Immediate hypersensitivity reactions to iodinated contrast media despite drug prophylaxis-a comparative retrospective cohort study of breakthrough reactions in Bern (Switzerland) and Seoul (South Korea).

Background: Although several studies deal with breakthrough reactions (BTRs) in patients with contrast media (CM) hypersensitivity reactions, the phenomenon is still unclear. Therefore, this study aimed to analyse in depth patients with BTR in two countries. Methods: We retrospectively analysed the electronic medical records of in- and outpatients (random sample enrolment) from two academic hospitals of tertiary care (Seoul/South Korea, with a special monitoring system exclusively for CM hypersensitivity, and Bern/Switzerland, manually operated) with respect to basic epidemiological data, number of BTRs per patient, and severity grades of severity in follow-up analyses. The study period lasted from 2013 (2000 Bern) to 2017. Results: We identified 445 BTR-patients (91.5% from Seoul) with 691 BTRs (94.5% from Seoul). Most reactions were mild, 11% moderate and 3.9% severe. In Seoul, we found patients with up to 10 BTRs, and in Bern, there were only patients with one BTR. Fatal reactions or deaths did not occur. In most cases, the severity of the BTRs and of the index reactions were identical (80.8%). Mild index reactions remained constant in 90.6%. In contrast, in moderate index reactions the severity decreased/remained identically in 86.8% and increased in 13.2%. In severe index reactions, 55.6% of BTR reactions were severe again, in 44.4% the severity decreased. In 158 BTRs (22.9%) the culprit iodinated contrast medium (ICM) of the index reaction induced the BTR. In the other 482 BTRs (69.8%) the culprit ICM was changed to another non-culprit ICM. Conclusions: To the best of our knowledge, this is the largest study on patients with BTRs, and the first study showing BTRs in two centers in two countries of two continents. The main differences between the two centers result from the different hospital size, the number of patients, and the different documentation [manual (Bern) vs. electronical screening (Seoul)]. BTRs are no contraindications for further ICM-application. We recommend performing an allergy skin test as basis for the decision-making process of the next contrast-enhanced image-guided examination.

Role of Neutrophil-to-Lymphocyte Ratio (NLR) in Patients with Mycosis Fungoides.

BACKGROUND: The neutrophil/lymphocyte ratio (NLR) at baseline has been demonstrated to correlate with higher stages of disease and to be a prognostic factor in numerous cancers. However, its function as a prognostic factor for mycosis fungoides (MF) has not been yet clarified. OBJECTIVE: Our work aimed to assess the association of the NLR with different stages of MF and to outline whether higher values of this marker are related to a more aggressive MF. METHODS: We retrospectively calculated the NLRs in 302 MF patients at the moment of diagnosis. The NLR was obtained using the complete blood count values. RESULTS: The median NLR among patients with early stage disease (low-grade IA-IB-IIA) was 1.88, while the median NLR for patients with high-grade MF (IIB-IIIA-IIIB) was 2.64. Statistical analysis showed positive associations of advanced MF stages with NLRs higher than 2.3. CONCLUSIONS: Our analysis demonstrates that the NLR represents a cheap and easily available parameter functioning as a marker for advanced MF. This might guide physicians in recognizing patients with advanced stages of disease requiring a strict follow-up or an early treatment.

Baseline neutrophil/lymphocyte ratio (NLR) and red blood cell distribution width (RDW) correlate with advanced stages in cutaneous squamous cell carcinoma.

BACKGROUND: The neutrophil/lymphocyte ratio (NLR) and red blood cell distribution width (RDW) at diagnosis have been shown to correlate with advanced disease and to be prognostic factors in many tumors. However, their role as a prognostic factor for cutaneous squamous cell carcinoma (cSCC) has not yet been studied. OBJECTIVE: Therefore, the aim of our study was to evaluate the correlation of NLR and RDW with stages of disease in patients with cSCC in order to define whether or not higher values of these two markers correlate with a more aggressive disease. METHODS: We retrospectively analyzed the NLR and RDW in a total of 51 newly diagnosed cSCC patients. NLR and RDW were calculated using data obtained from the complete blood count (CBC). RESULTS: Median NLR among patients with the non-advanced disease (in situ and stage I) was 2.2, whereas median NLR for patients with advanced disease was 4.87. Median RDW among patients with early stage disease was 13.7%, while median RDW in patients with advanced disease was 15.81%. Statistical analysis showed positive associations of advanced cSCC stages with NLR or RDW higher than 3.07 or 14.5%, respectively. CONCLUSIONS: Therefore, our analysis demonstrated how both NLR and RDW represent cheap and easily available factors that could be used as markers for advanced cSCC. They could help to identify patients with advanced stages disease that requires a strict follow-up.

Effectiveness of a cosmetic device containing a combination of alpha- and beta-hydroxy acids, urea, and thuja for the treatment of seborrheic keratoses.

BACKGROUND: Seborrheic keratosis is a benign epidermal tumor of cosmetic concern-as it progressively increases in size, thickness, and pigmentation-on which topical treatments are poorly effective. Considering its keratotic component, effective products may include active principles with keratolytic action. AIMS: Evaluate the efficacy and tolerability of a topical cosmetic product with urea and hydroxy acids, in the treatment of seborrheic keratoses. PATIENTS AND METHODS: Twenty patients were enrolled in an observational, prospective, open-label study. The topical device was applied on seborrheic keratoses twice daily for 30 days. We evaluated the progression of the treatment by clinical examination-using Daily Life Quality Index-and epiluminescence microscopy at baseline and day 30. RESULTS: After 30 days of treatment, we documented a significant reduction in seborrheic keratosis thickness and number, which was confirmed also by epiluminescence microscopy. On day 30, global Daily Life Quality Index improved by 99.95%. The tolerability of the cosmetic device was considered excellent, according to 19/20 subjects (95%). CONCLUSIONS: The results of our study showed the efficacy and tolerability of this cosmetic device. Its active compounds favor gradual removal of seborrheic keratoses, even in case of pigmented variants. This non-invasive treatment represents an alternative to surgical procedures, mainly for fragile patients and delicate skin areas. It is possible to speculate its usefulness in the topical treatment of circumscribed hyperkeratosis, palmoplantar keratoderma, and thick psoriatic plaques.

MCAM/MUC18/CD146 as a Multifaceted Warning Marker of Melanoma Progression in Liquid Biopsy.

Human malignant melanoma shows a high rate of mortality after metastasization, and its incidence is continuously rising worldwide. Several studies have suggested that MCAM/MUC18/CD146 plays an important role in the progression of this malignant disease. MCAM/MUC18/CD146 is a typical single-spanning transmembrane glycoprotein, existing as two membrane isoforms, long and short, and an additional soluble form, sCD146. We previously documented that molecular MCAM/MUC18/CD146 expression is strongly associated with disease progression. Recently, we showed that MCAM/MUC18/CD146 and ABCB5 can serve as melanoma-specific-targets in the selection of highly primitive circulating melanoma cells, and constitute putative proteins associated with disease spreading progression. Here, we analyzed CD146 molecular expression at onset or at disease recurrence in an enlarged melanoma case series. For some patients, we also performed the time courses of molecular monitoring. Moreover, we explored the role of soluble CD146 in different cohorts of melanoma patients at onset or disease progression, rather than in clinical remission, undergoing immune therapy or free from any clinical treatment. We showed that MCAM/MUC18/CD146 can be considered as: (1) a membrane antigen suitable for identification and enrichment in melanoma liquid biopsy; (2) a highly effective molecular "warning" marker for minimal residual disease monitoring; and (3) a soluble protein index of inflammation and putative response to therapeutic treatments.

Cutaneous mastocytosis: A dermatological perspective.

Mastocytosis is a rare disease characterised by expansion and collection of clonal mast cells in various organs including the skin, bone marrow, spleen, lymph nodes and gastrointestinal tract. The prevalence of mastocytosis has been estimated to be one in 10 000, while the estimated incidence is one per 100 000 people per year. Cutaneous mastocytosis is classified into (i) maculopapular cutaneous mastocytosis, also known as urticaria pigmentosa; (ii) diffuse cutaneous mastocytosis; and (iii) mastocytoma of the skin. In adults, cutaneous lesions are usually associated with indolent systemic mastocytosis and have a chronic evolution. Paediatric patients, on the contrary, have often cutaneous manifestations without systemic involvement and usually experience a spontaneous regression. Diagnosis of cutaneous mastocytosis may be challenging due to the rarity of the disease and the overlap of cutaneous manifestations. This short review describes pathogenesis and clinical aspects of cutaneous mastocytosis with a focus on diagnosis and currently available therapies.

Co-occurrence of malignant neoplasm and Hyperostosis Frontalis Interna in an Iron Age individual from Münsingen-Rain (Switzerland): A multi-diagnostic study.

OBJECTIVE: To re-analyze one of the oldest cases of malignant bone neoplasm with different analytical techniques. MATERIAL: The available skeletal remains of grave 138 (G138) from the Iron Age necropolis of Münsingen-Rain (Switzerland, 420-240 BC). METHODS: The bones are analyzed by means of morphological, radiographic, histological, and biogeochemical methods. RESULTS: The individual, a male aged between 35-50 years old, presents morphologically and radiographically a previously described coral-like bone neoformation on the proximal left humerus. The new analyses highlight previously undocumented coarse bone proliferation on the left scapula and lobular apposition on the endocranial surface of the frontal bone. The histological analysis of the humerus shows a 'lace-like' pattern of osteoid deposition without lamellation. CONCLUSIONS: Our data support a diagnosis of osteoblastic malignant neoplasm, probably an osteosarcoma or, more likely, a dedifferentiated chondrosarcoma for the humerus and scapula, and of hyperostosis frontalis interna on the frontal. The co-presence of a malignant neoplasm and hyperostosis frontalis interna may be related to a hormonal imbalance, a possibility also suggested by atypical funerary treatment. SIGNIFICANCE: This study confirms G138 as one of the oldest cases of malignant bone neoplasm, adds new paleopathological data on this individual, and demonstrates the advantages of a multidisciplinary approach. LIMITATIONS: The discussion of the pathological changes is limited by the representation and preservation of the skeletal elements. SUGGESTION FOR FUTURE RESEARCH: Biomolecular and protein biomarkers analyses may help to refine the diagnostic conclusions.

Minimal Residual Disease in Melanoma:molecular characterization of in transit cutaneous metastases and Circulating Melanoma Cells recognizes an expression panel potentially related to disease progression.

Isolating circulating melanoma cells (CMCs) represents a powerful method to monitor minimal residual disease. We documented that MCAM/MUC18/CD146 expression is strongly associated with disease progression. ABCB5 is melanoma-stem antigen with self-renewal, proliferation, differentiation, tumorigenicity capabilities. These findings supported us to improve CMC detection, investigating MCAM/MUC18/CD146 and ABCB5 as enrichment targets in MM progression. Moreover, we decided to compare possible molecular diversity of these CMC fractions with metastatic tissue expression, collecting concomitantly cutaneous in transit metastases (CTM). We enriched CMCs from eight melanoma patients staged ≥pT1b AJCC, who developed CTMs at baseline or during follow up. We assessed a gene expression panel comprising ABCB5, the differentiation markers (Tyrosinase, MART1), angiogenic factors (VEGF, bFGF), the cell-cell adhesion molecules (MCAM/MUC18/CD146 5'-portion, Long, and Short isoforms, E-Cadherin, N-Cadherin, VE-Cadherin) and matrix-metallo-proteinases (MMP2 and MMP9) via high-sensitive RT-PCR. Preliminary findings defined three distinct sub-populations: "endothelial" CD45-CD146+CMCs, "stem" CD45-ABCB5+CMCs and a "hybrid- stem-endothelial"- CD45-MCAM+ABCB5+CMCs. The expression panel documented that - almost high expression found in CTMs - like in 73.5% of CMCs resulted positive for at least one transcript at baseline, showing gene-expression variability. Longitudinal monitoring documented shut-down of all gene-expressions in "endothelial"- and "hybrid stem-endothelial"-subsets, whilst persistency or acquisition of MCAM/MUC18/CD146, VE-CADH and MMPs was documented in disease-progression status.Conversely, a drastic expression shut-down was documented when patients achieved clinical remission. The "stem"- CMCs fraction" showed quite lower gene expression frequencies. MCAM/MUC18/CD146 and ABCB5 as melanoma-specific-targets are effective in the selection of highly primitive CMCs and highlights those putative genes associated with disease spreading progression.

Efficacy of Vismodegib in pigmented basal cell carcinoma: Appearances are deceiving.

Basal cell carcinoma (BCC) is the most common skin cancer in humans. Pigmented basal cell carcinoma (pBCC) is a rare variant of BCC. Vismodegib, was the first drug to be approved for the treatment of locally advanced (laBCCs) or metastatic basal cell carcinoma. The aim of this study was to evaluate the efficacy of Vismodegib in patients with pBCCs. We retrospectively analyzed patients receiving Vismodegib as treatment for laBCCs presenting also various pBCCs. After 6 months of treatment, we performed excisional biopsies of pBCCs, that apparently at clinical and dermoscopic assessment did not respond to therapy. A total of nine patients were assessed. After 6 months of treatment, locally advanced target BCCs showed complete remission in four out of nine patients (44.4%), four patients (44.4%) were considered in partial remission and one patient (11%) showed no response to treatment. On the contrary, all the pBCCs showed both clinically and dermoscopically resistance to treatment. Therefore, clinically persistent pBCCs were surgically removed in three patients. Histology showed a complete elimination of the neoplastic cells together with features of previous regression. Our findings indicate that the efficacy of Vismodegib is higher than that documented by clinical or even dermatoscopic observation alone.

Diagnosis of pulmonary infarction in post-mortem computed tomography and post-mortem magnetic resonance imaging-a technical note.

Pulmonary thromboembolism may be accompanied by pulmonary infarction. Even though pulmonary thromboembolism (PTE) is a frequently found cause of death at autopsy, pulmonary infarction accompanying PTE is a less common finding and may therefore easily be misinterpreted as infectious or cancerous lung disease. Appearance of pulmonary infarction in post-mortem imaging and acquisition parameters helping to identify pulmonary infarctions are not described yet. Based on a case of a 50-year-old man who died due to PTE and presented pulmonary infarction, we suggest using a pulmonary algorithm in post-mortem computed tomography combined with post-mortem magnetic resonance imaging of the lungs using conventional T1- and T2-weighted sequences.

Layering of stomach contents in drowning cases in post-mortem computed tomography compared to forensic autopsy.

BACKGROUND: In forensic autopsy, the analysis of stomach contents is important when investigating drowning cases. Three-layering of stomach contents may be interpreted as a diagnostic hint to drowning due to swallowing of larger amounts of water or other drowning media. The authors experienced frequent discrepancies of numbers of stomach content layering in drowning cases between post-mortem computed tomography (PMCT) and autopsy in forensic casework. Therefore, the goal of this study was to compare layering of stomach contents in drowning cases between PMCT and forensic autopsy. METHODS: Drowning cases (n = 55; 40 male, 15 female, mean age 45.3 years; mean amount of stomach content 223 ml) that received PMCT prior to forensic autopsy were retrospectively analyzed by a forensic pathologist and a radiologist. Number of layers of stomach content in PMCT were compared to number of layers at forensic autopsy. RESULTS: In 28 of the 55 evaluated drowning cases, a discrepancy between layering of stomach contents at autopsy compared to PMCT was observed: 1 layer at autopsy (n = 28): 50% discrepancy to PMCT, 2 layers (n = 20): 45% discrepancy, and 3 layers (n = 7): 71.4% discrepancy. Sensitivity of correctly determining layering (as observed at forensic autopsy) in PMCT was 52% (positive predictive value 44.8%). Specificity was 46.6% (negative predictive value 53.8%). In a control group (n = 35) of non-drowning cases, three-layering of stomach contents was not observed. CONCLUSION: Discrepancies of observed numbers of stomach content layers between PMCT and forensic autopsy are a frequent finding possibly due to stomach content sampling technique at autopsy and movement of the corpse prior to PMCT and autopsy. Three-layering in PMCT, if indeed present, may be interpreted as a hint to drowning.

Perfusion pattern and time of vascularisation with CEUS increase accuracy in differentiating between benign and malignant tumours in 216 musculoskeletal soft tissue masses.

INTRODUCTION: Musculoskeletal Soft Tissue Tumours (STT) are frequent heterogeneous lesions. Guidelines consider a mass larger than 5 cm and deep with respect to the deep fascia potentially malignant. Contrast Enhanced Ultrasound (CEUS) can detect both vascularity and tumour neoangiogenesis. We hypothesised that perfusion patterns and vascularisation time could improve the accuracy of CEUS in discriminating malignant tumours from benign lesions. MATERIALS AND METHODS: 216 STT were studied: 40% benign lesions, 60% malignant tumours, 56% in the lower limbs. Seven CEUS perfusion patterns and three types of vascularisation (arterial-venous uptake, absence of uptake) were applied. Accuracy was evaluated by comparing imaging with the histological diagnosis. Univariate and multivariate analysis, Chi-square test and t-test for independent variables were applied; significance was set at p<0.05 level, 95% computed CI. RESULTS: CEUS pattern 6 (inhomogeneous perfusion), arterial uptake and location in the lower limb were associated with high risk of malignancy. CEUS pattern has PPV 77%, rapidity of vascularisation PPV 69%; location in the limbs is the most sensitive indicator, but NPV 52%, PPV 65%. The combination of CEUS-pattern and vascularisation has 74% PPV, 60% NPV, 70% sensitivity. No correlation with size and location in relation to the deep fascia was found. CONCLUSION: US with CEUS qualitative analysis could be an accurate technique to identify potentially malignant STT, for which second line imaging and biopsy are indicated in Referral Centers. Intense inhomogeneous enhancement with avascular areas and rapid vascularisation time could be useful in discriminating benign from malignant SST, overall when the lower limbs are involved.