Equivocal Cases Research Articles

Use of a Menstrual Cup to Assist in Diagnosis of Preterm Premature Rupture of Membranes [ID 2683492

INTRODUCTION: Several methods exist for diagnosis of preterm premature rupture of membranes (PPROM), including pooling on speculum exam, nitrazine test, arborization under microscopy, immunoassay, and amnio-dye test. Diagnostic accuracy is particularly important for PPROM because a missed diagnosis may result in life-threatening maternal and fetal consequences. We present a novel method for evaluating PPROM in equivocal cases using a menstrual cup. METHODS: Written informed consent was obtained for submission of a case report. A 36-year-old G6P5005 at 29 2/7 weeks presented with leakage of fluid. She was found to have negative pooling on speculum exam, negative arborization on microscopy, a maximum vertical pocket (MVP) of 4.0 cm, and a negative urinalysis. She was discharged with precautions and returned 2 days later with persistent symptoms. Workup again showed no pooling, no arborization, and a normal MVP. The patient suggested using a menstrual cup to capture her intermittent leakage of fluid. She wore a menstrual cup for 30 minutes in triage. A sample of the fluid tested positive for arborization. She was admitted to labor and delivery for latency antibiotics, betamethasone, and fetal and maternal monitoring. CONCLUSION: Preterm premature rupture of membranes can occur without overt vaginal pooling due to small volume leakage. Conventional testing is less sensitive when pooling is absent. In these cases, a menstrual cup may help facilitate diagnosis and avoid invasive tests such as the amnio-dye test. Care must be taken to use a clean menstrual cup without gel, limit the duration of menstrual cup use to avoid infection, and to distinguish arborization of amniotic fluid from that of cervical mucus.

HER2-low and Overexpression in Mucinous Ovarian Cancer: Analysis of ASCO/CAP and ToGA Immunohistochemical Scoring.

Mucinous ovarian carcinoma is an uncommon malignancy characterized by resistance to chemotherapy and poor survival in the metastatic setting. HER2 amplification is a frequent late event in carcinogenesis, yet the incidence of HER2-low in mucinous ovarian carcinoma is unknown. Further, the optimal method for determining overexpression in these tumors is not established. We sought to assess the ASCO/CAP and ToGA trial scoring methods for HER2 IHC with correlation to FISH, p53, and mismatch repair protein status and to determine the incidence of HER2-low in mucinous ovarian carcinoma. A total of 29 tumors from 23 patients were included. Immunohistochemistry for HER2, p53, MLH1, PMS2, MSH2, and MSH6 was performed. Scoring was performed according to the ASCO/CAP and ToGA trial criteria. HER2 FISH was performed and scored according to the ASCO/CAP criteria. The proportion of HER2-low, defined as 1+ or 2+ staining with negative FISH, was determined. Using ASCO/CAP, 26% demonstrated 3+ while 35% demonstrated 2+ staining. Using ToGA, 30% demonstrated 3+ while 57% demonstrated 2+ staining. By FISH, 26% were positive for HER2 amplification. Both systems captured all FISH-positive cases; the use of ASCO/CAP resulted in fewer equivocal and false-positive cases. Among HER2-negative cases, 88% were HER2-low. Aberrant p53 expression was detected in 55% of cases; mismatch repair deficiency was not identified in any cases. ASCO/CAP guidelines are accurate and resource-effective in determining HER2 overexpression in mucinous ovarian carcinoma. HER2-low is common in these tumors; further studies to determine the role of HER2-targeted therapy including antibody-drug conjugates are indicated.

Expression of regional brain amyloid-β deposition with [18F]Flutemetamol in Centiloid scale -a multi-site study.

The Centiloid project helps calibrate the quantitative amyloid-β (Aβ) load into a unified Centiloid (CL) scale that allows data comparison across multi-site. How the smaller regional amyloid converted into CL has not been attempted. We first aimed to express regional Aβ deposition in CL using [18F]Flutemetamol and evaluate regional Aβ deposition in CL with that in standardized uptake value ratio (SUVr). Second, we aimed to determine the presence or absence of focal Aβ deposition by measuring regional CL in equivocal cases showing negative global CL. Following the Centiloid project pipeline, Level-1 replication, Level-2 calibration, and quality control were completed to generate corresponding Centiloid conversion equations to convert SUVr into Centiloid at regional levels. In equivocal cases, the regional CL was compared with visual inspection to evaluate regional Aβ positivity. 14 out of 16 regional conversions from [18F]Flutemetamol SUVr to Centiloid successfully passed the quality control, showing good reliability and relative variance, especially precuneus/posterior cingulate and prefrontal regions with good stability for Centiloid scaling. The absence of focal Aβ deposition could be detected by measuring regional CL, showing a high agreement rate with visual inspection. The regional Aβ positivity in the bilateral anterior cingulate cortex was most prevalent in equivocal cases. The expression of regional brain Aβ deposition in CL with [18F]Flutemetamol has been attempted in this study. Equivocal cases had focal Aβ deposition that can be detected by measuring regional CL.

Exploring the Prevalence of Psychological Autopsy in Indian Context

Background: Psychological Autopsy is basically done in order to understand the cause of death in equivocal andsuicide death cases. It involves collecting information about the individual’s life history, mental health history, andcircumstances leading up to their death in order to gain insights into the complex factors that may have played arole.Methods: The main aim of this study is to find the prevalence of Psychological Autopsy (PA) in India and to knowhow frequently is it being used as a means of investigation through close ended questionnaire of academicians,forensic psychologists, practitioners and trainees in the field of mental health, this study seeks to discover outcomes.Conclusion: The fact that the majority of mental health professionals had never heard the phrase psychologicalautopsy, despite the fact that they had used it, was a significant weakness of this study.

Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Expression Rates in Invasive Breast Carcinoma: A Study of 21 Institutions.

Laboratories performing predictive marker testing for breast carcinoma are encouraged to compare patient results to published benchmarks. To collect expression rates for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) in invasive breast carcinoma from multiple laboratories. Participants submitted data from up to 50 primary cases during the study period. Participants reported ER, PgR, and HER2 results in addition to demographic and histologic information. Participants also provided annual institution-level expression rates. A total of 21 institutions submitted data for 687 cases. Aggregate positivity rates for ER and PgR were 85.6% and 75.1%, respectively. Receptor positivity rates were higher in well-differentiated (grade 1) tumors (ER, 97.4%; PgR, 88.0%) compared with moderately differentiated (grade 2) tumors (ER, 92.4%; PgR, 84.0%) and poorly differentiated (grade 3) tumors (ER, 61.8%; PgR, 48.0%). Expression rates were higher in postmenopausal women (ER, 87.2%) than premenopausal women (ER, 79.6%) and higher in lobular carcinomas (ER, 98.7%; PgR, 85.3%) than ductal carcinomas (ER, 84.1%; PgR, 74.5%). The aggregate HER2 positivity (score 3+) rate was 9.0%. The aggregate HER2 equivocal (score 2+) rate was 14.5%. Of 81 equivocal (score 2+) cases, 70 (86.4%) were nonamplified. The data from this study provide multi-institutional benchmark data to assist laboratories performing periodic comparisons as part of a quality management program. Overall expression rates were generally similar to those of other published reports, with the exception of the ER-negative and HER2-positive rates, both of which were somewhat lower.

The sural-sparing pattern in clinical variants and electrophysiological subtypes of Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis worldwide and can be classified into electrophysiological subtypes and clinical variants. This study aimed to compare the frequency of the sural-sparing pattern (SSP) in subtypes and variants of GBS. This retrospective cohort study analyzed clinical and electrophysiological data of 171 patients with GBS hospitalized in public and private hospitals of Natal, Rio Grande do Norte, Brazil, between 1994 and 2018; all cases were followed up by the same neurologist in a reference neurology center. Patients were classified according to electrophysiological subtypes and clinical variants, and the SSP frequency was compared in both categories. The exact Fisher test and Bonferroni correction were used for statistical analysis. The SSP was present in 53% (57 of 107) of the patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 8% (4 of 48) of the patients with axonal subtypes, and 31% (5 of 16) of the equivocal cases. The SSP frequency in the AIDP was significantly higher than in the axonal subtypes (p < 0.0001); the value was kept high after serial electrophysiological examinations. Only the paraparetic subtype did not present SSP. The SSP may be present in AIDP and axonal subtypes, including acute motor axonal neuropathy, but it is significantly more present in AIDP. Moreover, the clinical variants reflect a specific pathological process and are correlated to its typical electrophysiological subtype, affecting the SSP frequency.

Uterine smooth muscle tumors of uncertain malignant potential: a retrospective evaluation of clinical pathology and immunohistochemistry features

BackgroundUterine smooth muscle tumor of uncertain malignant potential (STUMP) is a group of uterine smooth muscle tumors which cannot be classified as a subtype of leiomyoma or leiomyosarcoma. Diagnosis, prognosis, and treatment of these tumors are challenging due to recurrence, potential of malignancy, and metastasis.MethodsA retrospective cohort study was conducted in southern Iran during 2011 to 2020. We included records of 21 patients with STUMP and 24 patients with leiomyoma by simple randomized sampling in the tertiary health care centers in Shiraz, southern Iran. Slides were reviewed by an expert pathologist for examining mitosis, necrosis, and atypia, and also proper blocks were selected for immunohistochemistry (IHC) staining.ResultsFrom 45 participants, 21 (46.7%) and 24 (53.3%) patients were in the STUMP and normal leiomyoma groups, respectively. Odds ratio and 95% confidence interval (OR (95% C.I)) of pathologic size in the range of 5–10 cm was significantly higher in the STUMP group compared with normal leiomyoma. (CI: 7.22 (1.44–36.22)). Additionally, hyaline necrosis 0.05 (0.0-0.91), mild to moderate atypia 0.02 (0.0-0.4), moderate to severe atypia 0.01 (0.0-0.22), focal atypia 0.01 (0-0.26) and diffuse atypia 0.01 (0-0.26) were significantly fewer in normal leiomyoma compared to the STUMP group. Negative P16 0.01 (0.0007-0.24) and negative Bcl2 0.22 (0.06–0.81) were significantly higher in the normal leiomyoma group compared with the STUMP group. The cut-off points for predicting STUMP were 2.5% (sensitivity = 62% and specificity = 100%) and 45% (sensitivity = 43% and specificity = 96%) for P16 and bcl2, respectively.ConclusionThe category and management of STUMP continues to progress. The diagnosis for STUMP mainly depends on the histopathological manifestations. No single IHC marker such as P53, P16, and Bcl-2 has proved robust enough in separating STUMP from other leiomyoma variants; however, according to our study, we suggest combination use of P16 and Bcl-2 (cut off 2.5 and 45%, respectively) to distinguish equivocal cases of STUMP.

Prediction of clinically significant prostate cancer using radiomics models in real-world clinical practice: a retrospective multicenter study

PurposeTo develop and evaluate machine learning models based on MRI to predict clinically significant prostate cancer (csPCa) and International Society of Urological Pathology (ISUP) grade group as well as explore the potential value of radiomics models for improving the performance of radiologists for Prostate Imaging Reporting and Data System (PI-RADS) assessment.Material and methodsA total of 1616 patients from 4 tertiary care medical centers were retrospectively enrolled. PI-RADS assessments were performed by junior, senior, and expert-level radiologists. The radiomics models for predicting csPCa were built using 4 machine-learning algorithms. The PI-RADS were adjusted by the radiomics model. The relationship between the Rad-score and ISUP was evaluated by Spearman analysis.ResultsThe radiomics models made using the random forest algorithm yielded areas under the receiver operating characteristic curves (AUCs) of 0.874, 0.876, and 0.893 in an internal testing cohort and external testing cohorts, respectively. The AUC of the adjusted_PI-RADS was improved, and the specificity was improved at a slight sacrifice of sensitivity. The participant-level correlation showed that the Rad-score was positively correlated with ISUP in all testing cohorts (r > 0.600 and p < 0.0001).ConclusionsThis radiomics model resulted as a powerful, non-invasive auxiliary tool for accurately predicting prostate cancer aggressiveness. The radiomics model could reduce unnecessary biopsies and help improve the diagnostic performance of radiologists’ PI-RADS. Yet, prospective studies are still needed to validate the radiomics models further.Critical relevance statementThe radiomics model with MRI may help to accurately screen out clinically significant prostate cancer, thereby assisting physicians in making individualized treatment plans.Key points• The diagnostic performance of the radiomics model using the Random Forest algorithm is comparable to the Prostate Imaging Reporting and Data System (PI-RADS) obtained by radiologists.• The performance of the adjusted Prostate Imaging Reporting and Data System (PI-RADS) was improved, which implied that the radiomics model could be a potential radiological assessment tool.• The radiomics model lowered the percentage of equivocal cases. Moreover, the Rad-scores can be used to characterize prostate cancer aggressiveness.Graphical

Abstract WP35: Elevated Risk of 1-month Post-Traumatic Stress Disorder Among Stroke Mimics Relative to Patients With Stroke

Introduction: A life-threatening medical event such as stroke can trigger symptoms of post-traumatic stress disorder (PTSD). Less is known about the risk of PTSD among individuals who present with stroke-like symptoms but are ultimately diagnosed with a stroke mimic. Aim: To examine the association between final diagnosis of stroke mimic, stroke, or TIA and risk of developing PTSD 1 month after the index event. Methods: We enrolled patients with suspected stroke or TIA from an urban academic medical center. The PTSD Checklist 5 for DSM-5 (PCL-5) was administered at enrollment to assess pre-existing PTSD, and at 1-month after discharge to assess PTSD related to the index event. The index event was adjudicated via chart review as a stroke, TIA, stroke mimic, or equivocal by a neurologist blinded to PTSD status. Logistic regression was used to determine odds of developing clinically significant PTSD (PCL-5 &amp;ge 33) for stroke mimics compared to stroke or TIA at 1 month after adjusting for age, gender, ethnicity, initial NIH Stroke Scale, discharge modified Rankin Score, and prior PTSD. Multiple imputation was used to account for missingness in data. Equivocal cases were excluded. Results: In our sample of suspected stroke ( n = 1,000, 51% female, age = 62 ± 15 y), 596 (59.6%) had a stroke, 79 (7.9%) had a TIA, 274 (27.4%) had a stroke mimic, and 51 (5.1%) were equivocal or missing. PTSD prevalence numbers (rates) at 1 month for stroke mimic, stroke, and TIA, respectively, were 30 (15.1%), 27 (6.3%), and 3 (5.5%). In the fully adjusted model, the odds of 1-month PTSD were higher for stroke mimics vs. patients with stroke, OR = 2.99, 95% CI [1.45, 6.18], p &amp;lt; .01, but not for stroke mimics vs. TIA, OR = 1.67, p = .45. Pre-existing PTSD was associated with increased odds of 1-month PTSD, OR = 10.32, 95% CI [5.30, 20.10], p &amp;lt; .01. No other covariates were associated with PTSD. Conclusion: Experiencing a stroke mimic compared to a stroke was associated with increased risk of having PTSD 1 month after the event. Clinicians should consider the risk of psychological distress particularly among individuals presenting with sudden stroke-like symptoms diagnosed as stroke mimics.

Human epidermal growth factor receptor 2/neu expression in urothelial carcinomas.

Urothelial carcinomas of the bladder are more common in males, making them the sixth-most common cancer in men and the tenth-most common cancer overall, worldwide. Current guidelines do not recommend routine testing for human epidermal growth factor receptor (HER2/neu) expression on the biopsy specimens of patients with urothelial carcinoma. This study was aimed at determining the expression pattern of HER2/neu and its usefulness in muscle-invasive and nonmuscle-invasive urothelial carcinoma. HER2/neu expression was assessed in 89 specimens of urothelial cancer by immunohistochemistry (IHC), and equivocal cases were subjected to fluorescent in situ hybridization (FISH). On IHC for HER2/neu, 17.9% (7/39) of the muscle-invasive bladder cancers (MIBCs) showed a 3+ expression, whereas 22% (11/50) of the non-muscle invasive cancers were positive with a score of 3+. A significant correlation between HER2/neu status and muscle invasion could not be established in the current study (P = 0.74, Fisher's exact test). Three cases of muscle-invasive (7.7%) and 2 cases (4%) among nonmuscle invasive cancers showed equivocal expression. All the cases with equivocal (2+) expression on IHC were subjected to FISH and none showed gene amplification on hybridization and were considered as negative. Overexpression of HER-2/neu was seen in 17.9% of MIBCs and 22% of non-MIBCs. There are no norms for routine testing of HER2/neu expression in the biopsy specimens of urothelial carcinoma. There is an unmet need to establish guidelines for HER2/neu scoring, similar to that for breast and gastric cancers, to determine the proportion of positive cases and help in identification of those who may benefit from targeted therapies.

HER2 amplification in cases with low HER2 expression by immunohistochemistry (IHC): A Single Institutional Experience

Abstract Introduction/Objective HER2 testing in invasive breast carcinoma (IBC) is the standard of care to determine patient eligibility for HER2 directed therapy with trasuzumab. Initial testing of tissue by HER2 immunohistochemistry (IHC) can be positive, negative, or equivocal. In equivocal cases as well as negative cases in our institution HER2 FISH is also performed. According to ASCO/CAP guidelines a subset of equivocal and negative IHC cases are considered HER2 positive if they meet criteria for increased HER2/CEP17 ratio and HER2 copy number by FISH, allowing more patients to be treated with HER2 directed therapies. HER2 grouping per ASCO is as follows; Group 1: HER2 copy number ≥4 signals/cell, Group 2: &amp;lt;4.0 signals/cell, Group 3: ≥6 signals/cell, Group 4: HER2 copy number ≥4 and &amp;lt;6 signals/cell, Group 5: HER2 copy number &amp;lt;4 signals/cell Methods/Case Report All cases of IBC resection with HER2 IHC and FISH results from Jan 2018-Dec 2021 were included in this study. All cases positive for HER2 by IHC alone (3+ staining) were excluded. The ASCO/CAP 2018 guidelines for HER2 testing in breast cancer were used to evaluate HER2 positivity by FISH and the relation to IHC scores Results (if a Case Study enter NA) A total of 2630 IBC cases with both HER2 IHC and FISH testing were included. Of these, 131 (5.0%) were in FISH group 1, 17 (0.7%) in group 2, 11 (0.4%) in group 3, 161 (6.1%) in group 4, and 2310 (87.8%) in group 5. A total of 142 (5.4%) cases that were HER2 equivocal or negative by IHC were HER2 positive by FISH. Specifically, 0.3% of cases with an IHC score of 0, 1.4% with a score of 1+, and 14.6% of cases with a score of 2+ were positive by FISH. Of the 14.6% IHC 2+ cases that were FISH positive 13.3% were in FISH group 1 (115 cases) and 1.3% (11 cases) in FISH group 3. Of FISH positive cases 1.4% had an IHC score of 0, 9.9% had an IHC score of 1 and 88.7% had a score of 2 Conclusion At our institution 14.6% of IBC with equivocal HER2 staining on IHC, 1.4% of cases with negative (1+) staining and 0.3% of cases with negative (0) were HER2 FISH positive. Since HER2 FISH is not reflexively performed on cases HER2 negative by IHC, this additional 1.7% will qualify for HER2 targeted therapy Interpretation of low HER2 expression by IHC by traditional IHC assay may miss a small percentage of cases eligible for HER2 directed therapy. Accurate interpretation of HER2 low by IHC is critical as recent clinical trials have shown that low HER2 expression with IHC scores of 1+ or 2+ without gene amplification by FISH could benefit from Trastuzumab Deruxtecan

Radiological evaluation of soft-tissue swellings

Background: Soft-tissue swellings (STSs) are commonly encountered by a radiologist in routine practice, either as the principal indication for diagnostic examination or as an incidental finding during an examination performed for other indications. Aims and Objectives: The aim of the study was to design a basic approach for the evaluation of STS with the help of available imaging modalities (ultrasound [USG], computed tomography [CT], and magnetic resonance imaging [MRI]) and analyzes its imaging characteristics so as to arrive at its final diagnosis. Materials and Methods: This prospective study (CTRI/2023/01/048933) was conducted in the Department of Radio-diagnosis, MLBMC, Jhansi, Uttar Pradesh, with 100 cases of STS were primarily evaluated by high-resolution grayscale USG, out of 100 cases, 72 diagnosed on USG and rest equivocal cases were secondarily evaluated with MRI, out of which 25 diagnosed and three cases needed CT evaluation. Three cases were evaluated with MRI+CT scan and finally diagnosed. Diagnosed cases followed by histopathology and surgery. Results: In our study, we found that USG is helpful in benign and superficial STS, as 72/100 cases diagnosed with the help of USG. In equivocal, deeply located, and malignant cases, MRI is more helpful in making a final diagnosis. In our study out of 28 cases, 25 diagnosed on MRI. CT scan used as accessory modality in the diagnosis of STS. Conclusion: USG remains the first-line imaging modality for the assessment of STS. MRI is an excellent modality in equivocal or suspicious lesion for characterisation of nature and extension. CT can be used for the detection of calcification and bone involvement.

COMPARISON OF RIPASA AND ALVARADO SCORING SYSTEM IN DIAGNOSIS OF ACUTE APPENDICITIS IN TERTIARY CARE

Introduction: Acute appendicitis is one of the most common surgical emergencies, with a lifetime prevalence rate of approximately one in seven. Different techniques have been devised to assist in equivocal cases in attempts to decrease negative appendectomy rates. RIPASA and ALVARADO scores are new diagnostic scoring systems for diagnosis of acute appendicitis . RIPASA scoring system has more sensitivity, specificity and diagnostic accuracy than ALVARADO score in diagnosis of acute appendicitis in Asian population. Hence this study conducted to compare RIPASA AND ALVARADO score in diagnosis of acute appendicitis in tertiary care hospital. RIPASA score includes more parameters than ALVARADO score such as age, gender, duration of symptoms prior to presentation Aims and objectives: To compare RIPASA and Alvarado score in diagnosing acute appendicitis using histopathology as gold standard Materials and Methods: Source of Data: Basaveshwar teaching and general hospital from august 1st to 30th september 2022 Study Design: Prospective observational study. Study Population: 74 patients Inclusion criteria All patients who presented with right lower quadrant abdomen pain and diagnosed as acute appendicitis. Exclusion Criteria: Patients under 18 years of age. Patients with right iliac fossa mass. Patients with features of peritonitis All these patients were scored as per RIPASA and Alvarado scoring system after taking history , clinical examination and laboratory investigations. RIPASA includes 18 parameters and Alvarado 8 parameters. A score of 7.5 taken as high probability of acute appendicitis as per RIPASA and score of 7 for Alvarado scoring system. The decision of appendicectomy solely based on surgeonÂ’s own clinical judgement After the surgery, histopathological reports of operated cases correlated with scoring systems.

EAACI guidelines on the diagnosis of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.

OR30-01 Waking Salivary 11-hydroxyandrostenedione And Cortisone As A Novel Non-invasive Test For Adrenal Insufficiency

Abstract Disclosure: N.R. Lawrence: None. B.G. Keevil: None. C. Elder: None. J. Fearnside: None. S. Caunt: None. S. Dixon: None. J.D. Newell-Price: Consulting Fee; Self; Diurnal, Recordati, Crinetics, HRA Pharma. R.J. Ross: Employee; Self; Diurnal. M. Debono: None. Background: The ACTH (Cosyntropin) stimulation test (AST) is the reference standard for diagnosis of adrenal insufficiency. We have demonstrated recently that home waking salivary cortisone accurately predicts the ACTH stimulation test outcome and confirms or excludes adrenal insufficiency in 70% of high-risk patients (in press: Home Waking Salivary Cortisone to Screen for Adrenal Insufficiency NEJM Evidence). 11-hydroxyandrostenedione (11-OHA4) is a weak adrenal androgen whose synthesis is dependent on CYP11B1. Since ACTH drives steroidogenesis, and adrenal androgens are low in patients with adrenal insufficiency, we hypothesised that waking 11-OHA4 could also predict adrenal status. Methods: A prospective, diagnostic accuracy study of waking salivary cortisone was performed in 173 patients at high risk of AI. All patients collected a salivary sample on waking, and then attended the endocrine clinic for an AST with the 30-minute cortisol used to diagnose AI. Salivary cortisone and 11-OHA4 was measured in the waking salivary sample. Biomarker discrimination was assessed by calculation of area under the curve (AUC) of the receiver operator characteristics (ROC) plot. Equivocal results were defined to maintain a sensitivity of 95% and specificity of 95%, and percentage of AST saved by calculating the number of AST needed if used only in equivocal cases. Results: The median (IQR) for 11-OHA4 for patients with AI and no AI was 55 (45 to 110) pmol/l vs 508 (255 to 765) pmol/l; p&amp;lt;0.0001. Salivary 11-OHA4 on waking was highly predictive of adrenal insufficiency (R2=0.63, ROC AUC 0.94), similar to waking salivary cortisone alone (R2=0.65, AUC 0.94). Waking 11-OHA4 performed better than either serum cortisol (R2=0.65, AUC 0.88) or salivary cortisone (R2=0.74, AUC 0.93) collected at the baseline of the AST. Combining both waking salivary 11-OHA4 with waking salivary cortisone further improved discrimination (R2=0.70, AUC 0.96), and using this combination would mean that 78% of ACTH-stimulation tests could be avoided. Conclusion: Waking salivary 11-OHA4 can accurately predict AI with similar discriminatory value as waking salivary cortisone. Combining waking 11-OHA4 with waking salivary cortisone improves discrimination for adrenal insufficiency, is a simple non-invasive test that can be used widely in clinical practice in the ambulatory setting, and obviates the need for AST in 78% of cases with greater patient convenience and lower costs. Presentation: Sunday, June 18, 2023

FRI298 Serum Prolactin To Tumor Size Ratio As An Effective Parameter To Accurately Distinguish Prolactinoma From NFPT

Abstract Disclosure: I. Mishra: None. A. Pradhan: None. A.K. Baliarsinha: None. Preoperative diagnosis of prolactinomas is critical because dopamine agonists therapy have been regarded as a primary treatment. Multiple studies have compared serum prolactin levels in clinically nonfunctioning (NF) tumors and prolactinomas to identify cutoffs that may distinguish primary tumoral secretion from stalk effect. Prolactin levels are correlated with the size of prolactinomas but are not associated with tumor size in non prolactin-secreting lesions or the degree of stalk deviation and compression. By using the tumor size, we investigated an effective parameter for the discrimination between prolactinoma and NFPT. 33 patients with pituitary lesion of histological diagnosis were retrospectively recruited for this study. The data obtained was entered into Microsoft Excel Worksheet and analysed using Statistical Package for Social Sciences (SPSS, IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.).The Prolactinoma group (n=16) showed higher serum prolactin (mean=418 ng/mL) than those in the NFPT group (n=17) (mean=33.34 ng/mL, p-values &amp;lt; 0.001).Using receiver operating curve analyses, we compared diagnostic performances of serum prolactin (PRL)/ tumor volume ratio in both groups. Unlike NFPT, serum prolactin values significantly correlated with tumor volume in Prolactinoma group. At a cut off of 12.2ng/ml/cm3,serum PRL/tumor volume was found to have a sensitivity of75.8% in diagnosing prolactinomas. However the specificity was 24.2%. Burke et al and Wright et al studied significantly smaller groups of patients and reported a linear relationship between prolactin levels and prolactinoma volume as estimated by a simplified ellipsoid volume equation. Our study demonstrates that the assessment of prolactin secretory density, based on a calculation of serum prolactin per unit tumor volume, can be used as a potential method to distinguish prolactinomas from hyperprolactinemia secondary to stalk effect and could be valuable in guiding patient management in equivocal or challenging patient cases wherein the etiology of hyperprolactinemia is uncertain. Reference: (1) Burke WT, Penn DL, Castlen JP, et al. Prolactinomas and nonfunctioning adenomas: preoperative diagnosis of tumor type using serum prolactin and tumor size. J Neurosurg. 2019:1e8.(2) Wright K, Lee M, Escobar N, et al. Tumor volume improves preoperative differentiation of prolactinomas and nonfunctioning pituitary adenomas.Endocrine.2021;74(1):138e145 Presentation: Friday, June 16, 2023

Attacking the Achilles heel of cardiac amyloid nuclear scintigraphy: How to reduce equivocal and false positive studies

BackgroundPlanar and single-photon emission computed tomography (SPECT) nuclear imaging techniques with bone seeking radiotracers have been increasingly adopted for diagnosis of ATTR cardiac amyloidosis. However, inherent limitations of these techniques due to lack of anatomical landmarks have been recognized, with consequent high numbers of equivocal or false positive cases. SPECT/computed tomography (CT) fusion imaging offers a significant advantage to overcome these limitations by substantially reducing inaccurate interpretations. The authors present the results of a 3-year imaging quality improvement project that focused on reducing the high number of equivocal studies that were noted in the first two years of the amyloidosis program, comparing SPECT only to SPECT/CT fusion technique. MethodsA retrospective, systematic analysis of 176 patient records was performed to test the premise that SPECT/CT fusion imaging has the potential to reduce equivocal and false positive results. ResultsOf a total of 176 patients, 35 equivocal (19.8%), 32 (18.18%) strongly suggestive, and 109 (61.93%) not suggestive cases were identified. Recognizing that this was not consistent with the international data, the authors set out on a comprehensive quality assessment project to reduce the number of equivocal and false positive cases. In patients who initially underwent SPECT only (Group A; n = 78), the addition of SPECT/CT fusion resulted in the net reclassification of 73% of cases: 100% of equivocal cases (n = 35) were reclassified to not suggestive (n = 34) or strongly suggestive (n = 1). 73% of strongly suggestive cases (n = 30) were reclassified to not suggestive (n = 22) while 8 strongly suggestive cases were confirmed as true positives. 13 not suggestive cases remained negative after SPECT/CT fusion. In cases where SPECT/CT fusion was utilized from the beginning (Group B; n = 98), there were no reclassification of any of the cases when these cases were reprocessed as a control group. ConclusionAddition of SPECT/CT imaging reduces the false positive or equivocal studies and increases the diagnostic accuracy of the test. All false positive and equivocal studies were eliminated using the fusion technique. Utilizing the fusion imaging technique increases the spatial resolution, with the ability to localize myocardial uptake and accurately differentiate from blood pool, which is a major source of error.

Artificial intelligence-based image analysis in clinical testing: lessons from cervical cancer screening.

Novel screening and diagnostic tests based on artificial intelligence (AI) image recognition algorithms are proliferating. Some initial reports claim outstanding accuracy followed by disappointing lack of confirmation, including our own early work on cervical screening. This is a presentation of lessons learned, organized as a conceptual step-by-step approach to bridge the gap between the creation of an AI algorithm and clinical efficacy. The first fundamental principle is specifying rigorously what the algorithm is designed to identify and what the test is intended to measure (eg, screening, diagnostic, or prognostic). Second, designing the AI algorithm to minimize the most clinically important errors. For example, many equivocal cervical images cannot yet be labeled because the borderline between cases and controls is blurred. To avoid a misclassified case-control dichotomy, we have isolated the equivocal cases and formally included an intermediate, indeterminate class (severity order of classes: case>indeterminate>control). The third principle is evaluating AI algorithms like any other test, using clinical epidemiologic criteria. Repeatability of the algorithm at the borderline, for indeterminate images, has proven extremely informative. Distinguishing between internal and external validation is also essential. Linking the AI algorithm results to clinical risk estimation is the fourth principle. Absolute risk (not relative) is the critical metric for translating a test result into clinical use. Finally, generating risk-based guidelines for clinical use that match local resources and priorities is the last principle in our approach. We are particularly interested in applications to lower-resource settings to address health disparities. We note that similar principles apply to other domains of AI-based image analysis for medical diagnostic testing.

Unexpected Outcomes for Headache Under Evaluation; A Case Series of Four Cases

Headache is a common cause of hospital visits and admissions throughout the world. Headaches may be primary or secondary; the primary one being far more common. Although the primary cases by far outnumber the secondary cases the role of the physician is to separate the benign causes from the more sinister ones. Using clinical examination and history alone this can often be a mountain-moving task. However, radiology can help as a problem-solving tool in equivocal cases. This case series highlights the role of radiological imaging in four cases of chronic headaches that were being treated empirically as primary headaches for a long time before neuroimaging revealed a secondary cause.

The Roles of USG and NCCT in the Diagnosis of Acute Appendicitis: A Study in a Tertiary Care Center in North Eastern India.

Acute appendicitis is a common cause of hospital admission and emergency laparotomy among children and young adults. Although the diagnosis is clinical, the use of radiological imaging has emerged over the past decades. Its principal use is as a problem-solving tool in equivocal cases. Owing to the increased use of imaging in the last few years, the negative appendicectomy rate has dropped significantly. In this prospective observational study, we compared the diagnostic accuracy of Ultrasonography and Non-Contrast Computed Tomography. One hundred and eighteen patients with clinically suspected appendicitis followed a designed protocol. Patients underwent appendicectomy after a first performed positive ultrasonography or after a positive Non-Contrast Computed Tomography when Ultrasonography was equivocal or nonspecific. When any other diagnosis was apparent in either imaging modality which could explain the symptomatology in the patient, they were considered negative for acute appendicitis and treated accordingly. The respective sensitivity, specificity, and accuracy for Ultrasonography, Non-Contrast Computed Tomography, and the whole diagnostic pathway for the diagnosis of acute appendicitis were 70.73%,80.83%, and 78.54; 100%,100%,100%, and 83.6%; and 100%,83.33% and 94.92%. Using Ultrasonography as the first-line diagnostic tool and Non-Contrast Computed Tomography as a complementary second-line diagnostic tool, appendicitis can be diagnosed with high accuracy and the negative laparotomy rate can be brought down significantly without any increase in the risk of complications. Computed Tomography is superior to Ultrasonography for the diagnosis of acute appendicitis.