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Growing evidence suggest that cycle threshold (CT)-value of reverse transcription polymerase chain reaction (RT-PCR) is correlated with transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and some kits set different CT-value cut-off. This report presents the discordant results of two widely used RT-PCR kits in Indonesia due to different CT-value cut-offs and highlights its potential consequence in SARS-CoV-2 containment.Nasopharyngeal swab samples with SARS-CoV-2 negative with a RT-PCR kit (manufacture pre-set CT-value cut-off was 35 amplification cycles) were retested with another RT-PCR kit with a higher pre-set CT-value of 40 amplification cycles. All procedures were performed according to the manufacturer protocols.In total, 30 samples with SARS-CoV-2 negative for the first kit were retested. We found that 25 out of 33 samples (75.5%) were positive using the second RT-PCR kit that had a higher manufacture pre-set CT-value cut-off. In addition, among 500 RT-PCR tests using the first RT-PCR kit, 103 of them (20.6%) were categorized as inconclusive results based on the second manufacturer' guideline.Our data suggest the possibility of discordant results of SARS-CoV-2 detection due to different pre-set cut-offs by the companies. As consequence, this could leave a fraction of individuals who were misclassified that could act as source of virus transmission within community.La evidencia creciente sugiere que el valor del ciclo umbral (CT) de la RT-PCR (reacción en cadena de la polimerasa por transcripción inversa) guarda relación con la transmisión del síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV-2), y algunos kits establecen diferentes puntos de corte para dicho valor. El presente informe presenta la discordancia de los resultados de dos kits RT-PCR de amplio uso en Indonesia debido a los diferentes puntos de corte del valor CT, y subraya su consecuencia potencial para la contención del SARS-CoV-2.Se reanalizaron las muestras de los hisopos nasofaríngeos negativos para SARS-CoV-2 con un kit RT-PCR (el punto de corte del valor CT preestablecido de fábrica fue de 35 ciclos de ampliación) con otro kit para RT-PCR con un valor CT establecido superior, de 40 ciclos de ampliación. Todos los procedimientos fueron realizados con arreglo a los protocolos de fabricación.En total se reanalizaron 30 muestras con SARS-CoV-2 negativas para el primer kit. Encontramos que 25 de entre 33 muestras (75,5%) eran positivas utilizando el segundo kit para RT-PCR, que tenía un punto de corte del valor CT preestablecido superior. Además, entre las 500 pruebas RT-PCR que utilizaron el primer kit para RT-PCR, 103 de ellas (el 20,6%) fueron categorizadas como resultados no concluyentes sobre la base de la guía del segundo fabricante.Nuestros datos sugieren la posibilidad de discordancia en los resultados de detección del SARS-CoV-2 debido a los diferentes puntos de corte preestablecidos por los fabricantes. Por tanto, esto podría suponer que la mala clasificación de una parte de los individuos fuera la causa de la transmisión del virus dentro de la comunidad.

Acute coronary syndrome (ACS) is a term used to describe major cardiovascular diseases, and treatment of in-stent restenosis in patients with ACS remains a major clinical challenge. Further investigation into molecular markers of ACS may aid early diagnosis, and the treatment of ACS and post-treatment recurrence. In the present study, total RNA was extracted from the peripheral blood samples of 3 patients with ACS, 3 patients with percutaneous coronary intervention (PCI)_non-restenosis, 3 patients with PCI_restenosis and 3 healthy controls. Subsequently, RNA library construction and high-throughput sequencing were performed. DESeq2 package in R was used to screen genes that were differentially expressed between the different samples. Moreover, the intersection of the differentially expressed mRNAs (DEmRNAs) and differentially expressed long noncoding RNAs (DElncRNAs) obtained. GeneCodis4.0 was used to perform function enrichment for DEmRNAs, and lncRNA-mRNA co-expression network was constructed. The GSE60993 dataset was utilized for diagnostic analysis, and the aforementioned investigations were verified using in vitro studies. Results of the present study revealed a large number of DEmRNAs and DElncRNAs in the different groups. We selected genes in the top 10 of differential expression and also involved in the co-expression of lncRNA-mRNA for diagnostic analysis in the GSE60993 dataset. The area under curve (AUC) of PDZK1IP1 (0.747), PROK2 (0.769) and LAMP3 (0.725) were all >0.7. These results indicated that the identified mRNAs and lncRNAs may act as potential clinical biomarkers, and more specifically, PDZK1IP1, PROK2 and LAMP3 may act as potential biomarkers for the diagnosis of ACS.

Esophageal cancer has high incidence and mortality rates and a low five-year survival rate of

BACKGROUND The high mortality rate of hepatocellular carcinoma (HCC) in Egypt is due mainly to the increasing prevalence of hepatitis C virus infection (HCV) and late diagnosis of the carcinoma. MicroRNAs (miRNA), which regulate tumor proliferation and metastasis in HCC, may serve as a useful diagnostic approach for the early detection of HCC, thus decreasing its mortality. Meanwhile, endocan is a protein with angiogenic and inflammatory properties that are associated with tumor progression and poor outcomes. AIM To analyze the levels of miRNA 9-3p and endocan in HCV-infected HCC patients and correlate them with clinicopathological parameters. METHODS We compared levels of endocan and circulating miRNA 9-3p from 35 HCV-related HCC patients to 33 patients with HCV-induced chronic liver disease and 32 age and gender matched healthy controls recruited from inpatient and outpatient clinics of the National Liver Institute, Menoufia University, Egypt in the period from January to March 2021 in a case-control study. Serum samples from all groups were analyzed for HCV. Endocan was measured by enzyme-linked immunosorbent assays, and the expression levels of circulating miRNA 9-3p were measured by real-time quantitative reverse transcriptase PCR. RESULTS The levels of circulating miRNA 9-3p were significantly lower in the HCC group compared to the chronic liver disease (P < 0.001) and control (P < 0.001) groups, while levels in the chronic liver disease were significantly lower than those in the control group (P < 0.001). The levels of serum endocan were significantly higher in the HCC group compared to the chronic liver disease (P < 0.001) and control (P < 0.001) groups. Moreover miRNA 9-3p and endocan performed better than α-fetoprotein in discriminating HCC patients from cirrhosis and healthy patients. The levels of miRNA 9-3p were significantly inversely correlated to vascular invasion (P = 0.002), stage of advancement of Barcelona Clinical Liver Cancer (P < 0.001) and the metastatic site (P < 0.001) of the HCC group. CONCLUSION Circulating miRNA 9-3p and endocan can be used as novel biomarkers for the early diagnosis of HCV-related HCC.

Background Several clinical tests used to identify patients with lumbar instability have reported diagnostic accuracy in separate studies with conflicting results. To augment the diagnostic process, tests that are better able to identify lumbar instability suitable for use in the clinical setting are required. The aim of this study was to identify the probability to diagnose patients with lumbar instability, using x-ray imaging as the reference standard. Methods This study was a cross-sectional, diagnostic validity study. One hundred forty participants with chronic low back pain underwent an x-ray assessment and 14 clinical examinations. Data were analysed using multivariate regression methods to determine which clinical tests were most diagnostic for lumbar instability when they were applied together. Results Eighteen (12.85%) participants had radiological lumbar instability. Three clinical tests i) interspinous gap change during flexion-extension, ii) passive accessory intervertebral movement tests, iii) posterior shear test demonstrated an ability to diagnose lumbar instability of 67% when they were all positive. At this probability threshold, sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (−LR) were 5.56, 99.18%, 6.78, and 0.95. Conclusions These 3 clinical tests could be useful in identifying patients with lumbar instability in the general community. These three tests are simple to perform by physical therapists, reliable to use in a clinical setting, and safe for patients. We recommend physical therapists use these three tests to assess patients who are suspected of having lumbar instability, in the absence of an x-ray assessment, to receive appropriate targeted intervention or referral for further investigation. Trial registration Thai Clinial Trial Registry (TCTR 20180820001; 19th August 2018).

Liang Chen,1,&ast; Yunhua Lin,2,&ast; Guoqing Liu,2 Rubin Xu,1 Yiming Hu,3 Jiaheng Xie,4 Hongzhu Yu1 1Department of General Surgery, Fuyang Hospital Affiliated to Anhui Medical University, Fuyang, Anhui, People’s Republic of China; 2The First Clinical Medical College, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3College of Pharmacy, Jiangsu Ocean University, Lianyungang, Jiangsu, People’s Republic of China; 4Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhu YuFuyang Hospital Affiliated to Anhui Medical University, Fuyang, Anhui, People’s Republic of ChinaTel +86 177 5686 0568Email hongzhu.620929@aliyun.comJiaheng XieDepartment of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaTel +86 177 5686 0568Email xiejiaheng@njmu.edu.cnObjective: Hepatocellular Carcinoma (HCC) has the characteristics of high incidence and poor prognosis. However, the underlying mechanism of HCC has not yet been fully elucidated. This study aims to investigate the potential mechanism and clinical significance of signal sequence receptor (SSR1) in HCC through bioinformatics methods.Methods: Four online (GEPIA, TIMER, TCGA, and GEO) databases were used to explore the expression level of SSR1 in HCC. The summary receiver operating characteristic (SROC) analysis and standardized mean difference (SMD) calculation were performed further to detect its diagnostic ability and expression level. The Human Protein Atlas (HPA) database was applied to verify the level of SSR1 protein expression. Chi-square test and Fisher’s exact test were carried out to determine the clinical relevance of SSR1 expression. KM survival analysis, univariate and multivariate COX regression analyses were employed to explore the prognostic impact of SSR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA) were implemented to reveal the underlying mechanism of SSR1. Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR) was used to verify the expression of SSR1 in HCC.Results: SSR1 was significantly overexpressed in HCC (SMD=1.25, P=0.03) and had the moderate diagnostic ability (AUC=0.84). SSR1 expression was significantly correlated with T stage, Gender, Pathologic stage (All P< 0.05). Patients with high SSR1 expression had shorter overall survival (OS). Univariate and multivariate Cox regression analyses showed that high SSR1 expression was an independent risk factor for poor prognosis. KEGG analysis showed that SSR1-related genes were enriched in the cell cycle, DNA replication, and TGF-beta signaling pathway. GSEA analysis also shows that the high expression of SSR1 is related to the activation of the above three signal pathways. qRT-PCR showed that the SSR1 expression in HCC was significantly higher than the Peri-carcinoma tissue (PHCC) and the corresponding normal liver tissue.Conclusion: SSR1 expression was significantly up-regulated, and it had the potential as a biomarker for the diagnosis and prognosis of HCC. It was very likely to participate in the occurrence and development of HCC by regulating the cell cycle. In summary, our study comprehensively analyzed the clinical value of SSR1 and also conducted a preliminary study on its potential mechanism, which will provide inspiration for the in-depth study of SSR1 in HCC.Keywords: hepatocellular carcinoma, signal sequence receptor, SSR1, prognosis, diagnostic

Objective: To investigate possible differences between laboratory profiles of symptomatic and asymptomatic patients. There are different of them available for COVID-19 diagnoses and surveillance, so this research was to evaluate the positive agreement the diagnostic methods. Methods: For symptomatic patients swab samples from nasal and oral mucosal were collected between first and second week after symptoms onset, to perform RT-PCR, blood samples were collected 7 days after to perform antibody detection test. For asymptomatic patients, only antibody detection was performed to confirm the infection. We investigated specific humoral immune response for symptomatic and asymptomatic patients and also analyzed the positivity index and kappa agreement between immunochromatographic and ELISA assays. Results: Most symptomatic patients presented negative RT-PCR with IgM and IgA detection. Symptomatic and asymptomatic patients have presented elevated IgM and IgA immunoglobulins, being this detection higher in symptomatic patients. The positivity index for immunochromatographic was higher than ELISA and there was no kappa agreement between IgM and IgA detection between these two methods. Conclusion: Symptomatic patients presented higher amounts of IgM and IgA than asymptomatic, suggesting a relation between antibody quantity and severity of disease. We verified no agreement between IgM and IgA detection, and observed higher positivity index for IMMUNO when compared to ELISA. The different kinetics may cause a variation in their detection. Also, many different virus proteins can be used as antigens in these methods, being able of altering their sensibility and specificity.

The present research aims to explore the relationship between circulating microRNA and carotid artery stenosis (CAS). To evaluate the diagnostic significance of miR-637 in CAS patients and its potential predictive value for cerebral ischemia events through clinical studies. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the differences in serum miR-637 between enrolled 97 CAS patients and 90 healthy individuals. Logistic regression analysis of the correlation between the level of miR-637 and the degree of carotid artery stenosis. The receiver operating characteristic (ROC) curve evaluated the diagnostic significance of miR-637 in identifying CAS patients from healthy individuals. Kaplan-Meier survival and Cox regression were used to evaluate the potential predictive ability of serum miR-637 levels during follow-up for cerebral ischemia events. Serum miR-637 of CAS patients was significantly reduced which was a good indicator of severe carotid stenosis (P

Background Sensitivity of culture for the detection of Streptococcus pneumoniae is limited by prior antibiotic exposure. Immunochromatographic test (ICT) is highly sensitive and specific for pneumococcal antigen detection in the cerebrospinal fluid (CSF) of meningitis cases. We determined the specificity and sensitivity of culture, ICT, and polymerase chain reaction (PCR) and the effect of antibiotic exposure on their performance. Methods CSF specimens from suspected meningitis cases admitted to Dhaka Shishu Hospital, Bangladesh, were tested using culture, ICT and PCR. Additionally, 165 specimens collected from 69 pneumococcal cases after antibiotic treatment were tested. Results Of 1883 specimens tested, culture detected 9, quantitative PCR (qPCR) detected 184, and ICT detected 207 pneumococcal cases (including all culture and qPCR positives). In comparison to ICT, sensitivity of culture was 4.4% and of qPCR was 90.6%; both were 100% specific. After antibiotic exposure, culture sensitivity plummeted rapidly; conventional PCR and qPCR sensitivity disappeared after day 6 and 20, respectively. ICT detected pneumococcal antigen for >10 weeks. Conclusions While culture provides the most information about bacterial characteristics, in high antibiotic exposure settings, ICT exhibits maximum sensitivity. We recommend culture and ICT as mainstay for pneumococcal diagnosis and surveillance; qPCR can generate additional molecular data where possible.

Objective: To determine the diagnostic accuracy of modified early obstetric warning system for predicting maternal morbidity keeping ICU admission as “gold standard”. Study Design: Cross sectional validation study. Place and Duration of Study: Department of Obstetrics and Gynecology, Pak Emirates Military Hospital, Rawalpindi, from Oct 2018 to Apr 2019. Methodology: A total of 205 patients of singleton pregnancy, post-natal period

The aim of this study was to develop a diagnostic strategy for esophageal squamous cell carcinoma (ESCC) that combines plasma metabolomics with machine learning algorithms. Plasma-based untargeted metabolomics analysis was performed with samples derived from 88 ESCC patients and 52 healthy controls. The dataset was split into a training set and a test set. After identification of differential metabolites in training set, single-metabolite-based receiver operating characteristic (ROC) curves and multiple-metabolite-based machine learning models were used to distinguish between ESCC patients and healthy controls. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic significance of the plasma metabolites. Finally, twelve differential plasma metabolites (six up-regulated and six down-regulated) were annotated. The predictive performance of the six most prevalent diagnostic metabolites through the diagnostic models in the test set were as follows: arachidonic acid (accuracy: 0.887), sebacic acid (accuracy: 0.867), indoxyl sulfate (accuracy: 0.850), phosphatidylcholine (PC) (14:0/0:0) (accuracy: 0.825), deoxycholic acid (accuracy: 0.773), and trimethylamine N-oxide (accuracy: 0.653). The prediction accuracies of the machine learning models in the test set were partial least-square (accuracy: 0.947), random forest (accuracy: 0.947), gradient boosting machine (accuracy: 0.960), and support vector machine (accuracy: 0.980). Additionally, survival analysis demonstrated that acetoacetic acid was an unfavorable prognostic factor (hazard ratio (HR): 1.752), while PC (14:0/0:0) (HR: 0.577) was a favorable prognostic factor for ESCC. This study devised an innovative strategy for ESCC diagnosis by combining plasma metabolomics with machine learning algorithms and revealed its potential to become a novel screening test for ESCC., Highlights • Six most prevalent diagnostic plasma metabolites were identified in ESCC. • Plasma-metabolite-based machine learning models (PLS, RF, GBM, and SVM) for ESCC diagnosis. • Acetoacetic acid was an unfavorable prognostic factor, while PC (14:0/0:0) was a favorable prognostic factor for ESCC.

Pancreatic cancer (PC) is a leading cause of cancer related mortality on a global scale. The disease itself is associated with a dismal prognosis, partly due to its silent nature resulting in patients presenting with advanced disease at the time of diagnosis. To combat this, there has been an explosion in the last decade of potential candidate biomarkers in the research setting in the hope that a diagnostic biomarker may provide a glimmer of hope in what is otherwise quite a substantial clinical dilemma. Currently, serum carbohydrate antigen 19-9 is utilized in the diagnostic work-up of patients diagnosed with PC however this biomarker lacks the sensitivity and specificity associated with a gold-standard marker. In the search for a biomarker that is both sensitive and specific for the diagnosis of PC, there has been a paradigm shift towards a focus on liquid biopsy and the use of diagnostic panels which has subsequently proved to have efficacy in the diagnosis of PC. Currently, promising developments in the field of early detection on PC using diagnostic biomarkers include the detection of microRNA (miRNA) in serum and circulating tumour cells. Both these modalities, although in their infancy and yet to be widely accepted into routine clinical practice, possess merit in the early detection of PC. We reviewed over 300 biomarkers with the aim to provide an in-depth summary of the current state-of-play regarding diagnostic biomarkers in PC (serum, urinary, salivary, faecal, pancreatic juice and biliary fluid).

MRI has been extensively used to identify anatomical and functional differences in Autism Spectrum Disorder (ASD). Yet, many of these findings have proven difficult to replicate because studies rely on small cohorts and are built on many complex, undisclosed, analytic choices. We conducted an international challenge to predict ASD diagnosis from MRI data, where we provided preprocessed anatomical and functional MRI data from > 2,000 individuals. Evaluation of the predictions was rigorously blinded. 146 challengers submitted prediction algorithms, which were evaluated at the end of the challenge using unseen data and an additional acquisition site. On the best algorithms, we studied the importance of MRI modalities, brain regions, and sample size. We found evidence that MRI could predict ASD diagnosis: the 10 best algorithms reliably predicted diagnosis with AUC∼0.80 – far superior to what can be currently obtained using genotyping data in cohorts 20-times larger. We observed that functional MRI was more important for prediction than anatomical MRI, and that increasing sample size steadily increased prediction accuracy, providing an efficient strategy to improve biomarkers. We also observed that despite a strong incentive to generalise to unseen data, model development on a given dataset faces the risk of overfitting: performing well in cross-validation on the data at hand, but not generalising. Finally, we were able to predict ASD diagnosis on an external sample added after the end of the challenge (EU-AIMS), although with a lower prediction accuracy (AUC=0.72). This indicates that despite being based on a large multisite cohort, our challenge still produced biomarkers fragile in the face of dataset shifts.

INTRODUCTION Identification of residual disease after neuroendocrine tumor (NET) resection is critical for management. Post-surgery imaging is insensitive, expensive, and current biomarkers ineffective. We evaluated whether the NETest, a multigene liquid biopsy blood biomarker, correlated with surgical resection and could predict recurrence. METHODS Multicenter evaluation of NET resections over 24 months (n = 103): 47 pancreas, 26 small bowel, 26 lung, 2 appendix, 1 duodenum, 1 stomach. Surgery: R0 (83), R1/R2 (20). One millilitre of blood was collected at D0 and posroperative day (POD) 30. Transcript quantification by polymerase chain reaction (normal: ≤20), CgA by NEOLISA (normal ≤108 ng/mL). Standard-of-care (SoC) follow-up costs were calculated and compared to POD30 NETest-stratification approach. Analyses: Wilcoxon-paired test, Chi-square test. RESULTS D BIOMARKERS NETest: 103 of 103 (100%)-positive, whereas 23 of 103 (22%) were CgA-positive (Chi-square = 78, P < 0.0001).In the R0 group, the NETest decreased 59 ± 28 to 26 ± 23 (P < 0.0001); 36% (30/83) remained elevated. No significant decrease was evident for CgA. In the R1/R2 group the NETest decreased but 100% remained elevated. CgA levels did not decrease.An elevated POD30 NETest was present in R0 and 25 (83%) developed radiological recurrences. Normal score R0 s (n = 53) did not develop recurrence (Chi-square = 56, P < 0.0001). Recurrence prediction was 94% accurate with the NETest. COST EVALUATION Using the NETest to stratify postoperative imaging resulted in a cost-savings of 42%. CONCLUSION NETest diagnosis is more accurate than CgA (100% vs 22%). Surgery significantly decreased NETest. An elevated POD30 NETest predicted recurrence with 94% accuracy and post-surgical POD30 NETest follow-up stratification decreased costs by 42%. CgA had no surgical utility. Further studies would define the accuracy and cost-effectiveness of the NETest in the detection of postoperative recurrent disease.

The article describes the approach to the formation of a simulation model of information signals, which are typical for objects with different types of defects. The dispersive analysis of the signal spectrum components in the bases of the discrete Hartley transform and the discrete cosine transform is carried out. The analysis of the form of the reconstructed information signal is carried out depending on the number of coefficients of the spectral alignment in Hartley bases and cosine functions. The basis of orthogonal functions of a discrete argument is obtained, which can be used for the spectral transformation of information signals of a flaw detector. A method of simulation of information signals has been developed and experimentally investigated, which allows taking into account the deterministic and random components of the characteristics of real information signals. References 24, figures 13, tables 3.

Tuberculosis (TB) is a major cause of morbidity and mortality in children, and early diagnosis and treatment are crucial to reduce long-term morbidity and mortality. In this study, we explore whether urine nuclear magnetic resonance (NMR)-based metabolomics could be used to identify differences in the metabolic response of children with different diagnostic certainty of TB. We included 62 children with signs and symptoms of TB and 55 apparently healthy children. Six of the children with presumptive TB had bacteriologically confirmed TB, 52 children with unconfirmed TB, and 4 children with unlikely TB. Urine metabolic fingerprints were identified using high- and low-field proton NMR platforms and assessed with pattern recognition techniques such as principal components analysis and partial least squares discriminant analysis. We observed differences in the metabolic fingerprint of children with bacteriologically confirmed and unconfirmed TB compared to children with unlikely TB (p = 0.041 and p = 0.013, respectively). Moreover, children with unconfirmed TB with X-rays compatible with TB showed differences in the metabolic fingerprint compared to children with non-pathological X-rays (p = 0.009). Differences in the metabolic fingerprint in children with different diagnostic certainty of TB could contribute to a more accurate characterisation of TB in the paediatric population. The use of metabolomics could be useful to improve the prediction of TB progression and diagnosis in children.

INTRODUCTION : Les pneumopathies d’hypersensibilité (PHS) font partie des pneumopathies interstitielles diffuses les plus courantes. Elles sont caractérisées par une réaction inflammatoire et/ou fibrosante pulmonaire vis-à-vis d’antigènes inhalés. ÉTAT DES CONNAISSANCES : Leur hétérogénéité de présentation et l’absence de recommandations internationales rend leur prise en charge complexe. En outre, le traitement actuel, qui repose principalement sur l’éviction de l’antigène causal et les médicaments immunosuppresseurs, est moins efficace dans les formes fibrosantes de PHS. Cet article établit une synthèse des dernières données et des nouvelles recommandations de l’American Thoracic Society (ATS) sur le diagnostic des PHS. CONCLUSIONS : Les nouvelles recommandations de l’ATS établissent une approche diagnostique plus précise et plus rigoureuse des PHS. La discussion multidisciplinaire joue un rôle pivot tant dans le diagnostic que dans le traitement de la maladie. Le nintedanib a récemment fait preuve de son efficacité dans les PHS fibrosantes. PERSPECTIVES : Il demeure des incertitudes sur la stratégie thérapeutique à adopter dans les PHS fibrosantes, ce qui souligne le besoin de réaliser des études à grande échelle. [New developments in the management of hypersensitivity pneumonitis] INTRODUCTION: Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases, characterized by an inflammatory and/or fibrotic reaction to inhaled antigens. BACKGROUND: The heterogeneity of presentation and the lack of international guidelines makes management complex. In addition, the current treatment, based on antigen eviction and immunosuppressive drugs, is less effective in the fibrotic forms of HP. This article summarizes the latest data on HP and the new recommendations of the American Thoracic Society (ATS) on the diagnosis of HP. CONCLUSION: The new ATS recommendations establish a more precise and rigorous diagnostic approach to HP. Multidisciplinary discussion plays a pivotal role both in the diagnosis and the treatment of the disease. Nintedanib has recently been shown to be effective in fibrotic HP. PERSPECTIVES: Questions remain unanswered about the optimal therapeutic strategy in fibrotic HP, which underlines the need to carry out large-scale studies.

Background and Purpose Stroke is the second leading cause of death and disability worldwide and its diagnosis, and assessment of prognosis, remains challenging. There is a need for improved diagnostic and prognostic biomarkers. MicroRNAs (miRNAs) play important roles in the post-transcriptional regulation of gene expression and their secretion and remarkable stability in biofluids highlights their potential as sensitive biomarkers in the diagnosis and prognosis of acute stroke.Methods We carried out a systematic review to assess current evidence supporting the potential of miRNAs to act as unique diagnostic and prognostic biomarkers in blood samples collected from patients suffering acute stroke within 24 hours of symptoms onset.Results We identified 22 studies eligible for inclusion with 33 dysregulated miRNAs having diagnostic potential in the acute phase of the disease. We identified miR-16, miR-126, and miR-335 as having the highest sensitivity as diagnostic and prognostic biomarkers in acute ischaemic stroke and present original bioinformatic and pathway enrichment analysis of putative miRNA–target interactions.Conclusions miRNAs represent unique biomarkers which have a promising future in stroke diagnosis and prognosis. However, there is a need for more standardized and consistent methodology for the accurate interpretation and translation of miRNAs as novel specific and sensitive biomarkers into clinical practice.

In recent years, there has been a significant increase in the prevalence of diseases of the nose and paranasal sinuses. Inflammatory diseases of the mucous membrane nasal cavities (rhinitis) are most commonly characterized as a syndrome in which the patient experiences some combination of persistent nasal symptoms, including rhinorrhea, sneezing, nasal congestion, itching and burning in the nasal cavity. Among the chronic forms of rhinitis, allergic rhinitis occupies a large place along with vasomotor, infectious, hypertrophic, catarrhal and atrophic rhinitis. Allergic rhinitis is a significant social and medico-economic problem, since it significantly reduces the quality of life of patients and requires significant treatment costs. This nosology is found in the practice of doctors of all specialties, however, the correct diagnosis and the appointment of adequate therapy can take many months and years. Currently, the concept of “common airways” is widely discussed, which demonstrates the close relationship between allergic rhinitis and bronchial asthma and proves that the inflammatory response can be supported and enhanced by interrelated mechanisms. Therefore, patients with allergic rhinitis should be examined for the presence of bronchial asthma. In turn, patients with bronchial asthma need to diagnose allergic rhinitis, and treatment should be aimed at suppressing allergic inflammation in both the upper and lower respiratory tract. This article discusses modern diagnostic and therapeutic approaches to patients with these diseases, which make it possible to efficiently and timely identify allergic rhinitis and initiate appropriate adequate treatment. The article also discusses the feasibility of using combined therapy with levocetirizine and montelukast in the above nosologies.

Aetiological diagnosis of gastrointestinal infections is challenging since a wide range of bacteria, parasites and viruses can be causal agents and derived clinical manifestations appear quite similar. Our aim was to evaluate contribution of the novel QIAstat-DxGastrointestinal Panel (GIP) to aetiological diagnosis of gastrointestinal infections and rational antimicrobial prescription in a reference paediatric hospital. Evaluation included comparison of diagnostic yield and agreement of results of QIAstat-Dx GIP and conventional microbiological methods. Parallel testing was performed on stool samples collected prospectively from children admitted to Sant Joan de Deu Barcelona Hospital (Spain) during the period February–March 2019. Influence of the panel test use on antimicrobial prescription was assessed using a pre–post study design. Eighty-six (68.8%) out of 125 specimens were positive by QIAstat-Dx GIP versus 44 (35.2%) positive by a composite of conventional methods (pClostridioides difficile detection (87.5%) was greater than that with bacterial culture (76.0%) and parasite microscopic identification (64.3%). Panel test results orientated antimicrobial prescription changes in 18 (14.4%) patients, including antimicrobial start in 11 cases initially untreated, targeted antimicrobial prescription in 5 and discontinuation in 2 cases empirically treated. Results showed that QIAstat-Dx GIP significantly expanded aetiological diagnosis of gastrointestinal infections compared to conventional microbiological methods while orientating a more judicious use of antimicrobial drugs in hospitalised children.

Syphilis, is sexually transmitted disease caused by spirochete Treponema pallidum subsp.pallidum. It have many diverse clinical manifestations that occur in distinct stages. Early diagnosis and management are the main things to prevent transmission and complication. Direct test or morphological observation is the definitive diagnosis of syphilis. This can be done through animal inoculation test, dark field microscopy, direct fluorescence antibody (DFA), and nucleid acid amplification test (NAAT). While the indirect test is a nontreponemal serologic test consist of Wasserman test, venereal disease research laboratory (VDRL), toluidine red unheated serum test (TRUST), unheated serum reagin (USR), rapid plasma reagin (RPR) and treponemal serologic test, such as T. pallidum passive particle agglutination (TPPA), T. pallidum haemagglutination assay (TPHA), fluorescent treponemal antibody absorption (FTA-Abs), enzyme immunoassay (EIA) and rapid test. The algorithm of serologic test can be divided into traditional or reverse.

Cerebral sinus thrombosis or cerebral venous thrombosis (CVT) is an important cause of nontraumatic intracranial hemorrhage in younger patients. CVT is associated with multiple risk factors and clinical conditions, is often undetected or verified late, and most importantly, has a relatively good prognosis if the treatment is started early. In this review, we describe CVT epidemiology and risk factors, analyze its pathophysiology and clinical symptoms and discuss modern diagnostic approaches to diagnosis, treatment and secondary prevention. The article emphasizes the hemorrhagic presentations of CVT, which in clinical settings are difficult to diagnose and treat.

One year into the coronavirus disease 2019 (COVID‐19) pandemic, diagnostic strategies, although central for contact tracing and other preventive measures, are still limited. To meet the global demand, lower cost and faster antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) detection are a convenient alternative to the gold standard reverse transcription‐polymerase chain reaction (RT‐PCR) assay. We tested laboratory‐based RT‐PCR RNA detection and two rapid antigen detection (RAD) tests, based on the immunochromatography test for nucleocapsid protein of SARS‐CoV‐2 (COVID‐19 Ag ECO Test, ECO Diagnóstica, and Panbio COVID‐19 Ag Rapid Test Abbott). Paired collection and testing were done in a small prospective open study in three clinical services in São Paulo, constituted of mostly symptomatic volunteers at collection (97%, 109/112) for a median of 4 days (interquartile range: 3–6), ranging from 1 to 30. Among the 108 paired RT‐PCR/RAD tests, results were concordant in 96.4% (101/108). The test's performance was comparable, with an overall sensitivity of 87% and a specificity of 96%. These observations add to other data that suggest that antigen tests may provide reasonable sensitivity and specificity and deserve a role to improve testing strategies, especially in resource‐limited settings., Research Highlights Testing and isolating individuals transmitting SARS‐CoV‐2, generally with high viral load, is crucial to pandemic control.We documented comparable performance (96%) of two rapid test to standard RT‐qPCR.Lower cost and immediate results of rapid antigen tests may allow innovative containment measures or, at least, complement current testing limitations, specially in resource limited setting.

BackgroundThe Treatable ID App was created in 2012 as digital tool to improve early recognition and intervention for treatable inherited metabolic disorders (IMDs) presenting with global developmental delay and intellectual disability (collectively ‘treatable IDs’). Our aim is to update the 2012 review on treatable IDs and App to capture the advances made in the identification of new IMDs along with increased pathophysiological insights catalyzing therapeutic development and implementation.MethodsTwo independent reviewers queried PubMed, OMIM and Orphanet databases to reassess all previously included disorders and therapies and to identify all reports on Treatable IDs published between 2012 and 2021. These were included if listed in the International Classification of IMDs (ICIMD) and presenting with ID as a major feature, and if published evidence for a therapeutic intervention improving ID primary and/or secondary outcomes is available. Data on clinical symptoms, diagnostic testing, treatment strategies, effects on outcomes, and evidence levels were extracted and evaluated by the reviewers and external experts. The generated knowledge was translated into a diagnostic algorithm and updated version of the App with novel features.ResultsOur review identified 116 treatable IDs (139 genes), of which 44 newly identified, belonging to 17 ICIMD categories. The most frequent therapeutic interventions were nutritional, pharmacological and vitamin and trace element supplementation. Evidence level varied from 1 to 3 (trials, cohort studies, case–control studies) for 19% and 4–5 (case-report, expert opinion) for 81% of treatments. Reported effects included improvement of clinical deterioration in 62%, neurological manifestations in 47% and development in 37%.ConclusionThe number of treatable IDs identified by our literature review increased by more than one-third in eight years. Although there has been much attention to gene-based and enzyme replacement therapy, the majority of effective treatments are nutritional, which are relatively affordable, widely available and (often) surprisingly effective. We present a diagnostic algorithm (adjustable to local resources and expertise) and the updated App to facilitate a swift and accurate workup, prioritizing treatable IDs. Our digital tool is freely available as Native and Web App (www.treatable-id.org) with several novel features. Our Treatable ID endeavor contributes to the Treatabolome and International Rare Diseases Research Consortium goals, enabling clinicians to deliver rapid evidence-based interventions to our rare disease patients.

Backgrounds The laboratory plays a critical role in tuberculosis (TB) control by providing testing for diagnosis, treatment monitoring, and surveillance at each level of the health care system. Weak accessibility to TB diagnosric services still represents a big concern in many limited resources’ countries. Here we report the experience of Burkina Faso in implementing a comprehensive intervention packages to strengthen TB laboratory capacity and diagnostic accessibility. Methods The intervention lasted from October 2016 to December 2018 and focused on two main areas: i) development of strategic documents and policies; ii) implementation of TB diagnostic technology. National TB laboratory data were collected between 2016 and 2018 and evaluated according to five programmatic TB laboratory indicators: i) Percentage of notified new and relapse TB cases with bacteriological confirmation; ii) Percentage of notified new and relapse TB cases tested by Xpert MTB/RIF; iii) Percentage of notified, bacteriologically confirmed TB cases with a drug susceptibility testing (DST) result for rifampin; iv) Percentage of notified MDR-TB cases on the estimated number of MDR-TB cases; v) The ration between the number of smear microscopy and Xpert MTB/RIF tests. We compared these indicators between a 1 year (2016–2017) and 2 years (2016–2018) timeframe. Results From 2016 to 2018, the percentage of bacteriologically confirmed cases increased from 67 to 71%. The percentage of new and relapse TB cases notified tested by Xpert MTB/RIF increased from 18% in 2016 to 46% in 2018 and the percentage of bacteriologically confirmed cases with an available DST result for rifampicin increased from 27% in 2016 to 66% in 2018.. The percentage of notified MDR-TB cases on the estimated number of MDR-TB cases in 2018 increased from 43% in 2016 to 78% in 2018. In 2018, the ratio between the number of smear microscopy and Xpert MTB/RIF tests decreased from 53% in 2016 to 21% in 2018. Conclusion We demonstrated that the implementation of a comprehensive package of laboratory strengthening interventions led to a significant improvement of all indicators. External technical assistance played a key role in speeding up the TB laboratory system improvement process.

Introducao O defeito congenito caracterizado por saida de ambas grandes arterias do ventriculo direito (VD), de forma completa ou mesmo em cavalgamento superior a 50% de uma das arterias sobre o septo interventricular, apresenta relacoes variaveis dessas arterias com a comunicacao interventricular (CIV), assim como associacao com outras variaveis anatomo-funcionais. No defeito mais comum associado, a CIV isolada, em posicao subaortica ou na nao relacionada as grandes arterias, o quadro funcional se expressa com predominio da sobrecarga de volume do [...]

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), has been the world’s driving fatal bacterial contagious disease globally. It continues a public health emergency, and around one-third of the global community has been affected by latent TB infection (LTBI). This is mostly due to the difficulty in diagnosing and treating patients with TB and LTBI. Exosomes are nanovesicles (40–100 nm) released from different cell types, containing proteins, lipids, mRNA, and miRNA, and they allow the transfer of one’s cargo to other cells. The functional and diagnostic potential of exosomal miRNAs has been demonstrated in bacterial infections, including TB. Besides, it has been recognized that cells infected by intracellular pathogens such as Mtb can be secreting an exosome, which is implicated in the infection’s fate. Exosomes, therefore, open a unique viewpoint on the investigative process of TB pathogenicity. This study explores the possible function of exosomal miRNAs as a diagnostic biomarker. Moreover, we include the latest data on the pathogenic and therapeutic role of exosomal miRNAs in TB.

Graphical abstract, Objective Viruses on environmental surfaces, in saliva and other body fluids represent risk of contamination for general population and healthcare professionals. The development of vaccines and medicines is costly and time consuming. Thus, the development of novel materials and technologies to decrease viral availability, viability, infectivity, and to improve therapeutic outcomes can positively impact the prevention and treatment of viral diseases. Methods Herein, we discuss (a) interaction mechanisms between viruses and materials, (b) novel strategies to develop materials with antiviral properties and oral antiviral delivery systems, and (c) the potential of artificial intelligence to design and optimize preventive measures and therapeutic regimen. Results The mechanisms of viral adsorption on surfaces are well characterized but no major breakthrough has become clinically available. Materials with fine-tuned physical and chemical properties have the potential to compromise viral availability and stability. Emerging strategies using oral antiviral delivery systems and artificial intelligence can decrease infectivity and improve antiviral therapies. Significance Emerging viral infections are concerning due to risk of mortality, as well as psychological and economic impacts. Materials science emerges for the development of novel materials and technologies to diminish viral availability, infectivity, and to enable enhanced preventive and therapeutic strategies, for the safety and well-being of humankind.

Recent severe acute respiratory syndrome 2 (SARS-CoV-2) known as COVID-19, presents a deadly challenge to the global healthcare system of developing and developed countries, exposing the limitations of health facilities preparedness for emerging infectious disease pandemic. Opportune detection, confinement, and early treatment of infected cases present the first step in combating COVID-19. In this review, we elaborate on various COVID-19 diagnostic tools that are available or under investigation. Consequently, cell culture, followed by an indirect fluorescent antibody, is one of the most accurate methods for detecting SARS-CoV-2 infection. However, restrictions imposed by the regulatory authorities prevented its general use and implementation. Diagnosis via radiologic imaging and reverse transcriptase PCR assay is frequently employed, considered as standard procedures, whereas isothermal amplification methods are currently on the verge of clinical introduction. Notably, techniques such as CRISPR-Cas and microfluidics have added new dimensions to the SARS-CoV-2 diagnosis. Furthermore, commonly used immunoassays such as enzyme-linked immunosorbent assay (ELISA), lateral flow immunoassay (LFIA), neutralization assay, and the chemiluminescent assay can also be used for early detection and surveillance of SARS-CoV-2 infection. Finally, advancement in the next generation sequencing (NGS) and metagenomic analysis are smoothing the viral detection further in this global challenge.

Background Differential etiologies of pediatric acute febrile respiratory illness pose challenges for all populations globally, but especially in malaria-endemic settings because the pathogens responsible overlap in clinical presentation and frequently occur together. Rapid identification of bacterial pneumonia with high-quality diagnostic tools would enable appropriate, point-of-care antibiotic treatment. Current diagnostics are insufficient, and the discovery and development of new tools is needed. We report a unique biomarker signature identified in blood samples to accomplish this. Methods Blood samples from 195 pediatric Mozambican patients with clinical pneumonia were analyzed with an aptamer-based, high-dynamic-range, quantitative assay (~1200 proteins). We identified new biomarkers using a training set of samples from patients with established bacterial, viral, or malarial pneumonia. Proteins with significantly variable abundance across etiologies (false discovery rate 90% sensitivity and >80% specificity, regardless of number of pathogen classes. Bacterial pneumonia was strongly associated with neutrophil markers—in particular, degranulation including HP, LCN2, LTF, MPO, MMP8, PGLYRP1, RETN, SERPINA1, S100A9, and SLPI. Conclusions Blood protein signatures highly associated with neutrophil biology reliably differentiated bacterial pneumonia from other causes. With appropriate technology, these markers could provide the basis for a rapid diagnostic for field-based triage for antibiotic treatment of pediatric pneumonia., Identification of new biomarkers to distinguish between viral and bacterial pneumonia is needed. These markers could provide the basis for a rapid diagnostic for field-based triage for antibiotic treatment of pediatric pneumonia.

Introduction The absence of a reliable, universal biomarker is a significant limitation in neuroendocrine neoplasia (NEN) management. We prospectively evaluated two CgA assays, (NEOLISA, EuroDiagnostica) and (CgA ELISA, Demeditec Diagnostics (DD)) and compared the results to the NETest. Methods NEN cohort (n = 258): pancreatic, n = 67; small intestine, n = 40; appendiceal, n = 10; rectal, n = 45; duodenal, n = 9; gastric, n = 44; lung, n = 43. Image-positive disease (IPD) (n = 123), image & histology- negative (IND) (n = 106), and image-negative and histology positive (n = 29). CgA metrics: NEOLISA, ULN: 108 ng/mL, DD: ULN: 99 ng/mL. Data mean ± s.e.m. NETest: qRT-PCR – multianalyte analyses, ULN: 20. All samples de-identified and assessed blinded. Statistics: Mann–Whitney U-test, Pearson correlation and McNemar-test. Results CgA positive in 53/258 (NEOLISA), 32 (DD) and NETest-positive in 157/258. In image- positive disease (IPD, n = 123), NEOLISA-positive: 33% and DD: 19%. NETest-positive: 122/123 (99%; McNemar’s Chi2= 79–97, P < 0.0001). NEOLISA was more accurate than DD (P = 0.0003). In image- negative disease (IND), CgA was NEOLISA-positive (11%), DD (8%), P = NS, and NETest (33%). CgA assays could not distinguish progressive (PD) from stable disease (SD) or localized from metastatic disease (MD). NETest was significantly higher in PD (47 ± 5) than SD (29 ± 1, P = 0.0009). NETest levels in MD (35 ± 2) were elevated vs localized disease (24 ± 1.3, P = 0.008). Conclusions NETest, a multigenomic mRNA biomarker, was ~99% accurate in the identification of NEN disease. The CgA assays detected NEN disease in 19–33%. Multigenomic blood analysis using NETest is more accurate than CgA and should be considered the biomarker standard of care.

Purpose of the review Robotics is a rapidly advancing field, and its introduction in healthcare can have a multitude of benefits for clinical practice. Especially, applications depending on the radiologist’s accuracy and precision, such as percutaneous interventions, may profit. This paper provides an overview of recent robot-assisted percutaneous solutions. Recent findings Percutaneous interventions are relatively simple and the quality of the procedure increases a lot by introducing robotics due to the improved accuracy and precision. The success of the procedure is heavily dependent on the ability to merge pre- and intraoperative images, as an accurate estimation of the current target location allows to exploit the robot’s capabilities. Summary Despite much research, the application of robotics in some branches of healthcare is not commonplace yet. Recent advances in percutaneous robotic solutions and imaging are highlighted, as they will pave the way to more widespread implementation of robotics in clinical practice.

Background Increased levels of microRNA-574-5p (miR-574-5p) have been found to be associated with increased survival of septic patients, indicating the potential role of miR-574-5p in protecting against septic progression and complications. Acute kidney injury (AKI) is one of the most common and serious complications of sepsis. Therefore, the aim of this study was to test these hypotheses: (1) in a renal cell culture line (HK-2), upregulated expression of miR-574-5p increases, and downregulated expression of miR-574-5p decreases cell viability, and (2) serum levels of miR-574-5p from patients with sepsis and AKI are lower than those of patients with sepsis but no AKI. Methods The expression of miR-574-5p was regulated by cell transfection in HK-2 cells, and HK-2 cell viability was measured using the Cell Counting Kit-8. Serum miR-574-5p expression was analyzed using qRT-PCR. The predictive value of miR-574-5p for AKI onset was evaluated using the receiver operating characteristic curve and logistic regression analysis. Results The overexpression of miR-574-5p promoted HK-2 cell viability. Fifty-eight sepsis patients developed AKI, who had significantly lower miR-574-5p expression. miR-574-5p expression was decreased with AKI stage increase and correlated with kidney injury biomarker and had relatively high accuracy to predict AKI occurrence from sepsis patients. Conclusion Overexpression of miR-574-5p in cultured HK-2 cells increases cell viability and knocked-down expression of miR-574-5p decreases cell viability. Consistently, septic patients with AKI were found to have less upregulation of miR-574-5p expression compared to septic patients without AKI. Thus, serum miR-574-5p may provide a novel biomarker for septic AKI.

After the havoc created by Spanish flu a century ago, the world is witnessing exactly a similar pandemic situation since the beginning of the year 2020. The unexplained respiratory illness with high morbidity & mortality which started in Wuhan, China and spread across the world was finally termed as COVID-19 disease caused by SARS-CoV-2 and later announced as pandemic by WHO. This novel virus SARS-CoV-2 is a new variant of SARS corona virus with high infectivity and mysterious pathophysiology. The major step towards containment of this pandemic is to scale up the testing for SARS-CoV-2 and thereby isolating and managing the patients at the earliest. Molecular amplification based methods such a Real time Polymerase chain reaction (RT-PCR), CBNAAT and TrueNAT are the most commonly used techniques for detection of SARS-CoV2. To utilize these diagnostic facilities optimally in the management of the suspected COVID 19 patients, it is of utmost importance for the healthcare providers to understand the intricacies related to these technologies. Thus, the technical details along with the pros & cons of these three amplification-based technologies for proper understanding of these diagnostic modalities for SARS COV-2 diagnosis are discussed herewith.

To evaluate the diagnostic role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in initial staging and restaging of anorectal melanoma. This was a single-institution, retrospective observational study; patients for initial staging and with clinical or radiological suspicion of disease recurrence referred for PET/CT between January 2006 and December 2015 were included in the study. Diagnostic performance of PET/CT was evaluated for baseline staging and disease recurrence. A total of 61 patients who were referred for initial staging were included. PET/CT correctly detected primary lesion in 57 (93.44%) cases, regional nodes in 46 (75.4%) cases, nonregional nodes in 22 (36%) cases, and distant metastases in 25 (41%) cases. The sensitivity (SN); specificity (SP); positive predictive value (PPV); negative predictive value (NPV); and accuracy for primary lesion, regional nodes, nonregional nodes, and distant metastases were 96.6%, 100%, 100%, 50%, and 96.7%; 97.9%, 100%, 100%, 93.3%, and 98.4%; 100%, 100%, 100%, 100%, and 100%; and 100%, 100%, 100%, 100%, and 100%, respectively. A total of 24 patients were included for suspected recurrence/restaging. All the patients were treated previously by surgery, radiotherapy, or chemotherapy. PET/CT detected disease recurrence in 20 (83.3%) patients. Ten patients had recurrence at the primary site, 8 of whom also had distant metastases and 2 had only locoregional metastatic nodes. In the remaining 10 patients, there was no primary site recurrence; however, 2 patients had locoregional nodal and distant metastases and 8 patients had only distant metastases. PET/CT was false negative in 1 patient, which missed liver metastasis. SN, SP, PPV, and NPV of PET/CT was found to be 95%, 100%, 100%, and 75%, respectively, with accuracy of 96%. PET/CT demonstrates overall high diagnostic accuracy in the initial staging and detection of recurrent disease in cases of anorectal melanoma.

Objective: To evaluate the current literature on the accuracy of fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (FDG PET-CT) for lymph node (LN) staging in urothelial carcinoma (UC), as robust evidence on the value of this technology in UC is still lacking. Methods: The Medical Literature Analysis and Retrieval System Online (MEDLINE)/PubMed, Cochrane Library, and Scopus databases were searched for eligible studies. We included all original studies evaluating FDG PET-CT in bladder or upper tract UC. The search results were restricted to the English language, and included prospective and retrospective studies without time restriction. We included only studies reporting the sensitivity and specificity of FDG PET-CT in detecting UC LN metastases. Results: We identified 23 articles meeting our inclusion criteria. In the preoperative setting, the sensitivity of FDG PET-CT for detecting LN metastases in patients with bladder cancer was widely variable ranging from 23% to 89%; the specificity ranged from 81% to 100%; and the overall accuracy ranged from 65% to 89%. During bladder cancer monitoring the sensitivity for detecting LN metastases ranged from 75% to 92% and the specificity ranged from 60% to 92%. The sensitivity for LN staging in upper tract UC ranged between 82% and 95%, with a specificity of 84–91%. Conclusion: Despite the inconsistencies in sensitivity between the reports, FDG PET-CT seems to have a high specificity for LN staging in patients with UC. Future prospective, well-designed studies are necessary to evaluate the role of FDG PET-CT in UC management. Abbreviations: FDG: fluoro-2-deoxy-D-glucose; LN: lymph node; PET: positron emission tomography; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; PSMA: prostate-specific membrane antigen; (N)(P)PV: (negative) (positive) predictive value; QUADAS-2: Quality Assessment of Diagnostic Accuracy Studies-2; SUVmax: maximum standard uptake value; (UT)UC: (upper urinary tract) urothelial carcinoma

Maturity-onset diabetes of the young (MODY) is a non-rare group of monogenic inherited diabetes which is commonly confused with type 1 and type 2 diabetes. Due to high costs of genetic tests that provide a definitive diagnosis, some screening scales are used to identify the high-risk patients. In this study, we aimed to evaluate whether (MODY Probability Calculator [MPC]) which is one of the screening tests will be helpful in identifying our high-risk patients among young patients with type 2 diabetes.The patients received the diagnosis of type 2 diabetes aged35 years were included in the study. The anthropometric characteristics of the patients, the treatments they received at the time of diagnosis, and the current treatments were recorded by retrospectively scanning patient files.The patients with the diagnosis of type 1 diabetes having autoantibodies to the pancreas were excluded from the study. The probability of MODY was calculated using MPC..The mean age of 72 patients (40% female) was 41.5±7.2 years. Eighteen of the patients (25%) were using insulin at the time of diagnosis. The mean HbA1c was 8.6±2.2% and C-peptide was 2.35±1.52 ng/ml. The mean MODY positive predictive score calculated by MPC for risk of MODY was 11.23 percent. There were 61 patients (84.7%) with a risk of ≤20%, 9 patients (12.5%) with a risk of 20-50%, and 2 patients (2.8%) with ≥50%. In the group with MODY PPV score20%, the age of onset of diabetes and the body mass index was significantly lower than the others (p0.05, for both). There was no significant difference between current treatments of both groups.It has been reported that MODY risk calculated by MPC may yield different results in different populations. The results of this study showed that 15% of our young-onset diabetes patients had an MPC score above 20 percent. Requesting MODY genetic tests in this 15% of the patient group can be presented as a practical suggestion.Gençlerde görülen erişkin tip diyabet (MODY), tip 1 ve tip 2 diyabetle karışan, monogenik geçişli, diyabetin nadir olmayan bir grubunu oluşturmaktadır. Kesin tanıyı sağlayan genetik testlerin maliyetlerinin yüksek olması nedeniyle yüksek riskli hastaları belirlemeye yönelik bazı tarama ölçekleri kullanılmaktadır. Biz bu çalışmamızda diyabet polikliniğine başvuran erken yaş tip 2 diyabet olgularında tarama testlerinden biri olan MODY Olasılık Hesaplayıcısının (MODY Probability Calculator [MPC]) yüksek riskli hastalarımızın belirlenmesin-de yardımcı olup olmayacağını değerlendirmeyi amaçladık .Otuz beş yaşından önce tip 2 diyabet tanısı almış hastalar çalışmaya alındı. Hastaların geriye dönük dosyaları incelenerek antropometrik özellikleri, tanı anında aldıkları tedaviler ve güncel tedavileri kaydedildi. Tip 1 diyabet tanılı veya pankreasa yönelik otoantikorları pozitif olan hastalar dışlandı. Hastalarda MPC kullanı-larak MODY olma olasılığı hesaplandı.Çalışmada incelenen 72 hastanın (%40’ı kadın), yaş ortalaması 41,5±7,2 yıldı. Hastaların 18’ine (%25) tanı anında insülin başlanmıştı. Hastaların ortalama HbA1c değerleri %8,6±2,2, ortalama C-peptidleri ise 2,35±1,52 ng/dl idi. Hastaların MPC ile hesaplanan risklerinde ortalama MODY pozitif predikte edici değeri %11,23 idi. Riski ≤%20 olan 61 (%84.7), %20-50 arasında olan 9 (%12.5), ≥50% olan 2 (%2.8) hasta mevcuttu. MODY PPV skoru%20 olan grupta, diyabet başlangıç yaşı ve vücut kitle indeksi diğerlerine göre anlamlı de-recede düşüktü (her ikisi için de p0.05). Her iki grubun mevcut tedavileri arasında fark yoktu.MPC ile hesaplanan MODY riskinin farklı topluluklarda farklı sonuçlar verebileceği bildirilmiştir. Bu çalışmanın sonuçları, bizim genç başlangıçlı diyabet hastalarımızın %15’inde MPC skorunun %20’nin üzerinde olduğunu göstermiştir. MODY genetik testlerinin bu %15’lik hasta grubunda istenmesi pratik bir öneri olarak sunulabilir.

Background: Central hypogonadism (CH) is a syndrome characterized by low levels of peripheral sex steroid hormones due to the lack of central (hypothalamic-pituitary) regulation of reproductive system. In females, CH clinically manifests by amenorrhea, anovulation, and infertility. The classical diagnostic criteria of CH in the absence of organic disease of hypothalamic-pituitary region (“idiopathic” CH) include low gonadotropin levels; however, their levels within the reference ranges do not exclude CH. Moreover, reference ranges for these parameters are different between laboratories. Thus, currently no clear laboratory diagnostic criteria for female CH are available.Aim: To determine the diagnostic value of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) basal levels for the confirmation of CH diagnosis in women and to identify cutoffs of basal gonadotropins levels, which can be considered as diagnostic criteria for female CH.Materials and methods: This cross-sectional study included 87 women: 49 with confirmed CH, aged 18 to 36 years (median, 24 [Q21; Q29]), and 38 healthy fertile women with regular menstrual cycles aged 21 to 45 years (median, 23 [Q23; Q28]). In all subjects, LH, FSH, estradiol, testosterone, prolactin, and free thyroxin levels were measured by chemiluminiscent immunoassay.Results: LH, FSH, estradiol, and prolactin levels in the CH patients were significantly lower than those in healthy subjects. The ROC analysis showed that LH level ≤ 1.95 ME/l indicated the central genesis of hypogonadism with sensitivity of 81.25% and specificity of 91.89%. Basal FSH level ≤ 5.075 ME/l had a 70.00% sensitivity and 77.14% specificity for CH diagnosis.Conclusion: Basal LH level ≤ 1.95 ME/l measured by chemiluminiscent immunoassay can be considered as an idiopathic CH diagnostic criterion in female with amenorrhea due to the hypoestrogenemia with sensitivity of > 80% and specificity > 90%.

Several pathogens and antibodies derived from serum or produced in tissues associated with the oral cavity are present in the oral fluid (OF). Considering the applicability of this alternative sample, recent studies in veterinary medicine have tested OF as a replacement for serum in diagnostic assays. The aim of this study was to standardize the immunoperoxidase monolayer assay (IPMA) to detect anti-Lawsonia intracellularis immunoglobulin A (IgA) and immunoglobulin G (IgG) in OF samples from experimentally infected pigs. Sixty-two pigs were divided into two groups: control (T1, n=30) and inoculated with L. intracellularis (T2, n=32). Blood, OF and fecal samples were collected at 0, 7, 14, 21, 28 and 42 days post-inoculation (dpi). Some adaptations of the standard technique for serum were made to IPMA for the detection of IgA and IgG in OF. The IPMA showed high specificity and sensitivity for serum samples and high specificity and moderate sensitivity for the detection of IgA and IgG in OF. There was high agreement between the results of serum IgG and OF IgA and IgG. Based on our results, oral fluid samples may be used for the evaluation and determination of anti-L. intracellularis antibodies in pigs, but not for individual diagnosis of swine proliferative enteropathy.

Complex dystonias are defined as dystonias that are accompanied by neurologic or systemic manifestations beyond movement disorders. Many syndromes or diseases can present with complex dystonia, either as the cardinal sign or as part of a multi-systemic manifestation. Complex dystonia often gradually develops in the disease course, but can also be present from the outset. If available, the diagnostic workup, disease-specific treatment, and management of patients with complex dystonias require a multi-disciplinary approach. This article summarizes current knowledge on complex dystonias with a particular view of recent developments with respect to advances in diagnosis and management, including causative treatments.

Objective: Molecular testing of thyroid nodules becomes important for improving the accuracy of fine-needle aspiration biopsy (FNAB). This study aimed to investigate the diagnostic utility of BRAF, NRAS, and TERT promoter mutation in thyroid nodules at Dharmais Cancer Hospital. Methods: We performed a prospective diagnostic study involving 50 patients with thyroid nodules who needed surgery between September 2013 and August 2014. Mutational hotspots in BRAF exon 15, NRAS exon 3, and TERT promoter region were analyzed by Sanger sequencing from FNAB specimens. Cytology and molecular data were compared to histopathology results. Results: Of the 50 cases included in the analysis, 39 cases (78%) were thyroid malignancies. Mutations of BRAF, NRAS, and TERT promoter were detected in 31% (12/39), 18% (7/39), and 13% (5/39) cases, respectively. BRAF and NRAS mutations were found mutually exclusive, while all of TERT promoter mutation was found coexistent either with BRAF (40%) or NRAS (60%). The combination of FNAB cytology and molecular testing resulted in 69% sensitivity, 100% specificity, 100% positive predictive value, 48% negative predictive value, and 76% accuracy. Conclusion: Molecular testing of BRAF, NRAS, and TERT mutations improve the sensitivity of thyroid FNAB and is beneficial for more definitive treatment in selective cases. However, the NPV is relatively low to avoid the need for diagnostic surgery. Therefore, further studies to identify more sensitive methods and more comprehensive molecular markers in the diagnosis of thyroid nodules are needed.

Background Pancreaticopleural fistula (PPF) is a rare disease, especially in children. Conservative treatment and surgery are traditional therapies, but surgery is invasive. The emergence of endoscopic retrograde cholangiopancreatography (ERCP) has provided a new noninvasive treatment for PPF and may become the first choice for children with PPF. Aim To explore the treatment response to ERCP for PPF in children. Methods Seven children with PPF were hospitalized in the Gastroenterology Department of Beijing Children's Hospital from December 2007 to May 2019. Data on these seven patients' clinical characteristics, diagnosis, treatments, and outcomes were analyzed, and their treatment responses following surgery and ERCP were compared. The correlation between the length of hospital stay and conservative treatment was analyzed. Peer-reviewed articles written in English and Chinese published from January 2009 to December 2019 were obtained from various open data sources and reviewed. Results The seven patients comprised three boys and four girls with a mean age of 6.57 ± 3.26 years. The main symptoms were chest tightness and pain (n = 4), intermittent fever (n = 3), dyspnea (n = 3), and abdominal pain (n = 1), and all patients had bloody pleural effusion. All seven patients were diagnosed with PPF by magnetic resonance cholangiopancreatography, and all were initially treated conservatively for a mean of 34.67 ± 22.03 d with a poor response. Among five patients who underwent ERCP, one required surgery because of intubation failure; thus, the success rate of ERCP was 80%. Two patients were successfully treated with surgery (100%). The postoperative hospital stay of the two patients treated by surgery was 20 and 30 d, respectively (mean of 25 d), and that of the four patients treated by ERCP ranged from 12 to 30 d (mean of 19.25 ± 8.85 d). The recovery time after ERCP was short [time to oral feeding, 4-6 d (mean, 5.33 ± 1.15 d); duration of closed thoracic drainage, 2-22 d (mean, 13.3 d)]. Analysis of previous cases of PPF published worldwide during the past decade showed that the treatment success rate of ERCP is not lower than that of surgery. There was no significant difference in the postoperative hospital stay between surgery (16 ± 10.95 d) and ERCP (18.7 ± 6.88 d, P > 0.05). A positive linear correlation was found between the overall hospital stay and ERCP intervention time (R 2 = 0.9992). Conclusion ERCP is recommended as the first-choice treatment for PPF in children. ERCP should be performed as early as possible if conditions permit.

Background Severe sepsis and septic shock are among the leading causes of death in the United States and sepsis remains one of the most expensive conditions to diagnose and treat. Accurate early diagnosis and treatment can reduce the risk of adverse patient outcomes, but the efficacy of traditional rule-based screening methods is limited. The purpose of this study was to develop and validate a machine learning algorithm (MLA) for severe sepsis prediction up to 48 h before onset using a diverse patient dataset. Methods Retrospective analysis was performed on datasets composed of de-identified electronic health records collected between 2001 and 2017, including 510,497 inpatient and emergency encounters from 461 health centers collected between 2001 and 2015, and 20,647 inpatient and emergency encounters collected in 2017 from a community hospital. MLA performance was compared to commonly used disease severity scoring systems and was evaluated at 0, 4, 6, 12, 24, and 48 h prior to severe sepsis onset. Results 270,438 patients were included in analysis. At time of onset, the MLA demonstrated an AUROC of 0.931 (95% CI 0.914, 0.948) and a diagnostic odds ratio (DOR) of 53.105 on a testing dataset, exceeding MEWS (0.725, P P P Conclusions The MLA accurately predicts severe sepsis onset up to 48 h in advance using only readily available vital signs extracted from the existing patient electronic health records. Relevant implications for clinical practice include improved patient outcomes from early severe sepsis detection and treatment.

С areful evaluation of patient history, including of anginal symptoms, and evaluation of risk factors and manifestation of coronary artery disease (CAD), as well as proper physical examination and basic testing, are crucial for the diagnosis and management of chronic coronary syndrome(s) (CCS) and non-cardiovascular comorbidities. Anti-ischaemic treatment must be adapted to the individual patient based on comorbidites, co-administered therapies, expected tolerance and adherence, and patient preferences. The choice of anti-ischaemic drugs to treat chronic coronary sydromes should be adapted to the patient’s heart rate, blood pressure, and left-ventricular (LV) function. In patients with active cancer treatment decisions should based on life be expectancy, additional comorbidities such as thrombocytopenia, increased thrombosis propensity. and potential interactions between drugs used in CCS management and antineoplastic agents. In asymptomatic patients with diabetes mellitus, a periodic resting electrocardiogram is recommended for cardiovascular detection of conduction abnormalities, atrial fibrillation, and silent myocardial infarction. Recommendations for chronic kidney disease (CRD): use iodinated contrast agents is minimized in patients with severe CKD and preserved urine production to prevent further deterioration. It is recommended that particular attention is paid to side effects of drugs, intolerance, and overdosing in elderly patients with chronic coronary syndromes. Hormone replacement therapy is not recommended for risk reduction in post- menopausal women. Тransmyocardial revascularization is not recommended in patients with debilitating angina refractory to optimal medical and revascularization strategies.

BACKGROUND. Inadequate tuberculosis (TB) diagnostics are a major hurdle in the reduction of disease burden, and accurate point-of-care tests (POCTs) are urgently needed. We assessed the diagnostic accuracy of Fujifilm SILVAMP TB lipoarabinomannan (FujiLAM) POCT for TB diagnosis in HIV-negative outpatients and compared it with Alere Determine TB LAM Ag (AlereLAM) POCT and a laboratory-based ultrasensitive electrochemiluminescence LAM research assay (EclLAM). METHODS. In this multicenter diagnostic test accuracy study, we recruited HIV-negative adults with symptoms suggestive of pulmonary TB presenting to outpatient health care centers in Peru and South Africa. Urine samples were tested using FujiLAM, AlereLAM, and EclLAM, and the diagnostic accuracy was assessed against a microbiological reference standard (MRS) and a composite reference standard. RESULTS. Three hundred seventy-two HIV-negative participants were included and the prevalence of microbiologically confirmed TB was 30%. Compared with the MRS, the sensitivities of AlereLAM, FujiLAM, and EclLAM were 10.8% (95% confidence interval [CI] 6.3%–18.0%), 53.2% (95% CI 43.9%–62.1%), and 66.7% (95% CI 57.5%–74.7%), respectively. The specificities of AlereLAM, FujiLAM, and EclLAM were 92.3% (95% CI 88.5%–95.0%), 98.9% (95% CI 96.7%–99.6%), and 98.1% (95% CI 95.6%–99.2%), respectively. Positive likelihood ratios of AlereLAM, FujiLAM, and EclLAM were 1.4, 46.2, and 34.8, respectively, and positive predictive values were 37.5%, 95.2%, and 93.7%, respectively. CONCLUSION. Compared with AlereLAM, FujiLAM detected 5 times more patients with TB in HIV-negative participants, had a high positive predictive value, and has the potential to improve rapid diagnosis of TB at the point-of-care. EclLAM demonstrated that additional sensitivity gains are possible, which highlights LAM’s potential as a biomarker. Additional research is required to assess FujiLAM’s performance in prospective cohorts, its cost-effectiveness, and its impact in real-world clinical settings. FUNDING. Global Health Innovative Technology Fund, the UK Department for International Development, the Dutch Ministry of Foreign Affairs, the Bill and Melinda Gates Foundation, the Australian Department of Foreign Affairs and Trade, the German Federal Ministry of Education and Research through Kreditanstalt für Wiederaufbau, and the NIH and National Institute of Allergy and Infectious Diseases.

Aim To evaluate the overall diagnostic performance of 14‐3‐3 η protein in patients with rheumatoid arthritis (RA). Methods PubMed, EMBASE, and Web of Science were searched to acquire eligible studies. Articles published in English before 20 February 2020 were included. Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the risk of bias and application concern of the included articles. Pooled analysis of diagnostic indicators of 14‐3‐3 η protein for RA was conducted by using a random effects model. Subgroup analysis was used to explore the sources of heterogeneity. Deeks' funnel plot asymmetry test was used to evaluate for the presence of publication bias. Results A total of 13 studies (1554 positive and 1934 negative participants) were included. The pooled sensitivity and specificity were 0.73 (95% CI 0.71‐0.75) and 0.88 (95% CI 0.87‐0.90), respectively. The pooled positive/negative likelihood were 5.98 (95% CI 4.39‐8.14) and 0.28 (95% CI 0.21‐0.37), respectively. In addition, the pooled diagnostic odds ratio was 23.48 (95% CI 13.76‐40.08) and the area under curve was 0.9245. The results of subgroup analysis indicated that ethnicity and control group might be the source of heterogeneity. The results of sensitivity analysis were stable. No significant publication bias was found. Conclusions The current evidence indicated that 14‐3‐3 η protein has moderate accuracy for the diagnosis of RA.

Stafne bone defect (SBD) is a bone cavity in the lingual surface of the mandible normally filled by salivary gland tissue. In conventional radiographs, SBD typically resembles a radiolucent unilocular lesion with welldefined margins, localized under the inferior alveolar canal. The diagnosis of SBD is often incidental due to the asymptomatic nature. The aim of this study was to investigate the prevalence of SBDs in a Brazilian population and to describe the radiographic features of the cases reported. This retrospective study evaluated 17,180 digital panoramic radiographs of patients with an indication of radiography for dental treatment seen at three centers located in the three Brazilian states. In each center, two researchers evaluated the images for establishment of the consensual diagnosis of SBD. In the case of disagreement, a third researcher was consulted to reach a final consensus. To assess the prevalence of SBDs, sex and age of patients were considered, and SBDs were classified according to their form and location. Data were submitted to descriptive analysis. Among the 17.180 patients, only 15 (0.08 %) had SDB, including 3 women and 12 men. The age range of the patients with SDB was 30-69 years (mean: 49.2). Fourteen cases were located in the posterior region of the mandibular body and one case in the ascending ramus. Stafne bone defect is a rare developmental anomaly that more commonly affects middle-aged men. The condition has a typical radiographic appearance and panoramic radiography is a valuable tool for its diagnosis.

Point‐of‐care tests (POCTs) offer considerable potential for improving clinical and public health management of COVID‐19 by providing timely information to guide decision‐making, but data on real‐world performance are in short supply. Besides SARS‐CoV‐2‐specific tests, there is growing interest in the role of surrogate (non‐specific) tests such as FebriDx, a biochemical POCT which can be used to distinguish viral from bacterial infection in patients with influenza‐like illnesses. This short report assesses what is currently known about FebriDx performance across settings and populations by comparison with some of the more intensively evaluated SARS‐CoV‐2‐specific POCTs. While FebriDx shows some potential in supporting triage for early‐stage infection in acute care settings, this is dependent on SARS‐CoV‐2 being the most likely cause for influenza‐like illnesses, with reduction in discriminatory power when COVID‐19 case numbers are low, and when co‐circulating viral respiratory infections become more prevalent during the autumn and winter. Too little is currently known about its performance in primary care and the community to support use in these contexts, and further evaluation is needed. Reliable SARS CoV2‐specific POCTs—when they become available—are likely to rapidly overtake surrogates as the preferred option given the greater specificity they provide.

Nondrug therapy for arrhythmia patients had been developed dramatically until recent years. Cardiac resynchronization therapy (CRT), a nondrug therapy for arrhythmia, is especially utilized for the treatment of left ventricular (LV) severe heart failure caused by cardiac dyssynchrony. Prolonged QRS duration (≧130 ms) is strongly used as a CRT indication criterion, but QRS is not the direct clinical index of mechanical contraction delay of the LV myocardium. Therefore, identifying the presence of dyssynchrony by diagnostic imaging is necessary. Echocardiography is widely used for the assessment of dyssynchrony as a standard diagnostic imaging. Several studies have addressed the efficacy of cardiovascular magnetic resonance feature tracking (CMR-FT) in the diagnosis of dyssynchrony for arrythmia patients. In addition, cardiac implantable electronic devices (CIEDs) were not available to examine CMR until recent years; however, new MR-conditional CIEDs have become available for use before and after CRT. Recently, diagnostic imaging using CMR-FT has been attracting attention for the assessment of dyssynchrony. However, a strong metal artifact caused by CIEDs may make the analysis difficult after CRT implantation. Strain analysis using short-axis (SA) cine CMR overcame this issue of artifact by enabling slice selection by avoiding artifact. Moreover, circumferential strain has superiority over other strain methods with respect to sensitivity, and we focused on these advantages. This case illustrates that circumferential strain with CMR-FT using SA cine CMR is useful in the assessment of improvement of myocardial motion after CRT and can provide useful additional information with imaging to determine the responders of CRT.