was performed, removing the mass along with approximately 0.5 cm of the surrounding normal bone without injury to the exposed frontal sinus mucosa. The exposed mucosa was reinforced with a galeal flap, and cranioplasty with bone cement was performed to repair the resulting bony defect. Pathological examination confirmed a diagnosis of intraosseous cavernous-type malformation with mixed cavernous and capillary histological features. We report this case of IVM and review the existing literature, highlighting the satisfactory functional and aesthetic outcomes after surgery.

Sural nerve grafts in subacute facial nerve injuries: a report of two cases.

Because facial nerve injuries affect the quality of life, leaving them untreated can have devastating effects. The number of patients with traumatic and iatrogenic facial nerve paralysis is considerably high. Early detection and prompt treatment during the acute injury phase are crucial, and immediate surgical treatment should be considered when complete facial nerve injury is suspected. Symptom underestimation by patients and clinical misdiagnosis may delay surgical intervention, which may negatively affect outcomes and in some cases, impair the recovery of the injured facial nerve. Here, we report two cases of facial nerve injury that were treated with nerve grafts during the subacute phase. In both cases, subacute facial nerve grafting achieved significant improvements. These cases highlight surgical intervention in the subacute phase using nerve grafts as an appropriate treatment for facial nerve injuries.

Pott's puffy tumor of the upper eyelid misdiagnosed as simple abscess: a case report and literature review.

A 76-year-old woman, initially thought to have a simple abscess on her right upper eyelid, presented to our department of plastic and reconstructive surgery. Enhanced three-dimensional facial computed tomography (CT) revealed an abscess on the right upper lid, with a pyomucocele present in the right frontal sinus, accompanied by bone erosion in the superior wall of the right orbit. Based on the results of the CT scan, we diagnosed an atypical Pott's puffy tumor (PPT) with an abscess on the upper lid originating from the frontal sinusitis. First, surgical incision and drainage were performed in our department, and a percutaneous vacuum drain was placed. To provide a more definitive treatment, endoscopic sinus surgery (ESS) was subsequently performed by otorhinolaryngologists. The patient was discharged without any complications 5 days after ESS. At a 1-year follow-up, no recurrence or notable neurological symptoms were observed. In the case we observed, the patient presented with an upper eyelid abscess and cellulitis, indicating possible orbital involvement. For such patients, a CT scan is necessary. Given the possibility of PPT, it is critical to perform a comprehensive differential diagnosis rather than defaulting to a straightforward approach involving abscess treatment.

Genetic characterization and pathogenicity in a mouse model of newly isolated bat-originated mammalian orthoreovirus in South Korea.

Mammalian orthoreoviruses (MRVs) infect a wide range of hosts, including humans, livestock, and wildlife. In the present study, we isolated a novel Mammalian orthoreovirus from the intestine of a microbat (Myotis aurascens) and investigated its biological and pathological characteristics. Phylogenetic analysis indicated that the new isolate was serotype 2, sharing the segments with those from different hosts. Our results showed that it can infect a wide range of cell lines from different mammalian species, including human, swine, and non-human primate cell lines. Additionally, media containing trypsin, yeast extract, and tryptose phosphate broth promoted virus propagation in primate cell lines and most human cell lines, but not in A549 and porcine cell lines. Mice infected with this strain via the intranasal route, but not via the oral route, exhibited weight loss and respiratory distress. The virus is distributed in a broad range of organs and causes lung damage. In vitro and in vivo experiments also suggested that the new virus could be a neurotropic infectious strain that can infect a neuroblastoma cell line and replicate in the brains of infected mice. Additionally, it caused a delayed immune response, as indicated by the high expression levels of cytokines and chemokines only at 14 days post-infection (dpi). These data provide an important understanding of the genetics and pathogenicity of mammalian orthoreoviruses in bats at risk of spillover infections.IMPORTANCEMammalian orthoreoviruses (MRVs) have a broad range of hosts and can cause serious respiratory and gastroenteritis diseases in humans and livestock. Some strains infect the central nervous system, causing severe encephalitis. In this study, we identified BatMRV2/SNU1/Korea/2021, a reassortment of MRV serotype 2, isolated from bats with broad tissue tropism, including the neurological system. In addition, it has been shown to cause respiratory syndrome in mouse models. The given data will provide more evidence of the risk of mammalian orthoreovirus transmission from wildlife to various animal species and the sources of spillover infections.