Diagnostic Adjunct Research Articles

Immunohistochemical analysis for C3d, C4d, IgG, IgG4, and CD123 in diagnosis of autoimmune skin diseases

To assess the value of immunohistochemical analysis for expressions of C3d, C4d, IgG, IgG4, and CD123 in the diagnosis of autoimmune skin diseases. Methods: We investigated the expressions of C3d, C4d, IgG, IgG4, and CD123 in paraffin-embedded, formalin-fixed tissues from 27 lupus erythematosus cases, including 8 discoid lupus erythematosus (DLE) cases, 4 subacute cutaneous lupus erythematosus (SCLE) cases, and 15 systemic lupus erythematosus (SLE) cases. Tissues from 15 dermatomyositis (DM) cases, 15 bullous pemphigoid (BP) cases, and 15 pemphigus cases were examined by immunohistochemical analysis. The differences in expression rates of C3d, C4d, IgG, IgG4, and CD123 between immunohistochemical staining and direct immunofluorescence were compared in the diagnosis of these diseases. Results: In the lupus erythematosus group, the positive rates of C3d and C4d deposited along the dermoepidermal junction were 85.2% and 51.9%, respectively. In the dermatomyositis group, the positive rates of C3d and C4d deposited along the dermoepidermal junction were 40% and 0, respectively. The expressions of C3d and C4d in lupus erythematosus tissues were significantly higher than those in DM tissues (P<0.05). The expression of CD123 protein in skin lesions of the lupus group was significantly higher than that in the DM group (P<0.05). In the BP group, the positive rates of C3d and C4d deposited along the dermoepidermal junction were 100% and 86.7%, respectively. In the pemphigus group, the positive rates of C3d and C4d deposited in the intercellular space of keratinocytes were 100% and 60%, respectively. The expressions of IgG and IgG4 in pemphigus tissues were higher than those in BP tissues (P<0.05). And the ratios of IgG4 to IgG in the pemphigus group was significantly higher than that in the BP group (P<0.05). Conclusion: The assays of C3d and C4d define an important diagnostic adjunct in evaluation of lupus erythematosus, BP and pemphigus. In some cases, it may even replace the direct immunofluorescence as a diagnostic adjunct. The expression of CD123 possesses certain clinical significance for the differential diagnosis of lupus erythematosus, and IgG4 and IgG expressions have adjunctive diagnostic significance for pemphigus.

Fournier Gangrene: A Review for Emergency Clinicians.

Fournier gangrene (FG) is a rare, life-threatening infection that can result in significant morbidity and mortality, with many patients requiring emergency department (ED) management for complications and stabilization. This narrative review provides an evidence-based summary of the current data for the emergency medicine evaluation and management of FG. Although originally thought to be an idiopathic process, FG has been shown to have a strong association for male patients with advanced age and comorbidities affecting microvascular circulation and immune system function, most commonly those with diabetes or alcohol use disorder. However, it can also affect patients without risk factors. The initial infectious nidus is usually located in the genitourinary tract, gastrointestinal tract, or perineum. FG is a mixed infection of aerobic and anaerobic bacterial flora. The development and progression of gangrene is often fulminant and can rapidly cause multiple organ failure and death, although patients may present subacutely with findings similar to cellulitis. Laboratory studies, as well as imaging including point-of-care ultrasound, conventional radiography, and computed tomography are important diagnostic adjuncts, though negative results cannot exclude diagnosis. Treatment includes emergent surgical debridement of all necrotic tissue, broad-spectrum antibiotics, and resuscitation with intravenous fluids and vasoactive medications. FG requires a high clinical level of suspicion, combined with knowledge of anatomy, risk factors, and etiology for an accurate diagnosis. Although FG remains a clinical diagnosis, relevant laboratory and radiography investigations can serve as useful adjuncts to expedite surgical management, hemodynamic resuscitation, and antibiotic administration.

Detection of splenic microabscesses with ultrasound as a marker for extrapulmonary tuberculosis in patients with HIV: A systematic review.

In 2015, 1.2 million new cases of tuberculosis (TB) were diagnosed in patients with HIV. Diagnostic limitations and resource shortages in endemic areas can delay diagnosis and treatment, particularly with extrapulmonary TB (EPTB). Research suggests that ultrasound can identify splenic microabscesses caused by EPTB, but data are limited on the frequency of this finding in patients with culture-proven EPTB. To estimate the frequency of splenic EPTB microabscesses detected with ultrasound in patients with HIV and TB co-infection. Studies published in six major databases as of November 2017 were systematically reviewed based on the PRISMA guidelines. Cohen's kappa test was used to determine inter-rater agreement. Articles included for data abstraction passed the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) evaluation. Freeman-Tukey transformation was used to calculate weighted proportions. Heterogeneity was evaluated by Forest plot and I2 calculation. After abstract screening, article review and QUADAS-2 evaluation, five studies were selected for data extraction. A total of 774 patients in these studies were infected with HIV. Splenic lesions were seen with ultrasound in 21.0% of patients with HIV (95% confidence interval (CI) 10.6 - 33.8). TB diagnosed by culture, biopsy, smear, or molecular methods was found to be the cause of 88.3% (95% CI 72.3 - 97.9) of splenic microabscesses seen on ultrasound in patients with HIV. Ultrasound evaluation of the spleen in patients with HIV and symptoms suggestive of TB in endemic regions is a viable diagnostic adjunct. Ultrasound detection of splenic microabscesses in HIV patients is probably sufficient indication to initiate TB treatment prior to obtaining culture data. Strong conclusions cannot be drawn owing to the high heterogeneity of this small number of studies.

The Malawi trauma score: A model for predicting trauma-associated mortality in a resource-poor setting

BackgroundGlobally, traumatic injury is a leading cause of morbidity and mortality in low-income countries. Current tools for predicting trauma-associated mortality are often not applicable in low-resource environments due to a lack of diagnostic adjuncts. This study sought to derive and validate a model for predicting mortality that requires only a history and physical exam. MethodsWe conducted a retrospective analysis of all patients recorded in the Kamuzu Central Hospital trauma surveillance registry in Lilongwe, Malawi from 2011 through 2014. Using statistical randomization, 80% of patients were used for derivation and 20% were used for validation. Logistic regression modeling was used to derive factors associated with mortality and the Malawi Trauma Score (MTS) was constructed. The model fitness was tested. Results62,354 patients are included. Patients are young (mean age 23.0, SD 15.9 years) with a male preponderance (72%). Overall mortality is 1.8%. The MTS is tabulated based on initial mental status (alert, responds to voice, responds only to pain or worse), anatomical location of the most severe injury, the presence or absence of a radial pulse on examination, age, and sex. The score range is 2–32. A mental status exam of only responding to pain or worse, head injury, the absence of a radial pulse, extremes of age, and male sex all conferred a higher probability of mortality. The ROC area under the curve for the derivation cohort and validation cohort were 0.83 (95% CI 0.78, 0.87) and 0.83 (95% CI 0.75, 0.92), respectively. A MTS of 25 confers a 50% probability of death. ConclusionsThe MTS provides a reliable tool for trauma triage in sub-Saharan Africa and helps risk stratify patient populations. Unlike other models previously developed, its strength is its utility in virtually any environment, while reliably predicting injury- associated mortality.

HPV RNA in-situ hybridization as a diagnostic aid in papillary laryngeal lesions.

In the larynx, differentiating squamous papillomas from de-novo papillary squamous dysplasias or squamous cell carcinomas (SCC) has significant consequences for management. Overlapping clinical presentations and cytologic changes across the spectrum of papillary lesions presents diagnostic challenges for otolaryngologists and pathologists. In this study, we evaluate whether ribonucleic acid (RNA) in-situ hybridization (ISH) for low-risk and high-risk human papillomavirus (HPV) can help distinguish these lesions. We constructed tissue microarrays from 97 papillary laryngeal lesions, including 61 squamous papillomas, two papillomas with dysplasia, two SCCs-ex papilloma, 14 papillary squamous dysplasias, and 18 papillary SCCs identified at the Johns Hopkins Hospital between 2000 and 2017. We performed RNA ISH using probes for low-risk and high-risk HPV types. Low-risk HPV RNA was identified in 55 benign papillomas (90%), two papillomas with dysplasia (100%), and two SCCs-ex papilloma (100%) but was absent in de-novo papillary dysplasias and SCCs (0%). High-risk HPV RNA ISH was positive only in four papillary SCC (22%). Overall, low-risk HPV RNA ISH was 90% sensitive and 89% specific for benign papillomas with a positive predictive value of 93% and negative predictive value of 84%. In contrast, high-risk HPV was 20% sensitive for SCC. Low-risk HPV RNA ISH is a useful diagnostic adjunct for distinguishing laryngeal squamous papillomas from papillary squamous dysplasia and SCC. However, it is not entirely specific for benign processes as it is also retained in papillomas with dysplasia and SCCs-ex papilloma. Because high-risk HPV is rare in papillary laryngeal lesions, high-risk HPV RNA ISH has limited utility. Level 4 Laryngoscope, 130:955-960, 2020.

Abstract 2734: Poly-ligand profiling of plasma samples as a potential predictor of prostate biopsy results

Abstract Prostate cancer is the most common cancer in men, excluding skin cancer, and is also one of the leading causes of cancer death. Currently the prostate-specific antigen (PSA) blood test is employed as an initial screening method in men without symptoms, and patients with blood PSA level higher than 4 ng/mL are commonly recommended for prostate biopsy for definitive diagnosis. However, other non-cancerous conditions may also cause elevation in PSA, such as prostatitis, benign prostatic hyperplasia and prostate intraepithelial neoplasia. Among men with PSA levels of 4-10 ng/mL, only about 1 in 4 will show positive (cancer) biopsy, and for those with PSA levels higher than 10 ng/mL, the chance of having prostate cancer increases to over 50%. Moreover, approximately 15% of men with a PSA levels below 4 ng/mL have a positive prostate biopsy. Because of these scenarios, as well as significant risks associated with prostate biopsies, there is a need for diagnostic adjuncts that provide additional data to inform decisions on whether or not to perform biopsies. Here we describe a method using single stranded oligonucleotide (ssODN) libraries to perform Poly-Ligand Profiling on plasma exosomes from men scheduled for biopsy to classify those with or without a subsequent diagnosis of prostate cancer. Through alternating rounds of positive and negative selection in binding assays, we isolated ssODNs that selectively bound to exosomes from prostate cancer patients (PSA level of at least 4 ng/mL; Gleason Score range 7-8, and at least 3 positive cores from at least 10 biopsy cores) and not to benign cases (all negative cores from at least 10 biopsy cores). An independent test set of 29 prostate cancer cases and 28 benign cases was then evaluated in binding assays. Based on 100 runs of 10-fold cross validation with multiple statistic models, an average successful classification rate of 82% was achieved with an area under the ROC curve of 0.89. While further refinement and testing on larger cohorts are needed, these results suggest that Poly-Ligand Profiling may provide an additional approach to stratify men with suspicious PSA levels for prostate biopsies. Citation Format: Xixi Wei, Xiaowei Liu, Radhika Santhanam, Daniel Magee, Anthony Helmstetter, Mark Miglarese, David Spetzler, Xixi Wei. Poly-ligand profiling of plasma samples as a potential predictor of prostate biopsy results [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2734.

Management of primary hyperparathyroidism in pregnancy: a case series.

SummaryPrimary hyperparathyroidism (PHPT) is characterised by the overproduction of parathyroid hormone (PTH) due to parathyroid hyperplasia, adenoma or carcinoma and results in hypercalcaemia and a raised or inappropriately normal PTH. Symptoms of hypercalcaemia occur in 20% of patients and include fatigue, nausea, constipation, depression, renal impairment and cardiac arrythmias. In the most severe cases, uraemia, coma or cardiac arrest can result. Primary hyperparathyroidism in pregnancy is rare, with a reported incidence of 1%. Maternal and fetal/neonatal complications are estimated to occur in 67 and 80% of untreated cases respectively. Maternal complications include nephrolithiasis, pancreatitis, hyperemesis gravidarum, pre-eclampsia and hypercalcemic crises. Fetal complications include intrauterine growth restriction; preterm delivery and a three to five-fold increased risk of miscarriage. There is a direct relationship between the degree of severity of hypercalcaemia and miscarriage risk, with miscarriage being more common in those patients with a serum calcium greater than 2.85 mmol/L. Neonatal complications include hypocalcemia. Herein, we present a case series of three women who were diagnosed with primary hyperparathyroidism in pregnancy. Case 1 was diagnosed with multiple endocrine neoplasia type 1 (MEN1) in pregnancy and required a bilateral neck exploration and subtotal parathyroidectomy in the second trimester of her pregnancy due to symptomatic severe hypercalcaemia. Both case 2 and case 3 were diagnosed with primary hyperparathyroidism due to a parathyroid adenoma and required a unilateral parathyroidectomy in the second trimester. This case series highlights the work-up and the tailored management approach to patients with primary hyperparathyroidism in pregnancy.Learning points:Primary hyperparathyroidism in pregnancy is associated with a high incidence of associated maternal fetal and neonatal complications directly proportionate to degree of maternal serum calcium levels.Parathyroidectomy is the definitive treatment for primary hyperparathyroidism in pregnancy and was used in the management of all three cases in this series. It is recommended when serum calcium is persistently greater than 2.75 mmol/L and or for the management of maternal or fetal complications of hypercalcaemia. Surgical management, when necessary is ideally performed in the second trimester.Primary hyperparathyroidism is genetically determined in ~10% of cases, where the likelihood is increased in those under 40 years, where there is relevant family history and those with other related endocrinopathies. Genetic testing is a useful diagnostic adjunct and can guide treatment and management options for patients diagnosed with primary hyperparathyroidism in pregnancy, as described in case 1 in this series, who was diagnosed with MEN1 syndrome.Women of reproductive age with primary hyperparathyroidism need to be informed of the risks and complications associated with primary hyperparathyroidism in pregnancy and pregnancy should be deferred and or avoided until curative surgery has been performed and calcium levels have normalised.

Correlation of fetal blood vessel Doppler measurements with fetal anemia among Rhesus isoimmunized pregnancies after two intrauterine transfusions.

To assess the correlation between fetal blood vessel Doppler measurements and fetal anemia among Rhesus isoimmunized pregnancies after two intrauterine transfusions as a potential guide to therapy. A prospective observational study was conducted among 30 women who attended a single hospital in India between April 2, 2015 and October 30, 2016. The participants underwent a third intrauterine transfusion based on a middle cerebral artery (MCA) peak systolic velocity (PSV) of greater than 1.50 multiples of the median (MoM). Cordocentesis was performed before the third intrauterine transfusion and hematocrit values correlated with the blood vessel Doppler measurements. The MCA PSV MoM and fetal hematocrit MoM had a correlation coefficient of -0.43 (95% confidence interval -0.68 to 0.08; P=0.017). The sensitivity, specificity, positive predictive value, and negative predictive value were 68%, 57%, 83%, and 33%, respectively. The descending aorta PSV δ and fetal hematocrit δ had a correlation coefficient of -0.54 (95% confidence interval -0.75 to -0.23; P=0.001). An area under the curve of 0.80 (standard error 0.085; P=0.017) had 87% sensitivity and 57% specificity for diagnosing fetal anemia. The descending aorta PSV could offer a useful diagnostic adjunct to MCA PSV after two intrauterine transfusions.

SUN-132 Investigating the Accuracy of Risk Factor Calculators in Diagnosing Maturity Onset Diabetes of the Young (MODY)

MODY is a rare form of diabetes caused by impaired insulin production attributable to autosomal dominant monogenic mutations. It is an important diagnosis as it results in a treatment change for 25% of patients, allows for the screening of 1st degree relatives and identifies patients who have MODY subtypes associated with reduced rates of micro- and macro-vascular complications. Diagnosing MODY is challenging and several MODY risk factor calculators have been proposed to guide rational genetic testing. The aim of this study was to retrospectively apply the MODY risk factor calculators to patients with diagnosed MODY who attended the diabetes service at a tertiary hospital in the West of Ireland to identify the most accurate calculator in predicting MODY in this patient cohort. MODY risk factor calculators in the literature focus on young age at diagnosis, low BMI and low HbA1c as defining features of MODY. Ellard, Bellanne-Chantelot et al. (2008) proposed age at diagnosis ≤25, BMI <30 and HbA1c ≤58.8 mmol/L as the recommended criteria for genetic testing in MODY, and this captured 6/21 (28.57%) patients with MODY in our cohort. Thanabalasingham, Pal et al. (2012) proposed age at diagnosis ≤30, BMI <30 and HbA1c ≤63.9 mmol/L, which accounted for 8/21 (38.1%) of our MODY patients. The MODY Probability Calculator proposed by Shields et al. (2012) was developed using logistic regression to determine the probability of MODY. Variables include current age, age at diagnosis, sex, treatment with insulin, time to insulin treatment, BMI, HbA1c and parental history of diabetes. The MODY Probability Calculator cannot be directly compared to the other calculators, as it does not define clinical criteria in a binary fashion but assigns a weighting to each factor. Patients have to be aged ≤35 at diagnosis for this calculator to be applied, which resulted in the exclusion of 3/22 patients in our cohort. 9/22 (40.9%) patients had a positive predictive value (PPV) of >50%, which conferred a 0.47/100 false negative rate and a 3/100 false positive rate if used as the basis for referring for genetic testing. 5/22 (22.73%) patients had a PPV of >75%, which conferred a 0.9/100 false negative rate and a 1.2/100 false positive rate, which is highly sensitive and specific. 12/22 (54.55%) patients had a PPV of >20%, which conferred a 0.14/100 false negative rate and a 16.8/100 false positive rate. This work demonstrates that the MODY Probability Calculator currently achieves the best balance of sensitivity / specificity in diagnosing patients with MODY. Nevertheless, a significant portion (10/22) of known MODY patients were not identified. Limitations include excluding patients aged >35 at diagnosis and excluding patients with a strong family history of diabetes who do not have an affected parent. These calculators are diagnostic adjuncts in the Endocrinologist’s toolbox to stratify MODY risk but do not replace clinical judgement.

Quantitative analysis of cochlear signal intensity on three-dimensional and contrast-enhanced fluid-attenuated inversion recovery images in patients with Meniere's disease: Correlation with the pure tone audiometry test

The purpose of this study was to correlate the quantitative analysis of cochlear signal intensity (SI) on 3-dimensional fluid-attenuated inversion recovery (3D-FLAIR) and contrast-enhanced (CE) 3D-FLAIR images with results of the pure tone audiometry (PTA) test in patients with Meniere's disease (MD). Over a 3-year period, 123 patients with MD underwent 3-Tesla (3 T) temporal magnetic resonance imaging (MRI), including 3D-FLAIR and CE-FLAIR sequences. The SI of membranous labyrinth of the cochlea in both ears of each patient was measured by drawing a region of interest (ROI) with a seed growing technique. The correlation between measured cochlear SIs on 3D-FLAIR and CE-FLAIR images, contrast enhancement index (CEI), and contrast enhancement ratio (CER) and clinical findings and pre- and post-treatment PTA results were assessed. Cochlear signal ratios of symptomatic ears on 3D-FLAIR and CE-FLAIR images were significantly higher than those of asymptomatic ears (P < 0.001). The area under the curve, from the receiver operating characteristic curve of cochlear SIs on 3D-FLAIR and CE-FLAIR images for discrimination between symptomatic and asymptomatic ears, was 0.729 and 0.728, respectively. Cochlear SIs on 3D-FLAIR and CE-FLAIR images were significantly correlated with patients' sex (P < 0.05 and P < 0.01, respectively), symptomatic ear (both P < 0.0001), and pre-treatment PTA (P < 0.0001 and P < 0.005, respectively), but were not significantly correlated with patients' age, post-treatment PTA or hearing threshold level at 0.5, 1.0, 2.0, or 4.0 kHz. Quantitative analysis of cochlear SI on 3D-FLAIR and CE-FLAIR images may be a helpful diagnostic adjunct for MD, but may be of little value in predicting the prognosis of MD.

Identifying systems delays in assessment, diagnosis, and operative management for testicular torsion in a single-payer health-care system

Testicular torsion (TT) is a common pediatric urologic emergency. Management of TT is time sensitiveand often confirmed on scrotal Doppler ultrasound (DUS). Acquiring DUS, however, can result in delays in the management of TT, affecting testicular salvage rates. The objective of this study is to identify delays in the assessment and diagnosis for patients presenting with TT to a Canadian academic hospital using patient flow analysis. A retrospective review was performed for patients presenting to the emergency department (ED) who received a scrotal DUS to rule out possible TT between 2012 and 2017. The primary outcome measured cycle-time measurements (median time) between points along the clinical flow pathway for a patient with suspected TT. The secondary outcome assessed diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value(NPV) of standard scrotal DUS components (Doppler flow, arterial waveform, heterogeneous echotexture). A total of 609 patients presented with an acute scrotum warranting a scrotal DUS to rule out TT; of which, 46 underwent scrotal exploration. Testicular salvage rate was 82.6% in the series (38 testes salvaged, 8 required orchiectomy). Median time from symptomonset to ED presentation for patients with possible TT was 4h. After triage, a median of 79.8min was required for ED physician assessment and an additional 48min for scrotal DUS to be performed. Absence of Doppler flow on scrotal DUS had a 97.4% PPV for diagnosing TT confirmed during scrotal exploration. Almost 4h of in-ED time is required from triage to surgical intervention for potential TT at the institution. One area of delay is the time needed to conduct a scrotal DUS (48-128min; Fig.1). This represents an area of opportunity for patient flow optimization through the use of standardized clinical pathways and diagnostic adjuncts, such as point-of-care ultrasound. This study is limited in its retrospective nature and does not include patients with overt signs of TT who underwent surgical detorsion without need for scrotal DUS. Patient flow delays to surgical intervention for patients with TT representa preventable cause of orchiectomy in young men. This study identifies intervention points in patient-care flow pathways where delays to surgical intervention can be potentially reduced by up to 2h. The findings support the need for further studies into the optimization of patient flow and management protocols to reduce delays in the diagnosis and management of TT.

The role and contribution of clonality studies in the diagnosis of lymphoproliferative disorders.

To explore the frequency, context and diagnostic impact of B- and T-lymphocyte clonality assay use in the assessment of possible lymphoproliferative disorders at a central haematopathology diagnostics hub. All cases reported by haematopathologists over a sixteen-month period were identified, n=4462, and those which had clonality studies undertaken analysed further. Clonality studies were requested in 9% of cases, directly contributing to a diagnosis being made in 79%. They were most frequently used to help distinguish reactive lymphoid infiltrates from low-grade B-cell lymphomas and in cases of possible T-cell lymphoma, facilitating a diagnosis being made in over 90% of these. In contrast when clonality assays were requested as a diagnostic adjunct in cases with an atypical cutaneous lymphoid infiltrate, and in occasional cases of lymphoid proliferations with Hodgkin-like cells or EBV-driven proliferations, a definitive final diagnosis was possible in less than 60% of cases. Clonality studies were used in 9% of cases assessed for a possible lymphoproliferative disorder and had a differing impact depending on the differential diagnoses being considered. These findings can be used to guide access to clonality assays by highlighting the likelihood of an informative result in different diagnostic settings.

Contribution of immunoglobulin lambda light chain gene rearrangement analysis in the diagnosis of B‐cell neoplasms

Identification of clonal IGH, IGK and IGL gene rearrangements offers diagnostic adjunct in suspected B-cell neoplasms. However, many centres omit IGL analysis as its value is uncertain. A review of 567 cases with IGH, IGK and IGL rearrangement assessed using BIOMED-2 assays showed clonal immunoglobulin gene rearrangement in 54% of cases, of which 24% had a clonal IGL rearrangement. In two cases, the clonal rearrangement was detected exclusively by IGL analysis. This finding demonstrates the added value of IGL analysis for clonality assessment, especially in suspected B-cell neoplasms in which a clonal IGH and/or IGK rearrangement is not detected or is equivocal.

Diagnostic impact of reflectance confocal microscopy as a second‐level examination for facial skin lesions

SummaryBackground and objectiveBenign and malignant facial skin lesions may be difficult to differentiate clinically and with dermoscopy. The present study aimed to evaluate the potential utility of in vivo reflectance confocal microscopy (RCM) as a second‐level examination for facial skin neoplasms.Patients and MethodsRetrospective and blinded evaluation of 160 consecutive facial lesions was carried out in two separate steps. Clinical and dermoscopic images were assessed first, followed by combined evaluation of clinical/dermoscopic and RCM images. Our study included 60 % malignant lesions, comprising 43 % melanomas, 9 % basal cell carcinomas, 5 % in situ squamous cell carcinomas and 3 % lymphomas.ResultsAncillary RCM significantly improved diagnostic specificity for the detection of malignancy compared to clinical/dermoscopic evaluation alone (58 % vs 28 %). However, sensitivity was slightly lower for RCM‐based image evaluation (93 % vs 95 %) due to misclassification of one in situ SCC and one lymphoma. In terms of melanoma diagnosis, RCM‐based image evaluation was generally superior; sensitivity was only slightly increased (88 % vs 87 %), but melanoma specificity was significantly higher (84 % vs 58 %).ConclusionRCM is a valuable diagnostic adjunct for facial skin lesions; unnecessary biopsies in this cosmetically sensitive area could be reduced by one third without missing a melanoma.

Can Increased Metabolic Status be a Grading Tool for Oral Squamous Cell Carcinoma? A Glucose Transporter 1 Immunoexpression Study.

Background:Glucose transporter-1 (GLUT-1) is a GLUT protein whose expression is upregulated in malignant cells where enhanced uptake of glucose is observed.Aim:The aim of this study is to evaluate the expression of GLUT-1 protein in oral squamous cell carcinoma (OSCC) tissue sections using immunohistochemistry and to describe the relationship between increased metabolic status and the grades of OSCC.Materials and Methods:This is cross-sectional study with 76 formalin-fixed paraffin-embedded tissue blocks of OSCC, obtained from the archives of the department. All the cases were scored using Bryne's grading system by three oral pathologists independently. The tissue sections were then stained using immunohistochemistry with anti-GLUT-1 rabbit monoclonal antibody.Results:Staining intensity and localization of positively stained slides were evaluated. Overall, a significant correlation between Bryne's histopathological grading system for OSCC and GLUT-1 immunohistochemical expression was observed. Thus, high GLUT-1 expressions are observed with increasing grades of OSCC.Conclusion:This study shows that a significant positive correlation exists between GLUT-1 immunoexpression and histological grading of OSCC. Thus, GLUT-1 expression can be used as a diagnostic adjunct and prognostic marker for OSCC patients.

D-dimer levels in patients with thromboangiitis obliterans.

Thromboangiitis obliterans (TAO) or Buerger disease is a recurring progressive segmental vasculopathy that presents with inflammation and thrombosis of small and medium arteries and veins of the hands and feet. The exact cause remains unknown, with tobacco use (primarily smoking but also smokeless tobacco) being highly associated with the disease. The diagnosis is clinical and the lack of a diagnostic gold standard is a deterrent to diagnosing it in patients with atypical presentations. Obliterative endarteritis occurs perhaps due to a mixture of thrombosis and inflammation. The diagnostic sensitivity and specificity of D-dimer as a biomarker for thrombosis is well reported from its use in other areas such as deep vein thrombosis. Identification of a biomarker linked to the causation yields a diagnostic adjunct with a role in therapeutic decision-making, aiding diagnosis in atypical presentation, monitoring disease activity and gauging response to therapy. Between April 2014 and May 2015, we studied serum D-dimer (a marker of thrombosis) in 62 patients with TAO and compared this to 330 normal age- and sex-matched controls. We included all patients with peripheral arterial disease clinically diagnosed to have TAO according to the Shionoya criteria. There was no history of thrombosis or arterial disease in the control group. The control group was matched for baseline characteristics such as age and sex. All patients underwent a standard diagnostic protocol including blood tests (haemoglobin and creatinine), electrocardiogram, chest X-ray and ankle brachial pressure index. Blood was collected using an evacuated tube system into a citrate anticoagulant tube for testing D-dimer. All the 62 patients diagnosed to have TAO were men with an average age of 40 years (range 18-65 years). They all had a history of tobacco use and did not have other atherogenic risk factors (part of the diagnostic criteria). Medium-vessel involvement was present in 53 patients (85%) and the rest presented with additional involvement of the popliteal and femoral vessels. Upper limb involvement or superficial thrombophlebitis was present in 95% of patients. Laboratory and imaging studies were consistent with TAO. The groups were well matched for age (p = 0.3). The median and interquartile range for D-dimer values were 61 ng/ml and 41-88 ng/ml in controls (n = 330) and 247 ng/ml and 126478 ng/ml in patients (n = 62), respectively (p<0.001). D-dimer levels are considerably elevated in patients with TAO. This indicates an underlying thrombotic process and suggests its potential role as a diagnostic adjunct. It also leads us to hypothesize a potential therapeutic benefit of anticoagulants in this disease.

Application of in vivo stain of methylene blue as a diagnostic aid in the early detection and screening of oral cancerous and precancerous lesions.

Background:Periodic clinical examination of the oral cavity is the mainstay for the early detection of oral cancers which can be further aided by screening individuals with high-risk factors that will identify candidates who should receive treatment to prevent cancer progression and reduce patient mortality. Among the diagnostic tools, in vivo staining is advocated as a simple, inexpensive and fairly sensitive method.Materials and Methods:The present study involved the examination of fifty patients suspected of oral malignant or precancerous lesions by methylene blue staining. The results of methylene blue uptake were compared with a simultaneous biopsy of these lesions, while benign epithelial lesions were included as the negative subjects of screening.Results:The results revealed a sensitivity of 89%, a specificity of 91%, a positive predictive value of 97% and a negative predictive value of 73%.Conclusion:We recommend that methylene blue staining is a useful diagnostic adjunct in a large, community-based oral cancer screening program for high-risk individuals.

VSICON 2018 Prize Paper Abstracts

VSICON 2018 Prize Paper Abstracts

Time to Detection of Yeast Isolates in Pediatric and Adult Patients with Fungemia and its Relevance to Clinical Profile and Outcome.

ABSTRACTContextTime to detection (TTD) given by continuous monitoring automated blood culture systems (CMABS) have been found to be a predictor of clinical outcome, drug resistance and type of microorganism in cases of bacteremia but the studies evaluating TTD with respect to fungemia are scarce especially from India.AimsTo evaluate TTD for yeast isolates in fungal bloodstream infections with respect to the type of yeast isolates, risk factors and outcome and to study yeast susceptibility and distribution of yeast isolates with respect to patient population.Materials and methodsAll blood culture specimens were processed in CMABS. The TTD for yeast isolates were recorded. The identification of yeast and susceptibility testing was done by automated methods. A correlation of TTD was done with respect to prior/concurrent yeast isolates, use of antifungal, risk factors and clinical outcome.ResultsOut of 80 yeast isolates, the maximum was C. parapsilosis (26.25%) followed by C. albicans (16.25%) and C. tropicalis (13.75%). A statistically significant difference in the occurrence of yeasts with early TTD (TTD < = 48 hours) and late TTD (TTD > 48 hours) was found. TTD of C. glabrata was significantly longer (p = 0.002) while TTD of C. tropicalis was significantly shorter (p = 0.013). There was an observable favorable outcome in shorter TTD (< = 48 hours). C. albicans and C. tropicalis depicted 100% susceptibility for Azoles, Amphotericin B and Echinocandins.ConclusionTTD may be used as both diagnostic and prognostic adjunct in fungal bloodstream infections. This study is a step towards this novel approach. We also emphasize on the importance of speciation of yeast isolates and susceptibility testing.How to cite this articleButta H, Sardana R, Mendiratta L, Sibal A, Gupta V, Chawla R, Jafri AA. Time to Detection of Yeast Isolates in Pediatric and Adult Patients with Fungemia and its Relevance to Clinical Profile and Outcome. Indian Journal of Critical Care Medicine, January 2019;23(1):27-30.

The role of alpha defensin in prosthetic joint infection (PJI) diagnosis: a literature review.

Prosthetic joint infection (PJI) management is not standardized worldwide and the outcome is frequently unsatisfactory.More and more arthroplasties are now being performed. An increasing number of highly virulent and antibiotic-resistant bacteria and an ageing population of patients presenting with many comorbidities make it necessary to focus on this important topic.Diagnosis of PJI remains challenging because the clinical signs and symptoms and elevation of systemic biomarkers (C-reactive protein, erythrocyte sedimentation rate) may be unclear.In the last few years, the clinical research has focused on synovial fluid biomarkers as a possible breakthrough in the complex scenario of PJI diagnosis.Synovial biomarkers have shown encouraging results and they should be used as diagnostic adjuncts to synovial white cell count and culture bacteriology. Synovial leukocyte esterase (LE) and synovial C-reactive protein (CRP) have been evaluated as good screening measures; however, the most promising synovial fluid biomarker in terms of sensitivity and specificity for PJI seems to be alpha defensin (AD).The laboratory-based alpha defensin enzyme-linked immunosorbent assay (ELISA) test demonstrated the highest ever reported accuracy for PJI diagnosis. However, an alpha defensin lateral flow test could have its place in ruling in a suspected PJI intraoperatively because of its high specificity and rapid results.Cite this article: EFORT Open Rev 2019;4:10-13. DOI: 10.1302/2058-5241.4.180029