Indeterminate Cases Research Articles

Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults

We carried out integrated host and pathogen metagenomic RNA and DNA next generation sequencing (mNGS) of whole blood (n = 221) and plasma (n = 138) from critically ill patients following hospital admission. We assigned patients into sepsis groups on the basis of clinical and microbiological criteria. From whole-blood gene expression data, we distinguished patients with sepsis from patients with non-infectious systemic inflammatory conditions using a trained bagged support vector machine (bSVM) classifier (area under the receiver operating characteristic curve (AUC) = 0.81 in the training set; AUC = 0.82 in a held-out validation set). Plasma RNA also yielded a transcriptional signature of sepsis with several genes previously reported as sepsis biomarkers, and a bSVM sepsis diagnostic classifier (AUC = 0.97 training set; AUC = 0.77 validation set). Pathogen detection performance of plasma mNGS varied on the basis of pathogen and site of infection. To improve detection of virus, we developed a secondary transcriptomic classifier (AUC = 0.94 training set; AUC = 0.96 validation set). We combined host and microbial features to develop an integrated sepsis diagnostic model that identified 99% of microbiologically confirmed sepsis cases, and predicted sepsis in 74% of suspected and 89% of indeterminate sepsis cases. In summary, we suggest that integrating host transcriptional profiling and broad-range metagenomic pathogen detection from nucleic acid is a promising tool for sepsis diagnosis.

THE CORRELATION OF USG FINDINGS WITH CT (COMPUTED TOMOGRAPHY) SCAN FOR EVALUATION OF BOWEL PATHOLOGY

Introduction: Bowel can be affected by diverse group of pathologies causing varied morphological alteration in and around the bowel. The radiological investigation of choice depends upon the availability, accessibility, affordability and the performance of the method. Methodology: It was a hospital based prospective comparative observational type of study. Study was conducted from January 01, 2020 to December 31, 2020. After applying exclusion criteria, 50 patients of any age group with bowel related symptoms and palpable abdominal mass,which were attending & referred to RNT Medical College and Associated Group of Hospitals included in the study. Ultrasonography and CT-scans were performed in every patient.The findings were observed and tabulated. Results: The gender distribution showed male predominance. Out of 50 patients, 15 patients (30%) were female and 35 patients (70%) were male with male to female ratio of 2:1. The peak age incidence was in the 21-30 years of age group with 12 patients (24%) falling in this age group followed by 41-50 years group. There were total of 36 benign bowel wall lesions and 14 malignant cases of bowel wall thickening. Adenocarcinoma was the commonest malignant cause of bowel wall thickening constituting 11 (22%) cases out of total 50 cases, while in benign cases it was abdominal Kochs in 18 (36%) cases out total 50 cases. Conclusion: USG is often the first imaging study performed in patients with symptoms related to the gastrointestinal tract and it less invasive, more comfortable for the patient and has a good diagnostic accuracy. For indeterminate cases in USG, CT should be considered for more specific diagnosis. Over all, agreement with final specific diagnosis and diagnostic accuracy of CT for benign and malignant bowel lesions was higher than USG.

47 A Host Protein Test Based on TRAIL, IP-10 and CRP for Differentiating Between Bacterial and Viral Infection Has Potential to Improve Patient Selection for Blood Culture Utilization

47 A Host Protein Test Based on TRAIL, IP-10 and CRP for Differentiating Between Bacterial and Viral Infection Has Potential to Improve Patient Selection for Blood Culture Utilization

Immunohistochemical Approach to Genetic Subtyping of Anaplastic Large Cell Lymphoma.

Anaplastic large cell lymphoma (ALCL) can be classified genetically based on rearrangements (R) of the ALK , TP63 , and/or DUSP22 genes. ALK- R defines a specific entity, ALK-positive ALCL, while DUSP22- R and TP63- R define subgroups of ALK-negative ALCLs with distinct clinicopathologic features. ALK -R and TP63 -R produce oncogenic fusion proteins that can be detected by immunohistochemistry. ALK immunohistochemistry is an excellent surrogate for ALK- R and screening with p63 immunohistochemistry excludes TP63- R in two third of ALCLs. In contrast, DUSP22 -R does not produce a fusion protein and its identification requires fluorescence in situ hybridization. However, DUSP22- R ALCL has a characteristic phenotype including negativity for cytotoxic markers and phospho-STAT3 Y705 . Recently, we also identified overexpression of the LEF1 transcription factor in DUSP22- R ALCL. Here, we sought to validate this finding and examine models for predicting DUSP22- R using immunohistochemistry for LEF1 and TIA1 or phospho-STAT3 Y705 . We evaluated these 3 markers in our original discovery cohort (n=45) and in an independent validation cohort (n=46) of ALCLs. The correlation between DUSP22- R and LEF1 expression replicated strongly in the validation cohort ( P <0.0001). In addition, we identified and validated a strategy using LEF1 and TIA1 immunohistochemistry that predicted DUSP22- R with positive and negative predictive values of 100% after exclusion of indeterminate cases and would eliminate the need for fluorescence in situ hybridization in 65% of ALK-negative ALCLs. This approach had similar results in identifying DUSP22- R in the related condition, lymphomatoid papulosis. Together with previous data, these findings support a 4-marker immunohistochemistry algorithm using ALK, LEF1, TIA1, and p63 for genetic subtyping of ALCL.

Indeterminate Thyroid Fine-Needle Aspirations in Pediatrics: Exploring Clinicopathologic Features and Utility of Molecular Profiling

Introduction: The diagnostic utility of molecular profiling for the evaluation of indeterminate pediatric thyroid nodules is unclear. We aimed to assess pediatric cases with indeterminate thyroid fine-needle aspiration (FNA) alongside clinicopathologic features and mutational analysis. Methods: A retrospective review of 126 patients with indeterminate cytology who underwent FNA between January 2010 and December 2021 at the Children’s Hospital of Philadelphia was performed. Indeterminate cases defined by The Bethesda System for Reporting Thyroid Cytopathology (AUS/FLUS or TBSRTC III; FN/SFN or TBSRTC IV; SM or TBSRTC V) were correlated to clinicopathologic and genetic characteristics. Results: Of the 114 surgical cases, 48% were malignant, with the majority of malignant cases diagnosed as follicular variant of papillary thyroid carcinoma (28/55). Risk of malignancy increased with TBSRTC category: 23% for AUS/FLUS, 51% for FN/SFN, and 100% for SM nodules. There were significant differences in surgical approach (p < 0.01), performance of lymph node dissection (p < 0.01), histological diagnosis (p < 0.01), primary tumor focality/laterality (p = 0.04), and lymphatic invasion (p = 0.02) based on TBSRTC classification, with resultant differences in post-surgical risk stratification per American Thyroid Association (ATA) Pediatric Guidelines (p = 0.01). Approximately 89% (49/55) of cases were classified as ATA low risk, and 5 of 6 patients with ATA intermediate- or high-risk disease had SM cytology. Somatic molecular testing was performed in 40% (51/126) of tumors; 77% (27/35) of malignant cases and 38% (6/16) of benign cases harbored driver alteration(s). Of the driver-positive malignant cases, 52% (14/27) were associated with low risk (DICER1, PTEN, RAS, and TSHR mutations), 33% (9/27) were associated with high risk (BRAF mutations and ALK, NTRK, and RET fusions), and 15% (4/27) had unreported risk for invasive disease (APC, BLM, and PPM1D mutations and TG-FGFR1 fusion). Incidence of high-risk drivers increased with TBSRTC category. Approximately 23% (8/35) of patients harboring thyroid malignancy did not have an identifiable driver alteration. Conclusions: Molecular analysis is useful to discriminate benign and malignant thyroid nodules with indeterminate cytology. Patients with driver genetic alteration(s) and indeterminate cytology should consider surgical management secondary to the high incidence (82%; 27/33) of thyroid malignancy in these patients.

Increasing role of imaging in differentiating MS from non-MS and defining indeterminate borderline cases.

Multiple sclerosis (MS) is a heterogenous condition with differences between patients regarding disease presentation, imaging features, disease activity, prognosis and treatment responses. Following the discovery of new biomarkers, the concept of MS has evolved, with syndromes previously considered to be its variants now recognised as separate entities, including aquaporin-4 (AQP4)-antibody (Ab) neuromyelits optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease (MOGAD). In line with their distinct pathology, the newly emerging conditions have imaging characteristics which are dissimilar to typical MS. Progress in reclassifying such demyelinating CNS conditions has highlighted the challenge in meaningful categorisation of atypical presentations at the borders of MS, such as antibody-negative neuromyelitis optica-like syndromes, tumefactive demyelinating lesions, or Balo's concentric sclerosis. In this review, we discuss the increasing role of imaging in distinguishing MS from non-MS CNS inflammatory/demyelinating conditions and defining undetermined borderline cases. This progress relies both on better characterisation of imaging features of these conditions on conventional imaging in terms of their appearance and location, as well as on the implementation of novel image acquisition and/or post-processing techniques allowing for more in-depth lesion assessment, including the presence of a central vein sign or paramagnetic rim.

Impact of dysphagia and its severity on long-term survival and swallowing function outcomes in patients with idiopathic inflammatory myopathies other than inclusion body myositis.

To investigate the impact of dysphagia on long-term survival and swallowing function outcomes in patients with idiopathic inflammatory myopathy other than inclusion body myositis. We retrospectively evaluated consecutive patients with idiopathic inflammatory myopathy other than inclusion body myositis to investigate the impact of dysphagia and its severity assessed using the Food Intake LEVEL Scale on survival and swallowing function outcomes. Time-to-event analyses were used, including Kaplan-Meier curves with log-rank (trend) test, cumulative incidence with Gray's test, and Cox proportional hazards models. Of the 254 patients, 26 were dysphagic, including eight severe (Food Intake LEVEL Scale [FILS] score 2, 3) and six most severe (FILS score 1) cases; 210 were non-dysphagic, and 18 were indeterminate cases. During the 5 years after myositis diagnosis, 15 (57.7%) dysphagic and 31 (14.8%) non-dysphagic patients died, and dysphagic patients had significantly shorter survival. However, multivariate analysis showed that shorter survival was significantly associated with baseline age-adjusted Charlson Comorbidity Index (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.36-1.82]), but not with dysphagia (HR 1.46, 95% CI 0.69-3.10). Dysphagia severity was significantly associated with delayed recovery of dysphagia. In 20 non-severe or severe dysphagic cases, 19 restored swallowing function within 1 year. The most severe cases had a significantly higher cumulative probability of death before recovery from dysphagia than severe cases. The poor survival of dysphagic myositis patients was largely confounded by advanced age and comorbid malignancies. However, patients with the most severe dysphagia had a significantly worse swallowing function and survival prognosis than those with milder dysphagia.

Evaluation of ACR TI-RADS cytologically indeterminate thyroid nodules and molecular profiles: a single-institutional experience.

The American College of Radiology (ACR) Thyroid Imaging Reporting and Data Systems (TI-RADS) was developed to standardize thyroid ultrasound reports and predict the likelihood of malignancy. In our study, we aimed to correlate indeterminate thyroid fine needle aspiration cytology cases with preceding ultrasound (US) ACR TI-RADS scores and concurrent molecular testing results to examine how well the use of the ACR TI-RADS in our institution predicted which patients with indeterminate cytology might harbor molecular alterations. We performed a retrospective review of thyroid nodules. Patients with US reports that included TI-RADS scores, fine needle aspiration specimens with indeterminate cytology (Bethesda class III-V), and molecular testing results were included. A total of 46 indeterminate cytology cases had had preceding US reports with TI-RADS scores and molecular testing (Bethesda class III, n = 37; Bethesda class IV, n = 6; Bethesda class V, n = 3). Most of the indeterminate cases had had a TI-RADS score of TR4 (31 of 46; 67.39%) or TR5 (9 of 46; 19.57%). RAS mutations were the most common alteration (n = 12). Of the 46 cases, 22 (47.85%) showed no alterations. Ten cases proceeded to surgery, of which seven displayed malignancies. Molecular testing in cytologically indeterminate thyroid nodules provided valuable information for TR4 and TR5 lesions; however, the TR2 and TR3 lesions often had no molecular alterations. These findings highlight the potential value of including US imaging features when assessing the significance of indeterminate cytology findings.

Evaluation of Production of Digital Twins Based on Blockchain Technology

A blockchain, as a form of distributed ledger technology, represents the unanimity of replication, synchronization, and sharing of data among various geographical sites. Blockchains have demonstrated impressive and effective applications throughout many aspects of the business. Blockchain technology can lead to the advent of the construction of Digital Twins (DTs). DTs involve the real representation of physical devices digitally as a virtual representation of both elements and dynamics prior to the building and deployment of actual devices. DT products can be built using blockchain-based technology in order to achieve sustainability. The technology of DT is one of the emerging novel technologies of Industry 4.0, along with artificial intelligence (AI) and the Internet of Things (IoT). Therefore, the present study adopts intelligent decision-making techniques to conduct a biased analysis of the drivers, barriers, and risks involved in applying blockchain technologies to the sustainable production of DTs. The proposed model illustrates the use of neutrosophic theory to handle the uncertain conditions of real-life situations and the indeterminate cases evolved in decision-makers’ judgments and perspectives. In addition, the model applies the analysis of Multi-criteria Decision Making (MCDM) methods through the use of ordered weighted averaging (OWA) and the Technique of Order Preference Similarity to the Ideal Solution (TOPSIS) to achieve optimal rankings for DT production providers based on consistent weighted decision-maker’s judgments in order to maintain and to assure sustainability. An empirical study is applied to the uncertain environment to aid decision-makers in achieving ideal decisions for DT providers with respect to various DT challenges, promoting sustainability and determining the best service providers. The Monte Carlo simulation method is used to illustrate, predict, and forecast the importance of the weights of decision-makers’ judgments as well as the direct impact on the sustainability of DT production.

RAI1 alternate probe identifies additional gastroesophageal adenocarcinoma cases as amplified following equivocal HER2 fluorescence in situ hybridization testing: experience from a national reference laboratory

The College of American Pathologists/American Society of Clinical Oncology recommends HER2 testing prior to initiation of targeted therapy for patients with advanced Gastroesophageal adenocarcinoma (GEA), using immunohistochemistry (IHC) followed by fluorescence in situ hybridization (FISH) in cases with an equivocal (score 2 + ) result on IHC. The FISH results are considered indeterminate if the HER2/CEP17 ratio is <2.0 with an average CEP17 copy number of ≥3.0 and a HER2 copy number ≥4.0 and ≤6.0 after counting additional tumor cells. Indeterminate results may be resolved by using an alternative chromosome 17 probe such as RAI1. The purpose of this study is to review our experience with RAI1 alternate probe in HER2 FISH testing of GEA in a large reference laboratory setting. Esophageal, gastroesophageal, and gastric adenocarcinomas received for HER2 FISH testing in our lab between 9/2018 and 1/2020 were included. HER2/CEP17 and HER2/ RAI1 ratios, and the average HER2, CEP17, RAI1 signals per cell were recorded. 328 GEA had HER2 testing performed in our lab during the study period. 101 (30.8%) were amplified, 169 (51.5%) were non-amplified and 58 (17.7%) were indeterminate. Following RAI1 testing, 42 (72.4%) of 58 indeterminate cases were reclassified as non-amplified and 16 (27.6%) were reclassified as amplified, increasing the total amplified cases to 117 (35.7%). The correlation between the average CEP17 and RAI1 copy number for all cases was weak (R2 = 0.095). In summary, using the alternate probe RAI1 reclassifies 27.6% of original HER2 FISH indeterminate gastroesophageal carcinomas as amplified, which makes them eligible for targeted therapies.

External Validation of the PediBIRN Screening Tool for Abusive Head Trauma in Pediatric Emergency Department Settings.

We conducted a retrospective, secondary analysis of an existing, deidentified, prospective data set captured to derive a bruising CDR. Subjects were patients under 3 years with bruising and confirmed acute head trauma. An expert medical panel had previously identified patients with AHT. Measures of the CDR's AHT screening performance (sensitivity, specificity, likelihood ratios) were calculated with 95% confidence intervals (CIs). Expert medical panel members had classified 78 of 117 eligible patients (67%) as AHT, 38 (33%) as non-AHT, and 1 as indeterminate. Excluding the indeterminate case, the PediBIRN-4 demonstrated a sensitivity of 0.96 (95% CI, 0.88-0.99), specificity of 0.29 (95% CI, 0.16-0.46), positive likelihood ratio of 1.35 (95% CI, 1.10-1.67), and negative likelihood ratio of 0.13 (95% CI, 0.04-0.46). Close inspection of the data revealed that 1 of the CDR's predictor variables had lowered specificity without impacting sensitivity. Eliminating this variable would have increased specificity to 0.84 (95% CI, 0.68-0.93). The PediBIRN 4-variable CDR demonstrated AHT screening sensitivity in the pediatric ED equivalent to pediatric intensive care unit and other inpatient settings, but lower specificity. Further study of a simplified 3-variable PediBIRN AHT screening tool for the ED setting is warranted.

Utility and safety of sole electromagnetic navigation bronchoscopy under moderate sedation for lung cancer diagnosis.

BackgroundElectromagnetic navigation bronchoscopy (ENB) is an emerging technique for diagnosing pulmonary lesions. However, limited data is available on its sole utility under a least invasive setting without general anesthesia. We aimed to evaluate the diagnostic performance and safety of sole ENB under moderate sedation for diagnosing pulmonary lesions suspicious for lung cancer and to determine clinical factors associated with a better diagnostic yield.MethodsWe performed a retrospective analysis of consecutive patients who underwent sole ENB under moderate sedation for lung lesion biopsy between August 2016 and June 2021 at Seoul National University Bundang Hospital, a tertiary center in South Korea. Diagnostic yield of the ENB-guided biopsy, safety endpoints defined by the incidence and severity of associated complications, and factors associated with higher diagnostic yield were evaluated.ResultsA total of 94 patients were evaluated. The final diagnostic yield of ENB was 81.5% (75/92), excluding two indeterminate cases. The diagnostic yield ranged from 79.8% to 81.9% assuming all indeterminate cases were false-negatives (79.8%) and true-negatives (81.9%). The sensitivity and specificity for malignancy were 77.6% (ranging from 75.6% to 77.6%) and 100%, respectively. Any-grade pneumothorax occurred in 4.3% of the patients, and 2.1% developed pneumothorax requiring additional intervention. Multivariable analyses identified the presence of a class 2 bronchus sign as the only significant predictor for a higher diagnostic yield (odds ratio =4.83, 95% CI: 1.16–20.12). The diagnostic yield of ENB among those with class 2 bronchus sign was 89.8% (53/59).ConclusionsSole ENB under moderate sedation for diagnosing pulmonary lesions displayed a good diagnostic yield and safety profile, thus confirming its utility in a least-invasive setting. Moreover, sole ENB could be possibly be superior to transthoracic needle aspiration for diagnosing lesions with class 2 bronchus sign accounting for similar yields and lower complication rates.

Is Free Breathing Possible During Computed Tomography-Guided Percutaneous Transthoracic Lung Biopsy? The Clinical Experience in 585 Cases.

The aim of the study was to retrospectively evaluate the safety and accuracy of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) of lung lesions during quiet breathing. We investigated the diagnostic performance and complication rate of 585 procedures in 563 patients (357 men; mean age, 67.7 years), who underwent CT-guided PTNBs during quiet breathing, aided by a respiratory targeting technique from May 2017 to July 2019. Differences between the cases with and without respiratory targeting were analyzed. Logistic regression analyses were performed to examine the development of pneumothorax and hemoptysis. Percutaneous transthoracic needle biopsy samples were successfully obtained in 574 of 585 procedures (98.1%). Final diagnoses included: 410 malignant cases, 119 benign cases, and 45 indeterminate cases. The sensitivity, specificity, and accuracy of diagnosis were 94.4%, 100%, and 95.7%, respectively. Use of respiratory targeting was associated with younger age (P = 0.004), smaller lesion size (P < 0.001), peripheral location (P = 0.003), shorter distance from the diaphragm (P < 0.001), lower lobe location (P < 0.001), prone position (P = 0.004), and visible motion artifact (P < 0.001). Pneumothorax and hemoptysis rates were 22.9% and 7.9%, respectively. Upon multivariate analysis, emphysema (P = 0.002) was the only independent risk factor for pneumothorax, whereas distance from the pleura greater than 2 cm (P < 0.001), tissue sampling 3 times or more (P = 0.003), and a less experienced operator (P < 0.001) were risk factors for hemoptysis. Computed tomography-guided PTNB during quiet breathing with respiratory targeting yielded high diagnostic performance with a slightly higher rate of complications. Free-breathing PTNB can be applied in clinical practice, based on lesion location and risk factors for complications.

Molecular Testing of Atypical Thyroid Nodules with Corresponding Surgical Correlation: Five-Year Retrospective Review in Veterans Population.

ObjectiveWe report the results of a retrospective five-year study within a veteran population aimed at correlating abnormal thyroid fine-needle aspiration (FNA) diagnosis with associated molecular testing to the histology of the surgical resection.MethodsA retrospective analysis of abnormal thyroid FNAs with associated molecular testing and surgical outcome was conducted from January 1, 2015 to December 31, 2020. Aspirates were classified using the Bethesda system for reporting thyroid cytopathology, including atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy (SM), and malignant. Pertinent data, including patient demographics, imaging, and ancillary testing were reviewed. A thyroid cancer mutation panel assessing the most common mutations and rearrangements associated with neoplasia was utilized. The results of molecular testing were directly compared and correlated with final cytological and histological diagnosis.ResultsA total of 1850 thyroid aspirates were performed, 200 of which were given an abnormal cytologic diagnosis. Thirty-six samples were submitted for molecular testing and subsequent surgical follow-up. Four were called malignant on cytology. 32 were placed in an indeterminate category (89%). Within indeterminate cases: 53% exhibited positive molecular mutations (n=17), 34% no mutation detected (n=11), and 13% insufficient quantity for testing (n=4). Upon surgical resection in the mutation-positive group: 18% had no malignancy (n=3), and the remaining 82% were positive for malignancy (n=14). Mutations in the histologically malignant group included: 57% BRAF (n=8), 21% NRAS (n=3), 7% HRAS (n=1), 7% KRAS (n=1), and 7% PAX8/PPAR gamma (n=1). In indeterminate cases with no mutation detected, 10 cases were found to be benign, and one case of malignancy was diagnosed. The probability of indeterminate diagnosis in combination with no mutation yielded a 91% chance of benign entity and 9% chance of malignancy. We demonstrated 93% sensitivity and 91% negative predictive value (NPV) for the risk of malignancy in indeterminate cytology specimens with ancillary molecular testing. There was 77% specificity and 82% positive predictive value (PPV) for our data set.ConclusionsIn indeterminate samples, the detection of a mutation was highly predictive of malignancy and a strong indicating factor for surgery with a high sensitivity and NPV. Molecular testing refined or established the diagnosis in 89% of the cases. Our results indicate that molecular testing of thyroid nodules enhances the accuracy of FNA cytology and the subsequent surgical outcome.

Molecular Pathological Diagnosis of Thyroid Tumors Using Spatially Resolved Metabolomics.

The pathological diagnosis of benign and malignant follicular thyroid tumors remains a major challenge using the current histopathological technique. To improve diagnosis accuracy, spatially resolved metabolomics analysis based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique was used to establish a molecular diagnostic strategy for discriminating four pathological types of thyroid tumor. Without any specific labels, numerous metabolite features with their spatial distribution information can be acquired by AFADESI-MSI. The underlying metabolic heterogeneity can be visualized in line with the cellular heterogeneity in native tumor tissue. Through micro-regional feature extraction and in situ metabolomics analysis, three sets of metabolic biomarkers for the visual discrimination of benign follicular adenoma and differentiated thyroid carcinomas were discovered. Additionally, the automated prediction of tumor foci was supported by a diagnostic model based on the metabolic profile of 65 thyroid nodules. The model prediction accuracy was 83.3% when a test set of 12 independent samples was used. This diagnostic strategy presents a new way of performing in situ pathological examinations using small molecular biomarkers and provides a model diagnosis for clinically indeterminate thyroid tumor cases.

Deficiency indices of block Jacobi matrices and Miura transformation

Abstract We study the infinite Jacobi block matrices under the discrete Miura-type transformations which relate matrix Volterra and Toda lattice systems to each other and the situations when the deficiency indices of the corresponding operators are the same. A special attention is paid to the completely indeterminate case (i.e., then the deficiency indices of the corresponding block Jacobi operators are maximal). It is shown that there exists a Miura transformation which retains the complete indeterminacy of Jacobi block matrices appearing in the Lax representation for such systems, namely, if the Lax matrix of Volterra system is completely indeterminate, then so is the Lax matrix of the corresponding Toda system, and vice versa. We consider an implication of the obtained results to the study of matrix orthogonal polynomials as well as to the analysis of self-adjointness of scalar Jacobi operators.

Diagnosis and Comparison of Three Invasive Detection Methods for Helicobacter pylori Infection.

The purpose of this study was to compare different invasive methods for Helicobacter pylori (H. pylori) detection, namely PCR for H. pylori specific ureC gene, Rapid urease test (RUT), and histopathological examination by modified Giemsa staining. Endoscopic gastroduodenal biopsy materials were collected from dyspeptic patients who underwent endoscopic examination upon fulfilling the inclusion criteria. Three to four samples were collected from each patient after taking informed consent and proper clinical history. A rapid urease test (RUT) was done on spot with in-house RUT media from 1 specimen. One to two specimens were preserved in 10% formaldehyde for histopathology and PCR for ureC gene was done from 1 specimen. Collected biopsy specimens from gastric and duodenal mucosa of 142 patients were categorized as H. pylori-positive cases and H. pylori-negative cases based on the case definition used in the study upon positivity of 3 diagnostic tests. Among 142 biopsy specimens, 34.5% were categorized as H. pylori-positive cases, 35.2% as H. pylori-negative cases, and finally 30.2% as doubtful or indeterminate cases. Rapid urease test was the most sensitive method, closely followed by ureC gene PCR and histopathology, with a sensitivity of 94.2%, 83.0%, and 76.5%, respectively. Whereas histology was the most specific, having 98.0% specificity followed by 83.0% in PCR. RUT was the least specific, with 55.5% specificity. While histopathology could detect H. pylori infection with the highest specificity, for definitive diagnosis combination of any 2 methods should be used, if available.

Optimizing the interpretation of Clostridioides difficile two-step diagnostic algorithm results through antimicrobial stewardship.

Over a 4-year period, the antimicrobial stewardship team reviewed all positive (PCR+/Tox+) and indeterminate (PCR+/Tox-) cases with the most responsible physician for classification of patients as infection or colonization. Among 501 indeterminate samples, 213 (43%) were considered to be clinical infection, suggesting the need for ongoing clinical assessment of indeterminates.

What shape grammars do that CAD should: the 14 cases of shape embedding

Abstract Shape queries based on shape embedding under a given Euclidean, affine, or linear transformation are absent from current CAD systems. The only systems that have attempted to implement shape embedding are the shape grammar interpreters albeit with promising but inconclusive results. The work here identifies all possible 14 cases of shape embedding with respect to the number of available registration points, four for determinate cases and ten for indeterminate ones, and an approach is sketched to take on the complexities underlying the indeterminate cases. All visual calculations are done with shapes consisting of straight lines in the Euclidean plane within the algebra U ij for i = 1 the dimension of lines and j = 2 the dimension of space in which the lines are defined, transformed and combined. Aspects of interface design and integration to current work design workflows are deliberately left aside.

Screening success: A virtual MDT can reduce the number of patients requiring respiratory follow-up post-COVID-19 pneumonia in line with British Thoracic Society guidance

We reviewed all patients with a clinico-radiological diagnosis of COVID-19 admitted to hospital during a 3-month period and assigned a follow-up stream based on British Thoracic Society guidance. We changed the follow-up pathway in 71% (277/392) and refined the pathway in 67% (261/392) of indeterminate cases. We also created an automated process for the general practitioner to book follow-up imaging and will use this process going forward. These findings highlight the importance of the MDT review of cases with suspected COVID-19 pneumonia prior to clinic attendance to ensure appropriate patients are followed up and to optimise utilisation of outpatient imaging and clinics.