Final Clinical Diagnosis Research Articles

Systematic evaluation of imaging techniques and baseline characteristics in patients with suspected vasculitis

PurposeTo assess the diagnostic value of different imaging modalities in distinguishing systemic vasculitis from other internal and immunological diseases. MethodsThis retrospective study included 134 patients with suspected vasculitis who underwent ultrasound, magnetic resonance imaging (MRI), or 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) between 01/2010 and 01/2019, finally consisting of 70 individuals with vasculitis. The main study parameter was the confirmation of the diagnosis using one of the three different imaging modalities, with the adjudicated clinical and histopathological diagnosis as the gold standard. A secondary parameter was the morphological appearance of the vessel affected by vasculitis. ResultsPatients with systemic vasculitis had myriad clinical manifestations with joint pain as the most common symptom. We found significant correlations between different imaging findings suggestive of vasculitis and the final adjudicated clinical diagnosis. In this context, on MRI, vessel wall thickening, edema, and diameter differed significantly between vasculitis and non-vasculitis groups (p < 0.05). Ultrasound revealed different findings that may serve as red flags in identifying patients with vasculitis, such as vascular occlusion or halo sign (p = 0.02 vs. non-vasculitis group). Interestingly, comparing maximal standardized uptake values from PET/CT examinations with vessel wall thickening or vessel diameter did not result in significant differences (p > 0.05). ConclusionsWe observed significant correlations between different imaging findings suggestive of vasculitis on ultrasound or MRI and the final adjudicated diagnosis. While ultrasound and MRI were considered suitable imaging methods for detecting and discriminating typical vascular changes, 18F-FDG PET/CT requires careful timing and patient selection given its moderate diagnostic accuracy.

Stroke Mimics in the Acute Setting: Role of Multimodal CT Protocol.

Ischemic stroke can be mimicked by nonischemic conditions. Due to emphasis on the rapid treatment of acute ischemic stroke, it is crucial to identify these conditions to avoid unnecessary therapies and potential complications. We investigated the performance of the multimodal CT protocol (unenhanced brain CT, CTA, and CTP) to discriminate stroke mimics from acute ischemic stroke. We retrospectively selected multimodal CT studies performed for clinical suspicion of acute ischemic stroke in our center in a 24-month period, including patients with at least 1 follow-up imaging study (brain CT or MR imaging). Hemorrhagic strokes were excluded. We measured the performance of multimodal CT, comparing the original diagnostic results with the final clinical diagnosis at discharge. Among 401 patients, a stroke mimic condition was diagnosed in 89 (22%), including seizures (34.8%), migraine with aura attack (12.4%), conversion disorder (12.4%), infection (7.9%), brain tumor (7.9%), acute metabolic condition (6.7%), peripheral vertigo (5.6%), syncope (5.6%), transient global amnesia (3.4%), subdural hematoma (1.1%), cervical epidural hematoma (1.1%), and dural AVF (1.1%). Multimodal CT sensitivity, specificity, and accuracy were 24.7%, 99.7%, and 83%. Multimodal CT revealed peri-ictal changes in 13/31 seizures and diagnosed 7/7 brain tumors, 1/1 dural AVF, and 1/1 subdural hematoma. CT perfusion played a pivotal diagnostic role. Multimodal CT demonstrated low sensitivity but high specificity in the diagnosis of stroke mimics in the acute setting. The high specificity of multimodal CT allows ruling out stroke and thereby avoiding unnecessary revascularization treatment in patients with diagnosis of a stroke mimic.

Pleural pathology in HIV-infected patients: features of morphological diagnostics

Background. The progression of HIV infection is accompanied by the development of opportunistic diseases, including pleural effusions of various origins. Morphological examination of pleura tissue in cases of pleural effusion serves as the basis for establishing the etiology of the pathological process and, therefore, the final clinical diagnosis. Objective – analysis of results of morphological diagnostics of pleura lesions in HIV-infected patients in comparison with other laboratory tests and clinical diagnosis. Methods. 103 cases of pleurisy of various origins were studied. Pleural biopsies were obtained by various types of minimally invasive diagnostic interventions with subsequent morphological examination. Results were compared with the available data of microbiological and molecular genetic studies of pleural biopsies. Results. At the time of hospitalization the preliminary clinical diagnosis was pleurisy of unknown etiology in 96,1 % of cases. A combined disease was diagnosed – hepatitis C in a third of all observations according to the results of laboratory tests. Due to routine staining with hematoxylin and eosin, tuberculosis lesions of the pleura were diagnosed in 59,2 %, the second most frequent was the diagnosis of nonspecific pleurisy, 20,4 %. According to the duration of the process, acute pleural tuberculosis was established in 19,7 % of cases, the subacute form of tuberculosis pleurisy – in 54,1 % of cases, and chronic pleural tuberculosis was established in 22,9 % of cases. In 17,5 % of cases, in order to clarify the etiology of pleurisy, additional histochemical staining for infectious agents was performed. The results of microbiological and molecular genetic studies were established in 76,7 % of cases. The greatest number of M. tuberculosis detection was obtained during the culture study of the biopsy material and exudates. When comparing the final clinical diagnosis and the level of CD4 cells in peripheral blood, it was found that in most cases (74,5 %) pleural effusions developed at low counts of CD4 cells, less than 350/l. Conclusion. Tuberculosis predominates in the etiological structure of pleural effusions in patients with HIV infection. Pleural tuberculosis can be the main secondary disease or be combined with pulmonary tuberculosis. In second place in terms of frequency of occurrence, nonspecific pleurisy was diagnosed as a complication of the main secondary disease. Pleural effusions develop when CD4 cell counts are low. Morphological diagnostics of pleural lesions is the main research method in the diagnostic algorithm of cases of pleural effusions of unknown etiology against the background of HIV infection.

Usefulness of brain FDG PET/CT imaging in pediatric patients with suspected autoimmune encephalitis from a prospective study

PurposeEarly diagnosis and treatment are of paramount importance for pediatric patients with autoimmune encephalitis (AE). The aim is to evaluate the usefulness of FDG PET/CT in pediatric patients with suspected AE from a prospective study.MethodsThe prospective study was conducted over a period of 23.5 months from May 14, 2019, to April 30, 2021. All patients (< 18-year-old) were hospitalized at the department of pediatric neurology and met the criteria of clinical suspected AE. The children underwent the tests of blood samplings, CSF, EEG, MRI, and 18F-FDG PET/CT. The criteria for FDG PET/CT diagnosis of AE were large lobar hypometabolism with or without focal hypermetabolism found on PET/CT. The clinical final diagnosis of AE includes seropositive and seronegative AE based on the diagnostic criteria.ResultsOne hundred four pediatric inpatients (57 boys, 47 girls) were included, of which 58 children were diagnosed with AE (seropositive, 16; seronegative, 42), 45 children were diagnosed with non-AE, and one boy remained indeterminate diagnosis. Large lobar hypometabolism was found in 61 children, of which 54 (88.5%) children were finally diagnosed with AE. The sensitivity, specificity, and accuracy of FDG PET/CT for diagnosis of AE were 93.1%, 84.4%, and 89.3%, respectively, with a positive predictive value of 88.5% and a negative predictive value of 90.5%. The most common involved with hypometabolism was the parietal lobe, followed by occipital and frontal lobes, finally the temporal lobe on PET/CT in children with AE.ConclusionBrain FDG PET/CT imaging has high specificity, sensitivity, and accuracy for diagnosis of AE in clinical suspected AE children.Trial registration.Clinical Trials.gov. NCT02969213. Registered 17 October 2016.

Clinico-pathological correlation of linear dermatoses along the lines of Blaschko: An observational study

Several epidemiological studies have described linear dermatoses; however, only few studies have correlated linear dermatoses along Blaschko’s lines with the histopathological findings. The aims of this study were to investigate the clinical patterns of various linear dermatological lesions along Blaschko’s lines and investigate the correlations between these dermatological lesions and their histopathological features. Patients who attended our dermatology out-patient department with linear dermatoses along the Blaschko’s lines were included in the study. Detailed history was obtained, clinical examination was performed, and a final provisional clinical diagnosis was noted. Subsequently, biopsy of the lesions was performed for histopathological examination. Of 62 patients who presented with linear lesions along the Blaschko’s lines, 45 patients underwent biopsy and histopathological examination. Of 45 patients who underwent biopsy, clinico-pathological correlation was observed in 100% of those diagnosed with lichen striatus and linear morphea, 89% of those diagnosed with hypomelanosis of Ito, 80% of those diagnosed with linear epidermal nevus, 75% of those diagnosed with lichen planus, and 67% of those diagnosed with nevus depigmentosus. The importance of correlation of linear lesions with their histopathological features in dermatology cannot be over emphasized. However, 100% correlation may be wishful thinking, and a correlation can help choose the appropriate line of management. Our results highlight this discrepancy and add to the knowledge on linear dermatosis.

Assessing the utility of the Xpert Mycobacterium tuberculosis/rifampin assay for analysis of bronchoalveolar lavage fluid in patients with suspected pulmonary tuberculosis

BackgroundThere is limited research assessing the utility of the Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF) assay for the analysis of bronchoalveolar lavage fluid (BALF) in Chinese patients with suspected pulmonary tuberculosis (PTB). Thus, our objective was to determine the diagnostic accuracy of the Xpert MTB/RIF assay and evaluate its utility for the determination of rifampicin resistance.MethodsWe retrospectively analyzed BALF from 214 patients with suspected PTB between January 2018 and March 2019. Using mycobacterial culture or final clinical diagnosis as the reference standard, the diagnostic accuracy of the smear microscopy (SM), tuberculosis bacillus DNA (TB‐DNA), Xpert MTB/RIF assay, and the determination of rifampicin resistance based on the Xpert MTB/RIF assay were compared.ResultsAs compared to mycobacterial culture, the sensitivity of the Xpert MTB/RIF assay, SM, and TB‐DNA were 85.5% (74.2%–93.1%), 38.7% (26.6%–51.9%), and 67.7% (54.7%–79.1%), respectively. As compared to the final diagnosis, the specificity of the Xpert MTB/RIF assay, SM, and TB‐DNA were 100.0% (95.9%–100.0%), 94.3% (87.1%–98.1%), and 98.9% (93.8%–100.0%), respectively. The sensitivity and specificity of the rifampicin resistance detection using the Xpert MTB/RIF assay were 100% and 98.0%, respectively, with liquid culture as the reference.ConclusionsThis study demonstrates that the analysis of BALF with the Xpert MTB/RIF assay provides a rapid and accurate tool for the early diagnosis of PTB. The accuracy of diagnosis was superior compared with the SM and TB‐DNA. Moreover, Xpert is a quick and accurate method for the diagnosis of rifampicin‐resistant tuberculosis and can also provide more effective guidance for the treatment of PTB or multidrug‐resistant tuberculosis (MDR‐TB).

Repeated Clinical Assessment Using Sensory Modality Assessment and Rehabilitation Technique for Diagnosis in Prolonged Disorders of Consciousness.

Purpose: The recommended way to assess consciousness in prolonged disorders of consciousness is to observe the patient’s responses to sensory stimulation. Multiple assessment sessions have to be completed in order to reach a correct diagnosis. There is, however, a lack of data on how many sessions are sufficient for validity and reliability. The aim of this study was to identify the number of Sensory Modality Assessment and Rehabilitation Technique (SMART) assessment sessions needed to reach a reliable diagnosis. A secondary objective was to identify which sensory stimulation modalities are more useful to reach a diagnosis.Materials and Methods: A retrospective analysis of all the adult patients (who received a SMART assessment) admitted to a specialist brain injury unit over the course of 4 years was conducted (n = 35). An independent rater analyzed the SMART levels for each modality and session and provided a suggestive diagnosis based on the highest SMART level per session.Results: For the vast majority of patients between 5 and 6 sessions was sufficient to reach the final clinical diagnosis. The visual, auditory, tactile, and motor function modalities were found to be more associated with the final diagnosis than the olfactory and gustatory modalities.Conclusion: These findings provide for the first time a rationale for optimizing the time spent on assessing patients using SMART.

Comparison of flow cytometry with other modalities in the diagnosis of myelodysplastic syndrome.

The myelodysplastic syndromes (MDSs) are heterogeneous myeloid malignancies, conventionally diagnosed by cytomorphology and cytogenetics, with an emerging role for flow cytometry. This study compared the performance of a 4-parameter flow cytometry scoring system, the Ogata Score, with other modalities in the diagnosis of MDS. Bone marrow aspirate and trephine biopsies from 238 patients performed to assess for possible MDS were analysed, and the flow cytometry score was retrospectively applied. The sensitivity and specificity of the flow cytometry score, the aspirate microscopy, the trephine microscopy with immunohistochemistry, and cytogenetic and molecular results were determined relative to the final diagnosis. The medical records of the 238 patients were reviewed to determine the final clinical diagnosis made at the time of the bone marrow examination. This final diagnosis of MDS, possible MDS or not MDS, was based on clinical features and laboratory tests, including all parameters of the bone marrow investigation, except for the flow cytometry score, which was only determined for this study. The flow cytometry score was 67.4% sensitive and 93.8% specific. Aspirate microscopy had higher sensitivity (83.7%) and similar specificity (92.0%), whereas trephine microscopy had similar sensitivity (66.3%) and specificity (89.4%) to flow cytometry. Although the flow cytometry score had a lower sensitivity than aspirate microscopy, in 18 patients (7.6% of the total) the flow cytometry score was positive for MDS, whereas aspirate microscopy was negative or inconclusive. The flow cytometry score and trephine microscopy exhibited reasonable sensitivity and high specificity, and complement aspirate microscopy in the assessment of MDS.

High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department.

Debate exists on the usefulness of high-sensitivity cardiac troponin (hs-cTn) testing in pediatric patients due to the perceived low incidence of myocardial injury and lack of data concerning its efficacy. We evaluated the contribution of an increased hs-cTnT above the 99th percentile upper-reference limit (URL) to clinical diagnoses made in pediatric patients presenting to the emergency department (ED). Retrospective cohort study including patients aged 0-18years presenting to the ED from 2018 to 2020 where hs-cTnT was measured. Sex-specific 99th percentile URLs of 15 and 10ng/L for males and females, respectively, were used, with concentrations above these thresholds considered indicative of myocardial injury. Overall, 356 patients were identified in whom hs-cTnT concentrations were measured during ED clinical evaluation. Hs-cTnT was increased above the 99th percentile on presentation in 36 patients (10.1%). Twelve patients (3.4%) had a clinical cardiac diagnosis made. Hs-cTnT was increased in 6 of these (50.0%). Serial hs-cTnT from 106 patients with an initial hs-cTnT < 99th percentile was subsequently elevated in 5 (4.6%); none of whom had a final clinical cardiac diagnosis. Hs-cTnT has high specificity, but low sensitivity when used as a screening tool for myocardial injury when the gold standard is mostly clinical assessment. In present practice, however, they do not appear to track well with clinical diagnoses. Further studies are needed to more clearly define the role of hs-cTnT in this patient population.

Parkinson's disease and parkinsonism: Clinicopathological discrepancies on diagnosis in three patients.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The cardinal neuropathological features of PD include selective and progressive loss of pigmented neurons in the substantia nigra, deficiencies in dopaminergic signaling in the striatum, and occurrence of phosphorylated α-synuclein-identified Lewy bodies in the nervous system. Parkinsonism, the clinical presentation of movement disorders seen in PD, is a feature shared commonly by other pathologically distinct neurodegenerative diseases, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA). Consequently, it is sometimes difficult to distinguish PD from such parkinsonism-related neurological disorders. In addition, parkinsonism is not always a feature of certain neurodegenerative diseases, and it can sometimes develop as a result of various forms of drug intoxication or cerebrovascular disease. Here, we describe the clinicopathological features of three patients (cases 1, 2, and 3) diagnosed as having PSP, MSA, and PD, respectively, in each of whom the postmortem histopathological diagnosis differed from the final clinical diagnosis. Neuropathologically, they had suffered from coexistent disorders: PD, MSA, and argyrophilic grain disease (case 1); PD (case 2); and vascular parkinsonism (case 3). The variety of patients showing features of parkinsonism underlines the importance of careful long-term follow up followed by postmortem neuropathological evaluation.

Diagnostic accuracy using low-dose versus standard radiation dose CT in suspected acute appendicitis: prospective cohort study.

Contrast-enhanced CT is the reference standard used in diagnostic imaging for acute appendicitis in adults. The radiation dose has been of concern. This study aimed to assess whether a lower radiation dose would affect the diagnostic accuracy of CT. This was a prospective single-centre cohort study of patients (aged over 16 years) with suspected appendicitis evaluated for enrolment in concurrent APPAC II-III trials. The diagnostic accuracy of contrast-enhanced low- and standard-dose CT was compared with study protocols guiding imaging based on BMI; this enabled direct CT imaging comparison only in patients with a BMI below 30 kg/m2. The on-call CT diagnosis was compared with the final clinical diagnosis. Among all 856 patients investigated, the accuracy of low-dose (454 patients) and standard-dose (402 patients) CT in identifying patients with and without appendicitis was 98·0 and 98·5 per cent respectively. In patients with a BMI under 30 kg/m2, respective values were 98·2 per cent (434 patients) and 98·6 per cent (210 patients) (P = 1·000). The corresponding accuracy for differentiating between uncomplicated and complicated acute appendicitis was 90·3 and 87·6 per cent in all patients, and 89·8 and 88·4 per cent respectively among those with a BMI below 30 kg/m2 (P = 0·663). The median radiation dose in the whole low- and standard-dose CT groups was 3 and 7 mSv respectively. In the group with BMI below 30 kg/m2, corresponding median doses were 3 and 5 mSv (P < 0·001). Low- and standard-dose CT were accurate both in identifying appendicitis and in differentiating between uncomplicated and complicated acute appendicitis. Low-dose CT was associated with a significant radiation dose reduction, suggesting that it should be standard clinical practice at least in patients with a BMI below 30 kg/m2.

Chest computed tomography in the diagnosis of COVID-19 in patients with false negative RT-PCR.

ABSTRACTObjective To evaluate the role of chest computed tomography in patients with COVID-19 who presented initial negative result in reverse transcriptase-polymerase chain reaction (RT-PCR).Methods A single-center, retrospective study that evaluated 39 patients with negative RT-PCR for COVID-19, who underwent chest computed tomography and had a final clinical or serological diagnosis of COVID-19. The visual tomographic classification was evaluated according to the Consensus of the Radiological Society of North America and software developed with artificial intelligence for automatic detection of findings and chance estimation of COVID-19.Results In the visual tomographic analysis, only one of them (3%) presented computed tomography classified as negative, 69% were classified as typical and 28% as indeterminate. In the evaluation using the software, only four (about 10%) had a probability of COVID-19 <25%.Conclusion Computed tomography can play an important role in management of suspected cases of COVID-19 with initial negative results in RT-PCR, especially considering those patients outside the ideal window for sample collection for RT-PCR.

How much time is needed in clinical practice to reach a diagnosis of clinically established Parkinson's disease?

IntroductionThe implementation of accepted clinical diagnostic criteria has improved the accuracy of a clinical diagnosis of Parkinson's disease (PD). Time frames of 3–10 years have been empirically proposed to reach a diagnosis of clinically established PD. MethodsWe explored the time to a Final Clinical Diagnosis (FCD) and the factors that predict faster diagnoses in patients presenting with parkinsonism and/or tremor between 2009 and 2015 at our tertiary center. All patients underwent a standardized workout process to reach a FCD, which included an acute levodopa challenge (LDC) after the first visit. ResultsAmong the 326 patients included, 215 (66%) received a FCD within the first six months after the LDC. A FCD was reached in 95% and 100% of patients in 33 and 108 months, respectively. PD was the FCD in 196 patients (60.1%). The FCD was reached faster in patients with a positive response to levodopa and when the FCD was PD. ConclusionThe time needed to reach a final diagnosis in the clinical setting was 2.75 years in 95% of patients presenting initially with parkinsonism and/or tremor. Patients with positive responses to levodopa at the LDC, benefited from shorter delays until the FCD.

Technetium-99m methylene diphosphonate bone scan in evaluation of insufficiency fractures - A pictorial assay and experience from South India.

ABSTRACTInsufficiency fractures (IFs) can be challenging to diagnose due to varied presentations, and sometimes, it changes the course of treatment, as in cancer patients in whom it has to be differentiated with metastatic disease. We present the role of Technetium 99m methylene diphosphonate (99mTc-MDP) bone scan, which is a low-cost, simple to perform, whole body diagnostic investigation in the diagnosis of IFs. This is a retrospective analysis of all patients who underwent a 99mTc-MDP bone scan in a tertiary care teaching hospital during 2013–2017 and were diagnosed as having an IF on bone scan. The bone scans were performed on a dual-head gamma camera using low-energy high-resolution collimators. Of all the bone scan performed during 2013–2017, a total of 138 patients with a mean age of 57.5 ± 14.7 years were diagnosed as having IFs based on bone scan and final clinical diagnosis. Among them, the most common complaint was regional bony pain in 62% of patients, while the most common cause was osteoporosis in 47% of patients, both postmenopausal and senile osteoporosis. In all, 265 sites of fractures were identified with a fracture average of 1.9/patient, the most common site being dorsolumbar vertebrae, followed by ribs and lower limb bones. Many unusual sites were also identified such as talus, sternum, clavicle, and scapula. 99mTc-MDP bone scan, being noninvasive whole-body imaging, is a useful investigation for evaluation of IFs and in correlation with biochemical analysis and other imaging can be used to determine the etiology of IF.

Болезнь Норри: основные симптомы заболевания и важность раннего генетического анализа (клинический случай)

We present a clinical case of Norrie disease in a 6-year-old boy. The parents had in time an ophthalmologist consultation when the child was 4 months old, but the final diagnosis was made more than 5 years later. A specific feature of this case in addition to vitreoretinopathy and bilateral retinal detachment was the presence of a congenital malformation of the iris - aniridia, which is not a typical sign of Norrie disease. A modern method of genetic testing (next generation sequencing - NGS) made it possible to detect a previously undescribed mutation in the NDP gene and make a final clinical and genetic diagnosis. Key words: Norrie disease; vitreoretinopathy; retinal detachment; NDP gene.

Ultrasound-guided percutaneous needle biopsies of peripheral pulmonary lesions: diagnostic efficacy and risk factors for diagnostic failure.

To evaluate the diagnostic performance of ultrasound-guided percutaneous needle biopsy (US-PNB) for peripheral pulmonary lesions on the basis of the intention-to-diagnose principle and to identify the risk factors for diagnostic failure. Patients with peripheral pulmonary lesions who underwent US-PNB in the Department of Ultrasound, the First Affiliated Hospital of Guangxi Medical University, China, from January 2017 to December 2019 were retrospectively enrolled in this study. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ultrasound-guided biopsy in peripheral pulmonary lesions was assessed. The proportion of diagnostic failure was calculated and the associated risk factors were identified. A total of 930 patients were enrolled in this study, including 957 US-PNBs. The overall diagnostic accuracy, sensitivity, and specificity was 90.3% [864/957; 95% confidence interval (CI): 0.88-0.922], 87.2% (495/568; 95% CI: 0.84-0.90), and 94.9% (369/389; 95% CI: 0.92-0.97), respectively. The PPVs and NPVs were 99.4% (495/498; 95% CI: 0.98-0.99) and 88.1% (369/419; 95% CI: 0.85-0.91), respectively. The diagnostic failure rate was 9.72% (93/957; 95% CI: 0.08-0.12). The independent risk factors for diagnostic failure were history of smoking [odds ratio (OR) 1.78, 95% CI: 1.13-2.78], 18G biopsy needle (OR 2.97, 95% CI: 1.06-8.30), and final clinical diagnosis of malignant lesions (OR 2.72, 95% CI: 1.63-4.55). US-PNB of peripheral pulmonary lesions show high diagnostic efficacy. A history of smoking, use of 18G biopsy needle, and final clinical diagnosis of malignant lesions are independent risk factors for diagnostic failure of US-PNB in peripheral pulmonary lesions. Identification of the independent risk factors for diagnostic failure can help reduce the diagnostic failure rate.

Genetic evaluation supports differential diagnosis in adolescent patients with delayed puberty.

ContextPubertal delay can be the clinical presentation of both idiopathic hypogonadotropic hypogonadism (IHH) and self-limited delayed puberty (SLDP). Distinction between these conditions is a common but important diagnostic challenge in adolescents.ObjectiveTo assess whether gene panel testing can assist with clinical differential diagnosis and to allow accurate and timely management of delayed puberty patients.DesignRetrospective study.MethodsPatients presenting with delayed puberty to UK Paediatric services, followed up to final diagnosis, were included. Whole-exome sequencing was analysed using a virtual panel of genes previously reported to cause either IHH or SLDP to identify rarely predicted deleterious variants. Deleterious variants were verified by in silico prediction tools. The correlation between clinical and genotype diagnosis was analysed.ResultsForty-six patients were included, 54% with a final clinical diagnosis of SLDP and 46% with IHH. Red flags signs of IHH were present in only three patients. Fifteen predicted deleterious variants in 12 genes were identified in 33% of the cohort, with most inherited in a heterozygous manner. A fair correlation between final clinical diagnosis and genotypic diagnosis was found. Panel testing was able to confirm a diagnosis of IHH in patients with pubertal delay. Genetic analysis identified three patients with IHH that had been previously diagnosed as SLDP.ConclusionThis study supports the use of targeted exome sequencing in the clinical setting to aid the differential diagnosis between IHH and SLDP in adolescents presenting with pubertal delay. Genetic evaluation thus facilitates earlier and more precise diagnosis, allowing clinicians to direct treatment appropriately.

Diagnostic value of the combinations of bronchoalveolar lavage fluid pathogen detection and cryptococcal antigen test in pulmonary cryptococcosis

Objective: To evaluate the diagnostic value of bronchoalveolar lavage fluid pathogen detection combined with cryptococcal antigen test(CrAg) for pulmonary cryptococcosis(PC). Methods: A retrospective case analysis was performed on non-acquired immunodeficiency syndrome patients admitted to Ninghai First Hospital for suspected PC from January 2018 to December 2019. Fifty-nine patients were included. Sixteen cases (8 males and 8 females) were diagnosed with PC, aged from 18 to 76 years[an average age of (52±14) years], while 43 cases were diagnosed as having Non-PC. All patients had undergone both serum CrAg test and BALF pathogen detection(cultures and direct examination) combined with BALF-CrAg test. The sensitivity and specificity of the combined method of BALF was evaluated, and a parallel comparison of the diagnostic efficiencies of the two methods were made. Results: Of the 16 confirmed PC cases, serum CrAg tests were positive in 11 and negative in 5 cases, while the combined method showed that 14 were positive and 2 were negative. Compared with the clinical final diagnosis, the sensitivity, specificity, positive predictive value and negative predictive value showed that the serum CrAg tests were 68.8% (11/16), 97.7% (42/43), 91.7% (11/12), 89.3% (42/47) respectively, versus 87.5% (14/16), 100.0% (43/43), 100% (14/14), 95.6% (43/45) by the combined method of BALF. The results displayed no statistical difference between the two diagnostic methods (P =1.000). Among the 5 initially serum CrAg-negative cases, 4 were later confirmed as proven PC via the combined method of BALF and the other one by percutaneous lung biopsy. Conclusion: The combined method of BALF pathogen detection with BALF-CrAg showed a similar statistical efficiency rate for diagnosing pulmonary cryptococcosis compared with serum CrAg tests. It may serve as an efficient diagnosis method for PC cases with negative serum CrAg tests.

O-234 Using serum metabolomics to identify biomarkers of viable early, intrauterine pregnancy: an untargeted 1H NMR-based approach

Abstract Study question Which metabolites are associated with a viable intrauterine pregnancy (VIUP) when compared to other early pregnancy outcomes (failed intrauterine and ectopic pregnancies)? Summary answer Serum levels of four metabolites (phenylalanine, alanine, glutamate and glutamine) were significantly altered in VIUPs compared to other early pregnancy outcomes. What is known already Around 10% of all intrauterine pregnancies are lost in the first trimester. A further 1-2% of pregnancies are located outside the endometrial cavity; these ectopic pregnancies are the leading cause of maternal mortality in the first trimester of gestation. Early miscarriages may also cause significant morbidity when bleeding or infection occurs. The symptoms of miscarriages and ectopic pregnancy are often similar (pain and bleeding), however, such symptoms are also common in VIUPs. To date, no biomarkers have been identified to differentiate VIUPs from non-viable and ectopic pregnancies. Study design, size, duration This is a prospective cohort study that included 332 pregnant women at less than ten weeks of gestation, who attended the early pregnancy assessment unit (EPAU) at Liverpool Women’s Hospital with pain and/or bleeding. Participants/materials, setting, methods Blood samples were collected from the 332 pregnant women prior to final clinical diagnosis of pregnancy outcome. Serum samples were subjected to NMR metabolomics profiling (14 spectra that did not meet the recommended minimum reporting standards were removed from subsequent analysis). 1D 1H-NMR spectra were acquired at 37 °C on a 700 MHz spectrometer. Relative metabolite abundances underwent statistical analysis using MetaboAnalyst 5.0 (p-value FDR adjusted). Main results and the role of chance Final pregnancy outcomes were as follows: one hydatidiform mole (0.3%), 48 ectopic pregnancies (14.4%), three pregnancies of unknown location (PULs, 0.9%), 78 failed pregnancies of unknown location (FPULs, 23.4%), 47 miscarriages (14.1%), two vanishing twin pregnancies (0.6%) and 153 VIUPs (45.8%). Due to small sample numbers, the hydatidiform mole, PULs and vanishing twin pregnancies were excluded from further analysis. To compare VIUPs to other pregnancy outcomes, ectopic pregnancies, FPULs and miscarriages were grouped together. Univariate analysis of serum metabolite concentrations identified four metabolites (phenylalanine, alanine, glutamate and glutamine) as significantly different in VIUPs compared to other pregnancy outcomes. Multivariate partial least squared discriminant analysis provided only weak correlation between the serum metabolome and pregnancy outcome. In summary, we have identified differences in the metabolome of women with VIUPs compared to other common pregnancy outcomes, which may provide diagnostic utility. Limitations, reasons for caution In this study, women with VIUPs presented with pain and/or bleeding. The presence of symptoms may influence the metabolome of this group versus VIUPs without symptoms, thus limiting the translation of our findings. Furthermore, environmental factors were not controlled (e.g. fasting status), making it likely that cohort heterogeneity was enhanced. Wider implications of the findings This study identifies a metabolite profile associated with VIUPs. These findings may be useful in the development of a diagnostic test to confirm VIUPs and thus exclude potentially life-threatening pregnancy outcomes. Such a test would be invaluable in clinical emergencies. Trial registration number NA

Lung Cryobiopsy Outside of the Operating Room: A Safe Alternative to Surgical Biopsy.

ObjectiveTransbronchial lung cryobiopsy (TBLC) is a promising technique that can provide a histologic diagnosis in interstitial lung diseases (ILD) and is an alternative to surgical lung biopsy. The main concerns with the procedure are safety and diagnostic accuracy. The technique is applicable in patients unable to undergo surgical biopsy due to severe comorbidities or when patient transport to the operating room is dangerous. This study reports the initial experience with TBLC on a thoracic surgical service as a first attempt at diagnosis in patients with diffuse parenchymal lung diseases (DPLD).MethodsBetween May 2018 and July 2020, 32 patients underwent TBLC using bedside flexible bronchoscopy for suspected ILD on a thoracic surgical endoscopy service. Retrospective evaluation of the procedure details, complications, and diagnostic yield were analyzed and reported.ResultsA total of 89 pathological samples were obtained (mean 2.8 per patient). Pneumothorax and minor bleeding occurred in 25% and 16.7% of patients, respectively. Sixty-seven percent of complications occurred with use of the 2.4 mm cryoprobe (P = 0.036). Concordance between the histologic diagnosis and final clinical diagnosis was observed in 62.5% of patients and the pathology guided the final treatment in 71% (P = 0.027) with Kappa-concordance of 0.60 (P < 0.001).ConclusionsCryobiopsy is becoming part of the diagnostic evaluation in patients with indeterminate DPLD or hypoxemic respiratory failure. TBLC is easy to perform and has a favorable safety profile. Thoracic specialists should consider adding TBLC to their procedural armamentarium as a first option for patients with indeterminate PLD.