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Introduction: Hidradenitis suppurativa is a chronic inflammatory skin disease with a typical formation of inflamed nodules, abscesses, and sinus tracts usually in the axillary, inguinal, and anogenital region. We decided to investigate the possible association of hidradenitis suppurativa and total IgE elevation and to explore the patients’ characteristics which can be related to high IgE levels.

Introduction: Biology therapies in a various medical specializations and for a broad spectrum of indications were launched during last two decades. As a new in class the therapies were obliged to provide additional data re gar ding efficacy and safety after their real medical practice integration. Patient registries, databases collecting various patient data, were introduced to grant data on the treatment effectiveness, safety, and long-term on treatment survival. Satisfactory treatment effect and acceptable safety profile were confirmed after couple of years of careful observation. However, the benefits were usually offered at much higher treatment costs compared to the standard therapies. Biologically similar drugs, so-called biosimilars (B.S), are being launched after original molecule patent protection expiry during recent years. They were expected as an ideal solution to avoid distinct impact on the medical budget: comparable effect for less money. The unsubstantiated doubts about biosimilar efficacy and safety were the reason of the late launch in many markets. Since biosimilars are considered as new therapy entities, the cautiousness to certain extent should be required. Information gained from post-marketing observations and patient registries over several years, confirmed the biosimilar product comparable quality. Healthcare budget savings could secure easier therapy access for more new patients.

Internal malignancy may be presented in the form of paraneoplastic syndromes, which may indicate either formation or recurrence of a previously treated malignancy. Furthermore cutaneous paraneoplastic disorders often precede a diagnosis of cancer. We present 2 unique case reports with cutaneous paraneoplastic manifestations. The first one describes a patient with sudden progression of long-term stabilized morphea in connection with newly diagnosed hepatocellular carcinoma (HCC). The second one describes female patient with breast cancer preceded by the development of extragenital lichen sclerosus (LS) with typical sclerotic lesions and hemorrhagic bullae.

Burning, itching and dyspareunia are typical symptoms of many genital diseases. These subjective complaints can be misdiagnosed because of different clinical presentations. We present a case report of a postmenopausal woman treated for genital warts over a period of three years followed by the development of leukoplastic lesions in the whitish area clinical classified as Lichen sclerosus (LS). Histology of this lesion revealed carcinoma in situ. After radical surgical removal, vulvar Paget’s disease was histologically verified. LS and extramammary Paget's disease (EMPD) belong to a group of uncommon dermatoses which mainly affect the skin of the genitals in postmenopausal women. Ulceration, erosions and leukoplastic lesions can signalize the development of squamous cell carcinoma in association of lichen sclerosus, on the other hand, they can be the sign of EMPD after a long period of time using different topical agents. The importance of reaching the correct diagnosis is essential and can influence current patient investigations and invasive or non-invasive treatment.

The introduction of new pharmacotherapy entities in the last decade accentuate the necessity to set up treatment guidelines based on real life evidence. Randomized controlled trials remain golden standard of a research. Data derived from studies aiming on daily clinical practice should bring needed, added value. Disease prevalence growth, due to increased life expectancy, better diagnostic procedures and earlier medical intervention, as well as ever growing demand for highly priced, sophistically produced drugs put stress on healthcare budgets even in developed countries. Large databases commonly called - therapy registries are implemented to collect data on therapy effectivity in terms of effectiveness, safety and patient long-term on therapy survival. Registries importance rose together with biological therapies introduction. New in class molecules entered the market conditionally being obliged to provide additional e.g. safety data. Such procedures require involvement of many different professionals, e.g. physicians, professional medical bodies, IT experts, database administrators, statisticians and government institutions. Paper based, followed by computer based forms were distributed among physicians to collect these data. eHealth technologies provide physicians with centralized, more intuitive applications. The particularities of different diagnosis caused great variations within each specific registry launched. Important information was missing since they were pointed out as optional and many were redundant causing frustration among physicians due to inadequate administrative workload. The main objective of this work was to set up the therapy registry standards and procedures. Methodology of „ideal“ moderate to severe plaque psoriasis biology therapy registry development, introduction, administration and evaluation was prepared to assist any government institution or professional body when planning registry deployment. Electronic application based on widely used MS Excel platform was developed and installed in the biological therapy centers as a standalone application for the pilot use.

Background: After acute myocardial infarction (AMI), inflammatory processes promote tissue remodeling at the infarct site. Procollagen III amino-terminal propeptide (PIIINP) is a circulating biomarker of type III collagen synthesis that has been shown to be associated with changes in left ventricular ejection fraction (LVEF) and predicts the occurrence of heart failure after AMI. We hypothesize that sleep-disordered breathing (SDB) promotes inflammation and myocardial fibrosis, leading to reduced myocardial salvage. Therefore, in patients with first-time AMI successfully treated with percutaneous coronary intervention (PCI), we aimed to investigate whether circulating levels of high-sensitivity C-reactive protein (hs-CRP) and PIIINP are elevated in patients with SDB compared to patients without SDB., Methods and Results: This cross-sectional analysis included a total of 88 eligible patients with first AMI and PCI pooled from two prospective studies and stratified according to the apnea-hypopnea index (AHI, with SDB: AHI ≥ 15 h -1 ). We analyzed circulating levels of hs-CRP and PIIINP 3-5 days after PCI. Patients with SDB had significantly higher levels of hs-CRP (18.3 mg/L [95% CI, 8.0-42.6] vs. 5.8 mg/L [95% CI, 4.2-19.8], p = 0.002) and PIIINP (0.49 U/mL [95% CI, 0.40-0.60] vs. 0.33 U/mL [95% CI, 0.28-0.43], p < 0.001). In a multivariable linear regression model accounting for important clinical confounders, SDB significantly predicted circulating levels of hs-CRP ( p = 0.028). Similarly, only SDB was independently associated with PIIINP ( p < 0.001). Only obstructive but not central AHI correlated with circulating levels of hs-CRP ( p = 0.012) and PIIINP ( p = 0.006) levels., Conclusions: The presence of obstructive SDB after AMI was independently associated with increased circulating levels of hs-CRP and PIIINP. Our results emphasize the important role of SDB as a common comorbidity and indicate increased inflammation and myocardial fibrosis in these patients.

Background: Coronary collateral flow in angiography has been linked with lower mortality rates in patients with coronary artery disease. However, the relevance of the underlying mechanism is sparse. Therefore, we tested the hypothesis that in patients with acute myocardial infarction (AMI), relevant coronary collateral flow is associated with more salvaged myocardium and lower risk of developing heart failure., Methods and Results: Patients with first AMI who received a percutaneous coronary intervention within 24 h after symptom onset were classified visually by assigning a Cohen-Rentrop Score (CRS) ranging between 0 (no collaterals) and 3 (complete retrograde filling of the occluded vessel). All 36 patients included in the analysis underwent cardiac magnetic resonance examination within 3 to 5 days after myocardial infarction and after 12 weeks. Patients with relevant collateral flow (CRS 2-3) to the infarct-related artery had significantly smaller final infarct size compared to those without (7 ± 4% vs. 20 ± 12%, p < 0.001). In addition, both groups showed improvement in left ventricular ejection fraction early after AMI, whereas the recovery was greater in CRS 2-3 (+8 ± 5% vs. +3 ± 5%, p = 0.015)., Conclusion: In patients with first AMI, relevant collateral flow to the infarct-related artery was associated with more salvaged myocardium at 12 weeks, translating into greater improvement of systolic left ventricular function. The protective effect of coronary collaterals and the variance of infarct location should be further investigated in larger studies.

Aims: Sleep disordered breathing (SDB) is known to cause left atrial (LA) remodeling. However, the relationship between SDB severity and LA dysfunction is insufficiently understood and may be elucidated by detailed feature tracking (FT) strain analysis of cardiac magnetic resonance images (CMR). After myocardial infarction (MI), both the left ventricle and atrium are subjected to increased stress which may be substantially worsened by concomitant SDB that could impair consequential healing. We therefore analyzed atrial strain in patients at the time of acute MI and 3 months after., Methods and Results: 40 patients with acute MI underwent CMR and polysomnography (PSG) within 3-5 days after MI. Follow-up was performed 3 months after acute MI. CMR cine data were analyzed using a dedicated FT software. Atrial strain (ε) and strain rate (SR) for atrial reservoir ([ε s ]; [SR s ]), conduit ([ε e ]; [SR e ]) and booster function ([ε a ]; [SR a ]) were measured in two long-axis views. SDB was defined by an apnea-hypopnea-index (AHI) ≥15/h. Interestingly, LA ε s and ε e were significantly reduced in patients with SDB and correlated negative with AHI as a measure of SDB severity at both baseline and follow-up. Intriguingly, patients that exhibited a reduced AHI at follow-up were more likely to have developed improved atrial reservoir and conduit strain (linear regression, p =0.08 for ε s and ε e ). Patients with improved SDB (ΔAHI < -5/h) exhibited a mean improvement of LA reservoir strain of +7.2 ± 8.4% whereas patients with SDB deterioration (ΔAHI> + 5/h) showed a mean decrease of -5.3 ± 11.0% ( p = 0.0131). Similarly, the difference for LA conduit function was +4.8 ± 5.9% (ΔAHI < -5/h) vs -3.6 ± 8.8% (ΔAHI> +5/h). Importantly, conventional volumetric parameters for atrial function (LA area, LA volume index) did not correlate with AHI at baseline or follow-up., Conclusion: Our results show that LA function measured by CMR strain but not by volumetry is impaired in patients with SDB during acute cardiac injury. Consistent with a mechanistic association, improvement of SBD at follow-up resulted in improved LA strain. LA strain measurement might thus provide insight into atrial function in patients with SDB., Competing Interests: MA received lecture and consulting fees from ResMed, Philips Respironics, Boehringer-Ingelheim, NRI, Novartis, JAZZ pharmaceuticals, Bayer, Inspire and Bresotec and grant support from ResMed Foundation, ResMed, and Philips Respironics outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wester, Pec, Lebek, Fisser, Debl, Hamer, Poschenrieder, Buchner, Maier, Arzt and Wagner.)

Sleep-disordered breathing (SDB) is highly prevalent in patients with cardiovascular disease. We have recently shown that an elevation of the electrocardiographic (ECG) parameter P wave terminal force in lead V 1 (PTFV 1 ) is linked to atrial proarrhythmic activity by stimulation of reactive oxygen species (ROS)-dependent pathways. Since SDB leads to increased ROS generation, we aimed to investigate the relationship between SDB-related hypoxia and PTFV 1 in patients with first-time acute myocardial infarction (AMI). We examined 56 patients with first-time AMI. PTFV 1 was analyzed in 12-lead ECGs and defined as abnormal when ≥4000 µV*ms. Polysomnography (PSG) to assess SDB was performed within 3-5 days after AMI. SDB was defined by an apnea-hypopnea-index (AHI) >15/h. The multivariable regression analysis showed a significant association between SDB-related hypoxia and the magnitude of PTFV 1 independent from other relevant clinical co-factors. Interestingly, this association was mainly driven by central but not obstructive apnea events. Additionally, abnormal PTFV 1 was associated with SDB severity (as measured by AHI, B 21.495; CI [10.872 to 32.118]; p < 0.001), suggesting that ECG may help identify patients suitable for SDB screening. Hypoxia as a consequence of central sleep apnea may result in atrial electrical remodeling measured by abnormal PTFV 1 in patients with first-time AMI independent of ventricular function. The PTFV 1 may be used as a clinical marker for increased SDB risk in cardiovascular patients.

Aims: There is a lack of diagnostic and therapeutic options for patients with atrial cardiomyopathy and paroxysmal atrial fibrillation. Interestingly, an abnormal P-wave terminal force in electrocardiogram lead V 1 (PTFV 1 ) has been associated with atrial cardiomyopathy, but this association is poorly understood. We investigated PTFV 1 as a marker for functional, electrical, and structural atrial remodelling., Methods and Results: Fifty-six patients with acute myocardial infarction and 13 kidney donors as control cohort prospectively underwent cardiac magnetic resonance imaging to evaluate the association between PTFV 1 and functional remodelling (atrial strain). To further investigate underlying pathomechanisms, right atrial appendage biopsies were collected from 32 patients undergoing elective coronary artery bypass grafting. PTFV 1 was assessed as the product of negative P-wave amplitude and duration in lead V 1 and defined as abnormal if ≥4000 ms*μV. Activity of cardiac Ca/calmodulin-dependent protein kinase II (CaMKII) was determined by a specific HDAC4 pull-down assay as a surrogate for electrical remodelling. Atrial fibrosis was quantified using Masson's trichrome staining as a measure for structural remodelling. Multivariate regression analyses were performed to account for potential confounders. A total of 16/56 (29%) of patients with acute myocardial infarction, 3/13 (23%) of kidney donors, and 15/32 (47%) of patients undergoing coronary artery bypass grafting showed an abnormal PTFV 1 . In patients with acute myocardial infarction, left atrial (LA) strain was significantly reduced in the subgroup with an abnormal PTFV 1 (LA reservoir strain: 32.28 ± 12.86% vs. 22.75 ± 13.94%, P = 0.018; LA conduit strain: 18.87 ± 10.34% vs. 10.17 ± 8.26%, P = 0.004). Abnormal PTFV 1 showed a negative correlation with LA conduit strain independent from clinical covariates (coefficient B: -7.336, 95% confidence interval -13.577 to -1.095, P = 0.022). CaMKII activity was significantly increased from (normalized to CaMKII expression) 0.87 ± 0.17 to 1.46 ± 0.15 in patients with an abnormal PTFV 1 (P = 0.047). This increase in patients with an abnormal PTFV 1 was independent from clinical covariates (coefficient B: 0.542, 95% confidence interval 0.057 to 1.027, P = 0.031). Atrial fibrosis was significantly lower with 12.32 ± 1.63% in patients with an abnormal PTFV 1 (vs. 20.50 ± 2.09%, P = 0.006), suggesting PTFV 1 to be a marker for electrical but not structural remodelling., Conclusions: Abnormal PTFV 1 is an independent predictor for impaired atrial function and for electrical but not for structural remodelling. PTFV 1 may be a promising tool to evaluate patients for atrial cardiomyopathy and for risk of atrial fibrillation., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Abstract: The objective of this study was to ascertain changes in symptoms of patients with borderline personality disorder undergoing psychodynamic day treatment with a duration of 9 months and the factors that predict clinical outcome or dropouts from the program.In an observational study, demographic characteristics (age, number of psychiatric hospitalizations, number of suicide attempts, current involvement in work or study activities), day doses of antipsychotic and antidepressant medication, psychiatric symptoms, and social functioning (Health of the Nation Outcome Scales), and symptoms of dissociation (Dissociative Experiences Scale) were assessed in patients at the beginning of treatment (N = 105). Further, psychiatric symptoms and social functioning were assessed at 3 stages: beginning of the program, end of the program, and 1-year follow-up. To study the differences between baseline values and values at the end of the treatment and follow-up values, the Wilcoxon signed-rank test was used. To discover baseline factors related to the effect of the treatment, Spearman correlation coefficients were calculated. To evaluate the differences between patients who completed the program (N = 67) and patients who dropped out (N = 38), differences in baseline factors between both groups were compared, using the Mann-Whitney test for independent samples.Improvement in symptoms (Health of the Nation Outcome Scales - version for external evaluators) at the end of the therapy (N = 67, P < .001) and at the 1-year follow-up (N = 46, P < .001) was found. Experience of an intimate relationship was positively related to clinical improvement at follow-up examinations (P < .001). Predictors of dropout included a higher number of psychiatric hospitalizations (P = .004), suicide attempts (P = .004), more severe pretreatment symptoms (P = .002), and symptoms of dissociation (P = .046).The results indicate that a psychodynamic day treatment is feasible for the treatment of less clinically disturbed patients with a history of intimate relationships. Patients with a higher number of previous psychiatric hospitalizations, more suicide attempts in the past, more severe pretreatment symptoms, and symptoms of dissociation are more likely not to complete the program., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cannabis sativa L. plants produce a diverse array of secondary metabolites. Cannabis cell cultures were treated with jasmonic acid (JA) and pectin as elicitors to evaluate their effect on metabolism from two cell lines using NMR spectroscopy and multivariate data analysis. According to principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA), the chloroform extract of the pectin-treated cultures were more different than control and JA-treated cultures; but in the methanol/water extract the metabolome of the JA-treated cells showed clear differences with control and pectin-treated cultures. Tyrosol, an antioxidant metabolite, was detected in cannabis cell cultures. The tyrosol content increased after eliciting with JA.

Cannabis sativa L. plants produce a diverse array of secondary metabolites. Cannabis cell cultures were treated with biotic and abiotic elicitors to evaluate their effect on secondary metabolism. Metabolic profiles analysed by (1)H NMR spectroscopy and principal component analysis (PCA) showed variations in some of the metabolite pools. However, no cannabinoids were found in either control or elicited cannabis cell cultures. Tetrahydrocannabinolic acid (THCA) synthase gene expression was monitored during a time course. Results suggest that other components in the signaling pathway can be controlling the cannabinoid pathway.

Cough sensitivity is increased in patients with atopic dermatitis, although they have no clinical symptoms from the lower airways. In the present study we examined the cough sensitivity to capsaicin in patients, who had no clinical respiratory symptoms, with sclerodermia localized to the skin. Cough sensitivity was defined as the lowest capsaicin concentration, which evokes 2 or more coughs. Twelve patients and 12 healthy matched volunteers, as a comparison group, inhaled deep breaths (2 L) of a capsaicin aerosol in doubled concentrations (from 0.02 to 200 micromol/L). Cough sensitivity, expressed as a geometric mean (95% CI) of capsaicin concentration, was 0.15 micromol/L (0.04 to 0.56) in the patients with localized sclerodermia and 4.96 micromol/L (2.50 to 9.85) in controls, which made a significant difference towards higher cough sensitivity in sclerodermia, respiratory symptom-free patients. Thus, disease processes localized outside the respiratory tract may have surreptitious pulmonary manifestation that is brought to light by the capsaicin cough test.