Diagnostic Test In Patients Research Articles

Straight-to-Test Pathway in Faecal Immunochemical Testing (FIT)-Negative Patients: A Cost-Effective Approach.

Colorectal cancer (CRC) is the fourth most common malignancy in the UK and represents a high-volume diagnostic and clinical burden on the National Health Service (NHS). To maximise the use of limited diagnostic resources and increase efficiency, the colorectal services at University Hospitals North Midlands Trust (UHNM) developed the triage-to-test (TTT) service with risk stratification for diagnostic testing in patients with suspected colorectal cancer using faecal immunochemical testing (FIT) result. Our retrospective cohort study looked at the pick-up rate of colorectal cancer (CRC) and non-colorectal cancer (non-CRC) in FIT-negative patients. The study was a retrospective review of all symptomatic patients over 18 years of age who had undergone FIT testing in the community between 1November 2021 and 11February 2022 and whowere referred directly to the UHNM colorectal pathway from primary care (n=2,374). FIT negativity was set at <9.9 μg/g of faeces, as per the National Institute for Health and Care Excellence (NICE) DG30 guidelines. Patients were investigated and risk stratified in accordance with their FIT result and presenting symptoms. About 61.5% of patients referred were FIT negative (n=1,459) and 38.5% were FIT positive (n=915). Of those FIT-negative patients, 82 were excluded as their clinical outcomes were pending at the time of analysis. FIT positivity conferred a greater likelihood of colorectal cancer when compared with FIT-negative patients (p<0.0001). FIT-negative patients were most likely to have no significant pathology (32.5%, n=474). Incidence of colorectal cancer in the FIT-negative group was 0.5% (n=7) compared with 9.8% (n=89) in the FIT-positive group (odds ratio: 5.252, 95% CI: 4.012-6.875). Within the FIT-negative cohort, five patients were diagnosed with rectal cancer, one proximal descending colon cancer and one caecal cancer. The use of a FIT-negative TTT pathway ensures that any symptomatic patients presenting with red flag symptoms can be investigated appropriately. It also provides reassurance to clinicians who have an ethical duty to investigate patients in whom they suspect sinister pathology. Moreover, a triage-to-Test pathway reduces outpatient capacity burden onhealthcare trusts as they may send patients directly for investigation.

Transcriptomic identification of genes associated with thrombosis and coagulation in lipopolysaccharide-exposed bovine monocyte-derived macrophages.

The objective of this study was to investigate the differential expression of genes associated with coagulation in bovine monocyte-derived macrophages (MoMΦ) exposed to lipopolysaccharide (LPS) in vitro. We hypothesized that MoMΦ stimulated with LPS would have upregulation of procoagulant genes and downregulation of genes protecting against coagulation. MoMΦ were isolated from Holstein steers and exposed to Escherichia coli-derived LPS or a control for 3 hours. We used transcriptomics (RNA sequencing) to characterize the differential expression of genes associated with coagulation in the LPS-exposed MoMΦ relative to the control group. 1,602 genes were upregulated and 1,209 genes downregulated 3 hours after exposure to LPS. Monocyte-derived macrophages exposed to LPS displayed statistically significant upregulation of 4 proinflammatory genes, 2 anti-inflammatory genes, 8 genes involved in promoting coagulation, and 5 genes considered protective against coagulation. There was significant downregulation of 1 gene involved in the promotion of coagulation. Our results showed increased expression of most genes investigated promoting and protecting against coagulation and increased expression of proinflammatory and anti-inflammatory genes. These findings suggest that MoMΦ exhibit a multifaceted response in the early response to LPS, promoting and protecting against excessive coagulation. This multifaceted response highlights the interplay between different pathways involved in early sepsis. Our data demonstrate the utility of using MoMΦ as a model system to investigate sepsis-associated coagulopathies. These insights into the early transcriptomic changes in response to LPS may help guide future research on the development of treatment modalities or diagnostic tests for patients with sepsis.

Diagnostic Utility of a 90-Gene Expression Assay (Canhelp-Origin) for Patients with Metastatic Cancer with an Unclear or Unknown Diagnosis.

Metastatic cancers with unclear or unknown origins pose significant challenges in diagnosis and management, frequently leading to suboptimal outcomes. Studies have demonstrated that a 90-gene expression assay is effective in predicting the primary origin and guiding the site-specific therapy to improve prognosis. This study aimed to evaluate the clinical effectiveness of a 90-gene expression assay in patients with unclear or unknown diagnoses. The study encompassed patients for whom a 90-gene expression assay was requested as part of standard care. Data on patient demographics, tumor characteristics, and clinical history were collected. The assay's performance was evaluated by comparing its predicted tumor type with the final histopathological diagnosis. Among 303 cases analyzed, a 90-gene expression assay successfully identified a molecular-based tumor type for 295 (97.4%) patients. Comparison with histopathological diagnosis revealed an overall agreement of 88.5% (170/192). In patients with a single suspected primary site (n = 140), the assay confirmed the suspected diagnosis in 90.7% of cases. For those with a differential diagnosis (n = 52), the assay narrowed down the possibilities in 82.7% of cases. Moreover, in cases where the histopathology report indicated cancer of unknown primary (n = 103), the assay offered a molecular tumor type prediction with potential clinical significance. This study demonstrates the significant impact of a 90-gene expression assay on diagnosis and potential treatment selection for difficult-to-diagnose patients, highlighting its clinical value as a standardized molecular approach to streamline further diagnostic testing for patients with metastatic cancer of unclear or unknown origin. Further prospective study is required to assess whether employing molecular diagnostic classifiers enhances clinical outcomes in these patients.

Comparison of Duplex Ultrasound and Digital Subtraction Angiography for Assessing Tibial Vessel Disease.

Background Duplex ultrasonography (DUS) is readily available and often used as the first diagnostic test for patients with peripheral artery diseases (PADs). PAD is a disease that affects the general population but more commonly affects diabetics.To date, the role of DUS in the assessment of tibial vessel disease is inconclusive at best. The goal of our study is to assess the validity of DUS in characterizing the presence and severity of tibial diseasesvia comparison with digital subtraction angiography (DSA) findings. Methods This is a single-center retrospective cohort study analyzing three arterial segments (anterior tibial, posterior tibial, and fibular arteries) in patients who received a duplex study followed by DSA within a 30-day period. All arterial segments were graded from normal (Grade 0) to occluded (Grade 4), based on duplex interpretationand directly compared to direct visualization findings from DSA. Using statistical methods, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of DUS were determined. Results A total of 171 tibial vessel segments from 57 enrolled subjects with critical limb ischemia symptoms were analyzed in this study. The agreement between both modalities was poor (Kappa=0.19, p < 0.05), with DUS demonstrating a significant underestimation of vessel pathologies. This is also reflected by the overall sub-optimal sensitivity (23%), specificity (84%), PPV (69%), and NPV (41%) in DUS when compared to DSA results as the gold standard. Conclusion Significant disagreements were noted in this study between DUS and DSA findings, primarilysignificant underestimation of tibial vessel disease by the DUS when compared with the DSA. Caution is advised in the clinical application of DUS in patients with chronic limb-threatening ischemia (CLTI) symptoms and multi-segment tibial vessels due to its demonstrated limitations in this study.

Abstract P399: Defining A Negative Space: A Scoping Review of Hypertension

Study Objectives: This scoping review seeks to examine the existing body of literature to reveal consensus or absence thereof regarding the definition and management strategies for asymptomatic hypertension. Methods: The review was conducted using Joanna Briggs Institute guidelines. We searched the CINAHL (EBSCO), Scopus, Ovid EMBASE, and PubMed (MEDLINE) databases using keywords and index terms (“hypertension”, “high blood pressure”, “elevated blood pressure”, “asymptomatic”, “symptomless”, “symptom free”, “emergenc*”, “urgent”) to identify adult patients with hypertension in an emergency or outpatient setting. After review and quality assessment, we retained 35 texts for inclusion. Results: The definition of “asymptomatic hypertension” varied widely between the texts. There was significant variation in which society or academic guideline served as the reference and what the blood pressure cut offs were; all specified a lack of end-organ damage. A majority included a definition for hypertensive urgency, most commonly based on elevated blood pressure with vague symptoms. End-organ damage was poorly defined – studies instead described the absence of hypertensive emergency. The most common emergencies mentioned were myocardial infarction, renal failure, and hypertensive encephalopathy. Of the texts which provided recommendations, all recommended a thorough history and physical examination. Only one study recommended additional testing for asymptomatic patients – an ECG and creatinine test. Treatment recommendations for asymptomatic patients relied predominantly on ACEP clinical policy, with a majority of studies advocating for gradual reduction of blood pressure rather than an immediate one, as well as referral for outpatient management. Conclusion: There is a need for unified guidelines on the definition and management of asymptomatic hypertension to ensure effective and consistent patient care. Additionally, there is no consensus for further diagnostic testing in patients with a negative history and physical exam, and there is strong agreement that rapid blood pressure decrease in asymptomatic patients can be detrimental. Addressing this gap in guideline consistency and evidence base could enhance clinical outcomes and streamline healthcare processes across different settings. Future research should focus on establishing consensus and developing management strategies that are adaptable to both emergency and primary care environments.

Effect of antigen removal in hypersensitivity pneumonitis

BackgroundAntigen removal is a cornerstone of treatment of hypersensitivity pneumonitis (HP), but its association with transplant-free survival remains unclear. Further, HP guidelines conflict as to whether antigen removal is a recommended diagnostic test in patients with suspected HP.ObjectiveThe purpose of this study is to (1) evaluate the impact of antigen removal on transplant-free survival and (2) to describe the impact of antigen removal on pulmonary function testing and imaging in a retrospective cohort of patients with HP.MethodsWe retrospectively identified HP patients evaluated between 2011 and 2020. Demographic, physiologic, radiographic, and pathologic data were recorded.Results212 patients were included in the cohort. Patients who identified and removed antigen had a better transplant-free survival than patients who did not identify antigen and patients who identified but did not remove antigen. Antigen removal was associated with improvement in FVC by 10% predicted in 16.9% of patients with fibrotic HP and 56.7% of patients with nonfibrotic HP.DiscussionOur results suggest that over 50% of nonfibrotic HP patients and 16.9% of fibrotic HP patients improve with exposure removal. In addition, antigen removal, rather than antigen identification, is associated with transplant-free survival in HP.

Idiopathic megacolon: relationship between clinical features and diagnostic tests results

AIM: to assess the relationship between clinical features and diagnostic tests results in idiopathic megacolon/megarectum patients.PATIENTS AND METHODS: the retrospective analysis of clinical manifestations and diagnostic tests included 157 patients with idiopathic megacolon/megarectum in 2002-2023. The diagnosis of megacolon/megarectum was verified with a barium enema, Hirschsprung’s disease was excluded byanorectal manometry and (if needed) rectal Swenson’s biopsy.RESULTS: the rate of integral parameter “abdominal discomfort” and Wexner constipation scale rate do not significantly correlate with barium enema, gut transit test, defecography and rectal compliance test results, besides of sigmoid colon width (p = 0.03). The rate of integral parameters “defecation difficulties” correlates with rectum width (p &lt; 0.001) and do not correlate with gut transit time, results of defecography and rectal compliance test (p &gt; 0.05). Distal contrast retention during gut transit test is associated with rectum width only (p &lt; 0.01). The parameters of defecography do not correlate neither clinical features nor other diagnostic tests results (p &gt; 0.05).CONCLUSION: there was not significant relationship between rate of abdominal discomfort, Wexner constipation scale rate and diagnostic tests results. The rate of integral parameters “defecation difficulties” significantly correlates with rectum width (based on barium enema) only. Rectum width seems to be most important parameter to assess the rectum function and in a minor degree — rectal compliance test. The defecography do not correlate either with the severity of clinical symptoms or with the results of other diagnostic methods, which casts doubt on the appropriateness of using this diagnostic test in patients with megacolon.

Diagnostic Strategy Using Color Doppler Ultrasound of Temporal Arteries in Patients With High Clinical Suspicion of Giant Cell Arteritis : A Prospective Cohort Study.

Giant cell arteritis (GCA) is the most prevalent systemic vasculitis in people older than 50 years. Any delay in diagnosis impairs patients' quality of life and can lead to permanent damage, particularly vision loss. To evaluate a diagnostic strategy for GCA using color Doppler ultrasound of the temporal artery as a first-line diagnostic test, temporal artery biopsy (TAB) as a secondary test, and physician expertise as the reference method. Prospective multicenter study with a 2-year follow-up. (ClinicalTrials.gov: NCT02703922). Patients were referred by their general practitioner or ophthalmologist to a physician with extensive experience in GCA diagnosis and management in one of the participating centers: 4 general and 2 university hospitals. 165 patients with high clinical suspicion of GCA, aged 79 years (IQR, 73 to 85 years). The diagnostic procedure was ultrasound, performed less than 7 days after initiation of corticosteroid therapy. Only ultrasound-negative patients underwent TAB. Bilateral temporal halo signs seen on ultrasound were considered positive. Ultrasound and TAB results were compared with physician-diagnosed GCA based on clinical findings and other imaging. Diagnosis of GCA was confirmed in 44%, 17%, and 21% of patients by ultrasound, TAB, and clinical expertise and/or other imaging tests, respectively. Their diagnosis remained unchanged at 1 month, and 2 years for those with available follow-up data. An alternative diagnosis was made in 18% of patients. The proportion of ultrasound-positive patients among patients with a clinical GCA diagnosis was 54% (95% CI, 45% to 62%). Small sample size, no blinding of ultrasound and TAB results, lack of an objective gold-standard comparator, and single diagnostic strategy. By using ultrasound of the temporal arteries as a first-line diagnostic tool in patients with high clinical suspicion of GCA, further diagnostic tests for patients with positive ultrasound were avoided. Tender "Recherche CH-CHU Poitou-Charentes 2014."

A Systematic Review of Symptoms of Pernicious Anemia.

Pernicious anemia (PA) is a type of macrocytic anemia caused by autoimmune gastritis. To facilitate timely diagnosis and treatment of PA there is a pressing need for improved understanding among Healthcare providers of the condition's symptoms and diagnostic criteria. This systematic review aims to extend existing clinical knowledge on the presentation of PA by determining which symptoms and clinical complications are reported in published adult case studies. Relevant studies were identified through electronic searches of PsycINFO, Embase, and MEDLINE, via OvidSP. During data extraction symptoms were categorized according to the International Classification of Diseases and were grouped based on frequency. Symptoms were documented for 103 adults with a diagnosis of PA; the most frequent symptoms were fatigue (55%), loss of sensation in limbs (32%), excessive weight loss (27%), and a sore tongue (23%). This review highlights the diverse symptomology of adults who are diagnosed with PA. Most symptoms documented in case studies are consistent with the core signs of B12 and folate deficiencies. Research is needed to identify if there are common clusters of PA symptoms that can be used as prompts for diagnostic testing in patients with suspected B12 deficiency.

Diagnostic testing of patients with hepatic encephalopathy (review)

Hepatic encephalopathy (HE) is a serious complication of the hepatobiliary region. One of the main consequences of the pathology is dysfunction of the brain. Diagnosis of this condition can be challenging due to the variety of clinical manifestations and severity. The key to preventing the HE progression and improving the patient’s quality of life is diagnosis in the early stages of the disease. The use of psychometric tests appears promising in determining HE due to their high sensitivity and low cost. It should be noted that results may vary depending on a number of factors, including the age and level of education of the patient. In order to assess the full picture of the disease, it is necessary to conduct an extensive evaluation and combine various examination methods, such as clinical scales, psychometric tests, and computerized tests, to achieve the most accurate diagnosis and determine the severity of HE.

The EAN-NeuPSIG guideline on the diagnosis of neuropathic pain-asummary

In this joint guideline of the scientific societies and working groups mentioned in the title, evidence-based recommendations for the use of screening questionnaires and diagnostic tests in patients with neuropathic pain were developed. The systematic literature search and meta-analysis yielded the following results: Of the screening questionnaires, Douleur Neuropathique en 4Questions (DN4), I‑DN4 (self-administered DN4), and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) received astrong recommendation, while S‑LANSS (self-administered LANSS) and PainDETECT received weak recommendations for their use in the diagnostic workup of patients with possible neuropathic pain. There was astrong recommendation for the use of skin biopsy and aweak recommendation for quantitative sensory testing and nociceptive evoked potentials. The role of confocal corneal microscopy is still unclear. Functional imaging and peripheral nerve blocks are helpful in elucidating the pathophysiology, but current literature does not support their use in diagnosing neuropathic pain. In selected cases, genetic testing in specialized centers may be considered.

Genetic Alterations in a Large Population of Italian Patients Affected by Neurodevelopmental Disorders.

Neurodevelopmental disorders are a group of complex multifactorial disorders characterized by cognitive impairment, communication deficits, abnormal behaviour, and/or motor skills resulting from abnormal neural development. Copy number variants (CNVs) are genetic alterations often associated with neurodevelopmental disorders. We evaluated the diagnostic efficacy of the array-comparative genomic hybridization (a-CGH) method and its relevance as a routine diagnostic test in patients with neurodevelopmental disorders for the identification of the molecular alterations underlying or contributing to the clinical manifestations. In the present study, we analysed 1800 subjects with neurodevelopmental disorders using a CGH microarray. We identified 208 (7%) pathogenetic CNVs, 2202 (78%) variants of uncertain significance (VOUS), and 504 (18%) benign CNVs in the 1800 patients analysed. Some alterations contain genes potentially related to neurodevelopmental disorders including CHRNA7, ANKS1B, ANKRD11, RBFOX1, ASTN2, GABRG3, SHANK2, KIF1A SETBP1, SNTG2, CTNNA2, TOP3B, CNTN4, CNTN5, and CNTN6. The identification of interesting significant genes related to neurological disorders with a-CGH is therefore an essential step in the diagnostic procedure, allowing a better understanding of both the pathophysiology of these disorders and the mechanisms underlying their clinical manifestations.

Performance of CBNAAT on Pleural Biopsies Obtained by Semirigid Thoracoscopy for Diagnosis of Unexplained Pleural Effusion: A Prospective Study from North India.

Exudative pleural effusions are commonly encountered in clinical practice, but in about one-fourth of cases, etiology remains elusive after initial evaluation. Medical thoracoscopy with semirigid thoracoscope is a minimally invasive procedure with high diagnostic yield for diagnosing pleural diseases, especially these undiagnosed exudative pleural effusions. In tubercular endemic areas, often, these effusions turn out to be tubercular, but the diagnosis of tubercular pleural effusion is quite challenging due to the paucibacillary nature of the disease. Although culture is the gold standard, it is time-consuming. Cartridge-based nucleic acid amplification test (CBNAAT) is a novel rapid diagnostic test for tuberculosis (TB) and has been recommended as the initial diagnostic test in patients suspected of having extrapulmonary TB (EPTB). We conducted a prospective observational study of 50 patients with undiagnosed pleural effusion admitted to our tertiary care hospital. The primary aim of the study is to evaluate the diagnostic performance of CBNAAT on thoracoscopic guided pleural biopsy and compare it with conventional diagnostic techniques like histopathology and conventional culture. Of 50 undiagnosed pleural effusions, TB (50%) was the most common etiology. The overall diagnostic yield of semirigid thoracoscopy in this study was 74%. Our study showed that CBNAAT of pleural biopsies had a sensitivity of 36% only but a specificity of 100%. The sensitivity of CBNAAT was not far superior to the conventional culture. Tuberculosis (TB) is a common cause of undiagnosed pleural effusion in our set-up. CBNAAT testing of pleural biopsy, though, is a poor rule-out test for pleural TB, but it may aid in the early diagnosis of such patients.

Performance of oxygenation indices and risk scores to predict invasive mechanical ventilation and mortality in COVID-19

BackgroundInformation on the performance of oxygenation indices (OIs) and risk scores in patients requiring invasive mechanical ventilation (IMV) is limited. We determine the performance of the OIs and risk scores in hospitalized patients with COVID-19 to predict the requirement of IMV and death at 28 days after admission.MethodsA retrospective study of diagnostic tests in patients admitted to the emergency department, hospitalization, and intensive care unit diagnosed with COVID-19. The receiver operating characteristic curve (ROC-curve) were built with the OIs and risk scores to predict IMV and mortality.ResultsA total of 1402 subjects entered the final analysis, of whom 19.5% (274/1402) received IMV and 23.0% (323/1402) died at 28 days. The ROC-curve of the delta PaO2/FiO2 ratio for the requirement of IMV and mortality at 28-day was 0.589 (95% CI: 0.546–0.632) and 0.567 (95% CI: 0.526–0.608), respectively. PaO2/FiO2 ≤ 300 shows a ROC curve of 0.669 (95% CI: 0.628–0.711) to predict IMV. PaO2/FiO2 ≤ 300 and 4 C mortality score in mortality at 28 days showed an ROC-curve of 0.624 (95% CI: 0.582–0.667) and 0.706 (95% CI: 0.669–0.742), respectively.ConclusionPaO2/FiO2 ≤ 300, 4 C mortality score ≥ 8, SOFA score ≥ 4 y SaO2/FiO2 ≤ 300 were weak predictors of the IMV requirement from admission, and 4 C mortality score ≥ 8 was weak predictors of the mortality from admission in patients with pulmonary involvement by COVID-19.

Operational characteristics of ultrasound in the diagnosis of Sjögren’s syndrome

Background and objectiveTo determine the operational characteristics of salivary gland ultrasound (SGU) in the diagnosis of Sjögren’s syndrome (SS) in a population of colombian patients with dry symptoms. Materials and methodsStudy of diagnostic tests in patients with dry symptoms who consecutively attended the rheumatology consultation (2018–2020). Sociodemographic and clinical data were obtained through a survey, paraclinical and ophthalmological tests, minor salivary gland biopsy, unstimulated salivary flow and SGU (score 0–6 based on De Vita) were done. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values (Stata 15®) were calculated. The receiver operating characteristics (ROC) curve was developed. Results102 patients were included (34 SS and 68 non-SS), mean age 55.69 (±11.93) years, 94% women. Positive ultrasound (score of 2 or more) was more frequent in the SS group, (70.6% vs. 22.1%, P<0.0001). The sensitivity was the same for grade 2 and 3 (70.59%), with a higher specificity (89.71%) for grade 3 (PPV 77.42% NPV 85.92). The ROC curve from the sum of the glands by means of ultrasound was better than those of the independent glands. The ROC curve of the ultrasound presented a greater area under the curve (0.72 [0.61−0.82]) than that of the histological analysis (focus score) (0.68 [0.59−0.78]), P=0.0252. ConclusionSalivary gland ultrasound is a useful and reliable method for the classification of SS. Its use could be considered in the future within the SS classification criteria.

Clinical impact of rapid molecular diagnostic tests in patients presenting with viral respiratory symptoms: A systematic literature review.

Molecular tests can detect lower concentrations of viral genetic material over a longer period of respiratory infection than antigen tests. Delays associated with central laboratory testing can result in hospital-acquired transmission, avoidable patient admission, and unnecessary use of antimicrobials, all which may lead to increased cost of patient management. The aim of this study was to summarize comparisons of clinical outcomes associated with rapid molecular diagnostic tests (RMDTs) versus other diagnostic tests for viral respiratory infections. A systematic literature review (SLR) conducted in April 2023 identified studies evaluating clinical outcomes of molecular and antigen diagnostic tests for patients suspected of having respiratory viral infections. The SLR included 21 studies, of which seven and 14 compared RMDTs (conducted at points of care or at laboratories) to standard (non-rapid) molecular tests or antigen tests to detect SARS-CoV-2 and influenza, respectively. In studies testing for SARS-CoV-2, RMDTs led to reductions in time to test results versus standard molecular tests (range of the reported medians: 0.2-3.8 hours versus 4.3-35.9 hours), with similar length of emergency department stay (3.2-8 hours versus 3.7-28.8 hours). Similarly, in studies testing for influenza, RMDTs led to reductions in time to test results versus standard molecular tests (1-3.5 hours versus 18.2-29.2 hours), with similar length of emergency department stay (3.7-11 hours versus 3.8-11.9 hours). RMDTs were found to decrease exposure time of uninfected patients, rate of hospitalization, length of stay at the hospitals, and frequency of unnecessary antiviral and antibacterial therapy, while improving patient flow, compared to other tests. Compared to other diagnostic tests, RMDTs improve clinical outcomes, test turnaround time, and stewardship by decreasing unnecessary use of antibiotics and antivirals. They also reduce hospital admission and length of stay, which may, in turn, reduce unnecessary exposure of patients to hospital-acquired infections and their associated costs.

The Role of Preprocedure Genetic Counseling in Pregnancies Interrupted for Fetal Abnormalities.

Congenital birth defects affect 3 to 5% of pregnancies. Genetic counseling can help patients navigate the testing process and understand results. The study objective was to identify predictors and utility of genetic counseling at the time of pregnancy termination. Additionally, we aimed to see what proportion of patients would benefit from additional testing based on the results of the genetic testing. This was a retrospective cohort review of all terminations performed for fetal anomalies by an academic center from July 2016 to May 2020. Indications were stratified by abnormal serum screening or types of abnormal ultrasound findings. Data were abstracted regarding uptake of genetic counseling and testing results. Abnormal results that warranted additional testing regarding recurrence risks were noted. Multivariable logistic regression was performed to identify predictors of receipt of genetic counseling and testing. Of 387 patients, 57% (n = 220) received preprocedure genetic counseling and 43% (n = 167) did not. Among patients who received diagnostic testing, 62% (n = 194) had genetic counseling compared with 38% (n = 121) without counseling (adjusted odds ratio 2.46, 95% confidence interval [1.41-4.29], p < 0.001). Among the entire cohort, 38% (n = 148) had suspected aneuploidy based on serum screening. Of these, 89% (n = 132/148) had definitive testing, 92% (n = 122/132) confirming the aneuploidy. Among the other 68% (n = 239) with structural anomalies, 76% (n = 183) had diagnostic testing with 29% (n = 53) yielding an abnormal result. Among those fetuses with structural anomalies, 36% (n = 19/53) of genetic diagnoses warranted additional parental testing because of risk of recurrence compared with only 2% (n = 2/122) of patients with abnormal serum screening results alone. Genetic counseling was associated with increased uptake of diagnostic testing, which yielded useful information and prompted additional testing. This is important for determining etiology and recurrence risk and should be offered to patients presenting for termination for fetal indications, as well as providing diagnostic closure for patients. · Genetic counseling increases the uptake of diagnostic testing in patients with fetal anomalies.. · Patients with ultrasound anomalies received less diagnostic testing despite actionable results 36% of the time.. · Genetic testing is invaluable for recurrence risk counseling even if patients chose to terminate..

Plasma Glycosaminoglycans (GAGS) Levels as a Biomarker in Renal Cell Carcinoma Patients

Objective: To determine the diagnostic accuracy of plasma Glycosaminoglycans (GAGs) in Renal Cell Carcinoma (RCC), taking histological findings as the reference standard. Study Design: Cross-sectional study. Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, in collaboration with Armed Forces Institute of Urology, Rawalpindi Pakistan, from Sep 2020 to Jun 2021. Methodology: The study comprised sixty-two (62) diagnosed cases of RCC. All the patients had nephrectomy, and histopathological findings confirmed the diagnosis. Plasma samples for GAG levels were collected in EDTA tubes and assayed by manual ELISA. The Receiver Operating Characteristic (ROC) curve was constructed, and the Area Under the Curve (AUC) was calculated. Results: The mean age of the study population was 52.7+10.5 years. At a cut-off of 34 ng/ml, the sensitivity and specificity of plasma GAG levels were 83.9% and 94.2%, respectively, in diagnosing RCC taking biopsy as a gold standard. Positive predictive value (PPV) and negative predictive value (NPV) at this cut-off were 93.7% and 84.9% respectively. The area under the curve (AUC) for plasma GAG levels was 0.97, which further supported the use of this test in diagnosing RCC. Conclusion: Plasma GAG levels can be used as a promising diagnostic test in patients with RCC. It can prove relatively more convenient and cost-effective for diagnosing such cases.

The Main Genome is a Source of Adaptogens and the Basis for the Development of a New Vaccination Technology

The appearance of viruses in mammals and plants is provoked by environmental factors - xenobiotics, formed mainly due to unreasonable human activity and resulting from the formation of an ecological (epidemiological) niche filled with molecular motifs of the microbiota - the intestines of mammals and the root system of plants. To do this, bacteria and archaea use retrovirus-like “cut and paste” mechanisms, including, for example, the CRISPR/Cas system, when the molecular motifs of the microbiota try to adapt the immune and hormonal systems. It all depends on how much xenobiotics damage the immune and hormonal systems. Therefore, viruses are not the cause, but the consequence of the disease. The fight against viruses with the help of vaccines prepared on their basis has been violating and restraining the natural mechanisms of regulation of biological processes in plants and mammals. Thus, molecular motifs arising from microbiota bacteria become either apaptogens (viruses) or adaptogens. In the first and second cases, genetic information is released into the environment. In the latter case, there is an adaptation or a kind of vaccination of others by a natural mechanism. This mechanism is also applicable to somatic diseases, such as cardiovascular, autoimmune, oncological, etc. As for the original properties of coronaviruses, it is their ability to suppress innate and acquired nonspecific viral immunity in the respiratory tract. This leads to the reactivation of chronic, mainly bacterial, respiratory infections - pneumococci, staphylococci, hemophiluses, however, fungal infections can also be observed – mucormycosis, aspergillosis, etc. This feature of the virus prompted doctors at the beginning of the epidemic (2020) to use a pneumococcal vaccine, which, as it turned out, similarly to the coronavirus vaccine reduces the severity of the disease and mortality. As for the diagnosis of coronavirus infection and its treatment, as practice has shown, everything depends on the stage of the disease, starting with a viral and ending with a bacterial infection. Similar and identical antigenic determinants in coronavirus and respiratory group bacteria often caused confusion when analyzing the results of serological and molecular biological diagnostic tests in patients with COVID-19. Moreover, the justified use of antibiotics in the post-viral, that is, in bacterial periods, made it possible to successfully treat patients with a positive PCR test for coronavirus on an outpatient basis.

Acquired Von Willebrand Syndrome, Epidemiology, Laboratory Findings and Molecular Alterations on Classic Myeloproliferative Neoplasms in Mexican Population

Introduction: Acquired von Willebrand syndrome (AvWS) has been associated with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) since 1984. However, the epidemiology of these disorders is not precise and has been underestimated worldwide but prevalence of 10-20% has been described in other series. Determinations of the antigenic von Willebrand factor (VWF:Ag) and its activity (VWF:RCo) are only performed when patients present thrombocytosis over 1,000 x10 3/µL. Essential Thrombocythemia (ET) is the most commonly associated MPN, found in 5-30%. Some cases have been described in patients with polycythemia vera (PV) and primary myelofibrosis (PMF) who develop AvWS even with platelet counts below 1,000 x10 3/µL. The epidemiology of AvWS in MPN and its association between laboratory and molecular parameters among the Mexican population have not been described. Objectives - Describe the clinical, biochemical and molecular characteristics of patients who develop AvWS with the aim of establishing the difference between cut-off scores of platelets to suspect AvWS in Mexican patients. - Establish the association between mutations in JAK2, CALR and MPL, and the appearance of AvWS. Material and methods: Retrospective, descriptive, observational, and single-center analysis. Patients over 18 years of age with a diagnosis of MPN from the INCMNSZ were recruited. The mutational analysis in peripheral blood (PB) for JAK2, CALR and MPL was assessed, with at least one follow-up between 2012 and 2022, excluded whose medical record were incomplete. Information was consecutively collected from 184 patients with MPN diagnosis between 01/01/2000 to 05/31/2022. Thirty patients were identified as having AvWS with a VWF:RCo/VWF:Ag diagnostic ratio of &amp;lt; 0.7. The epidemiology, clinical, laboratory and mutational alterations of the patients who developed AvWS by was analyzed using descriptive statistics with SPSS. This study was approved by the institutional bioethics committee. Results: AvWS developed in 16.4% (n = 30) of patients with MPN with an annual incidence of 2.4 cases per year was identified. Most patients were women in 66% (n = 20), with a median age of 57 years (IQR 20-72 years). Of the thirty cases with AvWS, 46.7% (n =14) corresponded to PMF, 40% (n =12) to PV, and 13.3% to ET (n = 4). The most frequently found mutation was JAK2 exon 14 with 76.7%, followed by CALR in 13.3% and triple negatives in 10%, no patient presented MPL mutations. The global median of VWF:RCo/VWF:Ag was 0.47 [PV 0.47 (IQR 0.31-0.64), ET 0.53 (IQR 0.5-0.64) and PMF 0.48 (0.29-0.65)] (Figure 1) and the median of the VWF:Ag 118 U/dL with FVW:RCo of 44.6 UI/dL (Table 1). The median platelet count for patients with the JAK2 mutation was 987.9 x103/µL (IQR 218 - 2307 x10 3/µL), while those with CALR and triple negatives were 1,033 x10 3/µL (IQR 713 - 1339 x10 3/µL), and 1,325 x10 3/µL (IQR 760 - 2059 x10 3/µL), respectively. Regarding hemoglobin (Hb) and hematocrit (Hto) levels, patients with PV and JAK2 mutation with AvWS presented medians of 17.45 g/d and 54.4% respectively, highlighting that AvWS was generated in some patients with platelet counts below 1,000 x10 3/µL. At diagnosis, bleeding episodes occurred in 13.3%. Lastly, 96.7% of the patients were treated with hydroxyurea, which corrected cellular alterations and laboratory abnormalities found in AvWS. Conclusions: AvWS can be found in patients with platelet counts below 1,000 x10 3/µL, especially among those with PV with elevated Hb and Hct levels. This may deem it necessary to carry out diagnostic tests in patients with MPN and any degree of thrombocytosis. To our knowledge, this is the most comprehensive study among latin american patients that describes the coexistence of PMF and AvWS; even though the mechanism by which some PMF patients develop AvWS is not perfectly understood. In our study, patients with PMF presented AvWS more frequently; this is a contrasting result from other international reports where ET was most attributed. We attribute this finding to changes made to the WHO criteria between 2008 and 2016.