High Pretest Probability Research Articles

Unexpected Elevation of Infection Parameters in a Heart Transplanted Patient with Chronic Kidney Disease: A Case Report

Patients with end-stage kidney disease are under an increased risk for morbidity and mortality due to cardiovascular reasons. Yet, patients might show only atypical symptoms during cardiac events and routinely performed pre-transplant diagnostic measures are discussed controversially. A heart transplanted 50-year-old male with end-stage kidney disease was assessed for kidney transplantation. Myocardial scintigraphy, chest x-ray, pulmonary function test, urological and gastrointestinal assessment showed normal results. A routinely performed blood test revealed elevated procalcitonin, C-reactive protein and leucocytes. Measured vital parameters and physical examination revealed no pathologies. Coughing, shortness of breath or chest pain were denied. CT-scan showed no signs of infection but lack of contrast media enhancement in the heart. Myocardial infarction was confirmed in electrocardiogram and transthoracic echocardiogram demonstrated an impaired ejection fraction of 20%. Treatment with anti-platelet medication and anticoagulation was followed by invasive heart catheterization, which revealed no acute stenosis but a dissolved in-stent thrombosis. Since kidney failure was progressing the patient required dialysis treatment. Microbiological analyses of blood and urine samples stayed negative. Chronic kidney disease patients are at increased cardiovascular risk. However, invasiveness of cardiac diagnostics for potential kidney transplant is debated controversially. KDIGO guideline 2020 advises non-invasive screening for coronary artery disease for asymptomatic patients at high risk. However, there is no specific guideline for previously heart transplanted candidates for kidney transplant and patients with high pretest probability benefit from invasive diagnostics. A risk stratification for cardiac complications and pre-kidney transplant evaluation should be executed in clinical practice.

Improving predictability of IgE-high type 2 chronic sinusitis with nasal polyps in the biologic era

BackgroundChronic rhinosinusitis (CRS) is an inflammatory disease that may require biological therapy. Omalizumab is an anti-IgE biologic that was recently approved by the FDA and Health Canada for use in severe CRS with nasal polyps (CRSwNP) recalcitrant to intranasal corticosteroids. Dosing is based on weight and pre-treatment serum IgE, with elevated levels of the latter being an indication for biologic treatment according to EPOS and EUFOREA guidelines. The goal of this study was to identify variables that predict IgE-high type 2 inflammation and serve as indicators for biologic treatment in CRS.MethodsPatients ≥ 19 yo diagnosed with CRS undergoing functional endoscopic sinus surgery were included retrospectively. Demographics, past medical history, preoperative blood work, Lund-Mackay (LM), Lund Kennedy (LK), and SNOT-22 scores were extracted. Descriptive statistics and binary logistic regression analyses were conducted. Model superiority was based on Nagelkerke R2 scores and receiver operating characteristic curves.ResultsSixty-five patients, average age 49.96 ± 13.59 years, were included. Sixty-one binary logistic regression models for elevated serum IgE were created. Among the top 3 models, the best model had sensitivity, specificity, positive predictive value and negative predictive values of 82.1, 69.2, 80.0, and 72.0. All performance measures except sensitivity exceeded the Canadian Biologics Guideline model. Serum eosinophils ≥ 300 cell/uL, CRSwNP and LM ≥ 17 increased the odds of elevated IgE.ConclusionsIgE-high type-2 inflammation can be predicted by a model that includes eosinophil ≥ 300 cell/uL, CRSwNP, LM ≥ 17, asthma diagnosis and SNOT-22 ≥ 40. Patients meeting these parameters have a high pretest probability for elevated IgE and would benefit from IgE serology to determine qualification for omalizumab. This could reduce unwarranted IgE serology in patients with CRSwNP but also target a patient population for further workup that will lead to optimization of resource allocation and improve healthcare equity in rural and remote areas within Canada.

Sleep position, patient comfort, and technical performance with two established procedures for home sleep testing

PurposeIn patients with a high pre-test probability of suffering from obstructive sleep apnea (OSA), (cardio)-respiratory polygraphy (RP; level 3) is commonly used for home sleep testing (HST); however, testing based on peripheral arterial tonometry (PAT) is increasingly recognized as an alternative method. The aim of the study was to compare sleep position, patients’ comfort, and technical failure rates of HST with RP and PAT in patients with suspected OSA.MethodsSleep position, patients’ comfort, and technical failure rates of RP and PAT were compared in 56 patients receiving two nights of HST with either RP or PAT in a randomized fashion.ResultsTime in supine position with PAT was significantly lower (173.7±88 min) compared to RP (181.7±103.7 min; p < 0.001), although the absolute mean difference was not clinically significant. Patients reported to sleep better, feeling less disturbed when falling asleep, losing less sensors, and fewer nightly awakenings with PAT, but experienced more pain at the side of the finger probe. Forty-five out of 56 patients (80%) rated PAT as being the superior sleep test and 49 out of 56 (88%) would prefer PAT for further investigations (p<0.001). PAT testing was associated with less technical failures.ConclusionThe results demonstrate that HST with PAT leads to less time in supine sleep positioning, which may be clinically relevant in selected patients. Moreover, PAT is associated with less technical failures and is perceived with less discomfort during testing and a reduced number of nocturnal awakenings in patient self-reports.

Prospective validation of a brief questionnaire for predicting the severity of pediatric obstructive sleep apnea

IntroductionPediatric obstructive sleep apnea (OSA) is diagnosed and stratified by polysomnography. However, due to cost and inaccessibility, up to 90% of children undergo tonsillectomy and adenoidectomy (T&A) solely based on clinical criteria. We previously developed a data-driven brief screening questionnaire (‘Selected Features,’ SF) that predicted OSA severity than alternatives. The SF asks the parent whether a child: (i) has had breath-holding spells at night over the past 4 weeks, (ii) is a mouth-breather during the day, (iii) has stopped growing at a normal rate any time since birth, and (iv) is overweight. This study sought prospectively validate the SF questionnaire. MethodsWe conducted a prospective assessment of the predictive accuracy of SF compared to the Pediatric Sleep Questionnaire—Sleep Related Breathing Disorder (PSQ-SRBD) scale in otherwise healthy children with sleep disordered breathing referred for T&A. We compared the model fits of PSQ-SRDB and SF for (i) a linear regression model for the prediction of OSA, and (ii) a logistic regression model for severe OSA, defined as apnea hypopnea index (AHI) > 10. P < 0.05 was significant. ResultsA total of 124 patients were included. The average age was 7.3 years (95% confidence interval, 6.6–8.0) and 66 (54%) were male. The racial composition was 54 (44%) black, 41 (33%) white, and 28 (23%) other. The median AHI was 4.8 (interquartile range 12) and 43 (35%) of patients had severe OSA. In linear and logistic regression models, SF outperformed the PSQ-SRBD and null models as measured by Akaike Information Criteria. The overall accuracy in predicting AHI >10 for PSQ-SRBD was 0.65 (0.56–0.73, P = 0.54) compared to 0.73 (0.64–0.80, P = 0.04) for SF. ConclusionBy eliminating redundancy, we have developed a questionnaire with improved prediction of OSA and its severity, in children with high pre-test probability of the condition. While multi-site validation is necessary, SF demonstrates value in screening children prior to T&A in resource-limited environments.

Safety of COVID-19 vaccination in patients with polyethylene glycol allergy: A case series

Safety of COVID-19 vaccination in patients with polyethylene glycol allergy: A case series

Palla's sign and the challenge of optimizing the imaging strategy in patients with high pretest probability of pulmonary embolism.

Palla's sign and the challenge of optimizing the imaging strategy in patients with high pretest probability of pulmonary embolism.

Response to: Palla's sign and the challenge of optimizing the imaging strategy in patients with high pretest probability of pulmonary embolism.

Response to: Palla's sign and the challenge of optimizing the imaging strategy in patients with high pretest probability of pulmonary embolism.

Assessing the clinical probability of pulmonary embolism during pregnancy: The Pregnancy‐Adapted Geneva (PAG) score

BackgroundThe diagnosis of pulmonary embolism (PE) in pregnant women represents an ongoing challenge. As in the general population, the first step in pregnant women with suspected PE consists of assessing clinical pre‐test probability (PTP). However, no dedicated clinical decision rule has been developed in this population. ObjectiveTo propose a new version of the Geneva score adapted to pregnant women with suspected PE. MethodsData from a multicenter, prospective management outcome study including 395 women with suspected PE, in whom PTP was assessed using the Geneva score, were used. We first removed items which were present in none of the patients (cancer, age >65 years). Receiver operating characteristic (ROC) curve analysis was then performed for quantitative variables and the optimal threshold defined. The obtained Pregnancy‐Adapted Geneva Score (PAG Score) comprised seven items, including an age 40 years or older and a heart rate >110 beats per minute. ResultsThe PAG Score showed a high discriminative power to identify patients with a low, intermediate, or high PTP, associated with increasing prevalence of PE, 2.3%, 11.6%, and 61.5%, respectively. The ROC curves showed an area under the curve of 0.795 for the PAG Score compared to 0.684 for the Geneva score. ConclusionIn pregnant women with suspected PE, the PAG Score shows a high discriminative power to identify patients at low, intermediate, or high PTP. It has the strength of being a fully objective decision rule, is clinically relevant, easy to compute, and should now be tested in a prospective outcome study.

Combined cCTA and TAVR Planning for Ruling Out Significant CAD: Added Value of ML-Based CT-FFR

ObjectivesThe purpose of this study was to analyze the ability of machine-learning (ML)-based computed tomography (CT)-derived fractional flow reserve (CT-FFR) to further improve the diagnostic performance of coronary CT angiography (cCTA) for ruling out significant coronary artery disease (CAD) during pre-transcatheter aortic valve replacement (TAVR) evaluation in patients with a high pre-test probability for CAD. BackgroundCAD is a frequent comorbidity in patients undergoing TAVR. Current guidelines recommend its assessment before TAVR. If significant CAD can be excluded on cCTA, invasive coronary angiography (ICA) may be avoided. Although cCTA is a very sensitive test, it is limited by relatively low specificity and positive predictive value, particularly in high-risk patients. MethodsOverall, 460 patients (age 79.6 ± 7.4 years) undergoing pre-TAVR CT were included and examined with an electrocardiogram-gated CT scan of the heart and high-pitch scan of the vascular access route. Images were evaluated for significant CAD. Patients routinely underwent ICA (388/460), which was omitted at the discretion of the local Heart Team if CAD could be effectively ruled out on cCTA (72/460). CT examinations in which CAD could not be ruled out (CAD+) (n = 272) underwent additional ML-based CT-FFR. ResultsML-based CT-FFR was successfully performed in 79.4% (216/272) of all CAD+ patients and correctly reclassified 17 patients as CAD negative. CT-FFR was not feasible in 20.6% because of reduced image quality (37/56) or anatomic variants (19/56). Sensitivity, specificity, positive predictive value, and negative predictive value were 94.9%, 52.0%, 52.2%, and 94.9%, respectively. The additional evaluation with ML-based CT-FFR increased accuracy by Δ+3.4% (CAD+: Δ+6.0%) and raised the total number of examinations negative for CAD to 43.9% (202/460). ConclusionsML-based CT-FFR may further improve the diagnostic performance of cCTA by correctly reclassifying a considerable proportion of patients with morphological signs of obstructive CAD on cCTA during pre-TAVR evaluation. Thereby, CT-FFR has the potential to further reduce the need for ICA in this challenging elderly group of patients before TAVR.

Abstract 12183: Multi-Center Evaluation of Inter-Site Variability in SPECT Myocardial Blood Flow Measurement

Introduction: Myocardial blood flow (MBF) imaging with SPECT is possible using cardiac-specific cameras. Single-center studies have shown that SPECT MBF is accurate compared with PET MBF and angiography. Clinical implementation requires consistency of SPECT MBF measurements across multiple sites. This study is the first multi-center evaluation of the inter-site processing variability of SPECT MBF. Objective: To compare SPECT MBF obtained locally to MBF calculated at the core lab in Ottawa, Canada. Methods: Six sites (2 in Canada and one each from Japan, Singapore, Italy, and Germany) each acquired 25 rest/stress MBF studies using Tc99m-tetrofosmin (377 MBq at rest; 1060 MBq at stress) on a pinhole-collimated cadmium-zinc-telluride(CZT)-based cardiac SPECT camera. Patients had intermediate to high pre-test probability of coronary artery disease. MBF was analyzed locally and at a core lab using commercially available software. The time that a room was occupied for a MBF study was compared to that for a standard rest/stress myocardial perfusion study. Results: Preliminary results from 4 sites showed a correlation in MBF between the core lab and the local site of an average of 0.96 (range 0.95 to 0.97) at rest and 0.89 (range 0.77 to 0.96) at stress. From Bland-Altman analysis, the mean bias from zero in global MBF between local and core-lab analysis was 3.3% +/- 13.4% at rest and 3.0 % +/- 18.6% at stress. Between the 4 sites, the bias ranged from -4.1% to 9.9% at rest and from -6.3% to 12.8% at stress; the standard deviation (SD) ranged from 10.5% to 14.0% at rest and from 12.0% to 24.5% at stress. There was no significant difference between sites in the SD. The SD of the local-to-core-lab MBF differences is less than the SD of the test-retest difference of 30%, measured in a previous single-center study. The average additional time to perform a MBF study acquisition varied between sites from 45 to 76 min. This additional time includes the time needed to pharmacologically stress the patient which is normally done outside the camera room. Conclusions: This multi-center evaluation supports the feasibility of consistently measuring MBF using CZT-based cardiac SPECT cameras, as has been suggested from previous single-center studies.

Testing for Heparin Induced Thrombocytopenia in Hospitalized Patients: In Line with Evidence?

Background: Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Both clinical probability and laboratory testing are needed for establishing a diagnosis of HIT. The 4Ts clinical scoring system, due to a very high negative predictive value when low, offers a robust means to exclude a diagnosis of HIT. However, these strategies are under-employed in clinical practice and limited evidence indicates a high prevalence of over-testing for HIT.Methods: This retrospective analysis was conducted to identify patients who underwent heparin/PF4 antibody testing over a period of 12 months. The testing was performed using an ELISA-based IgG anti-heparin/PF4 antibody assay and an optical density (OD) of 0.4 was used as a cut-off for a positive value. Electronic medical records were reviewed for 4T score documentation, anti-PF4 results, SRA testing and 4T scores were retrospectively calculated for all the patients. SAS v9.4 (Cary, NC) was used for statistical analysis.Results: A total of 105 patients who underwent anti-PF4 antibody testing were included for analysis. Majority of the patients in our cohort were admitted in an intensive care unit setting (75/105,71.4%). On chart review, only 17 patients (16.2%) were noted to have documentation of 4T score. Based on the retrospectively calculated 4T scores, 60 patients (57.1%) had low pre-test probability, 41 (39%) had intermediate pre-test probability and 4 (3.8%) patients were noted to have high pre-test probability. Anti-PF4/heparin antibodies were positive in 9 patients, of which 5 (55.5%) patients did not undergo concomitant SRA testing. Out of 9, 4 (44.4%) had weakly positive (0.4-1.0 OD units), 2 (21.1%) had strongly positive (1.0-2.0 OD units) and 2 (21.1%) patients had very strongly positive (>2 OD units) anti-PF4 antibody titers. Out of 105 patients, SRA was tested in 11 patients (10.5%) and was noted to be positive in 1 (0.95%). Overall, 2 patients were diagnosed and treated for HIT, out of which the diagnosis was not confirmed with SRA in 1 patient (due to high pre-test probability and very strong anti-PF4 titers). In the remaining patients, sepsis (48, 46.6%) and drug-induced thrombocytopenia (29, 28.2%) emerged as the most common possible causes of thrombocytopenia.Conclusion: Among hospitalized patients, over-testing for HIT is common. Practices to promote 4T score documentation and evidence-based anti-PF4 testing may help prevent unnecessary costs associated with serological testing and costly alternate anticoagulants. To improve overall outcomes, clinicians should also attempt to identify and treat other more likely causes of thrombocytopenia, especially in patients with low pre-test probability for HIT. DisclosuresNo relevant conflicts of interest to declare.

The Laboratory Diagnosis of Clostridioides difficile Infection: An update of current laboratory practice.

Clostridioides difficile can cause colitis and is associated with hospital acquired infections. The C. difficile infection (CDI) is due to production of toxins A and B which bind to epithelial cell surface receptors and triggers signaling pathways, leading to loss of epithelial barrier function, apoptosis, and inflammation, culminating in diarrheal disease. In early days, laboratory diagnosis of CDI was based on cell culture, identification of toxins, and their cytopathic effects. These assays were replaced by enzyme immunoassays for the detection of C. difficile toxins and the GDH house-keeping gene for improved specificity. Later, molecular assays with higher sensitivity were introduced which are becoming easier to incorporate into the test algorithm. The diagnosis of CDI and significance of laboratory results can be challenging with asymptomatic colonization of C. difficile in some patients. Test result interpretation is even more challenging due to multiple guidelines, emerging resistant C. difficile ribotypes, as well as differences in disease prevalence. An accurate test result for diagnosis of CDI depends on selecting patients with high pre-test probability, collecting an acceptable stool specimen, and a thorough understanding of current test methods.

Comprehensive proteomics profiling identifies patients with late gadolinium enhancement on cardiac magnetic resonance imaging in the hypertrophic cardiomyopathy population

Abstract Introduction Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) represents myocardial fibrosis. In patients with hypertrophic cardiomyopathy (HCM), LGE on CMR has been associated with an increased risk of sudden cardiac death (SCD), which can be prevented with implantable cardioverter-defibrillators. Yet, CMR is expensive, resource-intensive, and, in certain patients, contraindicated. Therefore, it is important to determine which patients with HCM have a high pre-test probability of LGE on CMR. Proteomics profiling is a recently developed technology that simultaneously measures thousands of protein concentrations in plasma with a single blood draw. To date, no studies have examined the ability of proteomics profiling to identify which patients with HCM are more likely to have LGE on CMR. Purpose To test the hypothesis that plasma proteomics profiling can distinguish patients with and without LGE on CMR in the HCM population. Methods We performed a multicenter case-control (i.e., LGE vs. no LGE) study of 147 patients with HCM who underwent CMR between July 2006 and October 2020. We carried out plasma proteomics profiling of 4979 proteins using the SOMAscan assay. Using the 17 most discriminant proteins, we performed logistic regression analysis with elastic net regularization to develop a discrimination model with data from 1 institution (the training set; n=111) and tested the discriminative ability in independent samples from the other institution (the test set; n=36). We calculated the area under the receiver-operating-characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Furthermore, we performed pathway analysis of proteins that were differentially regulated between patients with and without LGE with p&amp;lt;0.05. Results The mean age was 57 years and 67% were male. Overall, 82 of the 147 patients (56%) had LGE on CMR. The AUC of the 17-protein model was 0.83 (95% CI, 0.75–0.90) in the training set and 0.71 in the independent test set for validation (95% CI, 0.54–0.88; Figure). The sensitivity, specificity, PPV, and NPV are shown in the Figure. The pathway analysis revealed that multiple signaling pathways were dysregulated in patients with LGE (Table). The list included signaling pathways that have been previously associated with myocardial fibrosis (e.g., pathways related to inflammation) and previously unrecognized pathways (e.g., glycolysis, amino acid metabolism). Conclusions In this multicenter study of 147 patients with HCM, comprehensive proteomics profiling identified a panel of 17 plasma protein biomarkers to specify patients with LGE on CMR and revealed associated signaling pathways. This 17-protein plasma protein biomarker panel would help physicians specify patients with LGE, in whom CMR is more likely to change the clinical management of HCM. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health, USA

S2484 Endoscopic Ultrasound With Fine Needle Aspiration for Diagnosis of Pancreatic Tumors in Patients With Benign Magnetic Resonance Imaging: Single Center Case Series

Introduction: Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Computed tomography (CT) scan and Magnetic resonance imaging (MRI) are used for early detection of small pancreatic lesions and cancer risk stratification. Endoscopic ultrasonography (EUS) with FNA (Fine Needle Aspiration) provides accurate diagnosis of pancreatic tumors. This case series introduces four cases of pancreatic tumors diagnosed using EUS/FNA that have been missed on MRI studies Case Description/Methods: Case 1 64-year-old male was referred for evaluation of pancreatic duct dilation on MRI with no detected mass. EUS revealed 15mm x 15mm mass of pancreas. FNA was performed and pathology was consistent with adenocarcinoma Case 2 55-year-old female was referred for evaluation of pancreatic cystic lesion found on MRI with no worrisome features. EUS revealed 15mm x 15mm pancreatic lesion. FNA was performed and pathology was consistent with pancreatic neuroendocrine tumor. Case 3 82-year-old female was referred for evaluation of pancreatic duct dilation on MRI with no discrete mass identified. EUS revealed 26mm x 27mm pancreatic lesion. FNA was performed and pathology was consistent with invasive adenocarcinoma. Case 4 62-year-old male was referred for evaluation of pancreatic lesion on MRI abdomen with features consistent with lipoma. EUS revealed 15mm x 13mm pancreatic lesion. FNA was performed and pathology was consistent with adenocarcinoma. Discussion: The diagnosis of pancreatic neoplasms relies heavily on identification of lesions on CT and MRI. While the sensitivity of MRI is similar to that of CT, the former is preferred in patients with high pre-test probability of pancreatic neoplasms. Sensitivity of EUS has been shown to be significantly higher in detecting pancreatic tumors when compared to CT, However, studies evaluating EUS to MRI are scarce. This case series presents four patients in whom pancreatic tumors were missed on MRI. Two patients had no radiologic evidence of a tumor, while the other two demonstrated lesions with no malignant features. EUS has the added benefit of tumor sampling and higher sensitivity in detecting pancreatic lesions. This case series highlights the potential limitations in the use of MR imaging in diagnosis of pancreatic cancers. Some evidence suggests that EUS is more sensitive than MRI and CT in detecting pancreatic lesions. However, the cost effectiveness and risks associated with routine EUS in the detection of pancreatic lesions has not been evaluated.Figure 1.: (A): Case 3 EUS with arrow pointing at 26mm x 27mm pancreatic lesion (B): Case 4 EUS with arrow pointing at 15mm x 13mm pancreatic lesion.

Development and Internal Validation of a Predictive Model for Adult GH Deficiency Prior to Stimulation Tests.

BackgroundThe diagnosis of adult GH deficiency (GHD) relies on a reduced GH response to provocative tests. Their diagnostic accuracy, however, is not perfect, and a reliable estimation of pre-test GHD probability could be helpful for a better interpretation of their results.MethodsEighty patients showing concordant GH response to two provocative tests, i.e. the insulin tolerance test and the GHRH + arginine test, were enrolled. Data on IGF-I values and on the presence/absence of other pituitary deficits were collected and integrated for the estimation of GHD probability prior to stimulation tests.ResultsAn independent statistically significant association with the diagnosis of GHD was found both for IGF-I SDS (OR 0.34, 95%-CI 0.18-0.65, p=0.001) and for the presence of other pituitary deficits (OR 6.55, 95%-CI 2.06-20.83, p=0.001). A low (<25%) pre-test GHD probability could be predicted when IGF-I SDS > +0.91 in the presence of other pituitary deficits or IGF-I SDS > -0.52 in the absence of other pituitary deficits. A high (>75%) pre-test GHD probability could be predicted when IGF-I SDS < -0.82 in the presence of other pituitary deficits or IGF-I SDS < -2.26 in the absence of other pituitary deficits.ConclusionThis is the first study that proposes a quantitative estimation of GHD probability prior to stimulation tests. Our risk class stratification represents a simple tool that could be adopted for a Bayesian interpretation of stimulation test results, selecting patients who may benefit from a second stimulation test and possibly reducing the risk of wrong GHD diagnosis.

The accuracy of ACTH as a biomarker for pituitary pars intermedia dysfunction in horses: A systematic review and meta-analysis.

Accuracy of baseline ACTH for the diagnosis of PPID in horses varies between studies. To estimate the diagnostic accuracy of ACTH as a biomarker for PPID in adult horses and appraise potential causes of heterogeneity. Systematic review and meta-analysis. A literature review identified studies reporting diagnostic accuracy data for extraction. Risk of bias was evaluated using QUADAS-2. Two random-effects models, the hierarchical summary receiver operating curve (HSROC) and the bivariate binomial normal model (BBN) were used to pool accuracy measurements. We performed meta-regression using study-level variables. The impact of diagnostic test accuracy on the frequency of false-positive and false-negative results at various pretest probabilities was calculated using the BBN model's accuracy results. Patient selection and index test evaluation demonstrated significant risk of bias. Mean and 95% confidence intervals for sensitivity and specificity for all studies (n=11) based upon the HSROC model were (0.72, 95% CI: 0.62 to 0.82) and (0.88, 95% CI: 0.79 to 0.93), respectively. When studies with a common positivity threshold of 35pg/mL ACTH were evaluated (n=6), sensitivity and specificity were (0.66, 95% CI:0.54 to 0.77) and (0.87, 95% CI: 0.74 to 0.94). In a hypothetical group of one thousand horses with PPID prevalence of 2%, 20%, and 90%, the frequency of resulting false-positive and false-negatives would be (127 and 7), (104 and 68) and (13 and 306), respectively. Factors leading to increased accuracy were case-control design, clinical reference standard and data-driven choice of ACTH threshold. A small number of primary studies (n=11) were available, demonstrating significant biases. Less biased studies examining diagnostic accuracy of ACTH are needed. In horses with a high pretest probability of PPID, ACTH may be a functional "rule-in" test. Baseline ACTH is not recommended for screening purposes or use in horses without clinical signs of PPID.

Tuberculosis in Cirrhosis – A Diagnostic and Management Conundrum

Diagnosis and management of tuberculosis (TB) in patients with cirrhosis remains challenging. We studied the clinical spectrum, diagnosis, and management of TB along with the assessment of the diagnostic utility of various laboratory investigations in this cohort. A retrospective review of records of patients with cirrhosis (July 2017 and December 2019) was done. Out of 30 patients with cirrhosis and TB, 20 patients with pleural/peritoneal TB (cases) were compared with 20 consecutively selected spontaneous bacterial peritonitis (SBP) controls. Composite of clinical, laboratory, radiologic features and response to antituberculosis therapy (ATT) was taken as the gold standard to diagnose TB. Extrapulmonary TB (EPTB) (n= 23, 76.7%) was more common. Overall, 9 (30%) patients presented with ATT-induced hepatitis. Patients with pleural/peritoneal TB had less severe hepatic dysfunction as compared to SBP group with significantly lower CTP [8±1.5 vs. 9±1.7 (P= 0.01)], MELD [16.3±5.8 vs. 20.2±6.6 (P= 0.02)] and MELD-Na [18.8±5.9 vs. 22.5±7.1 (P= 0.03)] scores. Median ascitic/pleural fluid total protein [2.7 (2.4-3.1) vs. 1.1 (0.9-1.2); P < 0.0001] and adenosine deaminase (ADA) levels [34.5 (30.3-42.7) vs. 15 (13-16); P < 0.0001] were significantly higher in the TB group. Total protein levels had a sensitivity and specificity 81% and 93.3%, respectively, at cut off value of >2g/dl with an AUROC of 0.89 [(0.79-0.96); P < 0.001] whereas ADA levels at cutoff >26 IU/L showed 80% sensitivity and 90% specificity to diagnose pleural/peritoneal TB with an AUROC of 0.93 [(0.82-0.97); P < 0.001]. Only 11 (36.7%), and 8 (26.6%) patients showed positivity on GeneXpert and mTB-PCR, respectively. Patients with Child-Turcotte-Pugh scores of ≤7 and 8-10 tolerated well two and one hepatotoxic drugs, respectively. EPTB is more frequent in patients with cirrhosis. Relatively lower cutoffs of ascitic/pleural fluid total protein and ADA may be useful to diagnose EPTB in patients with high pretest probability. Individualized ATT with close monitoring and dynamic modifications is effective and well-tolerated.

Lung Ultrasound Severity Index: Development and Usefulness in Patients with Suspected SARS-Cov-2 Pneumonia-A Prospective Study.

Coronavirus disease 2019 (COVID-19) has spread across the world with a strong impact on populations and health systems. Lung ultrasound is increasingly employed in clinical practice but a standard approach and data on the accuracy of lung ultrasound are still needed. Our study's objective was to evaluate lung ultrasound diagnostic and prognostic characteristics in patients with suspected COVID-19. We conducted a monocentric, prospective, observational study. Patients with respiratory distress and suspected COVID-19 consecutively admitted to the Emergency Medicine Unit were enrolled. Lung ultrasound examinations were performed blindly to clinical data. Outcomes were diagnosis of COVID-19 pneumonia and in-hospital mortality. One hundred fifty-nine patients were included in our study; 66% were males and 63.5% had a final diagnosis of COVID-19. COVID-19 patients had a higher mortality rate (18.8% vs. 6.9%, p = 0.04) and Lung Ultrasound Severity Index (16.14 [8.71] vs. 10.08 [8.92], p < 0.001) compared with non-COVID-19 patients. This model proved able to distinguish between positive and negative cases with an area under the receiver operating characteristic (AUROC) equal to 0.72 (95% confidence interval [CI]: 0.64–0.78) and to predict in-hospital mortality with an AUROC equal to 0.81 (95% CI: 0.74–0.86) in the whole population and an AUROC equal to 0.76 (95% CI: 0.66–0.84) in COVID-19 patients. The Lung Ultrasound Severity Index can be a useful tool in diagnosing COVID-19 in patients with a high pretest probability of having the disease and to identify, among them, those with a worse prognosis.

Typical, rare and atypical CT findings in COVID-19 pneumonia: A pictorial review

Objectives: The objective of this pictorial review is to make radiologists and clinicians familiar with the typical, atypical and rare CT findings of COVID-19 pneumonia to help in diagnosis as well as in monitoring disease. Main text: Bilateral ground-glass opacities, whether isolated or coexisting with consolidations, and typically in basal, posterior and peripheral lungs are the key findings in COVID-19 pneumonia. With further analysis other typical, atypical and rare CT findings are described and we need to keep in mind that the radiological presentation is dynamic with a rapid evolutive phase, peaking at 10-11 days, and a subsequent absorption phase after 14 days with a decrease in opacities and increase in repairing signs. Conclusion: The presence of typical findings of COVID-19 pneumonia on a chest CT scan during the pandemic outbreak of SARSCoV-2 helps in diagnostic analysis. Chest CT scan has a reported sensitivity of 97-98% in times with a high pre-test probability. Some CT findings (crazy paving pattern and pleural effusion) as well as an increasing percentage of lung opacities are associated with a worse patient outcome, emphasizing the role of chest CT in determining the risk of disease progression. Furthermore chest CT scan is also useful in monitoring disease control. With these acknowledgement we want to give a useful overview of the chest CT manifestations in COVID-19 pneumonia to help decision making in daily practice. Keywords: COVID-19; SARS-CoV-2; tomography; X Ray computed; diagnosis.

Revisiting level II sleep studies in the era of COVID-19: a theoretical economic decision model in patients with suspected obstructive sleep apnea

BackgroundThe recent pandemic has made it more challenging to assess patients with suspected obstructive sleep apnea (OSA) with in laboratory polysomnography (PSG) due to concerns of patient and staff safety. The purpose of this study was to assess how Level II sleep studies (LII, full PSG in the home) might be utilized in diagnostic algorithms of suspected OSA using a theoretical decision model.MethodsWe examined four diagnostic algorithms for suspected OSA: an initial PSG approach, an initial LII approach, an initial Level III approach (LIII, limited channel home sleep study) followed by PSG if needed, and an initial LIII approach followed by LII if needed. Costs per patient assessed was calculated as a function of pretest OSA probability and a variety of other variables (e.g. costs of tests, failure rate of LIII/LII, sensitivity/specificity of LIII). The situation in British Columbia was used as a case study.ResultsThe variation in cost per test was calculated for each algorithm as a function of the above variables. For British Columbia, initial LII was the least costly across a broad range of pretest OSA probabilities (< 0.80) while initial LIII followed by LII as needed was least costly at very high pretest probability (> 0.8). In patients with a pretest OSA probability of 0.5, costs per patient for initial PSG, initial LII, initial LIII followed by PSG, and initial LIII followed by LII were: $588, $417, $607, and $481 respectively.ConclusionsUsing a theoretical decision model, we developed a preliminary cost framework to assess the potential role of LII studies in OSA assessment. Across a broad range of patient pretest probabilities, initial LII studies may provide substantial cost advantages. LII studies might be especially useful during pandemics as they combine the extensive physiologic information characteristic of PSG with the ability to avoid in-laboratory stays. More empiric studies need to be done to test these different algorithms.