Diagnostic Work-up Research Articles

Epiglottis calcification: forgotten cause of dysphagia in elderly population

BackgroundDysphagia is a relatively common clinical issue in elderly population with numerous causes, which are divided into oropharyngeal and substernal categories. Most of the causes of dysphagia can be diagnosed easily with clinical and radiological examinations. However, we encountered a rare cause of dysphagia in an elderly patient, which can be missed easily during diagnostic workup, that entity is epiglottis calcification.Case presentationA 91-year-old male presented with complaints of recurrent aspirations and difficulty in swallowing. Physical examination revealed no abnormalities in the oral cavity, pharynx and nose. Flexible fiberoptic laryngoscopic examination was performed, which mildly swollen and posteriorly moved epiglottis with limited mobility during swallowing. Computed tomography scan of the larynx revealed significant asymmetric amorphous calcification of the free edge of the aryepiglottic, pharyngoepiglottic, and epiglottis folds.ConclusionsAlthough dysphagia is a common problem in elderly, it has serious complications such as recurrent aspirations, pneumonia and nutritional deficiency. One of the rare causes of dysphagia in elderly is epiglottic calcifications, which impairs its flexibility and the functionality, and may predispose to difficulty in swallowing and recurrent aspirations.

Evaluation of a multimodal diagnostic algorithm for prediction of cognitive impairment in elderly patients with dizziness.

The current diagnostic workup for chronic dizziness in elderly patients often neglects neuropsychological assessment, thus missing a relevant proportion of patients, who perceive dizziness as a subjective chief complaint of a concomitant cognitive impairment. This study aimed to establish risk prediction models for cognitive impairment in chronic dizzy patients based on data sources routinely collected in a dizziness center. One hundred patients (age: 74.7 7.1years, 41.0% women) with chronic dizziness were prospectively characterized by (1) neuro-otological testing, (2) quantitative gait assessment, (3) graduation of focal brain atrophy and white matter lesion load, and (4) cognitive screening (MoCA). A linear regression model was trained to predict patients' total MoCA score based on 16 clinical features derived from demographics, vestibular testing, gait analysis, and imaging scales. Additionally, we trained a binary logistic regression model on the same data sources to identify those patients with a cognitive impairment (i.e., MoCA < 25). The linear regression model explained almost half of the variance of patients' total MoCA score (R2 = 0.49; mean absolute error: 1.7). The most important risk-predictors of cognitive impairment were age (β = -0.75), pathological Romberg's sign (β = -1.05), normal caloric test results (β = -0.8), slower timed-up-and-go test (β = -0.67), frontal (β = -0.6) and temporal (β = -0.54) brain atrophy. The binary classification yielded an area under the curve of 0.84 (95% CI 0.70-0.98) in distinguishing between cognitively normal and impaired patients. The need for cognitive testing in patients with chronic dizziness can be efficiently approximated by available data sources from routine diagnostic workup in a dizziness center.

Abstract PO2-28-12: Rapid diagnosis of breast biopsies with open-top light-sheet microscopy

Abstract Introduction: Breast cancer is typically diagnosed through a diagnostic work-up that involves specialized breast imaging, image-guided biopsy, and pathological assessment. Pathology results require 2 to 7 business days before a diagnosis is rendered, creating anxiety in women presenting with a breast abnormality. Decreasing pathology evaluation lead-time has the potential to reduce anxiety, streamline patient care, and reduce heathcare costs. In this pilot study, we evaluated the potential of open-top light-sheet microscopy to deliver a preliminary breast pathology diagnosis within 30 minutes of biopsy. Methods: Fresh 14-gauge breast biopsies (N=40) in normal saline were received directly from the breast imaging clinic and immediately stained using the nuclear marker SYBR Gold (Invitrogen) and pan-protein marker Atto 655 NHS Ester (Sigma) prepared in dimethyl sulfoxide, washed, and cleared for imaging at a refractive index of 1.46 using 2,2’-Thiodiethanol (Sigma). The full process requires approximately 14 minutes for staining and clearing. After staining, we placed the biopsy in an in-house-built specimen holder and imaged a 100 micron cross section along the full length of the biopsy using our custom open-top light-sheet microscope. Images were subsequently converted computationally to a standard H&amp;E color format using Fiji and Aivia (Leica) software and were ready for evaluation by a pathologist the same day they were collected. mages were assessed by two pathologists with subspecialization in breast pathology for a two-category diagnosis: benign or atypical. After imaging, the biopsy was frozen, a frozen section was cut, and an H&amp;E-stained slide was produced. Results: Using the protocol above, we demonstrated the ability to stain, clear, image, and visualize needle core biopsies within 30 minutes of receiving the tissue sample. Processing and converting the data to an H&amp;E color palette required additional time, surpassing the 30-minute turnaround time goal. The images contained readily identifiable stroma, epithelial cells, immune cells, and duct structures to a depth of 100 microns. 29/40 biopsies yielded interpretable results. 11/40 had insufficient staining, clearing, or imaging quality for diagnosis. The number of non-diagnostic images improved in the second half of the study (5%) compared to the first half of the study (50%) with sample prep and imaging optimization. Agreement between the two breast pathologists on classifying the biopsies as benign vs. atypical was 89.7%. Discussion: We describe a novel method to obtain a microscopic image of breast core biopsy specimens to facilitate preliminary diagnosis within 30 minutes of receipt of tissue. The quality of the images produced by the method shows promise for preliminary diagnosis, especially after protocol optimization for the second half of the study. Additional optimization is needed in data processing to meet the 30-minute turnaround time requirement. This optimization can be achieved by parallelization of the data processing on a cluster or cloud, which is currently under investigation by our team. Citation Format: Brandy Olin Pope, Rebeca Alvarez, Charles Childers, Suzanne Dintzis, Sarah Javid, Nicholas Reder, Habib Rahbar. Rapid diagnosis of breast biopsies with open-top light-sheet microscopy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-12.

Diagnostic challenges in patients with reninomas and extrarenal renin-producing tumours.

Renin-secreting tumours are rare causes of secondary hypertension and hypokalaemia. They are usually surgically curable, hence proper diagnostic work-up and tumour localisation is essential. In this paper, we present three Swedish patients recently diagnosed with renin secreting tumours, two with reninomas and one with an extrarenal renin-producing tumour, to illustrate diagnostic challenges. We also discuss the biochemical work-up, the pros and cons of different imaging techniques (computer tomography [CT], magnetic resonance imaging and [18F]fluorodeoxyglucose-positron emission tomography-CT), as well as how renal vein sampling (RVC) may contribute to localisation of the tumour.

Abstract PO4-25-10: Towards personalized medicine for DCIS - the role of hormone receptors, HER2, and Ki67 status in high-grade DCIS

Abstract Objective: This study aimed to investigate the molecular details in breast ductal carcinoma in situ (DCIS). Expression status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were investigated among luminal A (LumA), luminal B HER2-negative (LumB HER2-), luminal B HER2-positive (LumB HER2+), HER2-enriched, and triple-negative (TPN), subtypes of DCIS. Materials &amp; Methods: The study comprised formalin-fixed paraffin-embedded (FFPE) specimens of 357 DCIS grade 3 cases diagnosed between 1996 – 2018. Routine diagnostic immunohistochemical (IHC) staining were performed. DCIS cases were classified as LumA, LumB HER2-, LumB HER2+, HER2-enriched or TPN, according to the 2013 St. Gallen guidelines, which is used for molecular subtyping of invasive breast carcinoma (IBC). Each subtype was sorted into three subcategories: “pure” meaning those without an invasive component; “w/invasive” meaning those with an invasive component; and “all” meaning the entire group of the given subtype. Furthermore, ER and PR-receptor expression was registered for LumA, LumB HER2- and LumB HER2+ cases as intervals. The distribution of Ki67 was analyzed within each subtype. For some analyses, we combined the LumA and LumB HER2- subtypes into one entire group. The inter-observer variability of Ki67 was calculated by setting a cut-off value of 20% (2013 St. Gallen). A cohort (n = 47) of DCIS cases with a median Ki67 value of 18% was selected. Ki67 was calculated by analyzing 200 DCIS cells in two separate hotspots. Cohen's Kappa coefficient was calculated based on these data. HER2 (IHC) was scored based on ASCO/CAP guidelines established for routine diagnostic work-up for IBC. 16 equivocal cases (2+) were further investigated using dual SISH. Results: 98% of “all” cases of the LumA subtype showed an ER ≥ 50%. PR expression ≥ 50% was found in 91% of cases in this subtype. The incidence of ER-receptor at a cut-off ≥ 50% in the LumA subtype was significantly higher than that in the LumB HER2- and LumB HER2+ subtypes (p &amp;lt; 0.0001, Chi-square). In contrast, there was a statistically significant reduction in ER-receptor expression at a cut-off &amp;lt; 10% in LumA compared to the latter subtypes. The proportion of cases with PR-receptors with a cut-off of &amp;lt; 20% showed significant differences between LumA, LumB HER2- and LumB HER2+ subtypes (1.6%; 47% and 37%, respectively). There was also a significantly higher proportion of PR-receptor ≥ 50% cases among the LumA subtype. We found a significant association between PR &amp;lt; 20% and HER2 (3+) in luminal subtypes (p &amp;lt; 0.0004, Fisher's exact). There was no significant difference in ER/PR expression in “pure” cases of luminal subtypes of DCIS versus those with an invasive component (p = 0.1831, Chi-square). The Ki67 in the entire population (n = 357) varied from &amp;lt; 1% to &amp;gt; 80%. The mean and median were around 20% in those subtypes whose classifications were not depended on Ki67. There was a significant difference in the distribution of Ki67 when cases of LumA “all” and those of LumB HER2- “all” were combined as one entire group and were compared to LumB HER2+ “all” and HER2-enriched “all” (p-adjusted &amp;lt; 0.0001, Kruskal Wallis). The assessment of Ki67 among different observers showed a Cohen's kappa coefficient of 0.29 – 0.31 (fair agreement). We compared the HER2 (IHC) 0, 1+ and 2+ score among LumA and LumB HER2- subtypes and did not find a statically significant difference, when the “pure” and “w/invasive” were compared (p = 0.603, Chi-square). Conclusions: Ki67 was highly variable in DCIS grade 3. Inter-observer agreement was (as expected) suboptimal, and the cut-off at 20% defined by the 2013 St Gallen guidelines for IBC is not reliable for the distinction of LumA and LumB HER2 subtypes of DCIS. The LumB subtype of DCIS is heterogeneous with considerable variability among the four IHC markers used in the present study. A low PR is strongly associated with HER2 (3+), in luminal subtypes (p &amp;lt; 0.0004, Fisher's exact). Citation Format: Hossein Schandiz, Lorant Farkas, Daehoon Park, Solveig Norheim Andersen, Jürgen Geisler, Torill Sauer. Towards personalized medicine for DCIS - the role of hormone receptors, HER2, and Ki67 status in high-grade DCIS [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-10.

Accuracy of Repetitive Ocular Vestibular-Evoked Myogenic Potentials to Diagnose Myasthenia Gravis in Patients With Ptosis or Diplopia.

We developed repetitive ocular vestibular-evoked myogenic potentials (roVEMP) as an electrophysiologic test that allows us to elicit the characteristic decrement of extraocular muscles in patients with ocular myasthenia gravis (OMG). Case-control studies demonstrated that roVEMP reliably differentiates patients with OMG from healthy controls. We now aimed to evaluate the diagnostic accuracy of roVEMP for OMG diagnosis in patients with ptosis and/or diplopia. In this blinded prospective diagnostic accuracy trial, we compared roVEMP in 89 consecutive patients presenting with ptosis and/or diplopia suspicious of OMG with a multimodal diagnostic approach, including clinical examination, antibodies, edrophonium testing, repetitive nerve stimulation of accessory and facial nerves, and single-fiber EMG (SFEMG). We calculated the roVEMP decrement as the ratio between the mean of the first 2 responses compared with the mean of the sixth-ninth responses in the train and used cutoff of >9% (unilateral decrement) in a 30 Hz stimulation paradigm. Following a complete diagnostic work-up, 39 patients (44%) were diagnosed with ocular MG, while 50 patients (56%) had various other neuro-ophthalmologic conditions, but not MG (non-MG). roVEMP yielded 88.2% sensitivity, 30.2% specificity, 50% positive predictive value (PPV), and 76.5% negative predictive value (NPV). For comparison, SFEMG resulted in 75% sensitivity, 56% specificity, 55.1% PPV, and 75.7% NPV. All other diagnostic tests (except for the ice pack test) also yielded significantly higher positive results in patients with MG compared with non-MG. The study revealed a high sensitivity of 88.2% for roVEMP in OMG, but specificity and PPV were too low to allow for the OMG diagnosis as a single test. Thus, differentiating ocular MG from other neuro-ophthalmologic conditions remains challenging, and the highest diagnostic accuracy is still obtained by a multimodal approach. In this study, roVEMP can complement the diagnostic armamentarium for the diagnosis of MG. This study provides Class I evidence that in patients with diplopia and ptosis, roVEMP alone does not accurately distinguish MG from non-MG disorders. ClinicalTrials.gov: NCT03049956.

Ictal Cotard delusion as a manifestation of nonconvulsive status epilepticus: A case report and commentary.

Psychosis of epileptic origin can present a wide range of cognitive and affective symptoms and is often underrecognized. Usually occurring in the inter- and postictal phase, epileptic psychosis is mostly related to temporal lobe epilepsy. Here, we describe the clinical presentation and diagnostic workup including routine EEG recording and brain MRI of a 63-year-old woman expressing isolated nihilistic delusions comprising belief of being dead and denial of self-existence. EEG showed an ictal pattern fulfilling the Salzburg criteria of nonconvulsive status epilepticus and brain MRI revealed extensive peri-ictal hyperperfusion. Delusional symptoms and EEG abnormalities subsided after acute antiseizure treatment. Our case illustrates how nihilistic delusions can occur as a direct clinical correlate of seizure activity, thereby expanding the spectrum of ictal neuropsychiatric phenomena in temporal lobe epilepsy and highlighting the need to consider an epileptic origin in patients presenting with psychotic symptoms.

Herpes simplex (HSV1) encephalitis in an infant: a case report study

Introduction and importance: The herpes simplex virus (HSV) is the most common cause of acute sporadic encephalitis, a severe and often fatal disease in humans. It is associated with high mortality and morbidity rates in untreated patients. Case presentation: An 11-month-old child was admitted to the hospital presenting with acute fever and seizures characterized by staring episodes and spastic movements affecting the left side of the body. Diagnostic workup revealed abnormal T2 flair hyperintense foci in bi-temporoparietal lobes and right thalamus, and bilateral otomastoiditis were detected. A positive result for HSV-1 was obtained through HSV type 1/2 PCR testing, leading to a diagnosis of herpes encephalitis. Clinical discussion: While acyclovir has proven to be an effective therapeutic option, mortality and neurological sequelae continue to be reported in a notable fraction of patients. HSV encephalitis is mainly caused by two strains of the herpes simplex virus: HSV-1, more frequently observed in children and adults, and HSV-2, commonly seen in neonates and those with compromised immune systems. MRI scans often reveal that the brain lesions are localized to certain areas, although temporal involvement may not always be evident. The symptoms of herpetic encephalitis can greatly vary, making early diagnosis and treatment vital for improving patient outcomes. Conclusion: this case report highlights the clinical presentation, diagnostic challenges, and treatment strategies for HSV-1 encephalitis and underscores the importance of early recognition and prompt initiation of antiviral therapy in suspected cases of HSV-1 encephalitis.

Complex connective tissue convergence: A case report of scleroderma, systemic lupus erythematosus, and Sjögren's Syndrome overlap syndrome in an adolescent female

This case report illustrates the uncommon occurrence of an overlap syndrome involving systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Sjögren's syndrome in a 16-year-old female patient. Despite their distinct pathophysiological mechanisms and clinical manifestations, these connective tissue diseases converged in this patient, presenting a diagnostic challenge. The clinical presentation included features such as Raynaud's phenomenon, mouth and digit ulcers, alopecia, photosensitivity, and positive autoantibodies. Diagnostic workup revealed positive findings on antinuclear antibodies (ANA) and extractable nuclear antigen (ENA) panel, confirming the presence of autoantibodies associated with all three conditions. The patient was managed with a combination of symptomatic treatment, hydroxychloroquine, and prednisolone. This case underscores the complexity of overlapping autoimmune diseases and emphasizes the importance of a thorough clinical evaluation, appropriate diagnostic testing, and timely initiation of management to optimize patient outcomes.

Pulmonary diseases in patients with classical Hodgkin lymphoma relative to a matched background population: A Danish national cohort study.

Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin-containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population-based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age- and sex-matched comparators from the background population. Median follow-up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30-3.68]), with a 10-year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35-26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43-2.76]), with a 10-year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43-1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B-symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work-up of pulmonary symptoms.

Joubert syndrome presenting bilateral peroneal neuropathies: A case report.

Joubert syndrome (JS) is a rare genetic disorder that presents with various neurological symptoms, primarily involving central nervous system dysfunction. Considering the etiology of JS, peripheral nervous system abnormalities cannot be excluded; however, cases of JS accompanied by peripheral nervous system abnormalities have not yet been reported. Distinct radiological findings on brain magnetic resonance imaging were considered essential for the diagnosis of JS. However, recently, cases of JS with normal or nearly normal brain morphology have been reported. To date, there is no consensus on the most appropriate diagnostic method for JS when imaging-based diagnostic approach is challenging. This report describes the case of an adult patient who exhibited bilateral peroneal neuropathies and was finally diagnosed with JS through genetic testing. A 27-year-old man visited our outpatient clinic due to a gait disturbance that started at a very young age. The patient exhibited difficulty maintaining balance, especially when walking slowly. Oculomotor apraxia was observed on ophthalmic evaluation. During diagnostic workups, including brain imaging and direct DNA sequencing, no conclusive findings were detected. Only nerve conduction studies revealed profound bilateral peroneal neuropathies. We performed whole genome sequencing to obtain a proper diagnosis and identify the gene mutation responsible for JS. This case represents the first instance of peripheral nerve dysfunction in JS. Further research is needed to explore the association between JS and peripheral nervous system abnormalities. Detailed genetic testing may serve as a valuable tool for diagnosing JS when no prominent abnormalities are detected in brain imaging studies.

Parotid squamous cell carcinoma metastases: Application of human papillomavirus -DNA test on liquid-based cytology to recognize oropharyngeal origin of the neoplasm.

Malignancies of the parotid gland are relatively uncommon and in most cases are primary neoplasms; intraparotid metastases are rare. Oral and oropharyngeal squamous cell carcinoma (O- and OP-SCC) can potentially metastasize to the parotid gland or intraparotid lymph nodes. Fine-needle aspiration cytology (FNAC) serves as the initial diagnostic approach for this purpose. HPV status in FNAC specimens is relevant and can guide the diagnostic workup, indicating a potential oropharyngeal origin of the primary tumor. A small series of occult SCC metastases is presented below, in which HPV-DNA testing of FNAC specimens helped identify primary neoplasms located in the oropharynx. US-guided FNAC of parotid nodules was conducted by an experienced interventional cytopathologist in three cases. Each patient underwent assessment of direct smears, cell blocks, and liquid-based samples for HPV testing. The morphological and immunocytochemical features of SCC were documented, and real-time PCR was employed for the detection and genotyping of HPV. The role of HPV testing on FNAC specimens in pinpointing the primary neoplasms in the oropharynx is highlighted. Consequently, FNAC samples emerge as valuable diagnostic and prognostic tools in this context, providing essential insights for patient management.

The role of non-oropharyngeal biopsies in head and neck squamous cell carcinoma of unknown primary: A systematic review.

This systematic review aims to evaluate the role of biopsies in non-oropharyngeal subsites in patients with cervical metastasis from head and neck squamous cell carcinoma of unknown primary (HNSCCUP). This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles that encompassed non-oropharyngeal biopsies in HNSCCUP as part of the diagnostic work-up were selected and analysed. A comprehensive search strategy was used to search relevant literature in PubMed from inception to October 2021. Eleven articles out of 860 were included, comprising 990 patients. There are no randomised control trials comparing the outcomes of survival and or locoregional control between patients who have or have not undergone non-targeted biopsies of non-oropharyngeal sub-sites for HNSCCUP. Several retrospective studies which showed an extremely low yield from random biopsies (range of yield, 0%-9%) of non-oropharyngeal subsites. Even targeted biopsies showed a low yield (range of yield, 0.6%-16.6%) from non-oropharyngeal subsites. The primary site identified for Epstein-Barr virus (EBV) positive cervical lymph nodes with an unknown primary is mainly the nasopharynx (51.7%). Narrow band imaging (NBI) (sensitivity range, 64%-91%) helps in the detection of primaries to target biopsies in non-oropharyngeal subsites. On the basis of this systematic review, it is not appropriate to offer biopsies of clinically and radiologically normal upper aerodigestive tract mucosa at non-oropharyngeal sites. Offer nasopharyngeal biopsies when the cervical node sampling reveals EBV-positive metastasis. Where available, NBI should be used to help detect and target biopsies in non-oropharyngeal subsites.

Diagnosis, management and therapeutic options for eosinophilic esophagitis.

Eosinophilic esophagitis is a chronic and commonly evolving condition leading to relevant and potentially irreversible burden in terms of tissue damage and related functional impairment, thus significantly impacting on quality of life. The aim of the present review is to summarize the recent advances in terms of diagnostic work-up and pharmacological and nonpharmacological management of the disease, under the broader perspective of type 2 inflammation. Two major novelties have prompted an innovative approach to EoE. In terms of diagnosis, it has been proposed to dissect the disease heterogeneity in three endotypes, independent from tissue eosinophil number: EoEe1, characterized by normal appearing oesophagus; EoEe2, associated with type 2 inflammation and steroid-refractoriness; EoEe3, whose features include adult onset, a more fibro-stenotic aspect and loss of epithelial gene expression. Concerning treatment, two recently licensed drugs for EoE, oro-dispersible budesonide and dupilumab represent the first treatment options specifically developed for EoE and addressing EoE-related peculiar pathobiological features. In the era of precision medicine, managing EoE according to a phenotype-driven approach might be helpful in defining the best treatment options in the different disease forms or stages. In addition, exploring the coexistence or the previous occurrence of other type 2 conditions may suggest the opportunity to specifically target type 2 inflammation through biologic therapy. The complex EoE pathobiology combining inflammatory and functional features, both at organ and systemic level, requires a multidimensional approach relying on the strict integration of gastroenterologists and allergist-immunologists.

Emergency Surgical Treatment and Triage: Targeting Optimal Outcomes for Emergency Surgical Patients From Index Encounter Through Definitive Care.

Patients with emergency surgical conditions (ESCs) experience higher complication rates than those without emergency conditions. Our purpose was to improve time-based key performance indicators (KPIs) of care for ESC patients, including diagnostic workup, empiric stabilization, and referral to definitive care. A rapid response program (ESTAT) was developed to screen for and coordinate optimal, timely care for a spectrum of high-risk ESCs, from the patient's index clinical encounter up to definitive care. The Mann-Whitney test assessed whether any differences in KPIs were statistically significant (P < .05) before compared to after the implementation of ESTAT. 98 patients were identified: 44 in ESTAT group (70% age ≥55, 57% male); 54 in control group (57% age ≥55, 44% male). There were significant decreases from time of index clinical encounter to resuscitation (5min. vs 34min., P < .001), to diagnostic imaging (52min. vs 1hr. 19min., P = .004), and to definitive care (2hr. 17min. vs 3hr. 51min., P = .007) in the ESTAT group compared to the control group, respectively. Improving time-based KPIs for delivery of clinical services is a common goal of medical emergency response systems (MERS) in numerous specialties. Implementation of an ESTAT program provides a screening tool for at-risk patients and reduces time to stabilize, diagnose and triage to definitive surgical intervention. These time benefits may ultimately translate to reduced complication rates for ESC patients. ESTAT may also represent a patient onboarding mechanism for surgical specialty verification programs promoted by quality improvement committees of various professional societies.

Mutations in NSUN3, a Mitochondrial Methyl Transferase Gene, Cause Inherited Optic Neuropathy

Inherited optic neuropathies (IONs) are rare genetic diseases characterized by progressive visual loss due the atrophy of optic nerves. The standard diagnostic workup involving next-generation sequencing panels has a diagnostic yield of about forty percent. In the other 60% of the patients with a clinical diagnosis of ION, the underlying genetic variants remain unknown. In this case study, we describe a potentially new disease-associated gene, NSUN3, for IONs. The proband was a young woman with consanguineous parents. She presented with bilateral optic atrophy and nystagmus at the age of seven years. Genetic testing revealed the homozygous variant c.349_352dup p.(Ala118Glufs*45) in NSUN3, with a segregation in the family compatible with autosomal recessive inheritance. Additional functional analysis showed decreased NSUN3 mRNA levels, slightly diminished mitochondrial complex IV levels, and decreased cell respiration rates in patient fibroblasts compared to healthy controls. In conclusion, pathogenic variants in NSUN3 can cause optic neuropathy. Trio whole-exome sequencing should be considered as a diagnostic strategy in ION cases where standard diagnostic analysis does not reveal disease-causing variants.

[Paraneoplastic pemphigus with underlying Castleman's disease in a16-year-old girl].

Paraneoplastic pemphigus is arare, life-threatening autoimmune disease that is clinically characterized by mostly extensive and refractory mucosal erosions and polymorphous skin lesions. We report here on a16-year-old girl with isolated oral erosions, in whom mucosal pemphigoid was initially suspected and after treatment with prednisolone and dapsone marked improvement was achieved. However, afew months later the patient developed massive respiratory insufficiency as aresult of bronchiolitis obliterans, so that alung transplant was planned. As part of the preparatory diagnostic workup, unicentric, abdominally localized Castleman's disease was diagnosed, which ultimately led to the diagnosis of paraneoplastic pemphigus as evidenced by envoplakin autoantibodies. Tumor resection and subsequent lung transplantation achieved good results with sustained mucocutaneous remission.

Consideration of Hyoid Variability in the Diagnostic Workup of Fishbone Foreign Body Aspiration.

Fishbone foreign body (FFB) can lodge in the upper respiratory or gastrointestinal tracts and frequently cause discomfort. While FFBs are common, variations in the hyoid may present radiographically similarly. The authors present a case in which a 32-year-old woman presented with pain in the right neck with a globus sensation after eating fish. Examination, including flexible fiberoptic laryngoscopy, did not reveal a foreign body. Given the patients' persistent symptoms, a noncontrast computed tomography was performed, demonstrating a radiopaque body superior to the right lateral hyoid bone, consistent with FFB. Direct examination under anesthesia was performed, and no FFB was noted. A reassessment of the imaging suggested a likely aberrant hyoid bone. The authors report this case to remind clinicians that while rare, aberrant hyoid variants may mimic FFB. The authors also review the imaging findings of aberrant hyoid variants in this report, as recognition of hyoid variability can mitigate unnecessary intervention.

[The 1-cm lower calyx calculus: SWT, URS or Mini-PCNL? Guidelines vs. reality.]

Urinary stones of the upper urinary tract can be considered a widespread public health concern due to their high incidence and prevalence and their health policy-related and financial implications. A significant proportion of newly diagnosed kidney stones are lower-pole stones, i.e., stones affecting the lower calyx group of the renal pelvicalyceal system. These are often diagnosed by chance, i.e., as incidental findings during ultrasound or CT scans performed for other reasons, or as "secondary stones" detected during the diagnostic work-up of symptomatic urinary stones in other locations. Residual disintegrates after extracorporeal shock-wave lithotripsy (ESWL) or endoscopic stone therapy constitute a further, quantitatively significant group. These incidentally discovered lower-pole stones are often characterised by their small size and lack of symptoms. It stands to reason that some of these small, asymptomatic lower-pole stones do not always remain small and asymptomatic, and that treatment tends to become more complex with increasing size. There has been an astonishing lack of published studies with a high level of evidence over the last 20 years to provide a conclusive and reproducible answer to the question posed in this review. Small, asymptomatic stones can be monitored. Symptomatic and rapidly growing stones should be treated. There is a lack of valid risk factors allowing an identification of subgroups that should be treated prophylactically at the asymptomatic stage. In active therapy, a 10-to-20-year-old principle still holds true today: a high stone-free rate in one therapy session is offset by an increased complication rate, with increasing miniaturisation in endourology (retrograde and percutaneous) and increasingly effective laser disintegration shifting this basic principle more and more in favour of flexible URS and (mini, micro) PCNL. The range of indications for ESWL is undoubtedly becoming smaller, and this also applies to lower-pole stones. The results of an ongoing prospective randomised study comparing the different treatment modalities, albeit with recruitment difficulties, are still pending.

Diagnosing liposarcoma on (peri)-renal mass biopsy: A clinicopathological study of 30 cases.

Classification of renal neoplasms on small tissue biopsies is in increasing demand, and maintaining broad differential diagnostic considerations in this setting is necessary. When evaluating a renal or perirenal tumour biopsy with sarcomatoid morphology, together with sarcomatoid renal cell carcinoma and sarcomatoid urothelial carcinoma as top diagnostic considerations, it is vital to additionally consider the possibility of well-differentiated and de-differentiated liposarcoma. This study reports a series of 30 biopsy samples from sites in or around the kidney collected from four institutions in which the correct diagnosis was either well-differentiated or de-differentiated liposarcoma. The majority (26 of 30, 87%) of lesions were accurately diagnosed on biopsy sampling, all of which incorporated testing for MDM2 by immunohistochemistry (IHC), fluorescence in-situ hybridisation (FISH) or a combination of the two as part of the diagnostic work-up. Tumour expression of MDM2 by IHC without confirmatory FISH analysis was sometimes (30%) sufficient to reach a diagnosis, but demonstration of MDM2 amplification by FISH was ascertained in the majority (57%) of biopsy samples. A diagnosis of de-differentiated liposarcoma was not definitively established until resection in four (13%) patients, as no MDM2 testing was performed on the corresponding pre-operative biopsies. When a retroperitoneal tumour is not clinically suspected, histological consideration of a liposarcoma diagnosis may be overlooked. Implementation of ancillary immunohistochemical and cytogenetic testing can ultimately lead to a definitive diagnosis in this potentially misleading anatomical location.