High Negative Predictive Value Research Articles

Sensitivity and specificity of the posterolateral rotatory drawer test in the diagnosis of lateral collateral ligament insufficiency of the elbow.

Numerous clinical tests are described for the diagnosis of chronic lateral collateral ligament (LCL) insufficiency of the elbow; however, none of these tests have been adequately assessed for sensitivity, with at most 8 patients included in previous studies. Furthermore, no test has had specificity assessed. The posterolateral rotatory drawer (PLRD) test is thought to have improved diagnostic accuracy over other tests in the awake patient. The aim of this study is to formally assess this test using reference standards in a large cohort of patients. A total of 106 eligible patients were identified for inclusion from a single-surgeon database of operative procedures. Examination under anesthetic (EUA) and arthroscopy were chosen as the reference standards to compare the PLRD test against. Only patients with a clearly documented PLRD test finding performed preoperatively in the clinic, and a clearly documented EUA and/or arthroscopic findings from surgery were included. A total of 102 patients underwent EUA, 74 of whom also underwent arthroscopy. Twenty-eight patients had EUA, and then an open procedure without arthroscopy. Four patients had arthroscopy without a clearly documented EUA. Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were calculated with 95% confidence intervals. Thirty-seven patients had a positive PLRD test, and 69 had a negative test. Compared to the reference standard of EUA (n=102), the PLRD test had a sensitivity of 97.3% (85.8%-99.9%) and a specificity of 98.5% (91.7%-100%) (PPV=0.973, NPV=0.985). Compared to the reference standard of arthroscopy (n=78), the PLRD test had a sensitivity of 87.5% (61.7%-98.5%) and a specificity of 98.4% (91.3%-100%) (PPV=0.933, NPV=0.968). Compared to either reference standard (n=106), the PLRD test has a sensitivity of 94.7% (82.3%-99.4%) and a specificity of 98.5% (92.1%-100%) (PPV=0.973, NPV=0.971). The PLRD test demonstrated an overall sensitivity of 94.7% and specificity of 98.5% with high positive and negative predictive values. This test is recommended as the primary diagnostic tool for LCL insufficiency in the awake patient and should be widely incorporated into surgical training.

Prevalence and risk factors of urinary tract infection among children with bronchiolitis

BackgroundThe co-occurrence of bronchiolitis and urinary tract infections (UTI) in hospitalized children is associated with high morbidity and economic strain. However, due to a low prevalence (<3%) and inconsistent diagnostic criteria, there is ongoing debate regarding the necessity of systematic screening. This study estimated the prevalence of UTI among children admitted for bronchiolitis and analyzed the associated demographic and clinical factors. MethodsA 5-year (2016–2020) retrospective chart review was conducted among all children admitted for bronchiolitis at a referral pediatrics department in Jeddah, Saudi Arabia. UTI was diagnosed according to the American Association of Pediatrics criteria. Demographic, clinical, microbiological, and imaging data were extracted from the hospital electronic records. ResultsOf the 491 cases of children with bronchiolitis, urine culture and analysis were available for 320 patients. Based on urine culture criteria alone, the prevalence of UTI was 13.1% (95% CI 9.6–17.3), and the most common pathogens included E. coli (33.3%), K. pneumoniae (23.8%), and Enterococcus faecalis (14.3%), and 13 (31.0%) of the isolates were EBSL. By considering urinalysis criteria, i.e., pyuria or nitrituria, the estimated prevalence of UTI decreased to 3.4% (1.7–6.1%), and the most common pathogens were K. pneumoniae (5/11) and E. coli (3/11), with 6/11 ESBL-producing isolates. Regurgitation associated with a higher risk of UTI compared to absence of regurgitation (5.3% versus 0.8%; p = 0.031). Urinary tract ultrasound showed high specificity (98.7–100%) and negative predictive value (97.4–97.7%) in UTI using either criterion. ConclusionsThere is a higher prevalence of UTI among children with bronchiolitis in the study center, which has several implications in screening, diagnosis, and management. Further multicenter studies are required to enhance the external validity of these findings and assess the cost-effectiveness of screening strategy at a national level.

Virological characteristics and the rapid antigen test as deisolation criteria in immunocompromised patients with COVID-19: A prospective cohort study.

There are limited data supporting current Centers for Disease Control and Preventionguidelines for the isolation period in moderate to severely immunocompromised patients with coronavirus disease 2019 (COVID-19).Adult COVID-19 patients who underwent solid organ transplantation (SOT) or received active chemotherapy against hematologic malignancy were enrolled and weekly respiratory samples were collected. Samples with positive genomic real-time polymerase chain reactionresults underwent virus culture and rapid antigen testing (RAT).A total of 65 patients (40 with hematologic malignancy and 25 SOT) were enrolled. The median duration of viable virus shedding was 4 weeks (interquartile range: 3-7). Multivariable analysis revealed that B-cell depletion (hazard ratio [HR]:4.76) was associated with prolonged viral shedding, and COVID-19 vaccination (≥3 doses) was negatively associated with prolonged viral shedding (HR: 0.22). The sensitivity, specificity, positive predictive value, and negative predictive value of RAT for viable virus shedding were 79%, 76%, 74%, and 81%, respectively. The negative predictive value of RAT was only 48% (95% confidence interval [CI]: 33-65) in the samples from those with symptom onset ≤20 days, but it was as high as 92% (95% CI: 85-96) in the samples from those with symptom onset >20 days.About half of immunocompromised COVID-19 patients shed viable virus for ≥4 weeks from the diagnosis, and virus shedding was prolonged especially in unvaccinated patients with B-cell-depleting therapy treatment. RAT beyond 20 days in immunocompromised patients had a relatively high negative predictive value for viable virus shedding.

Value of pneumococcal PCR in respiratory samples for exclusion of pneumococcal pneumonia.

Streptococcus pneumoniae is the main aetiological agent in bacterial pneumonia. Therefore pneumococcal PCR is often included in respiratory multiplex PCR panels, both commercial and in-house. But respiratory PCR results for S. pneumoniae are difficult to interpret due to frequent non-pathogenic colonization on the mucosal surface of the upper airways with pneumococci or to cross-reaction of the PCR target in non-pneumococcal streptococci. In this study we investigated the value of lytA gene pneumococcal PCR in patients presenting with pneumonia. To assess the utility of lytA gene detection for S. pneumoniae in a respiratory multiplex quantitative PCR (qPCR) panel for patients presenting with pneumonia. A retrospective study was conducted for lytA gene results as target for S. pneumoniae in hospitalized patients who were diagnosed with pneumonia and for which a respiratory multiplex PCR panel was performed. Patients were classified as 'probable', 'possible' or 'unlikely' of having a pneumococcal pneumonia. A sensitivity of 71.4% and specificity of 89.6% were found, corresponding to a negative predictive value and positive predictive value of 97.6% and 34.2%, respectively, when considering 'probable' versus 'possible/unlikely'. In the PCR-positive cases we found a statistically significant difference in semi-quantitative Ct values between the 'probable' and the 'possible/unlikely' groups. We conclude that a negative qPCR for the lytA gene in a respiratory sample is highly predictive of a negative S. pneumoniae culture and is possibly sufficient to exclude S. pneumoniae as a causative agent. Respiratory pneumococcal PCR has a high negative predictive value for pneumococcal disease but the positive predictive value is low.

Serum Interleukin-6 as a Biomarker for Early Prediction of Post-Operative Infectious Complications After Elective Pancreatectomy.

Background: To investigate whether interleukin (IL)-6 could predict the post-operative complications of elective pancreatectomy early. Patients and Methods: Overall, 122 patients who underwent elective pancreatectomy from June 2020 to May 2021 in our hospital were enrolled. Interleukin-6 was measured on the day before and at six hours after surgery, and on post-operative day one, three, and five. The associations between IL-6 level and post-operative complications were analyzed, and the predictive value of IL-6 for complications was assessed. Results: Sixty-three patients developed post-operative complications. Higher IL-6 was observed in patients with post-operative complications on post-operative day one, post-operative day three, and post-operative day five, with odd ratios of 1.43, 1.68, and 2.54 (p = 0.01, p = 0.01, and p = 0.01), respectively. These trends were also observed in patients with infectious complications preoperatively, on post-operative day one, post-operative day three, and post-operative day five, with ORs of 2.46, 1.95, 2.01, and 2.49 (p = 0.00, 0.00, 0.01, 0.00) respectively. Multivariate regression revealed that IL-6 is the only predictor for infectious complications on post-operative day one (p = 0.016). Based on the optimal cutoffs, pre-operative IL-6, IL-6 on post-operative day one and post-operative day three for predicting infectious complications yielded area under the curve (AUC) of 0.73, 0.70, and 0.70, with high negative predictive value of 82.7%, 92.2%, and of 91.3%, respectively. Conclusions: This study validated the early predictive value of IL-6 on infectious complications after pancreatectomy. Because of the performance of serum IL-6 in predicting infectious complications and high NPV, we endorse that IL-6 could be a potential biomarker for early prediction and antibiotic optimization after pancreatectomy.

Rim lesions in MS at 3T: clinical correlation and possible radiological alternatives for daily practice at lower field strength

Background and purposeParamagnetic rim lesions (PRLs) have been described as an imaging feature specific to multiple sclerosis (MS) using high-field strength phase-sensitive MR imaging. These lesions are suggested to reflect chronic active inflammation associated with greater disease severity and a more rapid disability progression. The aim of our study is to investigate the relationship between PRLs, clinical parameters, other radiological findings and disease progression. Material and methodsThis cross-sectional study included MS patients treated with teriflunomide, fingolimod, natalizumab or ocrelizumab for at least 2 years. PRLs seen at 3T MRI were analysed and correlated with clinical data and radiological progression, defined as an increase of the T2/FLAIR-lesion load during therapy. In the search for alternatives for these PRLs, we defined two additional radiological markers: ‘FLAIR-bullet lesions’, and on post-contrast black-blood (BB) images, ‘BB-bullet lesions’. ResultsWe included 84 MS patients of whom 27 (32 %) had at least 1 PRL. PRLs were associated with radiological progression under therapy (p=0.039) and higher clinical disability scores, although only significant for 9-Hole Peg Test (p=0.023). Patients with FLAIR-bullet or BB-bullet lesions at 3T MRI had a higher chance of PRL (p<0.001) with a likelihood ratio of 13.2 for FLAIR-bullets and 12.6 for BB-bullet lesions, thanks to the high negative predictive value of respectively 83 % and 90 %. ConclusionPRLs are associated with an increase of T2/FLAIR-lesion load under therapy and unfavourable clinical outcome. Our newly defined ‘bullet lesions’ are associated with PRLs and might be an interesting MRI marker for centres without access to high-field SWI images.

Heads-Up Micronavigation Reliability of Preoperative Transcranial Magnetic Stimulation Maps for the Motor Function: Comparison With Direct Cortical Stimulation.

We aimed to assess the reliability of preoperative navigated transcranial magnetic stimulation (nTMS) maps for motor function as visualized intraoperatively with augmented reality heads-up display and to assess its accuracy via direct point-by-point comparison with the gold-standard direct cortical stimulation (DCS). From January 2022 to January 2023, candidates for surgical removal of lesions involving the motor pathways underwent preoperative nTMS assessment to obtain cortical maps of motor function. Intraoperatively and before tumor removal, nTMS maps were superimposed on the cortical surface, and DCS was performed on positive points with increasing current intensity until obtaining a positive response at 16 mA. The outcome of each stimulation was recorded to obtain discrimination metrics. Twelve patients were enrolled (5 females [42%] vs 7 males [58%], mean age 62.9 ± 12.8 years), for a total of 304 investigated points. Agreement between nTMS and DCS was moderate (κ = 0.43, P < .005), with 0.66 (0.53-0.78) sensitivity, 0.87 (0.82-0.90) specificity, 0.50 (0.39-0.62) positive predictive values, 0.93 (0.89-0.95) negative predictive value, and 0.83 (0.79-0.87) accuracy. A loss of accuracy was observed with higher DCS current intensities. We performed a point-by-point validation of preoperative nTMS maps for motor function using augmented reality visualization. The high negative predictive value and low positive predictive values highlight nTMS reliability to visualize safe cortical zones but not to identify critical functional areas, confirming previous findings of nTMS maps for the language function and suggesting the need for combined use of nTMS maps and DCS for optimal maximal safe resection.

Diagnostic performance of quantitative flow ratio in non-ST elevation acute coronary syndromes in comparison to non-hyperemic pressure ratios: a prospective study.

Quantitative flow ratio (QFR) is a new angiography-based coronary physiology tool aimed to evaluate functional relevance of intermediate coronary lesions. Aim of the study is to assess diagnostic performance of QFR in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in comparison to currently used non-hyperaemic pressure ratios (NHPRs). In this prospective, single-centre study, coronary physiology of intermediate coronary stenoses of non-culprit vessels in patients presenting with NSTE-ACS was evaluated using NHPRs (iFR, DFR or RFR). Subsequently, QFR was computed offline by a QFR analyst blinded to the NHPR results. Diagnostic performance of QFR was assessed in comparison to NHPRs as reference standard. A total of 60 vessels with intermediate coronary stenoses was investigated. The NHPRs were used as follows: RFR 38%, DFR 47% and iFR 15% of the cases. The NHPR result was positive, showing significant lesion, in 19 cases. A significant correlation was found between NHPR and QFR (r = 0.84, p < 0.001). Classification agreement of the two methods (95%) and diagnostic performance of QFR in comparison to NHPR (AUC: 0.962 [0.914-1.00]) were both high. Sensitivity, specificity, positive and negative predictive value of QFR in comparison to NHPR were 84.2%, 100%, 100% and 93.2% respectively. QFR has high diagnostic performance in detecting functionally significant lesions of non-culprit arteries in patients with NSTE-ACS and multivessel disease. Due to its high negative predictive value, it can be used to safely avoid unnecessary invasive physiological assessment of these lesions.

Predicting Superficial Surgical Site Infections: A Study of the Risk Factors and an Assessment Scale From Western India.

Introduction Superficial surgical site infections (SSSIs) are very common nosocomial infections that can complicate a range of surgeries, resulting in increased morbidity and mortality, and an overall decreased benefit of surgical interventions, along with exorbitant expenditure of healthcare resources. An assessment scale could help in the segregation of the high-risk patient population, and appropriate resources could be directed toward them. Methods A prospective observational study was carried out in a tertiary care hospital in Western India with 200 participants. Certain probable preoperative, intraoperative, and postoperative risk factors for SSSIs were assessed for significance of association, and each patient was given a score according to the assessment scale. The predictive power of the scale was calculated. Results Body mass index (BMI), preoperative laboratory investigations, and preoperative hospital stay showed a significant association with the complication. Clean-contaminated wounds had a higher incidence of postoperative SSSIs as compared to clean wounds. Postoperatively, fever and the presence of open drains predisposed the patient to complications. The assessment scale was found to have a positive predictive value of 40.94% and a negative predictive value (NPV) of 86.30%. Conclusion The factors that could significantly prevent the development of SSSIs are normal preoperative laboratory investigations, less than three days of preoperative hospital stay, and avoiding the use of open drains. The high NPV of the assessment scale means that it can be used as a screening tool to segregate high-risk patients.

Cross-validation of comorbidity items in two national databases in a sample of patients with end-stage kidney disease

BackgroundThe use of national medico-administrative databases for epidemiological studies has increased in the last decades. In France, the Healthcare Expenditures and Conditions Mapping (HECM) algorithm has been developed to analyse and monitor the morbidity and economic burden of 58 diseases. We aimed to assess the performance of the HECM in identifying different conditions in patients with end-stage kidney disease (ESKD) using data from the REIN registry (the French National Registry for patients with ESKD).MethodsWe included all patients over 18 years of age who started renal replacement therapy in France in 2018. Five conditions with a similar definition in both databases were included (ESKD, diabetes, human immunodeficiency virus [HIV], coronary insufficiency, and cancer). The performance of each SNDS algorithm was assessed using sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs), and Cohen’s kappa coefficient.ResultsIn total 5,971 patients were included. Among them, 81% were identified as having ESKD in both databases. Diabetes was the condition with the best performance, with a sensitivity, specificity, PPV, NPV, and Kappa coefficient all over 80%. Cancer had the lowest level of agreement with a Kappa coefficient of 51% and a high specificity and high NPV (94% and 95%). The conditions for which the definition in the HECM included disease-specific medications performed better in our study.ConclusionThe HECM showed good to very good concordance with the REIN database information overall, with the exception of cancer. Further validation of the HECM tool in other populations should be performed.

Osteocalcin associates with bone mineral density and VDR gene polymorphisms in type 1 and type 2 diabetes.

Bone metabolism is impaired in diabetes mellitus (DM). Our objective is to evaluate the association of bone turnover markers (BTM) and vitamin D receptor (VDR) gene polymorphisms with bone mineral density (BMD) in DM type 1 (T1D) and DM type 2 (T2D). A total of 165 patients (53 T1D and 112 T2D) were enrolled. BMD was measured by dual-energy X-ray absorptiometry (DEXA). Plasma osteocalcin (OC), beta-CrossLaps (β-CTX) and N-amino terminal propeptide of type I collagen (P1NP) and VDR gene polymorphisms were evaluated. Participants were 53 T1D (41 years [31-48]) and 112 T2D (60 years [51-66]). BMD were not statistically different between the groups. OC (p<0.001) and P1NP levels (p<0.001) were higher in patients with T1D. The areas under the curve for the prediction of bone pathology were 0.732 (p=0.038) for OC in T1D and 0.697 (p=0.007) in T2D. A significant association was found between lower lumbar BMD and the A allele of BsmI (p=0.03), the A allele of ApaI (p=0.04) and the allele C of the Taql (p=0.046). Also, a significant correlation was found with higher OC levels and the G allele of BsmI (p=0.044), C allele of ApaI (p=0.011), T allele of Taql (p=0.006) and with C allele of FokI (p=0.004). The high negative predictive value of the cut-off point for OC suggests that could be useful in excluding the risk suffering bone loss, allowing offering a personalized clinical approach to prevent this pathology.

Screening for coronary artery disease using primary evaluation with coronary CTA in aviation medicine (SUSPECT): study design

Background: Sudden in-flight incapacitation of aircrew may cause an airplane crash. Important causes are major adverse cardiac events, such as myocardial infarction and sudden cardiac arrest. Aircrew of the Royal Netherlands Air Force (RNLAF) are required to undergo periodic cardiac screening, including bicycle exercise-testing. Unfortunately, this modality lacks diagnostic accuracy for relevant coronary artery disease (CAD) in low-risk populations similar to military aircrew. Cardiac CT, however, comprising Coronary Artery Calcium score (CACS) and coronary CT angiography (CCTA), is able to adequately detect (subclinical) CAD with high negative predictive values in low-risk populations and may provide opportunity for early interventions. Methods: This was a prospective, single-center, cohort study of 250 military aircrew. Asymptomatic aircrew ≥40 years are asked to undergo a voluntary cardiac CT following routine aeromedical examination. Prevalence and severity of CAD will be described according to the CAD-RADS system, including coronary artery calcium score (CACS) and high risk plaque features. The primary endpoint is relevant CAD, defined as a composite of a coronary stenosis ≥50% and/or CACS &gt;100 Agatston Units. The secondary endpoint is ‘aeromedically significant CAD’, defined by national military regulations as a left main stenosis of &gt;30%, any luminal stenosis ≥50%, and/or an aggregate coronary stenosis of ≥120%. Conclusions: The aim is to assess the value of cardiac CT for routine aeromedical screening in asymptomatic Dutch military aircrew aged ≥40 years, in comparison to the current cardiac screening protocol which includes an exercise ECG. Trial Registration: Clinical trial registered on clinicaltrials.gov number NCT05508893.

Resting echocardiographic parameters can exclude significant coronary artery disease: A comparison with coronary computed tomography angiography.

Coronary computed tomography angiography (CCTA) is known to have a high negative predictive value (NPV) in identifying coronary artery disease (CAD). This study aimed to examine whether resting echocardiographic parameters could exclude significant CAD on CCTA. We recruited 142 patients who had undergone both CCTA and echocardiography within a 3-month window. Based on the CCTA findings, patients were divided into two groups: Group A (non-significant CAD, defined as all coronary segments having <50% stenosis) and Group B (significant CAD). Resting echocardiographic parameters were compared between the two groups to identify predictors of non-significant CAD on CCTA. A total 92 patients (mean age, 68±13years; males, 62%) were eligible for this study; 50 in Group A and 42 in Group B. Among the various echo parameters, left atrial volume index (LAVI) and left ventricular (LV) global longitudinal strain (GLS) were significantly lower in Group A (23.5±7.6 vs. 33.6±7.4mL/m2 , p<.001; -20.2±1.8% vs. -16.8±2.0%, p<.001, respectively). Analysis of the receiver operating characteristic curve revealed that the cutoff value to exclude significant CAD on CCTA was 29.0mL/m2 for LAVI (NPV 80.8%) and -18.1% for GLS (NPV 80.7%). The NPV increased to 95.0% when these parameters were combined (LAVI<29.0mL/m2 and GLS<-18.1%). The combination of resting LAVI and GLS was clinically useful in excluding significant CAD via CCTA.

Integrating SARS-CoV-2-specific interferon-γ release assay testing in the evaluation of patients hospitalized with COVID-19.

T cell-mediated immunity is crucial for protection against severe COVID-19. The performance of SARS-CoV-2-specific IFN-γ release assays (IGRAs) to measure T cell responses during severe acute infection is unknown. We conducted a prospective, longitudinal analysis of patients hospitalized for confirmed COVID-19. A standardized SARS-CoV-2-specific quantitative IGRA was measured on admission. Follow-up lasted 90 days. Two hundred forty-eight patients were included; 181 (73%) were vaccinated, 142 (57.3%) were infected with the Omicron variant, and 106 (42.7%) were infected with the Delta variant. The SARS-CoV-2-IGRA result was positive (>200 mIU/mL) in 125 (50.5%) patients, with 44 (35.2%) showing concomitant mitogen-induced IFN-γ response. Compared with patients with negative and borderline results, those with positive SARS-CoV-2 IGRA were younger and showed lower frequency of co-existing comorbidities, lower median Charlson comorbidity index, lower frequency of World Health Organization (WHO) severity score > 4, higher peripheral arterial oxygen saturation to inspired fraction of oxygen (SpO2/FiO2) ratio on admission, higher S-IgG and N-IgG antibody responses, and lower mortality at 28/60/90 days. These findings were consistent for both the Omicron and Delta variants. Similar patterns to those described above were observed in the subset of patients with positive SARS-CoV-2-IGRA and indeterminate mitogen-induced responses, as well as in those exhibiting both positive SARS-CoV-2-specific and mitogen responses. Twenty-eight (11.3%) patients had borderline (100-200 mIU/mL) SARS-CoV-2-IGRA results and shared several similarities with patients with negative SARS-CoV-2 IGRA. In an adjusted Cox model, a negative SARS-CoV-2-IGRA result was found to be an independent predictor of mortality. Using a receiver operating characteristics curve analysis, we found that an IFN-γ value of 150 mIU/mL was identified as the optimal cut-off point for predicting mortality, with 79% [95% confidence interval (CI) 61-93] sensitivity, 61% (95% CI 55-68) specificity, 18% (95% CI 15-22) positive predictive value, 96% (95% CI 93-98) negative predictive value, and an area under the curve (AUC) of 70%. The assay's performance remained consistent regardless of mitogen results or the presence of the Delta or Omicron variants. IMPORTANCE The cellular immune response is essential in the protection against severe disease in patients with established SARS-CoV-2 infection. The novelty of this study lies in the evaluation of the overall performance of a standardized assay to measure cellular immune response, the SARS-CoV-2-specific interferon-γ release assay (IGRA), in hospitalized patients with severe COVID-19. The SARS-CoV-2 IGRA was shown to accurately classify patients based on disease severity and prognosis, and the study revealed that test performance was not affected by the SARS-CoV-2 variant or control tube results. We identified an assay cut-off point with a high negative predictive value against mortality. The SARS-CoV-2 IGRA in patients hospitalized for COVID-19 may be a useful tool to assess cellular immunity and adopt targeted therapeutic and preventive measures.

Characterisation of Ferritin-Lymphocyte Ratio in COVID-19.

Introduction: The ferritin-lymphocyte ratio (FLR) is a novel inflammatory biomarker for the assessment of acute COVID-19 patients. However, the prognostic value of FLR for predicting adverse clinical outcomes in COVID-19 remains unclear, which hinders its clinical translation. Methods: We characterised the prognostic value of FLR in COVID-19 patients, as compared to established inflammatory markers. Results: In 217 study patients (69 years [IQR: 55-82]; 60% males), FLR was weakly correlated with CRP (R = 0.108, p = 0.115) and white cell count (R = -0.144; p = 0.034). On ROC analysis, an FLR cut-off of 286 achieved a sensitivity of 86% and a specificity of 30% for predicting inpatient mortality (AUC 0.60, 95% CI: 0.53-0.67). The negative predictive values of FLR for ruling out mortality, non-invasive ventilation requirement and critical illness (intubation and/or ICU admission) were 86%, 85% and 93%, respectively. FLR performed similarly to CRP (AUC 0.60 vs. 0.64; p = 0.375) for predicting mortality, but worse than CRP for predicting non-fatal outcomes (all p < 0.05). On Kaplan-Meier analysis, COVID-19 patients with FLR values > 286 had worse inpatient survival than patients with FLR ≤ 286, p = 0.041. Conclusions: FLR has prognostic value in COVID-19 patients, and appears unrelated to other inflammatory markers such as CRP and WCC. FLR exhibits high sensitivity and negative predictive values for adverse clinical outcomes in COVID-19, and may be a good "rule-out" test. Further work is needed to improve the sensitivity of FLR and validate its role in prospective studies for guiding clinical management.

Ampicillin-susceptible Enterococcus faecium infections: clinical features, causal clades, and contribution of MALDI-TOF to early detection.

Enterococcus faecium, a common resident of the human gastrointestinal tract, is also a major pathogen. Prompt initiation of appropriate treatment is essential to improve patient outcome in disseminated E. faecium infections. However, ampicillin resistance is frequent in this species, rendering treatment difficult. We used a comprehensive approach, including clinical data review, whole-genome sequencing, and mass spectrometry, to characterize ampicillin-susceptible (EFM-S) and ampicillin-resistant (EFM-R) isolates. We included all patients with culture-confirmed E. faecium infection attending our hospital over a 16-month period. A comparison of 32 patients infected with EFM-S strains and 251 patients infected with EFM-R strains revealed that EFM-R isolates were strongly associated with a longer hospital stay, history of prior hospitalization, and the carriage of multidrug-resistant organisms. An analysis of the genomes of 26 EFM-S and 26 EFM-R isolates from paired patients revealed a population structure almost perfectly matching ampicillin susceptibility, with resistant isolates in clade A1, and susceptible isolates in clades A2 and B. The clade B and A2 isolates mostly came from digestive or biliary tract samples, whereas clade A1 isolates were mostly obtained from urine and blood. Finally, we built a custom database for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which differentiated between clade B and clade A1/A2 strains with high-positive and high-negative predictive values (95.6% and 100%, respectively). This study provides important new insight into the clinical features and clades associated with EFM-S and EFM-R isolates. In combination with MALDI-TOF MS, these data could facilitate the rapid initiation of the most appropriate treatment.IMPORTANCEEnterococcus faecium is an important human pathogen in which the prevalence of ampicillin resistance is high. However, little is known about the clinical characteristics of patients infected with ampicillin-resistant and ampicillin-susceptible strains. Indeed, current knowledge is based on genus-wide studies of Enterococcus or studies of very small numbers of susceptible isolates, precluding robust conclusions. Our data highlight specific clinical features related to the epidemiology of EFM-S and EFM-R strains, such as length of hospital stay, history of prior hospitalization, carriage of multidrug-resistant organisms, and type of sample from which the isolate was obtained. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with a custom-built database may make it possible to distinguish clade B isolates, which are typically susceptible to ampicillin, from clade A1/A2 isolates (A1 being typically resistant), thereby facilitating the management of these infections.

Determining the Best Thyroid Imaging Reporting and Data System: A Prospective Study Comparing the Diagnostic Performance of ACR, EU, and K TIRADS in the Evaluation of Thyroid Nodules.

Background Many different risk stratification systems have been formulated for thyroid nodules, differing in their fine-needle aspiration cytology (FNAC) indication, suggesting a lack of consensus around the world. Purpose This prospective study was conducted to find the best guideline for risk stratification, for a better malignancy yield, and with reduced rates of negative FNACs among three Thyroid Imaging, Reporting, and Data System (TIRADS) guidelines. Materials and Methods A total of 625 thyroid nodules with conclusive FNAC or histopathological diagnosis were included in the study. Various sonographic parameters were recorded. They were classified into categories as per the three guidelines and compared with FNAC diagnosis. The guidelines were evaluated in terms of sensitivity, specificity, predictive values, and diagnostic accuracy. Sensitivity and specificity were compared by McNemar's test. Results American College of Radiology (ACR) TIRADS had the highest diagnostic accuracy (56.8%), specificity (50.75%), positive predictive value (23.92%), lowest rates of negative FNACs (76.08%), and high negative predictive value (97.84 %). Korean (K) TIRADS had the maximum sensitivity (97.75%), highest negative predictive value (98.44%), and gross malignancy yield. European TIRADS was between the two other guidelines in most parameters with specificity like K TIRADS. Conclusion All the three guidelines are very good screening tools, with comparable high sensitivity. ACR TIRADS is better in terms of specificity and reduced rates of negative FNACs. Including the presence of a suspicious cervical lymph node as a criterion and more frequent follow-up might further improve the diagnostic performance of the guideline.

Validation of the Swedish version of the safe environment for every kid (SEEK) parent screening questionnaire

BackgroundPsychosocial risk factors in the home may impair children’s health and development and increase the risk of maltreatment. The Safe Environment for Every Kid (SEEK) model was developed to provide pediatric primary care professionals with a structured way to identify common psychosocial problems. The SEEK model includes use of the Parent Screening Questionnaire (SEEK-PSQ) at routine preventive child health visits, discussion with parents about their responses and, when indicated, referral to relevant services. The SEEK-PSQ has not previously been available in Swedish. The aim of the present study was to evaluate the psychometric properties of an adapted Swedish version of the SEEK-PSQ (PSQ-S).MethodsThis study is part of a cluster-randomised controlled trial of SEEK in the Swedish child health services. To validate the PSQ-S, parents (n = 852) with children 0–18 months of age were invited to complete a survey including the PSQ-S as well as evidence-based standardized instruments for the targeted psychosocial risk factors: economic worries, depressive symptoms, parental stress, alcohol misuse and intimate partner violence (IPV). Baseline data from 611 (72%) parents were analysed regarding sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each risk factor.ResultsAs a whole, the PSQ-S had a sensitivity of 93%, specificity of 52%, PPV of 67% and NPV of 87%. For mothers and fathers combined, sensitivity was 80% for economic worries, 89% for depressive symptoms, 78% for parental stress, 47% for intimate partner violence (IPV) and 70% for alcohol misuse. Specificity was highest for IPV and alcohol misuse (91%) and lowest for depressive symptoms (64%). NPV values were high (81–99%) and PPV values were low to moderate (22–69%) for the targeted problems. Sensitivity was higher for mothers compared to fathers for economic worries, depressive symptoms and IPV. This difference was particularly evident for IPV (52% for mothers, 27% for fathers).ConclusionThe SEEK-PSQ-S demonstrated good psychometric properties for identifying economic worries, depressive symptoms, parental stress and alcohol misuse but low sensitivity for IPV. The PSQ-S as a whole showed high sensitivity and NPV, indicating that most parents with or without the targeted psychosocial risk factors were correctly identified.Trial registrationISRCTN registry, study record 14,429,952 (https://doi.org/10.1186/ISRCTN14429952) Registration date 27/05/2020.

Assessment of the diagnostic performance of serological tests in areas where Leishmania infantum and Leishmania tarentolae occur in sympatry

BackgroundVisceral leishmaniosis caused by infection with the zoonotic protozoan Leishmania infantum is a life-threatening disease affecting dogs and humans. The sympatric occurrence of L. infantum and Leishmania tarentolae in an area of southern Italy endemic for canine leishmaniosis, where dogs are also exposed to the latter species, suggests the persistence of herpetophilic L. tarentolae in a non-permissive host, therefore raising questions about the performance of serological diagnostic tests routinely employed.MethodsThe diagnostic performance of serological tests such as the immunofluorescence antibody test (IFAT), two commercial immunoenzymatic assays (i.e. NovaTec VetLine Leishmania ELISA® and rK39 ICT®) and an in-house enzyme-linked immunosorbent assay (ELISA) was evaluated in healthy dogs seropositive to L. infantum, whereas the only IFAT available was used to detect antibodies to L. tarentolae.ResultsWith the IFAT, out of a total of 104 dogs tested, 15 were seronegative for L. infantum of which three were L. tarentolae seropositive‚ and 89 were L. infantum seropositive. Of the latter 89 dogs, representing the highest proportion of seropositive animals (85.6%) detected by IFAT‚ 66 were also seropositive for L. tarentolae. Cohen's kappa (κ) agreement coefficient between the IFAT results and those of all the other tests was very low, and the IFAT results were significantly different from those of all the other serological tests as calculated by Cochran's Q-test. Analysis using the Bayesian latent class (Bayes-LCA) showed that the in-house ELISA and IFAT contributed the most towards identifying infected and non-infected dogs, respectively. The IFAT test showed low positive predictive value (59.5%), but high negative predictive value (100%).ConclusionsThese results demonstrate that the IFAT for L. infantum, although highly sensitive, may not be considered a useful diagnostic test due to its low specificity. Therefore, an accurate serological tool with high specificity is mandatory for avoiding cross-reaction in epidemiological contexts where the two species of Leishmania occur in sympatry.Graphical

Utility of Fractional Flow Reserve Computed Tomography Angiography in Patients With Stable Coronary Artery Disease

Coronary computed tomography angiography is a modality with high negative predictive value for evaluation of coronary artery disease (CAD). However, its diagnostic accuracy for obstructive CAD is limited by multiple factors. Fractional flow reserve (FFR) computed tomography (FFRCT) is an emerging analysis tool for identifying flow-limiting disease; nonetheless, the prognostic value of FFRCT is not well established. This meta-analysis aims to evaluate the association of FFRCT with clinical outcomes in patients with stable CAD. A literature search was conducted for studies reporting the association between FFRCT measurements and all-cause mortality, major adverse cardiovascular events (MACEs), acute myocardial infarction (AMI), and any need for coronary revascularization. Obstructive disease was defined as a FFR value ≤0.80; nonobstructive disease was defined as an FFR value >0.80. Ten studies were identified to meet the inclusion criteria; mean follow-up was 17months (range, 3 to 56months). There was no difference in risk of all-cause mortality between patients with obstructive and those with nonobstructive CAD on FFRCT. However, obstructive lesions were associated with increased risk of MACE, AMI, and any need for revascularization. FFRCT is a useful adjunctive modality for further risk stratification of patients with stable CAD. Obstructive lesions identified by FFRCT are associated with increased risk of MACE, AMI, and any need for revascularization.