Cardiac pacemaking is controlled by an inward current called If, which is activated by membrane hyperpolarization of pacemaker cells in the sinoatrial node. Recently, a family of hyperpolarization-activated and cyclic nucleotide-gated cation(HCN) channels comprising at least four members (HCN1－HCN4) has been cloned. Two of these channels, HCN2 and HCN4, are expressed in the heart. When expressed in heterologous cells, HCN2 and HCN4 reveal general features of native If. In the present review we describe the molecular diversity and functional expression of the HCN channels and discuss structural determinants of the channels.

Atopic eczema, also known as atopic dermatitis, is a frequent, highly pruritic, chronic skin disease, which is typically running in flares. The traditional treatment mainly consists of the reactive application of topical anti-inflammatory agents such as topical corticosteroids and topical calcineurin inhibitors. The short term benefit of this approach is well known, but long term remission between flares is difficult to achieve. Therefore, innovative long-term treatment strategies targeting flare prevention and skin barrier stabilization are needed. We and others have shown that normal looking, non-lesional skin of atopic dermatitis patients is immunobiologially not normal but characterized by an invisible inflammation and barrier defect. This has led to the novel concept of proactive therapy, which is defined as long-term, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin, together with an ongoing emollient treatment of unaffected skin. This review article describes the most important long-term treatment options for atopic dermatitis, which includes emollient therapy, the novel concept of proactive treatment, the different ultraviolet light modalities and a selection of systemic immunosuppressive drugs and biologics. Current trial data, licensed indications, off-label use and relevant side effects of the different treatment modalities are summarized.
Adrenal Cortex Hormones ; Anti-Inflammatory Agents ; Biological Agents ; Calcineurin ; Dermatitis, Atopic ; Emollients ; Humans ; Inflammation ; Off-Label Use ; Running ; Skin ; Skin Diseases ; Ultraviolet Rays

Background: and Purpose Anesthesia regimen in patients undergoing mechanical thrombectomy (MT) is still an unresolved issue. Methods: We compared the effect of anesthesia regimen using data from the German Stroke Registry-Endovascular Treatment (GSR-ET) between June 2015 and December 2019. Degree of disability was rated by the modified Rankin Scale (mRS), and good outcome was defined as mRS 0–2. Successful reperfusion was assumed when the modified thrombolysis in cerebral infarction scale was 2b–3. Results: Out of 6,635 patients, 67.1% (n=4,453) patients underwent general anesthesia (GA), 24.9% (n=1,650) conscious sedation (CS), and 3.3% (n=219) conversion from CS to GA. Rate of successful reperfusion was similar across all three groups (83.0% vs. 84.2% vs. 82.6%, P=0.149). Compared to the CA-group, the GA-group had a delay from admission to groin (71.0 minutes vs. 61.0 minutes, P<0.001), but a comparable interval from groin to flow restoration (41.0 minutes vs. 39.0 minutes). The CS-group had the lowest rate of periprocedural complications (15.0% vs. 21.0% vs. 28.3%, P<0.001). The CS-group was more likely to have a good outcome at follow-up (42.1% vs. 34.2% vs. 33.5%, P<0.001) and a lower mortality rate (23.4% vs. 34.2% vs. 26.0%, P<0.001). In multivariable analysis, GA was associated with reduced achievement of good functional outcome (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.71 to 0.94; P=0.004) and increased mortality (OR, 1.42; 95% CI, 1.23 to 1.64; P<0.001). Subgroup analysis for anterior circulation strokes (n=5,808) showed comparable results. Conclusions We provide further evidence that CS during MT has advantages over GA in terms of complications, time intervals, and functional outcome.

OBJECTIVE: The aim of this prospective study was to determine whether the additional use of the single photon emission computed tomography/CT (SPECT/CT) technique improves the diagnostic value of planar lymphoscintigraphy in patients presenting with primary lymph edema of the lower limb. MATERIALS AND METHODS: For a defined period of three years (April 2011-April 2014) a total of 34 consecutive patients (28 females; age range, 27-83 years) presenting with swelling of the leg(s) suspicious of (uni- or bilateral, proximal or distal) primary lymphedema were prospectively examined by planar lymphoscintigraphy (lower limbs, n = 67) and the tomographic SPECT/CT technique (anatomical sides, n = 65). RESULTS: In comparison to pathological planar scintigraphic findings, the addition of SPECT/CT provided relevant additional information regarding the presence of dermal backflow (86%), the anatomical extent of lymphatic disorders (64%), the presence or absence of lymph nodes (46%), and the visualization of lymph vessels (4%). CONCLUSION: As an adjunct to planar lymphoscintigraphy, SPECT/CT specifies the anatomical correlation of lymphatic disorders and thus improves assessment of the extent of pathology due to the particular advantages of tomographic separation of overlapping sources. The interpretation of scintigraphic data benefits not only in baseline diagnosis, but also in physiotherapeutical and microsurgical treatments of primary lymphedema.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lower Extremity/anatomy & histology/*radiography ; Lymphatic Vessels/radiography ; Lymphedema/*diagnosis/radiography ; Lymphoscintigraphy ; Middle Aged ; Radiopharmaceuticals/diagnostic use ; Retrospective Studies ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed

BACKGROUND: Perioral dermatitis (POD) is a common inflammatory skin disease without standard therapy. OBJECTIVE: We sought to evaluate the clinical value of a soothing fluid for the treatment of POD. METHODS: We included 51 patients with POD in this 8-week clinical trial. The Toleriane Fluide Efficacy in Perioral Dermatitis (TOLPOD) study had an open-label design and involved twice-daily application of Toleriane Fluide, a soothing cosmetic fluid. Clinical assessment of POD was performed with a predefined questionnaire including the POD severity index (PODSI). Control visits were made after 4 and 8 weeks of treatment. RESULTS: The results were compared with those of a historical control group treated with a vehicle cream. Patients treated with the soothing fluid showed a continuous and significant improvement of the PODSI over time. The improvement of PODSI observed with the soothing fluid was better, but not significantly better, than that observed in the historical controls. In addition, the subjective complaints of patients such as disease burden, itching, distension of the skin, and appearance improved during treatment. CONCLUSION: A soothing fluid could be a clinically useful treatment option for POD.
Dermatitis, Perioral* ; Humans ; Pruritus ; Skin ; Skin Diseases ; Surveys and Questionnaires

Background: and Purpose Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce. Methods: We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). Results We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031). Conclusions Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage.

Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer. Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls. Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers. We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type. From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history. Genome-wide miRNA profiles were generated and evaluated using machine learning techniques. For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P < 0.05), including members of the miR-320 family. The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P = 2.3 × 10). We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis. For selected miRNAs, qRT-PCR analysis was applied to validate the results. In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer.
Aged ; Biomarkers, Tumor ; genetics ; Cohort Studies ; Female ; Gene Expression Profiling ; Genome, Human ; Humans ; Male ; MicroRNAs ; genetics ; Neoplasms ; diagnosis ; etiology ; genetics ; Prognosis ; Pulmonary Disease, Chronic Obstructive ; complications