L-Ergothioneine slows the progression of age-related hearing loss in CBA/CaJ mice.

The naturally occurring amino acid, l-ergothioneine (EGT), has immense potential as a therapeutic, having shown promise in the treatment of other disease models, including neurological disorders. EGT is naturally uptaken into cells via its specific receptor, OCTN1, to be utilized by cells as an antioxidant and anti-inflammatory. In our current study, EGT was administered over a period of 6 months to 25-26-month-old CBA/CaJ mice as a possible treatment for age-related hearing loss (ARHL), since presbycusis has been linked to higher levels of cochlear oxidative stress, apoptosis, and chronic inflammation. Results from the current study indicate that EGT can prevent aging declines of some key features of ARHL. However, we found a distinct sex difference for the response to the treatments, for hearing - Auditory Brainstem Responses (ABRs) and Distortion Product Otoacoustic Emissions (DPOAEs). Males exhibited lower threshold declines in both low dose (LD) and high dose (HD) test groups throughout the testing period and did not display some of the characteristic aging declines in hearing seen in Control animals. In contrast, female mice did not show any therapeutic effects with either treatment dose. Further confirming this sex difference, EGT levels in whole blood sampling throughout the testing period showed greater uptake of EGT in males compared to females. Additionally, RT-PCR results from three tissue types of the inner ear confirmed EGT activity in the cochlea in both males and females. Males and females exhibited significant differences in biomarkers related to apoptosis (Cas-3), inflammation (TNF-a), oxidative stress (SOD2), and mitochondrial health (PGC1a).These changes were more prominent in males as compared to females, especially in stria vascularis tissue. Taken together, these findings suggest that EGT has the potential to be a naturally derived therapeutic for slowing down the progression of ARHL, and possibly other neurodegenerative diseases. EGT, while effective in the treatment of some features of presbycusis in aging males, could also be modified into a general prophylaxis for other age-related disorders where treatment protocols would include eating a larger proportion of EGT-rich foods or supplements. Lastly, the sex difference discovered here, needs further investigation to see if therapeutic conditions can be developed where aging females show better responsiveness to EGT.

Effectiveness of a standardized quality control management procedure for COVID-19 RT-PCR testing: a large-scale diagnostic accuracy study in China.

BACKGROUND: The study aimed to construct a standardized quality control management procedure (QCMP) and access its accuracy in the quality control of COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR). METHODS: Considering the initial RT-PCR results without applying QCMP as the gold standard, a large-scale diagnostic accuracy study including 4,385,925 participants at three COVID-19 RT-PCR testing sites in China, Foshan (as a pilot test), Guangzhou and Shenyang (as validation sites), was conducted from May 21, 2021, to December 15, 2022. RESULTS: In the pilot test, the RT-PCR with QCMP had a high accuracy of 99.18% with 100% specificity, 100% positive predictive value (PPV), and 99.17% negative predictive value (NPV). The rate of retesting was reduced from 1.98% to 1.16%. Its accuracy was then consistently validated in Guangzhou and Shenyang. CONCLUSIONS: The RT-PCR with QCMP showed excellent accuracy in identifying true negative COVID-19 and relieved the labor and time spent on retesting.

Genomic and proteomic characterization of Philadelphia-like B-lineage acute lymphoblastic leukemia: A report of Indian patients.

BACKGROUND: The gold standard for the identification of Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) patients is gene expression profiling. Because of its diverse nature, its identification is extremely difficult and expensive. On the genomic and proteomic landscape of Ph-like ALL patients, there is a paucity of published literature from developing countries. METHODS: The authors used digital barcoded nCounter NanoString gene expression profiling for its detection, followed by molecular and proteomic characterization using fluorescence in situ hybridization and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The authors found 32.05% Ph-like ALL patients and their median age at presentation was considerably higher than Ph-negative ALL cases (p = .0306). Furthermore, we identified 20% CRLF2 overexpressed cases having 8.33% CRLF2-IGH translocation with concomitant R683S mutation and 8.33% CRLF2-P2RY8 translocation. In 80% of CRLF2 downregulated cases, we identified 10% as having JAK2 rearrangement. Minimal residual disease-positivity was more common in Ph-like ALL cases (55.55% vs. 25% in Ph-negative ALL cases). Immunoglobulin J chain (Jchain), small nuclear ribonucleoprotein SmD1 (SNRPD1), immunoglobulin κ constant (IGKC), NADH dehydrogenase (ubiquinone) 1 α subcomplex subunit 2 (NDUFA2), histone H2AX (H2AFX), charged multivesicular body protein 4b (CHMP4B), and carbonyl reductase (NADPH) (CBR1) proteins were identified to be substantially expressed in Ph-like ALL patients, using LC-MS/MS. Gene enrichment analysis indicated that involvement of spliceosomal mediated messenger RNA splicing pathway and four microRNAs was statistically significant in Ph-like ALL patients. CONCLUSIONS: For the first time, we have described incidence, molecular, and proteomic characterization of Ph-like ALL, in developing nations. PLAIN LANGUAGE SUMMARY: In developing countries, detecting Philadelphia (Ph)-like B-lineage acute lymphoblastic leukemia is complicated and challenging due to its diverse genetic landscape. There is no well-defined and cost-effective methodology for its detection. The incidence of this high-risk subtype is very high in adult cases, and there is an urgent need for its accurate detection. We have developed an online PHi-RACE classifier for its rapid detection, followed by delineating the genomic and proteomic landscape of Ph-like acute lymphoblastic leukemias for the first time in Indian patients.

Cost-Benefit of Real-Time Multiplex PCR Testing of SARS-CoV-2 in German Hospitals.

BACKGROUND: The current Omicron COVID-19 pandemic has significant morbidity worldwide. OBJECTIVE: Assess the cost-benefit relation of implementing PCR point-of-care (POCT) COVID-19 testing in the emergency rooms (ERs) of German hospitals and in the case of inpatient admission due to other acute illnesses. METHODS: A deterministic decision-analytic model simulated the incremental costs of using the Savanna® Multiplex RT-PCR test compared to using clinical judgement alone to confirm or exclude COVID-19 in adult patients in German ERs prior to hospitalization or just prior to discharge. Direct and indirect costs were evaluated from the hospital perspective. Nasal or nasopharyngeal swabs of patients suspected to have COVID-19 by clinical judgement, but without POCT, were sent to external labs for RT-PCR testing. RESULTS: In probabilistic sensitivity analysis, assuming a COVID-19 prevalence ranging between 15.6-41.2% and a hospitalization rate between 4.3-64.3%, implementing the Savanna® test saved, on average, €107 as compared to applying the clinical-judgement-only strategy. A revenue loss of €735 can be avoided when SARS-CoV-2 infection in patients coming unplanned to the hospital due to other acute illnesses are excluded immediately by POCT. CONCLUSIONS: Using highly sensitive and specific PCR-POCT in patients suspected of COVID-19 infection at German ERs may significantly reduce hospital expenditures.

Dengue Burden and Circulation of Dengue-2 Serotype Among Children Along With Clinical Profiling in Uttarakhand, India: A Cross-Sectional Study From 2018 to 2020.

BACKGROUND: The multiple serotypes of the dengue virus (DENV) are always a major public concern for dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). OBJECTIVE: This study aimed to analyse the demographic characteristics and circulating serotypes of dengue among the paediatric age group. METHODOLOGY: One hundred forty-one clinically suspected children were enrolled in the study from 2018 to 2020 in a tertiary care hospital in Uttarakhand, India. Central tendency, frequency, and One-Way ANOVA were measured for continuous and categorical data. The Shapiro-Wilks test was used to calculate the normality assumption. Dengue NS1 Ag, IgM, and IgG antibodies ELISA were performed, and NS1-positive samples were further tested for molecular studies. RESULT: From one hundred forty-one suspected cases, 100 (70.92%) came positive for dengue NS1 antigen, 18 (12.76%), and three (2.12%) came positive for IgM and IgG antibodies respectively. Rest 20 (14.18%) samples came negative for dengue. Fever with chills (97.5%), headache (89%), and arthralgia (82%) were the most common clinical features. Molecular studies showed the dengue serotype-2 (DEN-2) was found in most cases, followed by the dengue-3 serotype (DEN-3). CONCLUSION: This is the preliminary study as the authors' best knowledge which demonstrate the burden of dengue in children with prevalent serotypes for consecutive three years in Uttarakhand. This study identifies that the serotype-2 (DEN-2) of the dengue virus was the primary cause of infection in children at the tertiary care hospital in northern India. These results will help further to understand the nature of the disease so that improved patient care management will imply. Further molecular studies on large sample sizes during the endemic would be helpful to gain knowledge of the actual load of the disease and the genetic characteristics of the virus.

Diagnostic accuracy of autoverification and guidance system for COVID-19 RT-PCR results.

Background: To date, most countries worldwide have declared that the pandemic of COVID-19 is over, while the WHO has not officially ended the COVID-19 pandemic, and China still insists on the personalized dynamic COVID-free policy. Large-scale nucleic acid testing in Chinese communities and the manual interpretation for SARS-CoV-2 nucleic acid detection results pose a huge challenge for labour, quality and turnaround time (TAT) requirements. To solve this specific issue while increase the efficiency and accuracy of interpretation, we created an autoverification and guidance system (AGS) that can automatically interpret and report the COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) results relaying on computer-based autoverification procedure and then validated its performance in real-world environments. This would be conductive to transmission risk prediction, COVID-19 prevention and control and timely medical treatment for positive patients in the context of the predictive, preventive and personalized medicine (PPPM). Methods: A diagnostic accuracy test was conducted with 380,693 participants from two COVID-19 test sites in China, the Hong Kong Hybribio Medical Laboratory (n = 266,035) and the mobile medical shelter at a Shanghai airport (n = 114,658). These participants underwent SARS-CoV-2 RT-PCR from March 28 to April 10, 2022. All RT-PCR results were interpreted by laboratorians and by using AGS simultaneously. Considering the manual interpretation as gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were applied to evaluate the diagnostic value of the AGS on the interpretation of RT-PCR results. Results: Among the 266,035 samples in Hong Kong, there were 16,356 (6.15%) positive, 231,073 (86.86%) negative, 18,606 (6.99%) indefinite, 231,073 (86.86%, negative) no retest required and 34,962 (13.14%, positive and indefinite) retest required; the 114,658 samples in Shanghai consisted of 76 (0.07%) positive, 109,956 (95.90%) negative, 4626 (4.03%) indefinite, 109,956 (95.90%, negative) no retest required and 4702 (4.10%, positive and indefinite) retest required. Compared to the fashioned manual interpretation, the AGS is a procedure of high accuracy [99.96% (95%CI, 99.95-99.97%) in Hong Kong and 100% (95%CI, 100-100%) in Shanghai] with perfect sensitivity [99.98% (95%CI, 99.97-99.98%) in Hong Kong and 100% (95%CI, 100-100%) in Shanghai], specificity [99.87% (95%CI, 99.82-99.90%) in Hong Kong and 100% (95%CI, 99.92-100%) in Shanghai], PPV [99.98% (95%CI, 99.97-99.99%) in Hong Kong and 100% (95%CI, 99.99-100%) in Shanghai] and NPV [99.85% (95%CI, 99.80-99.88%) in Hong Kong and 100% (95%CI, 99.90-100%) in Shanghai]. The need for manual interpretation of total samples was dramatically reduced from 100% to 13.1% and the interpretation time fell from 53 h to 26 min in Hong Kong; while the manual interpretation of total samples was decreased from 100% to 4.1% and the interpretation time dropped from 20 h to 16 min at Shanghai. Conclusions: The AGS is a procedure of high accuracy and significantly relieves both labour and time from the challenge of large-scale screening of SARS-CoV-2 using RT-PCR. It should be recommended as a powerful screening, diagnostic and predictive system for SARS-CoV-2 to contribute timely the ending of the COVID-19 pandemic following the concept of PPPM.

Detection of Apparent Early Rabies Infection by LN34 Pan-Lyssavirus Real-Time RT-PCR Assay in Pennsylvania.

The Pennsylvania Department of Health Bureau of Laboratories (PABOL) tested 6855 animal samples for rabies using both the direct fluorescent antibody test (DFA) and LN34 pan-lyssavirus reverse transcriptase quantitative PCR (RT-qPCR) during 2017-2019. Only two samples (0.03%) were initially DFA negative but positive by LN34 RT-qPCR. Both cases were confirmed positive upon re-testing at PABOL and confirmatory testing at the Centers for Disease Control and Prevention by LN34 RT-qPCR and DFA. Rabies virus sequences from one sample were distinct from all positive samples processed at PABOL within two weeks, ruling out cross-contamination. Levels of rabies virus antigen and RNA were low in all brain structures tested, but were higher in brain stem and rostral spinal cord than in cerebellum, hippocampus or cortex. Taken together, the low level of rabies virus combined with higher abundance in more caudal brain structures suggest early infection. These cases highlight the increased sensitivity and ease of interpretation of LN34 RT-qPCR for low positive cases.

PCR to CRISPR: Role of Nucleic Acid Tests (NAT) in detection of COVID-19.

COVID-19 infection has emerged as an unparalleled pandemic with morbidity and mortality tolls challenging diagnostic approaches and therapeutic interventions, and raising serious questions for healthcare policy-makers. From the diagnostic perspective, Reverse transcriptase polymerase chain reaction remains the gold standard. However, issues associated with gene primer variation in different countries, low analytical sensitivity, cross-reactivity with certain human coronaviruses have raised serious concerns within the scientific community. Alongside longer turnaround times, requirements of sophisticated equipment and trained technicians are the other challenges for conventional reverse transcriptase polymerase chain reaction testing. The recent biotechnological boom has now allowed newer nucleic acid testing options for diagnosing severe acute respiratory syndrome Coronovairus 2 (SARS-CoV2) with much better diagnostic efficiency, reduced turnaround times and possible benefit for use as a point-of-care test. Isothermal techniques with simple equipment requirements along with uniform temperature for analysis have emerged to be more sensitive and specific with turnaround times as low as 10-15 minutes. Similarly, Cluster Regularly Interspaced Short Palindromic Repeats have also been seen to play a very decisive role in COVID-19 diagnostics with much superior diagnostic efficiency and feasibility as a point-of-care test and its possible use for sequencing. The current narrative review was planned to consolidate data for all possible nucleic acid testing options under research/clinical use, and to provide a comparative assessment from the perspective of both the clinician and the laboratory.

Serum albumin levels monitoring in ICU in early days and mortality risk association in patients with moderate to severe COVID-19 pneumonia.

Objective: To establish correlation between serum albumin during early days of ICU admission and risk of death in COVID-19 pneumonia. Methods: In this retrospective study, we included 76 patients hospitalized in ICU, who stayed for at least four days with COVID-19 pneumonia, from May 1, 2020 to June 30, 2020 in Lahore Health Care Hospital and Al-Shafi Hospital. Patients were labelled as COVID-19 pneumonia on radiological basis as bilateral 'ground-glass opacity' in lower zones and RT-PCR positive result in nasopharyngeal swab. All patients were oxygen dependent, either on high flow oxygen via non rebreathing mask or invasive positive pressure ventilation support. Serum albumin levels were measured daily from first day to fourth day of ICU admission. The data was analyzed using SPSS version 26 and Microsoft excel 2016. Results: Out of 76 patients of COVID-19 pneumonia admitted in ICU who stayed for more than four days, 38 patients expired. The mean age of all the patients was 58.9±12.56 years, 38(50%) of the patients were ≥60 years and 49 (62%) of them were male. On day four of ICU admission, mean serum albumin of discharged patients was 3.83±0.22 g/dl while mean serum albumin level of expired patients was 2.96±0.46 g/dl. Strong negative correlation (r = -767) was found between decrease in serum albumin level and increase number of deaths from COVID-19 pneumonia. Weak correlation was observed between increase in serum CRP and increase number of deaths in the same patients. Conclusion: Daily monitoring of serum albumin level of COVID-19 pneumonia patients can be used as a biological marker for monitoring of cytokine storm and risk of death in COVID-19 pneumonia.

Comparison of Chest X-rays findings in COVID-19 suspected and confirmed cases at a university teaching hospital: A retrospective comparative study.

OBJECTIVES: To compare Chest X-rays findings in COVID -19 suspected and confirmed patients on RT-PCR, presented at corona filtration center, Benazir Bhutto hospital Rawalpindi. METHODS: In this study, Chest radiographs of 100 COVID-19 RT-PCR positive confirmed patients were compared with 100 RT-PCR negative suspected COVID-19 patients screened at corona filtration center, Benazir Bhutto Hospital Rawalpindi from November 2020 to December 2020. Data on demographics, presenting complaints, co-morbid, lesion characteristic, distribution and attenuation, lobar involvement, pleural effusion and lymphadenopathy were collected. Associations between imaging characteristics and COVID-19 pneumonia were analyzed with univariate and multivariate logistic regression modals. RESULTS: Chest X-rays findings revealed bilateral lung consolidation with peripheral and diffuse distribution, involving middle and lower lobe to be statistically significant (p<0.05) between RT-PCR positives and negative patients. Peripheral distribution was associated with an 11.08-fold risk in COVID-19 positive patients than diffuse distribution. Middle lobe involvement had four folds risk and lower lobe involvement had 11.04 folds risk in COVID-19 cases as compared to upper lobe involvement. Consolidation had 2.6 folds risk in COVID-19 positive cases. CONCLUSIONS: Bilateral, peripheral distribution of middle and lower lobes ground glass haze or consolidation with no pleural effusion is significantly related to COVID-19 pneumonia. Overlapping imaging features of the infectious and non-infectious COVID mimickers can be further excluded by detailed clinical evaluation and further radiological workup.

Multisystem inflammatory syndrome in neonates (MIS-N) associated with SARS-CoV2 infection: a case series.

Multisystem inflammatory syndrome in neonates (MIS-N) is hypothesised to be caused either following transplacental transfer of SARS-CoV2 antibodies or antibodies developed in the neonate after infection with SARS-CoV-2. In this paper, we aim to discuss the clinical manifestations, laboratory features, and management of neonates diagnosed with MIS-N. We collated information from five participating hospitals in western India. A cohort of newborn infants presenting with multi-system involvement, along with the presence of SARS-CoV2 antibodies, was identified. Current proposed international diagnostic criteria for MIS-N were used to group the cases into three categories of Most likely, Possible, and Unlikely MIS-N. A total of 20 cases were reported with a diagnosis of MIS-N, all having high titres of SARS CoV2 IgG antibodies and negative for SARS CoV2 antigens. Most likely MIS (n = 5) cases presented with respiratory distress (4/5), hypotension and shock (4/5), and encephalopathy (2/5). Inflammatory markers like CRP (1/5), Procalcitonin (1/5), Ferritin (3/5), D-dimer (4/5), and LDH (2/5) were found to be elevated, and four of them had significantly high levels of proBNP. The majority of them (4/5) responded to immunomodulators, three neonates were discharged home, and two died. Possible MIS infants (n = 9) presented with fever (7/9), respiratory distress (4/9), refusal to feed (6/9), lethargy (5/9), and tachycardia (3/9). ProBNP as a marker of cardiac dysfunction was noted to be elevated in four (4/9) infants, correlating with abnormal echocardiography findings in two. In the Unlikely MIS (n = 6) category, three (3/6) infants presented with respiratory distress, one (1/6) with shock and cardiac dysfunction, and only one (1/6) with fever. All of them had elevated inflammatory markers. However, there were other potential diagnoses that could have been responsible for the clinical scenarios in these six cases.   Conclusion: MIS-N requires a high index of suspicion and should be considered in a neonate presenting with two or more systems involvement, in the presence of SARS-CoV2 antibodies, along with elevated inflammatory markers, once other common neonatal conditions have been ruled out. What is Known: • Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) associated multisystem inflammatory syndrome in children (MIS-C) is  widely reported in paediatric population, however only few reports of newborn affection. • MIS-C is known to cause by virus-induced post-infective antibody mediated immune dysregulation with severe multi-system affection. What is New: • MIS-N may present with varied clinical manifestations with multi-system involvement of variable severity with milder disease in term and severe disease with cardiac dysfunction in preterm newborns. • Multisystem inflammatory syndrome in newborns (MIS-N) is postulated to occur following immune dysregulation associated with transplacental transfer of SARS-CoV2 antibodies or antibodies developed in the neonate after infection with SARS-CoV-2.

Point-of-care COVID-19 antigen testing in German emergency rooms - a cost-benefit analysis.

BACKGROUND: The current COVID-19 pandemic is causing significant morbidity and death worldwide and produces significant socio-economic losses. OBJECTIVE: To assess the cost-benefit relation of implementing point-of-care COVID-19 antigen testing (POCT) in emergency rooms (ER) of German hospitals. METHODS: A deterministic decision-analytic model simulated the incremental costs of using the Sofia® SARS Antigen FIA test compared to those of using clinical judgement alone to confirm or exclude COVID-19 in adult patients in German ER, prior to hospitalization. Direct and indirect costs, with and without subsequent RT-PCR confirmation, were evaluated from the hospital perspective. RESULTS: With respect to ER patients, in base-case analysis, considering a COVID-19 prevalence of 15.6% and a hospitalization rate among COVID-19 suspects of 10.1%, POCT testing reduces average costs of hospitalized patients by €213 per tested patient if nasopharyngeal swabs of patients suspected to have COVID-19 are also sent to external labs for RT-PCR testing. In probabilistic sensitivity analysis, under all reasonable assumptions, implementing the Sofia® SARS Antigen FIA saves on average about €210 as compared to applying the clinical-judgement-only strategy. The major part of cost savings, €159 or 75.9%, is due to the POC test´s high specificity resulting in a 21-fold lower proportion of unnecessary bed blocking at the first day of hospitalization. CONCLUSIONS: Using highly specific rapid COVID-19 tests in COVID-19 suspects at German ER, despite of their sub-optimal sensitivity, may significantly reduce hospital expenditure.

Management of COVID-19 on board the mixed cargo ship Aranui 5.

BACKGROUND: During cruises, the management of coronavirus disease 2019 (COVID-19) infections poses serious organizational problems such as those encountered in 2020 by the Zaandam, the aircraft carrier Charles de Gaulle or the Diamond Princess. In French Polynesia, the mixed cargo ship Aranui 5 transports both tourists and freight to the Marquesas Islands. The purpose of this article is to show how COVID-19 infections were diagnosed and contained before and after passengers boarded a cruise. MATERIALS AND METHODS: On October 15, 2020, 161 passengers including 80 crew members embarked for a 13-day voyage from Papeete to the Marquesas Islands. Prior to boarding, all passengers underwent a reverse transcriptase-polymerase chain reaction (RT-PCR) test; the tests results were all negative. On Day 0, 3, 5, 8 and 11, Biosynex® rapid antigen diagnostic tests were carried out on all or some of the crew members and tourists who may have had contact with new positive cases. Each day, forehead or temporal temperatures were measured using an infrared thermometer and questions were asked concerning the subjects' health status. When a subject was positive, the person and their contacts were isolated in individual cabins. The infected person then left the vessel to be received in a communal reception centre on the nearest island. RESULTS: A total of 9 positive cases were observed, including two before departure (a tourist and a crew member). During the trip, 7 crew members tested positive. The patients and their contacts were isolated and then disembarked at the earliest opportunity. At the time of sampling, the subjects were asymptomatic. The patients and their contacts all became symptomatic within 24 to 48 hours after sampling. CONCLUSIONS: In total, the voyage could be completed without any transmission on board among the tourists and with a minimum transmission among the crew members, thus maintaining the tourist and economic activity of the islands during the times of COVID-19 pandemic.

Point-of-Care COVID-19 Antigen Testing in Exposed German Healthcare Workers-A Cost Model.

BACKGROUND: Hospital staffing shortages are again (mid-year 2021) becoming a significant problem as the number of positive COVID-19 cases continues to increase worldwide. OBJECTIVE: To assess the costs of sending HCW into quarantine (Scenario 1) from the hospital's and the taxpayer's perspective versus the costs arising from implementing point-of-care COVID-19 antigen testing (POCT) for those staff members who, despite learning that they have been exposed to hospital patients later found to be infected with COVID-19, continue to report to work (Scenario 2). METHODS: A mathematical model was built to calculate the costs of a sample-and-stay strategy for exposed healthcare workers (HCW) in Germany by utilizing a high-quality antigen fluorescent immunoassay (FIA), compared to the costs of quarantine. Direct costs and wage costs were evaluated from the hospital as well as from the taxpayer perspective assuming a SARS-CoV-2 infection prevalence of 10%. RESULTS: Serial POCT testing of exposed HCW in Germany (Scenario 2) who do not go into quarantine but continue to work during a post-exposure period of 14 days at their working place raises costs of EUR 289 (±20%: EUR 231 to EUR 346, rounded) per HCW at the expense of the employing hospital while the extra-costs to the taxpayer per exposed HCW are limited to EUR 16 (±20%: EUR 13 to EUR 19). In contrast, sending HCW into quarantine (Scenario 1) would result in costs of EUR 111 (±20%: EUR 89 to EUR 133) per exposed HCW for the hospital but EUR 2235 (±20%: EUR 1744 to EUR 2727) per HCW at the expense of the taxpayer. CONCLUSIONS: Monitoring exposed HCW who continued working by sequential POCT may considerably reduce costs from the perspective of the taxpayer and help mitigate personnel shortages in hospitals during pandemic COVID-19 waves.

Increased Expression of Cardiotrophin-1 in Cardiomyopathy Patients.

Cardiomyopathy (CM) is a condition of cardiac dysfunction. It is one of the leading causes of mortality in which both genetic and environmental factors are involved. Cardiotrophin-1 (CT-1) level in plasma is associated with CM. It affects the cardiomyocyte differentiation. To evaluate the expression of CT-1 in cardiomyopathy, this study was done on CM subjects attending the Fatima Memorial Hospital, Lahore, Pakistan, between January and June, 2016. A total of 40 subjects were enrolled who were divided into two groups; CM group (n = 20) and a control group (n = 20). A self-designed questionnaire was filled in by each subject to collect data regarding age, body mass index (BMI) and CM history. RNA was isolated from blood after its quantification, cDNA was prepared and reverse-transcriptase-polymerase chain reaction (RT-PCR) was performed for expression of CT-1. The mean age in CM subjects was 40.1±6.03 years, while it was 35.0±3.7 years in the control group. The mean expression of CT-1 in the CM subjects was 5.2±0.66, while it was 1.00±0.001 in the control group. A highly significant difference was observed in CT-1 expression in the CM group, and expression was significantly correlated with age and BMI in CM subjects.

Performance- and cost-benefit analysis of an influenza point-of-care test compared to laboratory-based multiplex RT-PCR in the emergency department.

INTRODUCTION: Influenza poses a heavy burden on emergency departments (ED) and hospital wards. Fast and reliable bedside tests are invaluable in obtaining indications for (cohort) droplet isolation precautions and improving patient flow. We performed a cost-benefit analysis comparing influenza point-of-care testing (POCT) to laboratory-based multiplex ligation-dependent probe amplification. METHODS: Data of 275 ED presentations between January-April 2019 were analyzed. Patients received both POCT and MLPA to calculate POCT sensitivity and specificity. Costs were calculated for both a POCT and MLPA scenario, including costs for testing, admission, droplet isolation precautions and cleaning. RESULTS: In our study population, 34 patients (12%) were identified with influenza A. No cases of influenza B were identified. Mean age of the influenza positive patients was 75(18) years and 56% were male. The most common symptoms upon presentation were cough, malaise and fever, with 74%, 56% and 50%, respectively. Compared to MLPA, POCT yielded a sensitivity of 94%, a specificity of 98% and a negative predictive value of 99% for influenza A. Using POCT yielded a cost reduction of €93,26 per patient. CONCLUSIONS: Influenza POCT is an accurate and cost-beneficial method to differentiate between admission with or without droplet isolation precautions. It can be useful in clinical decision making and reducing pressure on ED and hospital beds in an influenza peak season, by enabling fast patient flow and cohort isolation.

Commercialized diagnostic technologies to combat SARS-CoV2: Advantages and disadvantages.

The current situation of the Covid-19 pandemic is indicated by a huge number of infections, high lethality, and rapid spread. These circumstances have stopped the activity of almost the entire world, affecting severely the global economy. A rapid diagnosis of the Covid-19 and a generalized testing protocol is essential to fight against the pandemic and to maintain health control in the population. Principal biosensing and diagnostic technologies used to monitor the spread of the SARS-CoV-2 are based on specific genomic analysis and rapid immune tests, both with different technology platforms that include advantages and disadvantages. Most of the in vitro diagnosis companies are competing to be the first on validating under different regulations their technology for placing their platforms for Covid-19 detection as fast as possible in this big international market. A comprehensive analysis of the commercialized technologies for the genomic based sensing and the antibody/antigen detection methods devoted to Covid-19 diagnosis is described in this review, which have been detailed and listed under different countries regulations. The effectiveness of the described technologies throughout the different stages of the disease and a critical comparison of the emerging technologies in the market to counterattack this pandemic have been discussed.

Conservatively Treated Femoral Intertrochanteric Fracture With Early Asymptomatic Novel Coronavirus Disease 2019 (COVID-19): A Case Report.

INTRODUCTION: The ongoing outbreak of novel coronavirus disease 2019 (COVID-19) is a worldwide problem. Although diagnosing COVID-19 in fracture patients is important for selecting treatment, diagnosing early asymptomatic COVID-19 is difficult. We describe herein a rare case of femoral intertrochanteric fracture concomitant with early asymptomatic novel COVID-19. CASE PRESENTATION: An 87-year-old Japanese woman was transferred to our emergency room with a right hip pain after she fell. She had no fever, fatigue, or respiratory symptoms on admission and within the 14 days before presenting to our hospital, and no specific shadow was detected in chest X-ray. However, chest computed tomography (CT) was performed considering COVID-19 pandemic, and showed ground-glass opacities with consolidation in the dorsal segment of the right lower lung field. Then, qualitative real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) was carried out and turned out to be positive. She was diagnosed right femoral intertrochanteric fracture with concomitant COVID-19 infection. Conservative treatment was applied to the fracture due to infection. After admission, fever and oxygen demand occurred but she recovered from COVID-19. Throughout the treatment period, no cross-infection from the patient was identified in our hospital. CONCLUSION: This case highlights the importance of considering chest CT as an effective screening method for infection on hospital admission in COVID-19-affected areas, especially in trauma patients with early asymptomatic novel COVID-19.

Current role of imaging in COVID-19 infection with recent recommendations of point of care ultrasound in the contagion: a narrative review.

Radiological studies have an important role in the diagnosis and follow up of many infectious diseases. With current pandemic of Coronavirus disease 2019 (COVID-19) though the molecular analysis with reverse transcriptase polymerase chain reaction (RT-PCR) remains the cornerstone of diagnosis, the critical role of chest imaging including CT scan and baseline X-ray became apparent early in the course due to concern for less than optimal sensitivity of PCR testing. Delay in molecular diagnosis due to a shortage of testing kits and laboratory personnel also makes imaging an important modality in early diagnosis for appropriate triage and isolation decisions. CT scan technology is widely available in developed parts of the world but in developing countries, CT scanner is not widely available especially in rural settings. CT imaging usually requires patient movement to the radiology department and the scanner is not easy to disinfect. Point of care ultrasound (POCUS) has been used for many years in the assessment of critically ill patients in emergency departments and intensive care units. It is rapidly gaining popularity across many specialties and part of many general medicine training programs across the United States. It can be learned rapidly and with experienced hands, POCUS can help identify disease patterns in the lung parenchyma, and during the current pandemic has been gaining special attention. In this article, we review the most prominent imaging findings on chest X-ray and CT scan in patients with COVID-19. We also focus on the background and evolution of POCUS with studies showing the promising role of this diagnostic modality in COVID-19 infection. In addition, we describe step by step guidance on the use and disinfection of the portable ultrasound machine.

Advances in laboratory assays for detecting human metapneumovirus.

Human metapneumovirus (HMPV) is one of the major causes of acute respiratory tract infection (ARI) and shows high morbidity and mortality, particularly in children and immunocompromised patients. Various methods for detecting HMPV have been developed and applied in clinical laboratories. When reviewing the literature, we found that polymerase chain reaction (PCR)-based assays have been most frequently and consistently used to detect HMPV. The most commonly used method was multiplex reverse transcriptase-PCR (RT-PCR; 57.4%), followed by real-time RT-PCR (38.3%). Multiplex RT-PCR became the more popular method in 2011-2019 (69.7%), in contrast to 2001-2009 (28.6%). The advent of multiplex PCR in detecting broader viral pathogens in one run and coinfected viruses influenced the change in user preference. Further, newly developed microarray technologies and ionization mass spectrometry were introduced in 2011-2019. Viral culture (including shell vial assays) and fluorescent immunoassays (with or without culture) were once the mainstays. However, the percentage of studies employing culture and fluorescent immunoassays decreased from 21.4% in 2001-2010 to 15.2% in 2011-2019. Meanwhile, the use of PCR-based methods of HMPV detection increased from 78.6% in 2001-2010 to 84.8% in 2011-2019. The increase in PCR-based methods might have occurred because PCR methods demonstrated better diagnostic performance, shorter hands-on and run times, less hazards to laboratory personnel, and more reliable results than traditional methods. When using these assays, it is important to acquire a comprehensive understanding of the principles, advantages, disadvantages, and precautions for data interpretation. In the future, the combination of nanotechnology and advanced genetic platforms such as next-generation sequencing will benefit patients with HMPV infection by facilitating efficient therapeutic intervention. Analytical and clinical validation are required before using new techniques in clinical laboratories.