Core content for venous and Lymphatic Medicine: 2022 revision.

The core content for a medical specialty outlines the scope of the discipline as well as the categories of knowledge considered essential to practice in the field. It provides a template for the development of curricula for medical school, graduate, and postgraduate education, as well as for creating certification standards. Venous and Lymphatic Medicine (VLM) is a specialty that has benefitted from contributions from specialists from several medical disciplines. Optimally, the societies, boards, and residency review committees representing these disciplines would uniformly recognize the scope of VLM to develop education and assessment standards to allow training and identification of qualified practitioners. In order to inform the standard setting bodies and other stakeholders of the current scope of VLM, a task force of VLM experts from cardiology, dermatology, emergency medicine, general surgery, interventional radiology, vascular medicine, and vascular surgery was formed to revise a 2014 consensus document defining the core content of the specialty of VLM.

Exploring the most visible websites on cutaneous T-cell lymphoma-revealing limited quality of patient health information on the internet.

BACKGROUND: Patients diagnosed with cancer frequently search the Internet for health information. Yet, the quality of CTCL online information has not been investigated so far. OBJECTIVES: The aim of this study was to identify and assess the most visible websites on CTCL. METHODS: An Internet search on the top three search engines Google, Yahoo and Bing was performed for the terms 'cutaneous T-cell-lymphoma', 'mycosis fungoides' and 'Sézary syndrome'. After selecting the most frequented websites suitable for patients' information, we investigated content quality, readability and popularity. Eighty-nine websites were evaluated for HONcode quality certification, social media popularity, Alexa popularity rank, topicality and readability levels. Furthermore, the websites' content on 13 major topics according to guidelines on CTCL was assessed. RESULTS: Twenty-three (25.8%) websites were HONcode certified. Evaluated websites were difficult to read requiring at least 9 years of US school education to properly understand the information. More than half of all websites (57.3%) have not been updated for three or more years (or did not contain any update information). We found greatly varying quality and popularity of online patient information. Out of 1157 topics (equivalent to 13 different topics on 89 websites), 59.44% were mentioned on the websites. Of these, 40% contained incorrect or incomplete information. Publicly provided websites presented the different topics more thoroughly. We could further show that HONcode certified websites received better quality and readability scores. CONCLUSIONS: We found major shortcomings regarding readability, completeness and reliability of websites on CTCL. Nevertheless, highly selected websites on CTCL can serve as a valuable and reliable source of patient information. As a consequence, oncologists have an obligation to be aware of and guide their patients to available websites that contain reliable and appropriate information.

Impact of the Covid-19 pandemic on melanoma and non-melanoma skin cancer inpatient treatment in Germany - a nationwide analysis.

BACKGROUND: SARS-CoV-2 has massively changed the care situation in hospitals worldwide. Although tumour care should not be affected, initial reports from European countries were suggestive for a decrease in skin cancer during the first pandemic wave and only limited data are available thereafter. OBJECTIVES: The aim of this study was to investigate skin cancer cases and surgeries in a nationwide inpatient dataset in Germany. METHODS: Comparative analyses were performed in a prepandemic (18 March 2019 until 17 March 2020) and a pandemic cohort (18 March 2020 until 17 March 2021). Cases were identified and analysed using the WHO international classification of diseases codes (ICDs) and process key codes (OPSs). RESULTS: Comparing the first year of the pandemic with the same period 1 year before, a persistent decrease of 14% in skin cancer cases (n = 19 063) was observed. The largest decrease of 24% was seen in non-invasive in situ tumours (n = 1665), followed by non-melanoma skin cancer (NMSC) with a decrease of 16% (n = 15 310) and malignant melanoma (MM) with a reduction of 7% (n = 2088). Subgroup analysis showed significant differences in the distribution of sex, age, hospital carrier type and hospital volume. There was a decrease of 17% in surgical procedures (n = 22 548), which was more pronounced in minor surgical procedures with a decrease of 24.6% compared to extended skin surgery including micrographic surgery with a decrease of 15.9%. CONCLUSIONS: Hospital admissions and surgical procedures decreased persistently since the beginning of the pandemic in Germany for skin cancer patients. The higher decrease in NMSC cases compared to MM might reflect a prioritization effect. Further evidence from tumour registries is needed to investigate the consequences of the therapy delay and identify the upcoming challenges in skin cancer care.

Apremilast effectively inhibits TNFα-induced vascular inflammation in human endothelial cells.

BACKGROUND: Patients with chronic inflammatory diseases (e.g. psoriasis and rheumatoid arthritis) are at increased risk for the development of atherosclerosis and cardiovascular diseases (CVD). Previous studies have suggested that phosphodiesterase 4 (PDE4) inhibitors possess anti-inflammatory properties. OBJECTIVES: Here we examined the effect of the PDE4 inhibitor apremilast, a well-established anti-psoriatic drug, on pro-inflammatory responses in TNFα-activated endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVEC) were treated with tumour necrosis factor-α (TNFα) in the presence or absence of apremilast. Expression levels of pro-inflammatory cytokines, chemokines and adhesion molecules were assessed by ELISA, western blot and RT-PCR. Effects of apremilast on adhesion and transendothelial migration (TEM) of THP-1 monocytic cells were analysed in transwell assays. RESULTS: Apremilast suppressed TNFα-induced expression and secretion of important endothelial and monocytic pro-inflammatory factors, including granulocyte-macrophage colony-stimulating factor (GM-CSF), C-X-C motif chemokine ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and matrix metalloproteinase-9 (MMP9). Functionally, apremilast reduced adhesion of THP-1 cells to activated HUVECs and TEM in response to TNFα. Mechanistically, apremilast suppressed activation of nuclear factor κB (NFκB) and mitogen-activated protein kinases (MAPK) signalling in activated HUVECs. Furthermore, inhibition of p38, C-Jun-N-terminale Kinase (JNK) and NFκB in activated HUVECs decreased expression of GM-CSF, VCAM-1 and E-selectin. Additionally, apremilast decreased IL-17A-induced secretion of IL-6 and CCL2. CONCLUSIONS: We demonstrate that apremilast has distinct anti-inflammatory effects in activated HUVECs, indicating that apremilast could have the therapeutic potential to prevent higher risk for CVD in patients with chronic inflammatory diseases.

Response durability after cessation of immune checkpoint inhibitors in patients with metastatic Merkel cell carcinoma: a retrospective multicenter DeCOG study.

BACKGROUND: Immune checkpoint inhibitors (ICI) have led to a prolongation of progression-free and overall survival in patients with metastatic Merkel cell carcinoma (MCC). However, immune-mediated adverse events due to ICI therapy are common and often lead to treatment discontinuation. The response duration after cessation of ICI treatment is unknown. Hence, this study aimed to investigate the time to relapse after discontinuation of ICI in MCC patients. METHODS: We analyzed 20 patients with metastatic MCC who have been retrospectively enrolled at eleven skin cancer centers in Germany. These patients have received ICI therapy and showed as best overall response (BOR) at least a stable disease (SD) upon ICI therapy. All patients have discontinued ICI therapy for other reasons than disease progression. Data on treatment duration, tumor response, treatment cessation, response durability, and tumor relapse were recorded. RESULTS: Overall, 12 of 20 patients (60%) with MCC relapsed after discontinuation of ICI. The median response durability was 10.0 months. Complete response (CR) as BOR to ICI-treatment was observed in six patients, partial response (PR) in eleven, and SD in three patients. Disease progression was less frequent in patients with CR (2/6 patients relapsed) as compared to patients with PR (7/11) and SD (3/3), albeit the effect of initial BOR on the response durability was below statistical significance. The median duration of ICI therapy was 10.0 months. Our results did not show a correlation between treatment duration and the risk of relapse after treatment withdrawal. Major reasons for discontinuation of ICI therapy were CR (20%), adverse events (35%), fatigue (20%), or patient decision (25%). Discontinuation of ICI due to adverse events resulted in progressive disease (PD) in 71% of patients regardless of the initial response. A re-induction of ICI was initiated in 8 patients upon tumor progression. We observed a renewed tumor response in 4 of these 8 patients. Notably, all 4 patients showed an initial BOR of at least PR. CONCLUSION: Our results from this contemporary cohort of patients with metastatic MCC indicate that MCC patients are at higher risk of relapse after discontinuation of ICI as compared to melanoma patients. Notably, the risk of disease progression after discontinuation of ICI treatment is lower in patients with initial CR (33%) as compared to patients with initial PR (66%) or SD (100%). Upon tumor progression, re-induction of ICI is a feasible option. Our data suggest that the BOR to initial ICI therapy might be a potential predictive clinical marker for a successful re-induction.

G protein-coupled receptor 40 expression in human melanoma - correlation with tumour thickness, AJCC stage and survival.

BACKGROUND: In melanoma, preclinical data suggest a possible role of polyunsaturated fatty acids inhibiting cell growth. A new target molecule for free fatty acids, the G protein-coupled receptor GPR40, was identified in melanoma cells. OBJECTIVES: The aim of this study was to investigate GPR40 expression in human melanocytic tissues and to evaluate its potential as a prognostic marker. METHODS AND RESULTS: A total of 114 tissue sections of naevi, primary melanoma and melanoma metastasis were immunohistochemically stained with anti-GPR40. The staining was evaluated, using the immunoreactivity scoring system. Compared to naevi, primary melanoma and melanoma metastasis showed significantly higher levels of GPR40 (P < 0.05). In primary melanoma, GPR40 expression positively correlated with tumour thickness (P = 0.044) and AJCC level (P = 0.017) and in melanoma metastasis with AJCC level (P = 0.035). Primary melanoma patients with high levels of GPR40 had a significantly poorer overall survival (P = 0.004) and shorter disease-free survival (0.040). CONCLUSION: The present study identified GPR40 as a novel target molecule in melanoma. First evidence for a potential role of the receptor in tumour progression and metastases was found, and it could be demonstrated that GPR40 expression is negatively correlated with patient's survival.

Direct study of structural phase transformation in single crystalline bulk and thin film BaFe2As2.

The ternary iron arsenide compound BaFe2As2 exhibits a structural phase transition from tetragonal to orthorhombic at a temperature of about 140 K. The twin lamellae arising below this transition temperature were studied in undoped single crystalline bulk and epitaxial thin film samples using electron backscatter diffraction in a scanning electron microscope equipped with a helium cryostat. Applying this technique on bulk single crystals a characteristic twin lamella size in the range of 0.1 µm up to a few µm was observed. In contrast, in epitaxially strained thin films the phase transition is not observed at temperatures above 19 K.

Directing adipose-derived stem cells into keratinocyte-like cells: impact of medium composition and culture condition.

BACKGROUND: Adipose-derived stem cells (ASC) are known to transdifferentiate into a wide range of different cell species in vitro including along the epidermal lineage. This property makes them a promising tool for regenerative medicine to restore the epidermal barrier. OBJECTIVE: This study is dedicated to identify in vitro conditions enabling transdifferentiation to a keratinocyte-like phenotype. In particular, the impact of different culture conditions (media compositions, 2D, 3D cultures) and extracellular matrix (ECM) molecules was evaluated. METHODS: Adipose-derived stem cells derived from subcutaneous abdominal fat were characterized by stemness-associated markers and subjected to different media. Epithelial differentiation in 2D cultures was monitored by pan-cytokeratin expression using flow cytometry and immunocytochemistry. To evaluate the impact of different ECM molecules on epidermal stratification, 3D cultures were produced, lifted to the air-liquid interface (ALI) and examined by histological analysis and quantitative real-time RT-PCR. RESULTS: We identified a medium composition containing retinoic acid, hydrocortisone, ascorbic acid and BMP-4 enabling maximum pan-cytokeratin expression in 2D cultures. Moreover, adhesion to type IV collagen further promotes the pan-cytokeratin expression. When cultures were lifted to the ALI, significant stratification was observed, particularly in supports coated with type IV collagen or fibronectin. Moreover, epidermal differentiation markers (involucrin, cytokeratin 1 and 14) become induced. CONCLUSION: Conditions with hampered wound healing such as non-healing ulcers demand new treatment regimes. The here introduced optimized protocols for transdifferentiation of ASC into keratinocyte-like cells may help to establish more effective treatment procedures.

[Physical and chemical emergencies in dermatology]. / Physikalische und chemische Notfälle in der Dermatologie.

Physical and chemical emergencies are often caused by household or work accidents. Regardless of the medical field and outside specialized clinics, the physician may be confronted with the situation for first or secondary care. The identification of the causing agent and a rapid assessment of the extent and severity of the tissue damage are essential to initiate early transfer to a specialized burn clinic. Grade 2b tissue damage is usually surgically treated. Smaller and superficial injuries can often be conservatively treated. Even supposedly safe and over-the-counter medicines can also lead to serious tissue damage.

Endoscopic and histopathologic reflux-associated mucosal damage in the remnant esophagus following transthoracic esophagectomy for cancer-5-year long-term follow-up.

Gastroesophageal reflux is a common problem following esophagectomy and reconstruction with gastric interposition. Despite a routine prescription of proton pump inhibitors, reflux-associated mucosal damage in the remnant esophagus is frequently observed. Purpose of this study is to evaluate mucosal damage in the esophageal remnant during long-term follow-up and to compare the prevalence of this damage between the subgroups of esophageal squamous cell and adenocarcinoma. All patients undergoing transthoracic Ivor-Lewis esophagectomy were prospectively entered in our IRB approved database. All patients underwent a routine check-up program with yearly surveillance endoscopies following esophagectomy. Only patients with a complete follow-up were included into this study. Endoscopic and histopathologic mucosal changes of the remnant esophagus were analyzed in close intervals. A total of 50 patients met the inclusion criteria, consisting of 31 adenocarcinomas (AC) and 19 squamous cell carcinomas (SCC). Mucosal damage was already seen 1 year after surgery in 20 patients macroscopically (43%) and in 21 patients microscopically (45%). At 5-year follow-up the prevalence for macroscopic and microscopic damage was 55% and 60%, respectively. The prevalence of mucosal damage was higher in AC patients than in SCC patients (1y-FU: 51% [AC] vs. 28% [SCC]; 5y-FU: 68% [AC] vs. 35% [SCC], P < 0.05). Newly acquired Barrett's esophagus was seen in 10 patients (20%) with two of those patients (20%) showing histopathologic proof of neoplasia. This study shows a high prevalence of reflux-associated mucosal damage in the remnant esophagus one year out of surgery and only a moderate increase in prevalence in the following years. Mucosal damage was more frequently seen in AC patients and the occurrence of de-novo Barrett's esophagus and de-novo neoplasia was high. Endoscopic surveillance with targeted biopsies seems to be an indispensable tool to follow patients after esophagectomy appropriately.

A microwave resonator integrated on a polymer microfluidic chip.

We describe a novel stacked split-ring type microwave (MW) resonator that is integrated into a 10mm by 10mm sized microfluidic chip. A straightforward and scalable batch fabrication process renders the chip suitable for single-use applications. The resonator volume can be conveniently loaded with liquid sample via microfluidic channels patterned into the mid layer of the chip. The proposed MW resonator offers an alternative solution for compact in-field measurements, such as low-field magnetic resonance (MR) experiments requiring convenient sample exchange. A microstrip line was used to inductively couple MWs into the resonator. We characterised the proposed resonator topology by electromagnetic (EM) field simulations, a field perturbation method, as well as by return loss measurements. Electron paramagnetic resonance (EPR) spectra at X-band frequencies were recorded, revealing an electron-spin sensitivity of 3.7·10(11)spins·Hz(-1/2)G(-1) for a single EPR transition. Preliminary time-resolved EPR experiments on light-induced triplet states in pentacene were performed to estimate the MW conversion efficiency of the resonator.

[Dermatosurgery in the elderly]. / Dermatochirurgie im Alter.

In recent decades, the portion of elderly has increased substantially due to demographic changes in developed countries. Dermatological surgery is particularly affected by this development, because a large proportion of the elderly suffer from skin tumors, which are primarily treated surgically. Physiological changes of age and multimorbidity, often associated with polypharmacy, present the treating physician with enormous challenges. What aspects of care are important? What must be considered? What are possible complications and how can they be prevented? These important questions are answered. Finally, selected surgical approaches for the care of very old patients are also described.

The Mercedes flap and its new variants: a 'workhorse' flap for the dermatological surgeon?

BACKGROUND: The plastic reconstruction of defects in problem regions, such as, e.g. the heel, temple, malleolar region, sternum and capillitium, is usually a challenge. OBJECTIVE: We describe the use of the Mercedes flap, a combination of the purse string and advancement flap, and new modifications for use in various body locations. These examples extend the scope of application in tumour surgery of the skin. METHODS: We demonstrate the different techniques and practical application of the repair and evaluate the benefits and limitations. RESULTS: The Mercedes flap and its modifications are an excellent method for repairing various defects in problem locations after tumour surgery of the skin. CONCLUSION: The Mercedes flap and its modifications prove to be a good alternative to other closure types, especially in problem regions such as the shoulder, malleolar region, heel, etc. The procedure is fast and simple, with few side-effects, and proves to be a 'workhorse' flap for the dermatological surgeon.

Immuno-magnetoliposomes targeting activated platelets as a potentially human-compatible MRI contrast agent for targeting atherothrombosis.

To detect unstable atherosclerotic plaques early and noninvasively would be of great clinical interest. Activated platelets are an interesting molecular target for detecting early lesions or unstable plaques. We therefore developed an MRI contrast agent consisting of magnetoliposomes (ML) linked to an antibody (anti-LIBS) specifically targeting the ligand-induced binding site of the activated GPIIb/IIIa receptor of platelets. ML were prepared by dual centrifugation (DC). ML pegylation up to a total PEG content of 7.5 mol% positively influenced the stability and amount of entrapped SPIOs, and also reduced SPIO-membrane interactions, while higher PEG contents destabilized PEG-ML. Stable anti-LIBS-ML with high amounts of entrapped SPIOs (∼86%, ∼0.22 mol Fe/mol liposomal lipid) and high MRI sensitivity (relaxivity r2 = 422 s(-1) mM(-1) and r2(∗) = 452 s(-1) mM(-1)) were obtained by coupling anti-LIBS to ML in a two-step post-insertion technique. We confirmed specific binding to the GPIIb/IIIa receptor's activated conformation on activated human platelets and cell lines expressing activated GPIIb/IIIa receptor ex vivo. The immuno-ML obtained in this study constitute an important step towards developing a potentially human-compatible MRI contrast agent for the timely detection of plaque rupture by targeting activated platelets.

Clinical outcome after treatment of pelvic congestion syndrome: sense and nonsense.

Chronic pelvic pain accounts for approximately 10% of outpatient gynecologic visits and among the varied causes, pelvic congestion syndrome is second only to endometriosis in frequency. Manifestations may include pelvic pain, dyspareunia, dysuria, and dysmenorrhea as well as external varices and a number of psychosocial symptoms. Although a variety of treatments have been proposed-including pharmacologic ovarian suppression, hysterectomy with or without oophorectomy, and ovarian vein resection-transcatheter embolization is the least invasive and most efficacious management option. Complete or partial symptom improvement has been reported in 68.2-100% of patients and there has been a consistent reduction in visual analog pain scores after treatment. Based upon these results, recommendation of either pharmacotherapy or other surgical procedures is difficult to justify. However, it is also clear that 6-31.8% of patients do not get substantial relief from pelvic venous embolization. Potential explanations for an inadequate response to treatment include patient variability, procedural variability, and inadequate outcome measures. The latter are particularly important and future investigation should focus on the development of disease-specific quality of life measures as well as identifying those aspects of the procedure, such as choice of embolic agents and extent of embolization, associated with the best clinical outcomes.

Chondrocutaneous helix rim advancement flap: two classical and two new modifications for very large defects of the ear.

BACKGROUND: The plastic reconstruction of the ear after microscopically controlled tumor surgery is a particular challenge. The chondrocutaneous helix rim advancement flap (CHRAF) is perfectly suited for the repair of different defects of the helix and even defects beyond. OBJECTIVE: Here, we describe two known and two new modifications of the CHRAF that enlarge the scope of application in tumor surgery of the ear. METHODS: We demonstrate the different techniques and practical application of the repair and evaluate the benefits and limitations. RESULTS: The CHRAF and its modifications is an excellent method for repair of various defects of the helical region of the ear. CONCLUSION: The CHRAF and its modifications proves to be an good alternative to other methods of closure by preserving the anatomical contour and mechanical and acoustic functions in a single-staged procedure with excellent aesthetic results. The two new modifications we introduced here, enlarge the known armentarium for very large defects of the upper pole and the mid-helix of the ear.

Combination of high on-treatment platelet aggregation and low deaggregation better predicts long-term cardiovascular events in PCI patients under dual antiplatelet therapy.

High on-treatment platelet reactivity is associated with short-term major cardiovascular (CV) events in patients undergoing percutaneous coronary intervention (PCI). Maximum and final aggregation assessed by light transmission aggregometry (LTA) have both been used to predict short-term outcome after PCI, however their long-term prognostic impact remains controversial. There is currently no information regarding the prognostic role of deaggregation and its added value in combination with established aggregation parameters. About 1279 patients with symptomatic coronary artery disease (CAD) undergoing PCI were enrolled in this monocentric study. On-treatment platelet aggregation under clopidogrel maintenance therapy, as well as deaggregation was determined by maximum and final aggregation (5 min after adding of the agonist). Deaggregation was defined as slope of the tangent between Aggmax +0.5 min. Primary endpoints were the composite of myocardial infarction, stroke, and CV death or stent thrombosis according to the ARC criteria. Low deaggregation, defined as values in the lowest tertile (<1.5), was more frequent in patients with acute coronary syndromes (ACS) compared to patients with stable angina pectoris (SAP), ACS: 29.6% vs. SAP: 22.0%, p = 0.001. The combination of high on-treatment platelet reactivity, defined by the upper tertile of Aggmax and low deaggregation, was associated with significantly increased risk for combined long-term CV events. The combination of low deaggregation and high on-treatment platelet reactivity is associated with higher risk for recurrent events in patients with CAD undergoing PCI. Thus, deaggregation might be a more sensitive parameter providing added value in terms of risk prediction for long-term recurrent CV events in relation with established aggregation parameters.