Diagnostic Approach In Patients Research Articles

Artificial intelligence model for enhancing the accuracy of transvaginal ultrasound in detecting endometrial cancer and endometrial atypical hyperplasia

ObjectivesTransvaginal ultrasound is typically the initial diagnostic approach in patients with postmenopausal bleeding for detecting endometrial atypical hyperplasia/cancer. Although transvaginal ultrasound demonstrates notable sensitivity, its specificity remains limited. The objective...

Molecular Diagnostic Yield and Safety Profile of Ultrasound-Guided Lung Biopsies: A Cross-Sectional Study.

The recent advances in precision oncology for lung cancer treatment has focused attention on the importance of obtaining appropriate specimens for tissue diagnosis as well as comprehensive molecular profiling. CT scan-guided biopsies and bronchoscopy are currently the main procedures employed for tissue sampling. However, growing evidence suggests that ultrasound-guided biopsies may represent an effective as well as safe approach in this diagnostic area. This study explores the safety and the diagnostic yield for cancer molecular profiling in ultrasound-guided percutaneous lung lesion biopsies (US-PLLB). One hundred consecutive patients with suspected lung cancer, between January 2021 and May 2024, who had ultrasound-guided lung biopsies have been retrospectively analyzed. Molecular profiling was conducted with next-generation sequencing Genexus using Oncomine precision assay or polymerase chain reaction according to specimen quality. Qualitative immunohistochemical assay of programmed death ligand 1 (PD-L1) expression was evaluated by the Dako PD-L1 immunohistochemistry 22C3 pharmDx assay. The co-primary endpoints were the molecular diagnostic yield and the safety profile of US-guided lung biopsies. From January 2021 to May 2024, 100 US-guided lung biopsies were carried out and 95 were considered for inclusion in the study. US-PLLB provided informative tissue for a histological evaluation in 93 of 95 patients with an overall diagnostic accuracy of 96.84% [Sensitivity: 92.63%; Specificity: 96.84%; PPV: 100%; NPV: 100%]. Sixty-Six patients were diagnosed with NSCLC (69.47%) and were considered for molecular diagnostic yield evaluation and PD-L1 testing. Four patients had malignant lymphoid lesions. US-PLLB was not adequate to achieve a final diagnosis in three patients (3.16%). Complete molecular profiling and PD-L1 evaluation were achieved in all patients with adenocarcinoma (molecular diagnostic yield: 100%). PD-L1 evaluation was achieved in 28 of 29 patients (96.55%) with either SCC or NOS lung cancer. The overall complication rate was 9.47% (n = 9). Six patients (6.31%) developed pneumothorax, while three patients (3.16%) suffered mild haemoptysis without desaturation. According to our findings, US-guided lung biopsy is a safe, minimally invasive procedure in patients with suspected lung malignancies, providing an excellent diagnostic yield for both comprehensive molecular profiling and PD-L1 testing. In addition, our results suggest that US-guided biopsy may also be an effective diagnostic approach in patients with suspected lung lymphoma.

Cardiac sarcoidosis and neurosarcoidosis - multidisciplinary approach for diagnosis.

The current review aims to highlight the role of multidisciplinary approach in the diagnosis of patients with cardiac and neurosarcoidosis. Multidisciplinary approach integrates the available clinical information, imaging and histopathological results aiming to reach a definite or at least provisional diagnosis and allow appropriate management. Multidisciplinary approach is the reference standard for diagnosis of interstitial lung disease and should be strongly considered in complex clinical conditions such as cardiac sarcoidosis (CS) and neurosarcoidosis. Histopathological confirmation of noncaseating granulomatous inflammation provides a definite diagnosis of sarcoidosis involving any organ. However, a provisional high confidence or even definite clinical diagnosis can be reached using multidisciplinary evaluation of all available evidence. The diagnosis of cardiac sarcoidosis and neurosarcoidosis requires the integration of different expertise based on the current diagnostic criteria sets. Identifying typical or at least compatible patterns on advanced imaging modalities (CMR and Fluro-Deoxy-Glucose Positron Emission Tomography (FDG-PET)) seems key for the diagnosis of CS, while a confident diagnosis of extra-cardiac disease supports an at least provisional diagnosis. Similarly, in neurosarcoidosis integrating compatible MRI appearances and cerebrospinal fluid results in patients with systemic sarcoidosis allows an at least provisional diagnosis. Exclusion of alternative differential diagnoses is crucial and requires high clinical suspicion, imaging review expertise and appropriate tests performance. There have been considerable advances in the diagnostic approach of patients with cardiac and neurosarcoidosis. Multidisciplinary approach for both diagnosis and management is required to reach a confident clinical diagnosis and should be applied when possible.

Outcome in pediatric celiac disease is independent of the diagnostic approach in patients with high antibody levels.

European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines enable the diagnosis of celiac disease (CD) without biopsies in patients with immunoglobulin A (IgA)-antibodies against tissue transglutaminase (TGA-IgA) ≥ 10× the upper limit of normal (ULN) and positivity of endomysial antibodies in a second blood sample. Limited data exist comparing the biopsy versus the nonbiopsy diagnostic approach regarding long-term outcomes in CD patients. Our study aimed to investigate the influence of the diagnostic approach on adherence to gluten-free diet (GFD), serological remission (defined as normalization of TGA-IgA during follow-up (FU)) and clinical remission in CD patients with TGA-IgA ≥ 10× ULN. Retrospective multicenter study. Patients with CD and TGA-IgA ≥ 10× ULN at diagnosis were included in the study. Patients with confirmed diagnosis by biopsy were compared to patients diagnosed by nonbiopsy approach using univariate analysis, Kaplan-Meier survival curve, and logistic regression models. A total of 282 CD patients (192 [68.1%] in the biopsy group; 90 [31.9%] in the nonbiopsy group) were analyzed. The median time to normalization of TGA-IgA was 16.5 months [interquartile range, IQR: 13, 28] in the biopsy and 15 months [IQR: 12, 26] in the nonbiopsy group; p = 0.14). Rates of normalized TGA-IgA at first to third-year FU were comparable between both groups. Adherence to GFD did not seem to be influenced by the diagnostic approach. The nonbiopsy approach is not inferior to the biopsy approach in terms of adherence to GFD and serological remission in patients with CD.

Enfoque diagnóstico en el paciente con derrame pleural

The diagnostic approach in patients with pleural effusion requires considering clinical aspects, fluid analysis, and, often, pleural biopsy. Currently, several procedures con be performed at the same time to speed up the diagnostic process, ideally in an outpatient setting. This article aims to describe the state of the art with regards to the diagnostic process.

Bedside clinical assessment of patients with common upper limb tremor and algorithmic approach.

The diagnostic approach for patients with tremor is challenging due to the complex and overlapping phenotypes among tremor syndromes. The first step in the evaluation of tremor is to identify the tremulous movement and exclude the tremor mimics. The second step is to classify the tremor syndrome based on the characteristics of tremor from historical clues and focused examination (Axis 1). Comprehensive tremor examinations involve the assessment of tremor in different conditions (rest, action or mixed, position or task-specific), distribution of tremor (upper limb, lower limb, head, jaw), positive signs for functional tremor (FT) if suspected (distractibility, entrainment, co-contraction), and associated neurological signs including parkinsonism, dystonic posture, cerebellar/brainstem signs, neuropathy, and cognitive impairment. A pivotal feature in this step is to determine any distinct feature of a specific isolated or combined tremor syndrome. In this review, we propose an algorithm to assess upper limb tremors. Ancillary testing should be performed if clinical evaluation is unclear. The choice of investigation depends on the types of tremors considered to narrow down the spectrum of etiology (Axis 2). Laboratory blood tests are considered for acute onset and acute worsening of tremors, while structural neuroimaging is indicated in unilateral tremors with acute onset, nonclassical presentations, and a combination of neurological symptoms. Neurophysiological study is an important tool that aids in distinguishing between tremor and myoclonus, etiology of tremor and document specific signs of FT. Treatment is mainly symptomatic based depending on the etiology of the tremor and the patient's disabilities.

Double Synchronous Primary Tumors: Metastatic Melanoma and Advanced Pulmonary Adenocarcinoma in a 32-Year-Old Adult: Case Report and Literature Review

Introduction: The presence of multiple primary malignant neoplasms is an unusual finding during the diagnostic approach of patients with cancer. The coexistence of melanoma with lung adenocarcinoma is extremely rare according to some cohort studies since a prevalence of 0.05% is estimated in this group of patients. The most relevant risk factors for the development of multiple malignant tumors are genetic, environmental exposures to carcinogenic substances, and treatment of a preexistent cancer. Case description: Male, 32 years old who denies family history of malignant neoplasms, drug addiction, chronic degenerative diseases, allergies, surgeries, and hospitalizations. His main symptom was a progressive weakness of the right upper and lower limb which, over a period of days, made it impossible to walk. During his hospitalization, MRI revealed metastatic lesions associated with vasogenic edema. For this reason, an evaluation was requested by the neurosurgery service, who performed a decompressive craniectomy with a biopsy that reported malignant cells consistent with metastatic melanoma. As part of the diagnostic approach, a thoracoabdominal CT with IV contrast was performed, which revealed another tumor at the lung level in the left lower lobe that obliterates the bronchus, not suggestive of metastatic activity, for this reason a lung biopsy was performed, which reported findings of poorly differentiated adenocarcinoma with angiolymphatic invasion present and extensive necrosis. The patient was discharged home with the palliative care measures due to the poor prognosis of both stage IV cancers reported synchronously. Conclusion: The coexistence of 2 primary different cancers in the same patient is an unusual phenomenon which represents a challenge for the multidisciplinary team that treats the patient. Likewise, the coexistence between melanoma and lung adenocarcinoma is exceptionally reported in the literature, which in advanced phases confers a poor prognosis and few therapeutic options.

Diffuse C-Cells Hyperplasia Is the Source of False Positive Calcitonin Measurement in FNA Washout Fluids of Thyroid Nodules: A Rational Clinical Approach to Avoiding Unnecessary Surgery.

The FNA-CT is useful for the diagnosis of MTC. The aim of this study was to evaluate the performance of FNA-CT in TNs coexisting with CCH. This study retrospectively reviewed the records of 11 patients with TNs submitted to thyroidectomy on the basis of elevated basal and/or stimulated serum CT values, which at histology were not confirmed to be MTC. The results obtained in this group were compared with those of a previously reported group of histologically proven MTC patients submitted to an identical presurgical evaluation. All patients, negative for known mutations in the RET proto-oncogene, were preoperatively submitted to neck ultrasound, FNA-cytology, and FNA-CT. Approximately 6 of 11 patients showed increased (>36 ng/mL, as established in previous studies not involving patients with CCH) FNA-CT. All these patients showed diffuse CCH at histology in the thyroid lobe submitted to FNA; 5 of them were benign at histology, while only one was malignant (papillary thyroid carcinoma, PTC). The remaining 5 of 11 patients had low FNA-CT (<36 ng/mL), and all of them showed only focal CCH in the lobe submitted to FNA; three of them were malignant (2 PTC, 1 follicular carcinoma), while two were benign. Employing the currently proposed cut-off values, false-positive FNA-CT results may be observed in benign/malignant TNs with coexisting diffuse CCH. FNA-CT must therefore be cautiously used in the diagnostic approach for patients with TNs and a slightly increased basal or stimulated serum CT concentration in order to avoid unnecessary surgery.

Recent guidelines for diagnostic and therapeutic management of accidentally detected adrenal tumours (incidentaloma) in adults.

At the end of 2023, the European Journal of Endocrinology published the latest guidelines of the European Society of Endocrinology (ESE) on the management of accidentally detected adrenal tumours (incidentalomas) in adults. Comparing them with the previous version of the ESE recommendations from 2016, a tendency towards far-reaching individualisation of the therapeutic and diagnostic approach in patients with adrenal incidentaloma can be seen - it is reflected by changes in the initial assessment of the malignancy of the lesion, in the scope of the proposed hormonal assessment, and qualification for surgery. The latest version of the guidelines includes 9 completely new recommendations, and 5 more recommendations have been significantly changed. Among the most important changes, the introduction of the term "mild autonomous cortisol secretion" (MACS) instead of the previously used term "autonomous cortisol secretion (ACS)" along with more precise recommendations regarding its management should be emphasised. An important novelty is also the modification of the criteria for benign adrenal adenoma, which does not require further imaging observation - due to the results of recent clinical studies, the authors have removed the criteria of size below 4 cm from the definition. Among others, the guidelines also encourage more proactive surgical treatment of indeterminate adrenal incidentaloma in people < 40 years of age and pregnant women. The authors of the recommendations repeatedly accentuate the importance of a multidisciplinary approach in making decisions regarding further management of patients with an unspecified adrenal tumour. Despite a few significant differences compared to the previous version of guidelines, the authors emphasise the presence of gaps in the current scientific evidence, which would not allow for the formulation of more unambiguous recommendations. The need to optimise ordered diagnostic tests, which generate additional socio-economic burdens without negative impact on patients' health, is also an important aspect of the latest guidelines.

Evaluation of point-of-care ultrasound use in the diagnostic approach for right upper quadrant abdominal pain management in the emergency department: a prospective study.

Point-of-care ultrasound (PoCUS) is commonly used at the bedside in the emergency department (ED) as part of clinical examinations. Studies frequently investigate PoCUS diagnostic accuracy, although its contribution to the overall diagnostic approach is less often evaluated. The primary objective of this prospective, multicenter, cohort study was to assess the contribution of PoCUS to the overall diagnostic approach of patients with right upper quadrant abdominal pain. Two independent members of an adjudication committee, who were blind to the intervention, independently evaluated the diagnostic approaches before and after PoCUS for the same patient. The study included 62 patients admitted to the ED with non-traumatic right upper quadrant abdominal pain from September 1, 2022, to March 6, 2023. The contribution of PoCUS to the diagnostic approach was evaluated using a proportion test assuming that 75% of diagnostic approaches would be better or comparable with PoCUS. Wilcoxon signed-rank tests evaluated the impact of PoCUS on the mean number of differential diagnoses, planned treatments, and complementary diagnostic tests. Overall, 60 (97%) diagnostic approaches were comparable or better with PoCUS (χ2 = 15.9, p < 0.01). With PoCUS, the mean number of differential diagnoses significantly decreased by 2.3 (95% CI -2.7 to -1.5) (p < 0.01), proposed treatments by 1.3 (95% CI -1.8 to -0.9) (p < 0.01), and complementary diagnostic tests by 1.3 (95% CI -1.7 to -1.0) (p < 0.01). These findings show that PoCUS positively impacts the diagnostic approach and significantly decreases the mean number of differential diagnoses, treatments, and complementary tests.

ERS International Congress 2023: highlights from the Sleep Disordered Breathing Assembly.

The topic of sleep-related breathing disorders is always evolving, and during the European Respiratory Society (ERS) International Congress 2023 in Milan, Italy, the latest research and clinical topics in respiratory medicine were presented. The most interesting issues included new diagnostic tools, such as cardiovascular parameters and artificial intelligence, pathophysiological traits of sleep disordered breathing from routine polysomnography or polygraphy signals, and new biomarkers and the diagnostic approach in patients with excessive daytime sleepiness. This article summarises the most relevant studies and topics presented at the ERS International Congress 2023. Each section has been written by early career members of ERS Assembly 4.

Prediction of genetic cardiomyopathy by whole exome sequencing and myocardial strain in patients with concentric left ventricle hypertrophy

Abstract Introduction Genetic cardiomyopathies (CMP) are a group of inherited diseases that can lead to heart failure and sudden cardiac death. Left ventricular hypertrophy (LVH) is common findings in these diseases, but the diagnosis can be challenging due to their heterogeneous clinical presentations. Myocardial strain and whole exome sequencing (WES) are a powerful tool for early detection of genetic CMP. Purpose We aim to investigate the utility of the combination of myocardial strain and WES in the diagnosis of genetic CMP in patients with LVH. Methods We performed WES with buccal swab test on a total of 65 patients who had concentric LVH and decreased global average strain (GAS) by echocardiography between July 2021 and December 2022. The genetic data was analyzed to identify disease-causing genetic variants, and the clinical data and echocardiographic findings were collected and analyzed. Logistic regression analysis was performed to identify the predictive factors of genetic cardiomyopathy, and receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy of these factors. Results Of the 65 patients, we identified 10 patients with genetic cardiomyopathy by WES, including hypertrophic CMP, cardiac amyloidosis, and Fabry disease. The diagnostic yield of WES was 15.4% for genetic CMP. Logistic regression analysis showed that sex, diastolic blood pressure, interventricular septal thickness at end diastole (IVSd) and end systole (IVSs), posterior wall thickness at end diastole (PWd), and GAS were significant predictors of genetic CMP (p&amp;lt;0.05 for all). ROC curve analysis showed that IVSs had the highest area under the curve (AUC) value of 0.711 (p=0.037), with a sensitivity of 60.0% and a specificity of 67.3%. Conclusion Our study highlights the utility of WES and myocardial strain with echocardiographic data in diagnosing genetic CMP, especially in patients with concentric LVH. These findings support the integration of genetic testing and advanced imaging techniques in the diagnostic approach for patients with suspected genetic cardiomyopathies.

Identifying patients with primary immunodeficiency using statistical modelling of unique genetic signatures from transcriptomic data

Primary immunodeficiencies (PID) are a group of rare disorders, most typically characterised by frequent and/or severe infections that are often caused by a genetic mutation. Early diagnosis is critical for patients as diagnostic delay is associated with increased morbidity and mortality. This study evaluated a novel diagnostic test for primary antibody deficiency, using whole blood from patients diagnosed with predominantly antibody deficiency (n = 15) as well as age-matched healthy donors (n = 18). PID patients comprised both adults (22–65 years, n = 18) and children (ages 6–18, n = 15), with 40% male (n = 13), 59% female (n = 19), and 1% gender not specified (n = 1). Inclusion criteria for patients were as follows: a) had an antibody deficiency b) an underlying in-born error of immunity and c) were under immunoglobulin replacement therapy.We used RNA-seq to characterise the transcriptome of each participant. We identified >2000 genes which were significantly differentially expressed between PID patients and healthy controls, with a p-value < 0.05. We used these signatures to train and test models to differentiate patients with PID from the healthy population. Additionally, in our blinded analysis, we identified the most variable genes in this cohort that were distinct from the differentially expressed genes and also evaluated their predictive utility. Using groups of differentially expressed genes and most variable genes in varying quantities, we generated multiple predictive models with an AUC > 0.9 for detection of primary immunodeficiency using leave-out-one cross validation.Our predictive algorithm using a transcriptomic signature, which we refer to as PrimDx, can help to identify patients with PID. This has the potential to accelerate time to diagnosis and initiation of treatment, thereby leading to better patient health outcomes. Future studies will verify this predictive algorithm in larger patient samples, and expand the application of this diagnostic approach in patients with other immunodeficiency conditions. [Display omitted]

The Potential of Liquid Biopsy in Detection of Endometrial Cancer Biomarkers: A Pilot Study.

Endometrial cancer belongs to the most common gynecologic cancer types globally, with increasing incidence. There are numerous ways of classifying different cases. The most recent decade has brought advances in molecular classification, which show more accurate prognostic factors and the possibility of personalised adjuvant treatment. In addition, diagnostic approaches lag behind these advances, with methods causing patients discomfort while lacking the reproducibility of tissue sampling for biopsy. Minimally invasive liquid biopsies could therefore represent an alternative screening and diagnostic approach in patients with endometrial cancer. The method could potentially detect molecular changes in this cancer type and identify patients at early stages. In this pilot study, we tested such a detection method based on circulating tumour DNA isolated from the peripheral blood plasma of 21 Slovak endometrial cancer patients. We successfully detected oncomutations in the circulating DNA of every single patient, although the prognostic value of the detected mutations failed to offer certainty. Furthermore, we detected changes associated with clonal hematopoiesis, including DNMT3A mutations, which were present in the majority of circulating tumour DNA samples.

Abstract 3814: In CLL the U1 snRNA driver mutation alters splicing in multiple genes and pathways

Abstract 5-10% of patients with the IGHV wild type form of chronic lymphocytic leukemia (CLL) carry a g.3A&amp;gt;C driver mutation in the U1 small nuclear RNA (snRNA). We investigatedthe patterns of mis-splicing and their pathway consequences in three U1-mutant CLL cellline models using long read sequencing in order to better understand the mechanisms ofoncogenicity in tumors carrying this mutation. CLL cell lines (HG3, JVM3 and MEC1) expressing the U1 mutation and their wild-type counterparts were submitted to Oxford Nanopore sequencing to generate full-length RNA transcripts. This transcriptomic datawas evaluated, together with previously obtained short-read data. The g.3A&amp;gt;C mutation occurs at a specific location of the U1 snRNA, a core component of the eukaryotic spliceosome, and acts by altering the 5' splice site (5'SS) recognition sequence to cause consistent patterns of mis-splicing. Long read analysis identified multiple instances of intron retention and suppression of exon skipping, and in silico translation of these mis-splicing events predicted stop-gain and other loss of function mutations in several expressed genes, as well as widespread changes in gene expression levels. We performed a pathway overrepresentation analysis of the altered gene expression patterns in the mutant cells using the Reactome knowledgebase and identified an enrichment in the processes of translation, non-sense mediated decay (NMD) and immune signaling, including interferon signaling. In particular, there was a marked down-regulation of genes related to ribosomal assembly and the translational machinery. A more comprehensiveanalysis of the U1 mutation phenotype in CLL may accelerate the development ofbetter therapeutic and diagnostic approaches in patients. Citation Format: Andrea Senff-Ribeiro, Fatemeh Almodaresi, Quang Trinh, Shimin Shuai, David Spaner, Xose S. Puente, Elias Campo, Lincoln D. Stein. In CLL the U1 snRNA driver mutation alters splicing in multiple genes and pathways. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3814.

A Review of Radiological Investigations in Cases of Acute Appendicitis in a Tertiary Care Hospital.

Acute appendicitis is the most common non-traumatic surgical emergency and early diagnosis and management are crucial to decrease morbidity and mortality. There is a variety of scoring systems and radiological investigations that have been used in the diagnosis of acute appendicitis. Hence, the aim of this study is to assess the diagnostic approach in patients with suspected appendicitis in a tertiary care hospital, focusing on the radiological burden. This is a cross-sectional study reviewing the electronic and manual medical records of all adult patients admitted with the diagnosis of acute appendicitis between January 2018 and December 2018 in Salmaniya Medical Complex, Manama, Bahrain. A review of the method of diagnosis (clinical, ultrasound, computed tomography, or others) was done, with a comparison to histopathological results in those that underwent surgical intervention to determine sensitivity and specificity. In the study period, 488 patients were admitted with acute appendicitis; out of these, 461 underwent surgical intervention. A total of 66 CT scans and 148 ultrasounds were conducted for these patients, out of which 57% of ultrasounds and 86% of CT scans accurately diagnosed acute appendicitis based on histopathological diagnosis, resulting in a sensitivity of 65% and 92%, respectively, and a specificity of 56% and 25%, respectively. The most accurate method of diagnosis of acute appendicitis (highest sensitivity) is CT scanning. However, a prospective study with a detailed assessment of complications of appendicitis is recommended.

Utility of diagnostic tests in vomiting dogs presented to an internal medicine emergency service.

Vomiting is a common sign in dogs presenting to emergency services. It can be self-limiting, a sign of a life-threatening extraintestinal, or intestinal disorder. Reasonable diagnostics should be performed to determine the underlying cause. This study aimed to assess the utility of diagnostic tests in vomiting dogs, and its correlation with patient history, and physical examination results. Additionally, parameters to differentiate uncomplicated vomiting from complicated vomiting were investigated. In this prospective, observational, clinical study, data from 99 client-owned dogs with vomiting, presenting as first opinion cases, were evaluated. History, physical examination, duration of clinical signs, overall number of episodes of vomiting, appetite, and additional clinical signs were recorded. The standardized diagnostic evaluation of all patients included venous blood gas analysis, complete blood count, serum biochemistry profile, canine pancreatic lipase, abdominal radiographs, ultrasound, and urinalysis. Follow-up was performed 4-5 days later. Based on severity of disease and clinical course, dogs were categorized to "uncomplicated vomiting" (UN), or "complicated vomiting" (COM). The utility of each test for diagnosing the cause of vomiting was evaluated. Spearman correlation coefficient, Chi-squared-, unpaired t-, and Mann-Whitney U-test were used. Statistical significance was defined as p ≤ 0.05. Out of the 99 dogs, 34 had uncomplicated courses of disease (UN). In 60/99 cases, a diagnosis was obtained, and in 39/99 cases, the cause for vomiting remained unknown. Longer duration of clinical signs, and reduced appetite were associated with higher utility of abdominal ultrasound. A poor mentation was associated with a higher utility of blood examinations and abdominal radiographs. Dogs presenting with an impaired mentation or with additional clinical signs other than diarrhea, were more likely to be in the COM group. Based on this investigation, general recommendations concerning the diagnostic approach for patients with vomiting could not be provided. For dogs who have exclusively vomiting as a clinical sign, and present in good mentation, further investigations might not be beneficial, and these dogs may recover with symptomatic treatment alone. Additional diagnostics could be indicated in dogs with additional clinical signs other than diarrhea.

Eosinophilia and elevated IgE serum levels: a red flag: when your diagnosis is not a common atopic eczema or common allergy.

The hallmark of type 2 inflammation is eosinophilia and/or high IgE serum levels, mostly in atopic dermatitis. Nevertheless, many dermatoses may present similar findings. Our aim is to explore the biological and clinical spectrum of cutaneous manifestations involving tissue and/or systemic eosinophilia, and distinct serum levels of IgE, where atopic dermatitis or other primary allergic eczema, not always is the definitive diagnosis. A total of 37 scientific papers were enrolled in this narrative review. A diagnostic approach for patients with elevated serum IgE level and a list of conditions not related to atopic dermatitis that runs through inborn errors of immunity, inflammatory disorders, lung disorders, malignancy, infections/infestations are displayed. Regarding to peripheral eosinophilia, differential diagnosis is also explored and clinical patterns of skin diseases associated with tissue eosinophilia are listed, to facilitate our diagnosis. We should maintain a high level of suspicion about other differential diagnosis involving eosinophilia and IgE dysregulation, especially in patients very young (when innate errors of the immunity may present) and in middle to elderly patients classified as having atopic dermatitis, due to the possibility of cutaneous hematological malignancies, paraneoplasia or autoimmune blistering diseases.

Clinical Diagnosis of Pleuroparenchymal Fibroelastosis

Pleuroparenchymal fibroelastosis (PPFE) is an extremely rare interstitial lung disease (ILD) characterised by fibroelastotic changes predominating in the subpleural lung parenchyma with visceral pleural fibrosis involving the upper lobes. It has distinctive clinical, radiological, and pathological manifestations. Diagnosis constitutes literally a stalemate because of its rarity, unavailability of an agreed diagnostic consensus, and requirement of tissue biopsy for an accurate final diagnosis that can not be performed in most of the patients owing to the comorbid complications of the disease itself. Identification of PPFE may also pose great difficulties due to the coexistence of other interstitial lung diseases. PPFE usually exhibits a persistently deteriorating prognostic course culminating in fatal complications including respiratory failure, pulmonary hypertension, cor pulmonale, or pneumothorax. Presence of disease relevant complications frequently preclude invasive tissue biopsy interventions in these patients leading to a diagnostic challenge for clinicians. This review aims to provide a definitive diagnosis based on entirely the clinical manifestatins of PPFE by shedding light on the pathogenesis, clinical, and radiologic findings of the disease. Histopathological tissue evaluation was also included in the diagnostic approach for patients whose condition was suitable for an invasive biopsy intervention. With this review, it is concluded that an approach consisting of exclusively clinical manifestations will ensure adequate support for an accurate PPFE diagnosis without any requirement for histopathological tissue examination.

Editors' Note: Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis.

Investigators at the Mitochondrial Disease Clinic at Royal North Shore Hospital (Sydney, Australia) prospectively recruited 242 patients who satisfied the Nijmegen criteria for possible, probable, or definite mitochondrial disease (MD). The investigators tested the variant detection rate for a variety of mitochondrial disorders using whole-genome sequencing (WGS) of peripheral blood. Disease-causing variants were found in 53.7% of tested individuals. With more widespread availability and the decreasing cost of WGS, it may become more frequently used as a first-line diagnostic approach in patients with suspected MD. Dr. Schon acknowledged one rare MD, alpha-methylacyl-CoA racemase deficiency, which has been reported in slightly more than a dozen cases to date. Although it may be rare, Dr. Schon maintains that the condition is likely underdiagnosed. The authors agreed and emphasized that dietary restriction of pristanic acid may lessen the risk of severe neurologic disease and manifestations such as seizures and stroke-like episodes. The growing use of technologies such as WGS may facilitate earlier identification and effective treatment of patients with this and other MDs, especially with enriched populations. Investigators at the Mitochondrial Disease Clinic at Royal North Shore Hospital (Sydney, Australia) prospectively recruited 242 patients who satisfied the Nijmegen criteria for possible, probable, or definite mitochondrial disease (MD). The investigators tested the variant detection rate for a variety of mitochondrial disorders using whole-genome sequencing (WGS) of peripheral blood. Disease-causing variants were found in 53.7% of tested individuals. With more widespread availability and the decreasing cost of WGS, it may become more frequently used as a first-line diagnostic approach in patients with suspected MD. Dr. Schon acknowledged one rare MD, alpha-methylacyl-CoA racemase deficiency, which has been reported in slightly more than a dozen cases to date. Although it may be rare, Dr. Schon maintains that the condition is likely underdiagnosed. The authors agreed and emphasized that dietary restriction of pristanic acid may lessen the risk of severe neurologic disease and manifestations such as seizures and stroke-like episodes. The growing use of technologies such as WGS may facilitate earlier identification and effective treatment of patients with this and other MDs, especially with enriched populations.