Scale for time and space experience in anxiety (STEA): Phenomenology and its clinical relevance.

Anxiety is a pervasive emotional state where, phenomenologically, subjects often report changes in their experience of time and space. However, a systematic and quantified examination of time and space experience in terms of a self-report scale is still missing which eventually could also be used for clinical differential diagnosis. Based on historical phenomenological literature and patients' subjective reports, we here introduce, in a first step, the Scale for Time and Space Experience of Anxiety (STEA) in a smaller sample of 19 subjects with anxiety disorders and, in a second step, validate its shorter clinical version (cSTEA) in a larger sample of 48 anxiety subjects. The main findings are (i) high convergent and divergent validity of STEA with both Beck Anxiety Inventory (BAI) (r = 0.7325; p < 0.001) and Beck Depression Inventory (BDI) (r = 0.7749; p < 0.0001), as well as with spontaneous mind wandering (MWS) (r = 0.7343; p < 0.001) and deliberate mind wandering (MWD) (r = 0.1152; p > 0.05), (ii) statistical feature selection shows 8 key items for future clinical usage (cSTEA) focusing on the experience of temporal and spatial constriction, (iii) the effects of time and space experience (i.e., for both STEA and cSTEA scores) on the level of anxiety (BAI) are mediated by the degree of spontaneous mind wandering (MWS), (iv) cSTEA allows for differentiating high levels of anxiety from the severity of comorbid depressive symptoms, and (v) significant reduction in the cSTEA scores after a therapeutic intervention (breathing therapy). Together, our study introduces a novel fully quantified and highly valid self-report instrument, the STEA, for measuring time-space experiences in anxiety. Further we develop a shorter clinical version (cSTEA) which allows assessing time space experience in a valid, quick, and simple way for diagnosis, differential diagnosis, and therapeutic monitoring of anxiety.

Differential diagnosis of thyroid nodules by DCE-MRI based on compressed sensing volumetric interpolated breath-hold examination: A feasibility study.

OBJECTIVES: To explore the potential and performance of quantitative and semi-quantitative parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on compressed sensing volumetric interpolated breath-hold (CS-VIBE) examination in the differential diagnosis of thyroid nodules. MATERIALS AND METHODS: A total of 208 patients with 259 thyroid nodules scheduled for surgery operation were prospectively recruited. All participants underwent routine and DCE-MRI. DCE-MRI quantitative parameters [Ktrans, Kep, Ve], semi-quantitative parameters [wash-in, wash-out, time to peak (TTP), arrival time (AT), peak enhancement intensity (PEI), and initial area under curve in 60 s (iAUC)] and time-intensity curve (TIC) types were analyzed. Differential diagnostic performances were assessed using area under the receiver operating characteristic curve (AUC) and compared with the Delong test. RESULTS: Ktrans, Kep, Ve, wash-in, wash-out, PEI and iAUC were statistically significantly different between malignant and benign nodules (P < 0.001). Among these parameters, ROC analysis revealed that Ktrans showed the highest diagnostic performance in the differentiation of benign and malignant nodules, followed by wash-in. ROC analysis also revealed that Ktrans achieved the best diagnostic performance for distinguishing papillary thyroid carcinoma (PTC) from non-PTC, follicular adenoma (FA) from non-FA, nodular goiter (NG) from non-NG, with AUC values of 0.854, 0.895 and 0.609, respectively. Type III curve is frequently observed in benign thyroid nodules, accounting for 77.4% (82/106). While malignant nodules are more common in type II, accounting for 57.5% (88/153). CONCLUSION: Thyroid examination using CS-VIBE based DCE-MRI is a feasible, non-invasive method to identify benign and malignant thyroid nodules and pathological types.

A rare case of TFEB/6p21/VEGFA-amplified renal cell carcinoma diagnosed by whole-exome sequencing: clinicopathological and genetic feature report and literature review.

BACKGROUND: TFEB/6p21/VEGFA-amplified renal cell carcinoma (RCC) is rare and difficult to diagnose, with diverse histological patterns and immunohistochemical and poorly defined molecular genetic characteristics. CASE PRESENTATION: We report a case of a 63-year-old male admitted in 2017 with complex histomorphology, three morphological features of clear cell, eosinophilic and papillary RCC and resembling areas of glomerular and tubular formation. The immunophenotype also showed a mixture of CD10 and P504s. RCC with a high suspicion of collision tumors was indicated according to the 2014 WHO classification system; no precise diagnosis was possible. The patient was diagnosed at a different hospital with poorly differentiated lung squamous cell carcinoma one year after RCC surgery. We exploited molecular technology advances to retrospectively investigate the patient's molecular genetic alterations by whole-exome sequencing. The results revealed a 6p21 amplification in VEGFA and TFEB gene acquisition absent in other RCC subtypes. Clear cell, papillary, chromophobe, TFE3-translocation, eosinophilic solid and cystic RCC were excluded. Strong TFEB and Melan-A protein positivity prompted rediagnosis as TFEB/6p21/VEGFA-amplified RCC as per 2022 WHO classification. TMB-L (low tumor mutational load), CCND3 gene acquisition and MRE11A and ATM gene deletion mutations indicated sensitivity to PD-1/PD-L1 inhibitor combinations and the FDA-approved targeted agents Niraparib (Grade C), Olaparib (Grade C), Rucaparib (Grade C) and Talazoparib (Class C). GO (Gene Ontology) and KEGG enrichment analyses revealed major mutations and abnormal CNVs in genes involved in biological processes such as the TGF-ß, Hippo, E-cadherin, lysosomal biogenesis and autophagy signaling pathways, biofilm synthesis cell adhesion substance metabolism regulation and others. We compared TFEB/6p21/VEGFA-amplified with TFEB-translocated RCC; significant differences in disease onset age, histological patterns, pathological stages, clinical prognoses, and genetic characteristics were revealed. CONCLUSION: We clarified the patient's challenging diagnosis and discussed the clinicopathology, immunophenotype, differential diagnosis, and molecular genetic information regarding TFEB/6p21/VEGFA-amplified RCC via exome analysis and a literature review.

Killer Function of Circulating Neutrophils in Relation to Cytokines in Uterine Myoma and Endometrial Cancer.

The study presents the killer functions of circulating neutrophils: myeloperoxidase activity, the ability to generate ROS, phagocytic activity, receptor status, NETosis, as well as the level of cytokines IL-2, IL-4, IL-6, IL-17A, and IL-18, granulocyte CSF, monocyte chemotactic protein 1, and neutrophil elastase in the serum of patients with uterine myoma and endometrial cancer (FIGO stages I-III). The phagocytic ability of neutrophils in uterine myoma was influenced by serum levels of granulocyte CSF and IL-2 in 54% of the total variance. The degranulation ability of neutrophils in endometrial cancer was determined by circulating IL-18 in 50% of the total variance. In uterine myoma, 66% of the total variance in neutrophil myeloperoxidase activity was explained by a model dependent on blood levels of IL-17A, IL-6, and IL-4. The risk of endometrial cancer increases when elevated levels of monocyte chemotactic protein 1 in circulating neutrophils are associated with reduced ability to capture particles via extracellular traps (96% probability).

Neurological Conundrum: A Case of Cerebellar Hemispheric Enlargement and Atypical Symptoms.

Cerebellar hemispheric enlargement with atypical neurological symptoms poses diagnostic challenges in clinical practice. We present the case of a 57-year-old female with persistent headache, left facial paraesthesia, dysarthria, gait ataxia, and longstanding neck swelling. Imaging studies revealed enlargement of the left cerebellar hemisphere with associated mass effect and compression of adjacent structures. The underlying etiology remained uncertain despite extensive evaluation, including magnetic resonance imaging and angiography. Differential diagnoses included neoplastic, vascular, inflammatory, and metabolic etiologies, but none fully accounted for the clinical findings. Management strategies focused on symptomatic relief and close monitoring. This case underscores the complexity of diagnosing and managing patients with rare neurological manifestations and highlights the need for continued research and collaborative approaches in optimising patient care.

Massive Silent abdominal ganglioneuroma in the setting of non-Hodgkin lymphoma : A rare case report.

INTRODUCTION AND IMPORTANCE: Ganglioneuroma is a rare benign neuroblastic tumor originating from sympathetic ganglion cells in the peripheral nervous system. It is often incidentally discovered during imaging studies and primarily affects children and young adults. CASE PRESENTATION: We present a case report of a 21-year-old female diagnosed with non-Hodgkin lymphoma who had an abdominal mass incidentally detected during imaging, Initially mistaken for lymphoma in the setting of the primary diagnose. After the chemotherapy for the lymphoma, the mass did not response to the treatment, so the mass was surgically excised, and histopathological examination confirmed the diagnosis of ganglioneuroma. The patient responded well to treatment for lymphoma and remains in good condition without signs of recurrence. CLINICAL DISCUSSION: To the best of our knowledge, this is the first case that describes an association between an intraabdominal ganglioneuroma and non-Hodgkin's lymphoma. CONCLUSION: This case highlights the importance of considering ganglioneuroma as a differential diagnosis when evaluating abdominal masses in patients with lymphoma.

Musculoskeletal mimics of lumbosacral radiculopathy.

Electrodiagnostic evaluations are commonly requested for patients with suspected radiculopathy. Understanding lower extremity musculoskeletal conditions is essential for electrodiagnostic medicine specialists, as musculoskeletal disorders often mimic or coexist with radiculopathy. This review delineates radicular pain from other types originating from the lumbosacral spine and describes musculoskeletal conditions frequently mimicking radiculopathy, such as those that cause radiating pain and sensorimotor dysfunction. In clinical evaluation, a history of pain radiating along a specific dermatomal territory with associated sensory disturbance suggests radiculopathy. Physical examination findings consistent with radiculopathy include myotomal weakness, depressed or absent muscle stretch reflexes, focal atrophy along a discrete nerve root territory, and potentially positive dural tension maneuvers like the straight leg raise. However, electrodiagnostic medicine specialists must be knowledgeable of musculoskeletal mimics, which may manifest as incomplete radiation within or beyond a dermatomal territory, non-radiating pain, tenderness, and give-way weakness, in the context of a normal neurological examination. A systematic approach to musculoskeletal examination is vital, and this review focuses on high-yield physical examination maneuvers and diagnostic investigations to differentiate between musculoskeletal conditions and radiculopathy. This approach ensures accurate diagnoses, promotes resource stewardship, enhances patient satisfaction, and optimizes care delivery. Musculoskeletal conditions resembling L1 to S4 radiculopathy are reviewed, emphasizing their distinctive features in history, physical examination, and diagnostic investigation. Among the more than 30 musculoskeletal disorders reviewed are hip and knee osteoarthritis, lumbar facet syndrome, myofascial pain syndrome, greater trochanteric pain syndrome, and plantar fasciitis.

Cerebral 18F-FDG PET/CT Metabolism as Diagnostic Signature for Central Nervous System Toxicity After Immune Checkpoint Blockade Cancer Treatment.

Our aim was to investigate probable biomarkers specific to immune-related central nervous system toxicity (CNST) in cancer patients treated with immune checkpoint inhibitors (ICI) by analysis of 18F-FDG PET/CT images. Methods: Cancer patients receiving ICI treatment were enrolled in a multicenter observational study that analyzed regional metabolic changes before and during CNST onset from January 2020 to February 2022. In 1:1 propensity score-matched pairs, the regional SUVmean of each bilateral brain lobe of CNST patients (CNST+) was compared with that of patients who had central nervous system infections (CNSIs) and patients without CNST or CNSI (CNST-). In a validation cohort, patients were recruited from February 2022 to July 2023 and followed up for 24 wk after the start of ICI. Early changes in regional SUVmean at 5-6 wk after therapy initiation were evaluated for ability to predict later CNST onset. Results: Of 6,395 ICI-treated patients, 2,387 underwent prognostic 18F-FDG PET/CT and 125 of the scanned patients had CNST (median time from ICI treatment to onset, 9 wk; quartile range, 2-23 wk). Regional 18F-FDG PET/CT SUVmean changes were higher in CNST+ than in CNST- patients (117 patient pairs) but were lower than in CNSI patients (50 pairs). Differentiating analysis reached an area under the curve (AUC) of 0.83 (95% CI, 0.78-0.88) for CNST+ versus CNST- and of 0.80 (95% CI, 0.72-0.89) for CNST+ versus CNSI. Changes in SUVmean were also higher before CNST onset than for CNST- (60 pairs; AUC, 0.74; 95% CI, 0.66-0.83). In a validation cohort of 2,878 patients, preonset changes in SUVmean reached an AUC of 0.86 (95% CI, 0.79-0.94) in predicting later CNST incidence. Conclusion: Brain regional hypermetabolism could be detected during and before CNST clinical onset. CNST may be a distinct pathologic entity versus brain infections defined by 18F-FDG PET/CT brain scans. Regional SUV differences may be translated into early diagnostic tools based on moderate differentiating accuracy in our study.

Optical coherence tomography angiography suggests different retinal pathologies in multiple sclerosis and Sjögren's syndrome.

BACKGROUND: While retinal vessel changes are evident in the eyes of patients with relapsing-remitting multiple sclerosis (RRMS), changes in the vasculature of possible MS mimics such as primary Sjögren's syndrome (pSS) remain to be determined. We investigated the potential of retinal optical coherence tomography (OCT) angiography (OCTA) as diagnostic tool to differentiate between patients with RRMS and pSS. METHODS: This cross-sectional study included patients with RRMS (n = 36), pSS (n = 36) and healthy controls (n = 30). Participants underwent clinical examination, assessment of visual acuity, retinal OCT, OCTA, and serum markers of glial and neuronal damage. We investigated the associations between OCTA parameters, visual functions, and serum markers. Eyes with a history of optic neuritis (ON) were excluded from analysis. RESULTS: We observed a significant thinning of the combined ganglion cell and inner plexiform layer in the eyes of patients with RRMS but not with pSS, when compared to healthy controls. Retinal vessel densities of the superficial vascular complex (SVC) were reduced in both patients with RRMS and pSS. However, retinal vessel rarefication of the deep vascular complex (DVC) was only evident in patients with pSS but not RRMS. Using multivariate regression analysis, we found that DVC vessel loss in pSS patients was associated with worse visual acuity. CONCLUSIONS: Compared to patients with RRMS, rarefication of deep retinal vessels is a unique characteristic of pSS and associated with worse visual function. Assuming a disease-specific retinal vessel pathology, these data are indicative of a differential affliction of the gliovascular complex in the retina of RRMS and pSS patients.

Optimizing ultrafast dynamic contrast-enhanced MRI scan duration in the differentiation of benign and malignant breast lesions.

OBJECTIVE: To determine the optimal scan duration for ultrafast DCE-MRI in effectively differentiating benign from malignant breast lesions. METHODS: The study prospectively recruited participants who underwent breast ultrafast DCE-MRI from September 2021 to March 2023. A 30-phase breast ultrafast DCE-MRI on a 3.0-T MRI system was conducted with a 4.5-s temporal resolution. Scan durations ranged from 40.5 s to 135.0 s, during which the analysis is performed at three-phase intervals, forming eight dynamic sets (scan duration [SD]40.5s: 40.5 s, SD54s: 54.0 s, SD67.5s: 67.5 s, SD81s: 81.0 s, SD94.5s: 94.5 s, SD108s: 108.0 s, SD121.5s: 121.5 s, and SD135s: 135.0 s). Two ultrafast DCE-MRI parameters, maximum slope (MS) and initial area under the curve in 60 s (iAUC), were calculated for each dynamic set and compared between benign and malignant lesions. Areas under the receiver operating characteristic curve (AUCs) were used to assess their diagnostic performance. RESULTS: A total of 140 women (mean age, 47 ± 11 years) with 151 lesions were included. MS and iAUC from eight dynamic sets exhibited significant differences between benign and malignant lesions (all p < 0.05), except iAUC at SD40.5s. The AUC of MS (AUC = 0.804) and iAUC (AUC = 0.659) at SD67.5s were significantly higher than their values at SD40.5s (AUC = 0.606 and 0.516; corrected p < 0.05). No significant differences in AUCs for MS and iAUC were observed from SD67.5s to SD135s (all corrected p > 0.05). CONCLUSIONS: Ultrafast DCE-MRI with a 67.5-s scan duration appears optimal for effectively differentiating malignant from benign breast lesions. CRITICAL RELEVANCE STATEMENT: By evaluating scan durations (40.5-135 s) and analyzing two ultrafast DCE-MRI parameters, we found a scan duration of 67.5 s optimal for discriminating between these lesions and offering a balance between acquisition time and diagnostic efficacy. KEY POINTS: Ultrafast DCE-MRI can effectively differentiate malignant from benign breast lesions. A minimum of 67.5-sec ultrafast DCE-MRI scan duration is required to differentiate benign and malignant lesions. Extending the scan duration beyond 67.5 s did not significantly improve diagnostic accuracy.

Primary central nervous system lymphoma: Imaging features and differential diagnosis.

Primary central nervous system lymphoma (PCNSL) represents 5% of malignant primary brain tumors. The clinical presentation typically includes focal neurological symptoms, increased intracranial pressure, seizures, and psychiatric symptoms. Although histological examination remains the gold standard for diagnostic confirmation, non-invasive imaging plays a crucial role for the diagnosis. In immunocompetent individuals, PCNSL usually appears as a single, well-defined, supratentorial lesion with a predilection for periventricular areas, iso- or hypointense on T1- and T2-weighted magnetic resonance imaging, with restricted diffusion, slightly increased perfusion, and homogenous gadolinium-enhancement. Differential diagnoses include high-grade glioma and pseudotumoral demyelinating disease. In immunocompromised patients, PCNSL may present as multiple lesions, with a higher likelihood of hemorrhage and necrosis and less restricted diffusion than immunocompetent individuals. Differential diagnoses include neurotoxoplasmosis, progressive multifocal leukoencephalopathy, and cerebral abscess. Atypical forms of lymphoma are characterized by extra-axial lymphoma, lymphomatosis cerebri, and intravascular lymphoma. Extra-axial lymphoma presents as single or multiple extra-axial dural lesions with diffuse leptomeningeal contrast-enhancement. Lymphomatosis cerebri appears as an infiltrative and symmetric lesion, primarily affecting deep white matter and basal ganglia, appearing hyperintense on T2-weighted imaging, without significant contrast-enhancement or perfusion changes. Intravascular lymphoma presents as multiple rounded or oval-shaped "infarct-like" lesions, located cortically or subcortically. This study aims to highlight the imaging characteristics of PCNSL, focusing on magnetic resonance imaging and its differential diagnosis.

Comprehensive proteogenomic characterization of rare kidney tumors.

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC.

A giant peripheral ossifying fibroma of the maxilla with extreme difficulty in clinical differentiation from malignancy: a case report and review of the literature.

BACKGROUND: Peripheral ossifying fibroma is a nonneoplastic inflammatory hyperplasia that originates in the periodontal ligament or periosteum in response to chronic mechanical irritation. Peripheral ossifying fibroma develops more commonly in young females as a solitary, slow-growing, exophytic nodular mass of the gingiva, no more than 2 cm in diameter. While various synonyms have been used to refer to peripheral ossifying fibroma, very similar names have also been applied to neoplastic diseases that are pathologically distinct from peripheral ossifying fibroma, causing considerable nomenclatural confusion. Herein, we report our experience with an unusual giant peripheral ossifying fibroma with a differential diagnostic challenge in distinguishing it from a malignancy. CASE PRESENTATION: A 68-year-old Japanese male was referred to our department with a suspected gingival malignancy presenting with an elastic hard, pedunculated, exophytic mass 60 mm in diameter in the right maxillary gingiva. In addition to computed tomography showing extensive bone destruction in the right maxillary alveolus, positron emission tomography with computed tomography revealed fluorodeoxyglucose hyperaccumulation in the gingival lesion. Although these clinical findings were highly suggestive of malignancy, repeated preoperative biopsies showed no evidence of malignancy. Since even intraoperative frozen histological examination revealed no malignancy, surgical resection was performed in the form of partial maxillectomy for benign disease, followed by thorough curettage of the surrounding granulation tissue and alveolar bone. Histologically, the excised mass consisted primarily of a fibrous component with sparse proliferation of atypical fibroblast-like cells, partly comprising ossification, leading to a final diagnosis of peripheral ossifying fibroma. No relapse was observed at the 10-month follow-up. CONCLUSIONS: The clinical presentation of giant peripheral ossifying fibromas can make the differential diagnosis from malignancy difficult. Proper diagnosis relies on recognition of the characteristic histopathology and identification of the underlying chronic mechanical stimuli, while successful treatment mandates complete excision of the lesion and optimization of oral hygiene. Complicated terminological issues associated with peripheral ossifying fibroma require appropriate interpretation and sufficient awareness of the disease names to avoid diagnostic confusion and provide optimal management.

Positive anti-nuclear antibody in patients with polyclonal hypergammaglobulinemia suggests the presence of multiple distinct comorbidities.

Objective Polyclonal hypergammaglobulinemia (PHGG) is a classic problem in internal medicine; however, its conditions and diagnostic procedures have not been well studied. We therefore conducted a retrospective study to characterize the PHGG disease spectrum. Methods We included all patients who underwent serum protein electrophoresis (SPEP) at a hematology tertiary referral center during a five-year period. For these patients, globulin clonality was determined and clinical data were extracted from the records. Results Out of 209 consecutive cases of hypergammaglobulinemia demonstrated by SPEP, 79 cases of PHGG were identified. A total of 46 diagnoses were associated with PHGG. Patients with PHGG were younger (median 71.0 years old (yo) vs. 65 years; P = 0.002) and had lower gamma-globulin levels (median, 26.5 g/L vs 24.8 g/L; P = 0.03) than those with monoclonal hypergammaglobulinemia. Interestingly, out of 79 patients with PHGG, 15 were associated with more than one diagnosis, and a female predominance was observed in this specific subset of patients. PHGG cases with multiple diseases showed higher gamma-globulin levels than those with monoclonal hypergammaglobulinemia, in a disease-dependent manner. Additionally, positive antinuclear antibodies (ANAs) had a discriminative ability with an area under the curve of 0.81 (95% confidence interval, 0.65-0.96) and were highly sensitive to multimorbidity in PHGG (sensitivity, 92.3%). Conclusion These results establish a previously underappreciated unique immunological state of multimorbidity in PHGG and indicate that the gamma-globulin levels and ANAs could serve as markers for the clinical assessment of comorbidities in PHGG.

Delivering the diagnosis of multiple system atrophy: a multicenter survey on Japanese neurologists' perspectives.

BACKGROUND: Multiple system atrophy (MSA) is a progressive, incurable, life-threatening neurodegenerative disease uniquely characterized by the risk of sudden death, which makes diagnosis delivery challenging for neurologists. Empirical studies on breaking a diagnosis of MSA are scarce, with no guidelines currently established. This study aimed to investigate neurologists' current practices and experiences in delivering the diagnosis of MSA. METHODS: We conducted a multicenter online survey and employed a mixed-methods (quantitative and qualitative) study design in which responses to open-ended questions were analyzed qualitatively using critical incident technique. RESULTS: Among the 194 neurologists surveyed, 166 opened the survey (response rate = 85.6%), of whom 144 respondents across various Japanese regions completed the survey. Accordingly, 92.3% and 82.8% of the participating neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, respectively. Factors independently associated with difficulties in diagnosis delivery included explaining the importance of the family decision making process in life-prolonging treatment, perceived difficulties in delivering information regarding the risk of sudden death, and perceived difficulties in differential diagnosis of MSA. CONCLUSIONS: Our findings showed that the majority of neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, which could have been associated with the difficulty of breaking the diagnosis of MSA. Difficulty in conveying bad news in MSA are caused by various factors, such as empathic burden on neurologists caused by the progressive and incurable nature of MSA, the need to explain complex and important details, including the importance of the family decision-making process in life-prolonging treatment, difficulty of MSA diagnosis, and communication barriers posed by mental status and cognitive impairment in patients or their family members. Neurologists consider various factors in explaining the risk of sudden death (e.g., patient's personality, mental state, and degree of acceptance and understanding) and adjust their manner of communication, such as limiting their communication on such matters or avoiding the use of the term "sudden death" in the early stages of the disease. Although neurologists endeavor to meet the basic standards of good practice, there is room for the multiple aspects for improvement.

IL21R hypomethylation as a biomarker for distinguishing benign and malignant breast tumours.

Some benign and malignant breast tumours are similar in pathological morphology, which are difficult to be distinguished in clinical diagnosis. In this study, we intended to explore novel biomarkers for differential diagnosis of benign and malignant breast tumours. Methylation EPIC 850K beadchip and RNA-sequencing were used to analyse 29 tissue samples from patients with early-stage breast cancer (BC) and benign breast tumours for differently methylated and expressed genes. The altered methylation of IL21R was semi-quantitatively validated in an independent study with 566 tissue samples (279 BC vs. 287 benign breast tumours) using mass spectrometry. Binary logistic regression analysis was performed to evaluate the association between IL21R methylation and BC. BC-associated IL21R hypomethylation and overexpression were identified in the discovery round. In the validation round, BC patients presented significant IL21R hypomethylation compared to women with benign breast tumours (ORs ≥1.29 per-10% methylation, p-values ≤ 5.69E-14), and this hypomethylation was even enhanced in BC patients with ER-negative and PR-negative tumours as well as with triple-negative tumours. The methylation of IL21R showed efficient discriminatory power to distinguish benign breast tumours from BC (area under curve (AUC) = 0.88), and especially from ER-negative BC (AUC = 0.95), PR-negative BC (AUC = 0.93) and triple-negative BC (AUC = 0.96). We disclosed significant IL21R hypomethylation in patients with BC compared to women with benign breast tumours, and revealed the somatic change of DNA methylation could be a potential biomarker for molecular pathology of BC.

Prospective Analysis of Squamous Cell Carcinoma Antigen-1 and -2 for Diagnosing Sinonasal Inverted Papilloma.

Background: The goal of this research was to confirm whether preoperative serum squamous cell carcinoma antigen (SCCA)-1 and -2 levels are useful diagnostic markers for sinonasal inverted papilloma (IP) in a prospective study. Methods: Participants were 102 patients who underwent consecutive endoscopic sinus surgery: 18 with IP, two with other types of papilloma, 77 with chronic rhinosinusitis, four with sinonasal cancer, and one with hemangioma. SCCA-1 and SCCA-2 were measured preoperatively by an automatic chemiluminescence immunoassay and an enzyme-linked immunosorbent assay, respectively. Results: SCCA-1 and SCCA-2 values were significantly correlated (r = 0.603, p < 0.001). Receiver operating characteristic analysis for differentiating papilloma (IP and other types of papilloma) from other diseases yielded an area under the curve of 0.860, with a Youden index of 1.75. Combined with SCCA-2 analysis, the detection system had a sensitivity and specificity of 0.65 and 0.98, respectively. While our study did not find a strong link between SCCA levels and skin or lung diseases, smoking status may influence SCCA levels in IP patients (p = 0.035). We recommend a cutoff value of 1.8 ng/mL for SCCA-1 in IP diagnosis. Conclusions: SCCA-1 and SCCA-2 when combined with imaging and pathology hold promise for enhancing the preoperative detection of IP, which would be a valuable contribution to clinical practice.

Proteomics-Derived Biomarker Panel Facilitates Distinguishing Primary Lung Adenocarcinomas With Intestinal or Mucinous Differentiation From Lung Metastatic Colorectal Cancer.

The diagnosis of primary lung adenocarcinomas with intestinal or mucinous differentiation (PAIM) remains challenging due to the overlapping histomorphological, immunohistochemical (IHC), and genetic characteristics with lung metastatic colorectal cancer (lmCRC). This study aimed to explore the protein biomarkers that could distinguish between PAIM and lmCRC. To uncover differences between the two diseases, we used tandem mass tagging-based shotgun proteomics to characterize proteomes of formalin-fixed, paraffin-embedded tumor samples of PAIM (n = 22) and lmCRC (n = 17).Then three machine learning algorithms, namely support vector machine (SVM), random forest, and the Least Absolute Shrinkage and Selection Operator, were utilized to select protein features with diagnostic significance. These candidate proteins were further validated in an independent cohort (PAIM, n = 11; lmCRC, n = 19) by IHC to confirm their diagnostic performance. In total, 105 proteins out of 7871 proteins were significantly dysregulated between PAIM and lmCRC samples and well-separated two groups by Uniform Manifold Approximation and Projection. The upregulated proteins in PAIM were involved in actin cytoskeleton organization, platelet degranulation, and regulation of leukocyte chemotaxis, while downregulated ones were involved in mitochondrial transmembrane transport, vasculature development, and stem cell proliferation. A set of ten candidate proteins (high-level expression in lmCRC: CDH17, ATP1B3, GLB1, OXNAD1, LYST, FABP1; high-level expression in PAIM: CK7 (an established marker), NARR, MLPH, S100A14) was ultimately selected to distinguish PAIM from lmCRC by machine learning algorithms. We further confirmed using IHC that the five protein biomarkers including CDH17, CK7, MLPH, FABP1 and NARR were effective biomarkers for distinguishing PAIM from lmCRC. Our study depicts PAIM-specific proteomic characteristics and demonstrates the potential utility of new protein biomarkers for the differential diagnosis of PAIM and lmCRC. These findings may contribute to improving the diagnostic accuracy and guide appropriate treatments for these patients.

Beyond vulvodynia: from a correct diagnosis to a multidisciplinary care program. A referral center experience.

BACKGROUND: Vulvodynia is a chronic pain condition without an identifiable cause. As such, it is a diagnosis of exclusion, and all other causes of vulvar pain should be excluded. Although a standard treatment for vulvodynia has not been established yet, multidisciplinary care programs appear to be effective. PUROPOSE: The aim of this retrospective monocentric study was to analyze the prevalence of vulvodynia among women referred to our institution for a suspected diagnosis and to evaluate the efficacy of a multidimensional treatment plan. The primary outcome was the prevalence of vulvodynia following differential diagnosis. Secondary outcomes included: prevalence of the differential diagnoses, symptom resolution rate following treatment, and the relation between persistence of symptoms and (a) patients' age; (b) coexisting chronic overlapping pain conditions (COPCs). RESULTS: After having ruled out all other causes of vulvar pain, only 40.1% of women were considered as affected by vulvodynia. The most frequent differential diagnoses included lower genital tract infections (25.3%), vulvar lichen sclerosus (17.6%) and vulvovaginal atrophy (8.2%). Following a multidisciplinary care program, resolution of symptoms was observed in 13.6% cases, improvement in 64.3% and persistence in 21.9%. We did not find a statistically significant association between persistence of symptoms and age > 38 years (OR 2.10; p = 0.30). Women with one or more COPCs other than vulvodynia had a 75% increased risk of not obtaining a resolution of symptoms (OR 1.75; p = 0.44). CONCLUSION: A thorough differential diagnosis and a multidisciplinary care program may represent a first way out of the muddle in the management of these patients.