Optimal Diagnostic Method Research Articles

CT Angiography for Aortic Arch Anomalies: Prevalence, Diagnostic Efficacy, and Illustrative Findings.

Aortic arch anomalies encompass a diverse spectrum of conditions. Elucidating the prevalence of these anomalies, their impact on patient wellbeing, and the most effective diagnostic tools are crucial steps in ensuring optimal patient care. This paper aims to explore the various presentations of aortic arch anomalies, emphasizing the remarkable utility of computed tomography (CT) angiography in their definitive diagnosis and characterization. We conducted a retrospective study on patients who were submitted to the CT angiography of the thoracic aorta or supra-aortic trunks, or the contrast-enhanced CT scans of the thorax and/or cervical region between January 2021 and February 2024 in our Hospital. Out of the total of 2350 patients, 18 were diagnosed with aortic arch anomalies, with an average age of approximately 55 years. The aortic arch anomalies identified in the study were as follows: left aortic arch with the aberrant origin of the right subclavian artery, right aortic arch (types I and II), double aortic arch, aortic coarctation, aortic pseudocoarctation, and ductus diverticulum. Although often asymptomatic, aortic arch anomalies require recognition and CT using advanced post-processing techniques is the optimal diagnostic method with the ability to also identify other associated cardiac or vascular malformations.

A Retrospective Comparison of Diagnostic Tools of Bullous Pemphigoid for Elderly Patients.

Older patients who are predisposed to bullous pemphigoid (BP) may exhibit reluctance to undergo skin biopsy due to potential complications. This study aimed to conduct a comparative evaluation among histology, direct immunofluorescence (DIF), and indirect immunofluorescence (IIF) to determine the optimal diagnostic tool in elderly patients. A retrospective study was conducted on 841 patients suspected of having BP. All cases were initially classified as BP and non-BP in accordance with the diagnostic criteria. Student's t-test and chi-squared test examined differences between the 2 groups. We evaluated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio detected by the 3 tools. We stratified the analysis by age to compare the performance of the diagnostic tools and examined the risk factors associated with BP using logistic regression. Overall, histology exhibited the highest sensitivity (89.4%), while DIF demonstrated the highest specificity (67.1%). In the elderly, the IIF test exhibited the highest specificity (57.5%), the highest positive likelihood ratio (2.047), and the lowest negative likelihood ratio (0.226). Among patients taking Dipeptidyl Peptidase-4 (DPP-4) inhibitors, IIF demonstrated the highest positive likelihood ratio (3.194) and the second-lowest negative likelihood ratio (0.235). In cases that elderly patients suspected of having BP are reluctant to undergo skin biopsy, IIF demonstrates the optimal diagnostic method due to its highest positive likelihood ratio, the lowest negative likelihood ratio among the 3 diagnostic measures. Moreover, IIF is found to be a more effective tool for detecting BP in patients using DPP-4 inhibitors.

Potential Predictive of Thoracic CT Value and Bone Mineral Density T-Value in COPD Complicated with Osteoporosis.

COPD, combined with Osteoporosis, has a high incidence and potential for great harm. Choosing an optimal diagnostic method to achieve bone mineral density (BMD) screening is crucial for COPD patients. Studies on COPD patients with BMD reduction are lacking. To identify the risk factors of BMD reduction and osteoporosis in COPD patients. We included a total of 81 patients with AECOPD, who were admitted to the hospital from July 1, 2019, to January 31, 2020. Patients were grouped into BMD normal group, BMD reduced group and OP group. The areas under ROC curve were used to explore the value of CT values in the diagnosis of bone abnormality, and clinical indicators were collected. The CT value of the vertebral cancellous bone is highly correlated with the T value of BMD (R > 5.5, P < 0.0001). Using multivariate Logistic regression analysis, we showed that COPD duration, BMI, 25-hydroxyvitamin D3, and long-term inhaled glucocorticoid were independent factors affecting different BMD levels in COPD patients. No significant difference in bone formation indexes between groups. β-crossL was negatively correlated with serum IL-6 (r=-0.254, P=0.022), and ALP was positively correlated with serum TNF-α (r=0.284, P=0.023). Thoracolumbar vertebral cancellous bone CT has potential value in the diagnosis of bone abnormality. COPD duration, BMI, 25-hydroxyvitamin D3, and long-term inhaled glucocorticoid may contribute to the BMD reduction in COPD patients, and serum IL-6 and TNF-α regulate bone metabolism in COPD patients.

Preoperative diagnosis of parathyroid gland pathology in patients with persistent or recurrent primary hyperparathyroidism: a retrospective study

INTRODUCTION: Localization of abnormal parathyroid glands in persistent or relapsed patients with primary hyperparathyroidism presents problems for surgeons before repeated surgery. There is no clear standard for the choice of diagnostic modality for localization of PG in this group of patients.OBJECTIVE: To search for the optimal diagnostic protocol of the parathyroid pathology preoperative diagnosis in patients with primary hyperparathyroidism with persistent or recurrent disease.MATERIALS AND METHODS: 55 patients diagnosed with persistence or recurrence of PHPT who underwent repeated surgical treatment were included in the study. Before surgical intervention all patients underwent laboratory and instrumental investigations in the volume of: blood tests for PTH, TTH, ionized calcium, 25(OH)D, creatinine, phosphorus, neck ultrasound, parathyroid scintigraphy by washout method, dual-isotope subtractive scintigraphy of parathyroid glands (early and delayed phases), SPECT of parathyroid glands (with uptake correction), computed tomography of the neck with intravenous bolus contrast.RESULTS: CT and planar subtraction dual-isotope scintigraphy showed the highest DA in the overall group (persistence and recurrence) (78% and 78%), with the DA of these methods differing slightly (88% and 92%) and overall accuracy being higher for CT (90% and 87%). Neck ultrasound showed the lowest rates among all methods (DA — 46%, DS — 80%, OA — 67%). Planar scintigraphy (washout) and SPECT were comparable in their informativeness: DA — 67% and 65%, DS — 96% and 98%, OA — 85% and 86%.DISCUSSION: The most commonly used current diagnostic search algorithm before reoperation is visualization of the thyroid gland by two modalities: Neck ultrasound and parathyroid scintigraphy (washout/subtraction) or SPECT-CT. In doubtful cases, the second step is computed tomography of the neck with contrast or PET/CT. It is extremely difficult to choose one optimal diagnostic method, as none of them has 100% diagnostic accuracy. In addition, each study has limitations, and the availability of some modalities is limited. In our study, the location of pathologically altered thyroid was correctly recognized in 90% of cases by CT with contrast and in 87% of cases by planar subtraction dual-isotope scintigraphy. The informativeness of neck ultrasound showed the lowest values of all modalities. SPECT and planar washout scintigraphy took an intermediate position in terms of diagnostic accuracy.CONCLUSION: Isolated ultrasonography of the neck has low diagnostic accuracy in patients with primary hyperparathyroidism with persistent or recurrent disease. We recommend the combination of US with contrast-enhanced computed tomography of the neck or US with dual isotope subtraction scintigraphy of the parathyroid glands, which have the same diagnostic accuracy. SPECT and planar washout scintigraphy can be used for the diagnosis of abnormal parathyroid glands in persistent or recurrent patients with primary hyperparathyroidism when more informative techniques are unavailable. When the techniques were combined, the combination of ultrasound/CT with contrast and ultrasound/planar subtraction dual isotope scintigraphy showed the best results with DA of 85% and 86%.

SAT456 Validation And Optimization Of TSH And FT4 Reference Interval Definitions During Pregnancy

Abstract Disclosure: J. Osinga: None. A. Derakhshan: None. W. Consortium on Thyroid and Pregnancy: None. T. Korevaar: None. Objective: While international guidelines recommend to diagnose gestational thyroid disease according to trimester specific TSH and FT4 reference intervals (RIs), most centers still rely on non-pregnancy RIs in combination with a fixed upper limit for TSH or by a deduction from this upper limit. Both strategies are based on expert opinion and have not been properly validated. We aimed to quantify the diagnostic accuracy of the alternative methods, and to identify the optimal diagnostic strategy to diagnose thyroid disease using a non-pregnancy TSH and FT4 RI. Methods: We performed an individual participant data meta-analysis of prospective birth cohorts. RIs and disease prevalences were calculated according to 1) trimester specific RIs, 2) non-pregnancy RIs, 3) non-pregnancy RIs with a fixed upper limit for TSH of 4.0mU/L and 4) non-pregnancy RIs with a 0.5mU/L subtraction from the TSH upper limit. Sensitivity and false discovery rates (FDR) of the alternative methods were calculated as compared to method 1), which is currently accepted as the best practice. We also varied non-pregnancy RIs with differing subtractions to identify the optimal diagnostic method. Participants with a treatment indication were defined as either overt hypothyroidism, subclinical hypothyroidism with TSH&amp;gt;10 or with concomitant TPOAb positivity. Results: The study population comprised 58,815 participants in 19 prospective cohorts. For first trimester overt hypothyroidism, sensitivity of all alternative methods (non-pregnancy RIs, fixed limit approach, subtraction approach) was similarly poor (0.43, 0.46 and 0.46) with a moderate FDR (0.22, 0.28 and 0.29). For first trimester subclinical hypothyroidism, results were slightly better for all methods, except for the FDR of the subtraction method; sensitivity (0.44, 0.54 and 0.55) and FDR (0.23, 0.23 and 0.35). Using the trimester specific approach, 2.01% of all women had a treatment indication in the first trimester. For this group, both the fixed limit and subtraction approach had a sensitivity of 0.65 and a FDR of 0.11 and 0.17 respectively. Furthermore, we leveraged our dataset to identify how non-pregnancy TSH and FT4 RIs can be used to approach pregnancy-specific RIs. We identified that for a treatment indication, subtraction of 20-25% of the non-pregnancy upper limit of TSH and subtracting 5-10% of the non-pregnancy lower limit of FT4 yielded a higher sensitivity (0.72-0.77) with a comparable FDR (0.20-0.25). Conclusion: Currently recommended alternative methods for defining RIs for TSH and FT4 in pregnancy have poor sensitivity when compared to the currently accepted trimester specific approach, and lead to substantial overdiagnosis. A relative subtraction from the non-pregnancy upper limit of TSH and lower limit of FT4 could considerably improve the diagnostic rates and would be directly available in daily practice. Presentation: Saturday, June 17, 2023

Clinical and genetic characteristics of primary hypertrophic osteoarthropathy

Background. Primary hypertrophic osteoarthropathy is a rare genetically heterogeneous disease with three clinical variants. The classic one is a combination of hyperostosis, arthropathy and pachyderma and two variants with damage to only bone structures or pachyderma. Two genes responsible for the occurrence of primary hypertrophic osteoarthropathy have been identified: HPGD (debut age up to one year) and SLCO2A1 (debut in puberty and adolescence), whose products are involved in prostaglandin E2 metabolism. Two recurrent variants were identified in the HPGD gene: c.175_176delCT(p.Leu59fs) in patients from Europe and c.310_311delCT in patients from China. There were no clinical and genetic correlations in patients with different variants in the identified genes, which may be due to a small number of observations. The analysis of clinical manifestations in patients with newly identified variants or previously unidentified combinations of variants in a compound‑heterozygous state helps to understand the pathogenesis and prognosis of the course of the disease.Aim. To present the clinical and genetic characteristics of two Russian patients with primary hypertrophic osteoarthropathy caused by a newly identified combination of nucleotide variants in a compound‑heterozygous state in the HPGD and SLCO2A1 genes.Materials and methods. Clinical examination, radiography of the skeleton and chest, electrocardiography, echocardiography. Confirmation of the pathogenicity of the identified variants and clarification of the type of disease was carried out using automatic Sanger sequencing.Results. The clinical and genetic characteristics of two unrelated patients with primary hypertrophic osteoarthropathy caused by an undescribed combination of variants in the compound heterozygous state in the HPGD and SLCO2A1 genes were analyzed. In a patient with variants in the SLCO2A1 gene, the disease debuts at the age of 14 with deformities of the fingers, nails on the hands and feet, followed by the addition of burning pain in the distal parts of the arms and legs. At the age of 33, the examination revealed deformity of the fingers of the hands and feet by the type of drumsticks and nails by the type of watch glasses, enlargement of the knee joints, pronounced arthralgia. There were no signs of pachyderma. The new generation sequencing revealed two variants in the SLCO2A1 gene c.764G&gt;A(p.Gly255Glu) in exon 6 and c.1333C&gt;T(p.Arg445Cys) in exon 10. These variants were identified earlier in a compound‑heterozygous combination with other variants in patients with the classical phenotype of the disease, which were not present in the patient we observed. A feature of the case was pronounced hyperhidrosis and burning pain in the extremities, which may be due to stimulation of nociceptors in the musculoskeletal structures.Deformities of the fingers, nails of the hands and feet occurred in a patient with variants in the HPGD gene at 6 months. At the age of 9 years, a change in shape, stiffness and arthralgia of the knee and elbow joints without pachyderma were revealed. The identified variant with c.175_176delCT(p.Leu59fs) in this gene is often found in patients from European countries, and the other is c.1A&gt;G(p.Met1?) discovered for the first time.Conclusion. The results allow us to conclude that when we found combinations of two variants in the HPGD and SLCO2A1 genes, there will be no pachyderma in the spectrum of clinical manifestations of primary hypertrophic osteoarthropathy. Sequencing of the new generation exome is the optimal diagnostic method.

Нейтрофильные и моноцитарные экстраклеточные ловушки в диагностике постковидного синдрома

Post-COVID syndrome (long covid, post COVID-19 condition) is characterized by cognitive and mental disorders, chest and joint pain, impaired sense of smell and taste, as well as by gastrointestinal and cardiac disorders. The diagnosis of post-COVID syndrome is based mainly on the patients' complaints. To date, no optimal diagnostic method has been proposed. The study was aimed to compare the informative value of the indicators obtained during conventional assessment of patients with post-COVID syndrome and the blood levels of neutrophil (NETs) and monocyte (METs) extracellular traps. The study involved neutropils and monocytes collected from 21 patients with post-COVID syndrome aged 18–59. Fluorescence microscopy and the SYBR Green (Evrogen) fluorescent dye for double-stranded DNA were used for enumeration and imaging of extracellular traps. Clinical and laboratory indicators make it impossible to identify the changes specific for post-COVID syndrome. At the same time, post-COVID syndrome is characterized by inflammation in the vascular endothelium. The filamentous forms of NETs found in blood are a laboratory feature of such aseptic inflammation. The filamentous forms of NETs have been detected only in those patients who have a history of mild to severe СOVID-19, while the filamentous forms of METs have been found in patients having a history of severe infection. The findings show that the detection of the filamentous forms of NETs and METs in blood is the most informative diagnostic feature of post-COVID syndrome.

Low-toxin Clostridioides difficile RT027 strains exhibit robust virulence

ABSTRACT Clostridioides difficile is a leading cause of healthcare-associated infections worldwide. Currently, there is a lack of consensus for an optimal diagnostic method for C. difficile infection (CDI). Multi-step diagnostic algorithms use enzyme immunosorbent analysis (EIA)-based detection of C. difficile toxins TcdA/TcdB in stool, premised on the rationale that EIA toxin-negative (Tox−) patients have less severe disease and shorter diarrhoea duration. The aim of this study was to characterize toxigenic (i.e. tcdA/tcdB-positive) C. difficile strains isolated from diarrheic patient stool with an EIA Tox− (i.e. “discrepant”) CDI diagnostic test result. Recovered strains were DNA fingerprinted (ribotyped), subjected to multiple toxin, genome and proteome evaluations, and assessed for virulence. Overall, of 1243 C. difficile-positive patient stool specimens from Southern Arizona hospitals, 31% were discrepant. For RT027 (the most prevalent ribotype)-containing specimens, 34% were discrepant; the corresponding RT027 isolates were cytotoxic to cultured fibroblasts, but their total toxin levels were comparable to, or lower than, the historic low-toxin-producing C. difficile strain CD630. Nevertheless, these low-toxin RT027 strains (LT-027) exhibited similar lethality to a clade-matched high-toxin RT027 strain in Golden Syrian hamsters, and heightened colonization and persistence in mice. Genomics and proteomics analyses of LT-027 strains identified unique genes and altered protein abundances, respectively, relative to high-toxin RT027 strains. Collectively, our data highlight the robust virulence of LT-027 C. difficile, provide a strong argument for reconsidering the clinical significance of a Tox− EIA result, and underscore the potential limitations of current diagnostic protocols.

Identification of Pathogenic Variant Burden and Selection of Optimal Diagnostic Method Is a Way to Improve Carrier Screening for Autosomal Recessive Diseases.

Cystic fibrosis, phenylketonuria, alpha-1 antitrypsin deficiency, and sensorineural hearing loss are among the most common autosomal recessive diseases, which require carrier screening. The evaluation of population allele frequencies (AF) of pathogenic variants in genes associated with these conditions and the choice of the best genotyping method are the necessary steps toward development and practical implementation of carrier-screening programs. We performed custom panel genotyping of 3821 unrelated participants from two Russian population representative samples and three patient groups using real-time polymerase chain reaction (PCR) and next generation sequencing (NGS). The custom panel included 115 known pathogenic variants in the CFTR, PAH, SERPINA1, and GJB2 genes. Overall, 38 variants were detected. The comparison of genotyping platforms revealed the following advantages of real-time PCR: relatively low cost, simple genotyping data analysis, and easier detection of large indels, while NGS showed better accuracy of variants identification and capability for detection of additional pathogenic variants in adjacent regions. A total of 23 variants had significant differences in estimated AF comparing with non-Finnish Europeans from gnomAD. This study provides new AF data for variants associated with the studied disorders and the comparison of genotyping methods for carrier screening.

Management of osteoporosis in patients with chronic kidney disease.

Patients with CKD have a 4-fivefold higher rate of fractures. The incidence of fractures increases with deterioration of kidney function. The process of skeletal changes in CKD patients is characterized by compromised bone strength because of deterioration of bone quantity and/or quality. The fractures lead to a deleterious effect on the quality of life and higher mortality in patients with CKD. The pathogenesis of bone loss and fracture is complex and multi-factorial. Renal osteodystrophy, uremic milieu, drugs, and systemic diseases that lead to renal failure all contribute to bone damage in CKD patients. There is no consensus on the optimal diagnostic method of compromised bone assessment in patients with CKD. Bone quantity and mass can be assessed by dual-energy x-ray absorptiometry (DXA) or quantitative computed tomography (QCT). Bone quality on the other side can be assessed by non-invasive methods such as trabecular bone score (TBS), high-resolution bone imaging methods, and invasive bone biopsy. Bone turnover markers can reflect bone remodeling, but some of them are retained by kidneys. Understanding the mechanism of bone loss is pivotal in preventing fracture in patients with CKD. Several non-pharmacological and therapeutic interventions have been reported to improve bone health. Controlling laboratory abnormalities of CKD-MBD is crucial. Anti-resorptive therapies are effective in improving BMD and reducing fracture risk, but there are uncertainties about safety and efficacy especially in advanced CKD patients. Accepting the prevalent of low bone turnover in patients with advanced CKD, the osteo-anabolics are possibly promising. Parathyroidectomy should be considered a last resort for intractable cases of renal hyperparathyroidism. There is a wide unacceptable gap in osteoporosis management in patients with CKD. This article is focusing on the updated management of CKD-MBD and osteoporosis in CKD patients. Chronic kidney disease deteriorates bone quality and quantity. The mechanism of bone loss mainly determines pharmacological treatment. DXA and QCT provide information about bone quantity, but assessing bone quality, by TBS, high-resolution bone imaging, invasive bone biopsy, and bone turnover markers, can guide us about the mechanism of bone loss.

Prospective Studies Comparing Structured vs Nonstructured Diagnostic Protocol Evaluations Among Patients With Fever of Unknown Origin

Patients meeting the criteria for fever of unknown origin (FUO) can be evaluated with structured or nonstructured approaches, but the optimal diagnostic method is unresolved. To analyze differences in diagnostic outcomes among patients undergoing structured or nonstructured diagnostic methods applied to prospective clinical studies. PubMed, Embase, Scopus, and Web of Science databases with librarian-generated query strings for FUO, PUO, fever or pyrexia of unknown origin, clinical trial, and prospective studies identified from January 1, 1997, to March 31, 2021. Prospective studies meeting any adult FUO definition were included. Articles were excluded if patients did not precisely fit any existing adult FUO definition or studies were not classified as prospective. Abstracted data included years of publication and study period, country, setting (eg, university vs community hospital), defining criteria and category outcome, structured or nonstructured diagnostic protocol evaluation, sex, temperature threshold and measurement, duration of fever and hospitalization before final diagnoses, and contribution of potential diagnostic clues, biochemical and immunological serologic studies, microbiology cultures, histologic analysis, and imaging studies. Structured protocols compared with nonstructured diagnostic methods were analyzed using regression models. Overall diagnostic yield was the primary outcome. Among the 19 prospective trials with 2627 unique patients included in the analysis (range of patient ages, 10-94 years; 21.0%-55.3% female), diagnoses among FUO series varied across and within World Health Organization (WHO) geographic regions. Use of a structured diagnostic protocol was not significantly associated with higher odds of yielding a diagnosis compared with nonstructured protocols in aggregate (odds ratio [OR], 0.98; 95% CI, 0.65-1.49) or between Western Europe (Belgium, France, the Netherlands, and Spain) (OR, 0.95; 95% CI, 0.49-1.86) and Eastern Europe (Turkey and Romania) (OR, 0.83; 95% CI, 0.41-1.69). Despite the limited number of studies in some regions, analyses based on the 6 WHO geographic areas found differences in the diagnostic yield. Western European studies had the lowest percentage of achieving a diagnosis. Southeast Asia led with infections at 49.0%. Noninfectious inflammatory conditions were most prevalent in the Western Pacific region (34.0%), whereas the Eastern Mediterranean region had the highest proportion of oncologic explanations (24.0%). In this systematic review and meta-analysis, diagnostic yield varied among WHO regions. Available evidence from prospective studies did not support that structured diagnostic protocols had a significantly better rate of achieving a diagnosis than nonstructured protocols. Clinicians worldwide should incorporate geographical disease prevalence in their evaluation of patients with FUO.

CYSTIC FIBROSIS SCENARIO IN INDIA

Abnormal transport of chloride ion in the epithelial cells is caused by a autosomal recessive monogenic condition known as cystic fibrosis (CF). It belongs to the rare genetic disease in India. Persistent coughing with phlegm, pneumonia, bronchitis, bulky stool and hard bowl movement are most symptoms of the disease. Mutation in CFTR (cystic fibrosis transmembrane conductance regulator) gene present on chromosome 7 having 230 kb nucleotides with 23 exons leads to development of disease. Determination of sweat electrolyte is considered as optimal diagnostic method. Results of previous studies have shown that cystic fibrosis increase the sodium and chloride concentrations. Mutations like ΔF508, G542X, R553X, N130K and 621+1 (G →T) are most common in CF patients in India. Among them ΔF508 is most severe and predominant mutation. Reports have shown as high as 56% frequency of ΔF508 in Indian patients. CF can be treated with anti-inflammatory drugs, CFTR modulators and combination therapies. Early screening can be an effective strategy for early diagnosis and treatment of cystic fibrosis.

Clinicopathologic characteristics and diagnostic methods of RET rearrangement in Chinese non-small cell lung cancer patients.

BackgroundRearranged during transfection (RET) rearrangement has been identified as one of the crucial oncogenic drivers in non-small cell lung cancer (NSCLC). Recently, two highly selective RET inhibitors have been approved by the US Food and Drug Administration and demonstrated remarkable responses. However, the clinical characteristics, outcomes and optimal diagnostic method of RET-rearrangements are not well understood. This study sought to evaluate the prevalence and characteristics of RET rearrangement, identify an effective diagnostic method for it, and correlate its presence with outcomes.MethodsA total of 9,431 Chinese NSCLCs from two cancer centers who have undertaken targeted DNA-NGS were enrolled and 167 RET-positive cases were screened. Non-canonical RET rearrangements were confirmed by targeted RNA-NGS. If material was sufficient, positive cases were analyzed by fluorescence in situ hybridization (FISH) (n=30) and immunohistochemistry (IHC) (n=57). Clinicopathologic characteristics, molecular profiling and treatment outcomes of RET rearrangement were evaluated.ResultsThe prevalence of RET rearrangement was 1.52% (138/9,101) in unfiltered cases and 8.79% (29/330) in EGFR/KRAS/BRAF/ALK-negative cases. RET rearrangement was common in females, never smokers, and lung adenocarcinoma patients. Additionally, 40.3% of stage IV RET-rearranged NSCLC patients developed brain metastases. TP53 was the most common concurrent mutation, and 8 patients harbored concurrent driver oncogenic alterations, including EGFR (N=5), KRAS (N=2), and ALK (N=1). Non-canonical fusion partners were identified in 13.8% (23/167) of cases by DNA-based NGS, and RNA-based NGS identified 3 new partners (EPS8, GOLGA5, and TNIP1). The concordance of FISH and NGS was 83.3% (25/30), while the concordance of IHC and NGS was only 28.1% (16/57). Both IHC and FISH demonstrated lower sensitivity for NCOA4-/other-RET fusions. The CCDC6-RET subgroup had significantly longer progression-free survival than the KIF5B-RET subgroup, both after chemotherapy (23 vs. 9.7 months; P=0.014).ConclusionsRET rearrangement occurs in 1.52% of Chinese NSCLCs and has identifiable clinicopathologic characteristics. RET IHC has a low sensitivity, disavowing its use in routine practice. While NGS and FISH has good performance in identifying RET rearrangement. Both IHC and FISH demonstrated lower sensitivity for NCOA4-/others-RET fusions. Clinical benefit with chemotherapy is different between CCDC6-RET and KIF5B-RET fusion patients, optimal treatment should be considered when selecting therapies for patients with RET-rearranged lung cancers.

Métodos diagnósticos para la detección de infección por Helicobacter pylori. ¿Cuál y cuándo deben solicitarse?

Gastric infection by Helicobacter pylori has a variable prevalence worldwide. In Latin America, it can exceed 50% of infected people. It is associated with peptic ulcer, gastric cancer, MALT lymphoma, immune thrombocytopenic purpura, among other pathologies. There is no optimal diagnostic method, and its presence can be detected by both invasive methods that require an upper gastrointestinal endoscopy, and non-invasive methods. Within the invasive, we have the rapid urease test, histology, molecular tests such as polymerase chain reaction and culture. On the other hand, non-invasive tests include the breath test, Helicobacter pylori antigen in stools, polymerase chain reaction in stools and serology. Depending on the clinical scenario, the diagnostic test to be used, its benefits and weaknesses should be known. It is important to consider the age of the patient, their gastric cancer risk factors, the need for endoscopy for this or another reason, the availability of diagnostic tests and the cost, among others.

Modern approaches to the diagnosis and treatment of coccygodynia

Currently, there are no clear clinical guidelines for the diagnosis and treatment of coccygodynia. There are still debatable issues related to the choice of the most optimal diagnostic method, evaluation of the effectiveness of blockades, establishment of indications for surgical treatment and the determination of the most appropriate method of surgery. The features of the anatomical structure of the coccyx are considered in the scientific paper. The clinical picture and neurological symptoms of coccygodynia are described in detail. Modern instrumental methods of diagnosis of this disease (spondylography, MSCT, MRI) are presented. Modern scientific works on evaluating the effectiveness of conservative and surgical treatment have been studied. The methods of surgical treatment of patients with coccygodynia are analyzed. Indications for surgical treatment and the results of surgeries in patients with coccygodynia are considered. In addition, the authors presented their classification of coccygodynia.

Маастрихтський консенсус-5: аналітичний огляд положень

У даній статті проаналізовано положення Ма­астрихтського консенсусу-5 з вивчення H. pylori-інфекції. Показано, як змінювались уяви щодо діагностики та лікування хелікобактерної інфекції в попередніх Маастрихтських консенсусах. Підкреслено, що сьогодні хелікобактерний гастрит вважається інфекційним захворюванням. Окремо розглянуто питання взаємозв’язку цієї інфекції з патологією гастродуоденальної зони, включаючи функціональну диспепсію, НПЗП-гастропатії та інші. Показані сучасні підходи до діагностики хелікобактеріозу з визначенням вибору найбільш оптимального методу діагностики в різних ситуаціях. Окремо розібрані підходи до антихелікобактерної терапії. Зроблено акцент на залежності сучасних схем терапії хелікобактеріозу від ступеня резистентності H. pylori до ключових антибіотиків. Підтверджена важливість ерадикації H. pylori щодо профілактики передракових змін шлунка. Показано зростаючий інтерес дослідників до нехелікобактерної флори в шлунку. Розглянута важлива роль пробіотиків в антихелікобактерній терапії.

Preventive technologies in geriatrics: focus on falls

Falls predict functional status declines in old age and institutionalization. Among the causes of the falls are sensory deficits, cognitive impairment, chronic diseases such as cardiovascular, endocrine diseases, musculoskeletal system pathology, the use of sedatives, antihypertensive drugs, neuroleptics and diuretics, as well as external causes, including inappropriate aids. The optimal diagnostic method in this case is a comprehensive geriatric assessment, which allows for focused history taking, detailing the circumstances of the fall, identification of risk factors and assessment of consequences, the gait and balance testing, determination of the lower limbs and joints functions are hold in the course of CGA along with orthostatic test that detects sensory deficits. Additional measures of mandatory recommendations should be a discussion of rational nutrition, with an emphasis on adequate intake of protein with food and fluids as prevention.

Diagnostic accuracy of apparent diffusion coefficient (ADC) value in differentiating malignant from benign solid liver lesions: a systematic review and meta-analysis.

We undertook a systematic review and meta-analysis of the diagnostic performance of mean apparent diffusion coefficient (ADC) values derived by diffusion-weighted (DW)-MRI in the characterization of solid benign and malignant liver lesions, and to assess their value in discriminating these lesions in daily routine practice. A systematic review of PubMed, Embase, Scopus, and Web of Science was conducted to retrieve studies that used ADC values for differentiating solid benign/dysplastic nodules and malignant liver lesions. A bivariate random-effects model with pooled sensitivity and specificity values with 95% CI (confidence interval) was used. This meta-analysis was performed on the per-lesion basis. Summary receiver operating characteristic (SROC) plot and area under curve (AUC) were created. A total of 14 original articles were retrieved. The combined (95% CI) sensitivity and specificity of mean ADC values for differentiating solid benign from malignant lesions were 78% (67-86%) and 74% (64-81%), respectively. The pooled (95% CI) positive and negative LRs were respectively 3 (2.3-3.8) and 0.3 (0.21-0.43). The DOR (95% CI) was 10 (7-15). The AUC (95% CI) of the SROC plot was 82% (78-85%). Reporting bias was negligible (p value of regression test = 0.36). Mean size of malignant lesions and breathing pattern of MRI were found to be sources of heterogeneity of pooled sensitivity. ADC measurement independently may not be an optimal diagnostic imaging method for differentiating solid malignant from solid benign hepatic lesions. The meta-analysis showed that ADC measurement had moderate diagnostic accuracy for characterizing solid liver lesions. Further prospective and comparative studies with pre-specified ADC thresholds could be performed to investigate the best MRI protocol and ADC threshold for characterizing solid liver lesions. ADC measurement by DW-MRI does not have a good diagnostic performance to differentiate solid malignant from solid benign lesions. Therefore, we suggest not using ADC values in clinical practice to evaluate solid liver lesions.

Diagnosis of osteoporosis in COPD patients: Estimation of the 10-year probability of a major osteoporotic fracture (FRAX), and Dual-energy X-Ray Absorptiometry

The aim of the study was to evaluate various methods of osteoporosis diagnostics (FRAX® and Dual-energy Х-Ray absorptiometry – DXA) and the sequence of their application in the diagnostic algorithm in COPD patients without a history of large bone fractures. Methods. Cross-sectional study of 115 COPD patients without exacerbation (93 men and 22 women, mean age 67.2 ± 7.1 years). The study included clinical examination, FRAX® estimation and comparison of the 10-year probability of a major osteoporotic fracture (MOF) with the Russian intervention threshold, spirometry, DXA of lumbar spine and proximal femur, semi-quantitative radiographic morphometry by Genant. All patients were examined using several methods that are possible in clinical practice: 1) FRAX® without DXA; 2) FRAX® + DXA in patients with intermediate 10-year probability of MOF and recalculation of FRAX® probability including femoral neck bone mineral density (BMD); 3) FRAX® + DXA in patients with intermediate 10-year probability of MOF. Take into account DXA results; 4) DXA without FRAX® ; 5) DXA + recalculation of FRAX ® for individuals with normal BMD or osteopenia. Results. In the whole sample of patients 1 – 5 diagnostic methods revealed 5.1, 7.0, 15.7, 44.3, 45.2% of individuals with osteoporosis, respectively. In men, the methods using FRAX ® (1 – 3) gave unsatisfactory results – the number of patients requiring treatment did not exceed 4.3%, while DXA revealed osteoporosis in 43%. FRAX® + DXA analysis in patients with intermediate 10-year probability of MOF (3 th method) was the best for women. The main independent predictors of low bone mineral density were post-bronchodilator FEV 1 ≤ 30% predicted and/or long-term oral glucocorticoid use. Asymptomatic vertebral fractures were detected in 11 patients. Before the radiographic morphometry, treatment would have been prescribed only 1 patient for the 1th or 2th methods; 5 patients – 3th method and 9 patients using 4th or 5th methods. Conclusion. The use of the Russian FRAX® model in men with COPD revealed a very low percentage of people who need osteoporosis treatment; DXA was the optimal diagnostic method. If it`s not possible to perform DXA in the most COPD patients, it should be prescribed to people with very severe bronchial obstruction and/or taking long-term oral glucocorticoid therapy. Regardless of the BMD parameters, semi-quantitative X-ray morphometry should be performed to diagnose asymptomatic vertebral fractures.

Clinical, laboratory and instrumental evaluation of structural and functional changes of the liver in patients with heart failure

Heart failure is detected in 2% of the population. The leading causes of heart failure are coronary heart disease, arterial hypertension, and valvular heart disease. The number of patients with chronic heart failure continues to increase despite the new methods of diagnosis and treatment. A special contribution is made by damage to target organs in the development of cardiovascular pathology. Impaired liver function or congestive liver is common in heart failure and increases the risk of death and requires further study. The mechanism of liver damage in chronic heart failure is complex and multicomponent. The sensitivity and specificity of standard clinical, laboratory and instrumental methods for the diagnosis of congestive liver are insufficient. With the increase, severity and duration of venous congestion, structural changes in the architectonics occur, leading to the formation of liver fibrosis. The development of cardiac liver fibrosis leads to a complication of the course of chronic heart failure and an increase in mortality.&#x0D; Among the new diagnostic methods, the most important are serological markers of liver fibrosis, which have high diagnostic accuracy, as well as histological determination of fibrosis, as well as ultrasound examination of the liver in B-mode and determination of liver stiffness by elastography. Direct and indirect serological markers have a higher diagnostic value when using their combination in the composition of panels in the development of hepatopathy of different origins. An increase in the concentration of markers of fibrosis and liver stiffness during elastography correlates with the severity of heart failure and a long-term prognosis for mortality, including from extrahepatic diseases. Performing liver elastography in dynamics allows to monitor the course and treatment of heart failure. The optimal diagnostic method is a combination of direct and indirect markers of fibrosis, ultrasound diagnostics and elastography, in addition to clinical assessment of signs and direct assessment of hemodynamic parameters.