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Background: As adults with congenital heart disease (ACHD) are getting older, acquired comorbidities play an important role in morbidity and mortality. Data regarding their prevalence in ACHD that are representative on a population level are not available. Methods: The German National Register for Congenital Heart Defects was screened for ACHD. Underlying congenital heart disease (CHD), patient demographics, previous interventional/surgical interventions, and comorbidities were retrieved. Patients <40 years of age were compared to those ≥40 years. Results: A total of 4673 patients (mean age 33.6 ± 10.7 years, female 47.7%) was included. At least one comorbidity was present in 2882 patients (61.7%) altogether, and in 56.8% of patients below vs. 77.7% of patients over 40 years of age (p < 0.001). Number of comorbidities was higher in patients ≥40 years (2.1 ± 2.1) than in patients <40 years (1.2 ± 1.5, p < 0.001). On multivariable regression analysis, age and CHD complexity were significantly associated with the presence and number of comorbidities. Conclusions: At least one acquired comorbidity is present in approximately two-thirds of ACHD. Age and complexity of the CHD are significantly associated with the presence of comorbidities. These findings highlight the importance of addressing comorbidities in ACHD care to achieve optimal long-term outcomes.
Chronisch-entzündliche Dermatosen sind in Deutschland weit verbreitet und haben einen enormen Einfluss auf die Lebensqualität der Erkrankten. Das umfassende Verständnis der molekularen Prozesse und Signalwege bildet die Basis, um mögliche Beziehungen zwischen den Hauterkrankungen aufzudecken. Der Nachweis von Ähnlichkeit und Übereinstimmung in den Signalwegen bietet die Aussicht, dass etablierte Therapien auch bei anderen Erkrankungen helfen können.
Der Zweck dieser Arbeit ist der Nachweis der Expression von IL-1β, IL-17A, IL-22, IL-23 und TNF-α in drei chronisch-entzündlichen Dermatosen: Acne inversa (AI), Sinus pilondalis (SP) und Perifolliculitis capitis abscedens et suffodiens (PCAS). Bei allen untersuchten Diagnosen handelt es sich um potentiell verwandte Erkrankungen der Haarfollikel, die durch Verlegung der Ausführungsgänge zu ausgedehnten Entzündungsreaktionen mit Bildung von Knoten, Abszessen und Fisteln führen. Bereits nachgewiesen ist, dass IL-1β, IL-17A, IL-22, IL-23 und TNF-α eine wichtige Rolle in der Pathogenese von Acne inversa spielen und Antikörpertherapien an einigen dieser Zielproteine spezifisch angreifen, um den Verlauf der Erkrankung zu verbessern.
Die Expression der Proteine wurde in Läsionen von Patienten mit den drei Indikationen immunhistochemisch an paraffiniertem Gewebe untersucht. Wie erwartet, zeigten sich in der überwiegenden Anzahl der Proben große entzündliche Infiltrate und hier wurde die Expression aller untersuchten Zytokine in unterschiedlicher Intensität nachgewiesen. Vielversprechend war insbesondere die Expression von IL-17A und IL-23 in SP und PCAS. Die Expression von IL-1β war insgesamt eher gering ausgeprägt; bei AI noch etwas höher als in SP und PCAS. Die Färbungen auf IL-22 zeigten sich kräftig in allen untersuchten Dermatosen. Allerdings gibt es bisher keine zugelassene Therapie zur Modulation dieses speziellen Zytokins. IL-22 scheint eine zentrale Rolle in
der Pathogenese der AI zu spielen. Mit TNF-α-Blockern wurden schon gute therapeutische Ergebnisse bei AI und PCAS erzielt. Deshalb ist der Nachweis von TNF-α in den entzündlichen Läsionen zu erwarten gewesen. Auch bei den SP-Proben fanden sich deutlich erhöhte Protein-Level, sodass auch hier eine gezielte Therapie von Vorteil sein könnte. Wegen des geringen Probenumfangs und der Methodik sind weitere gezielte Untersuchungen notwendig. Dennoch konnten viele Gemeinsamkeiten der Zytokinexpression ausgemacht werden, was vielversprechende Hinweise auf mögliche Behandlungsansätze bei AI, SP und PCAS zulässt. Diese Arbeit bietet einen ersten Blick auf den immunologischen Phänotyp der verwandten Dermatosen.
Background: Plaque psoriasis is a common, chronic and relapsing inflammatory skin disease clinically characterized by erythema and scaling desquamation. As over 90% of psoriasis patients benefit from topical therapies, local treatments continue to play an eminent role in management strategies. One such topical treatment is the fixed dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP).
Objectives: Pooled analysis of two different phase 3 clinical trails to compare superiority regarding efficacy, safety and quality of life (QoL) between CAL/BDP PAD-cream and CAL/BDP TS.
Methods: The data from two phase 3, multicentre, randomized, investigator-blind, active and vehicle-controlled trials enrolling patients with psoriasis were pooled and analysed. Investigational products included a CAL/BDP cream based on PAD™ Technology (PAD-cream) designed for high skin penetration and increased patient preference, an active control (marketed CAL/BDP topical suspension/gel, in the following abbreviated as CAL/BDP TS) and cream vehicle, which were applied once daily for 8 weeks.
Results: Efficacy and safety of the novel CAL/BDP PAD-cream formulation for the topical treatment of psoriasis demonstrated superiority for all efficacy end points after 8 weeks of treatment. PGA treatment success for CAL/BDP PAD-cream (43.2%) was greater than CAL/BDP TS (31.9%; P < 0.0001), the mean per cent reduction in mPASI for CAL/BDP PAD-cream was 64.6% compared to 56.4% for CAL/BDP TS (P < 0.0001) and DLQI 0/1 was obtained by 43.8% in the CAL/BDP PAD-cream group versus 34.2% in the CAL/BDP TS group (P = 0.0005). There was no adverse drug reaction reported with a frequency of >1%, associated with the CAL/BDP PAD-cream.
Conclusions: The novel fixed dose combination CAL/BDP PAD-cream offers greater efficacy, superior patient QoL and equivalent favourable safety for the topical treatment of psoriasis, in comparison to the currently available topical suspension/gel.
Objectives and Methods: Intracranial hemorrhage (ICH) in acute myeloid leukemia (AML) patients is a major concern due to the increased risk of mortality. Few studies have examined ICH specifically in newly diagnosed AML patients receiving intensive induction chemotherapy (IC) and prophylactic platelet transfusions during thrombocytopenia <10/nL. This retrospective cohort study included 423 newly diagnosed AML patients without acute promyelocytic leukemia who underwent IC between 2007 and 2019. We assessed risk factors, clinical features, and outcomes of ICH.
Results: 17 of 423 patients (4%) suffered ICH during hospital stay, and 4 patients (24%) died directly because of ICH despite routine prophylactic platelet transfusions. Patients with ICH had a negatively impacted overall survival (median OS, 20.1 vs. 104.8 months) and were more likely not to continue with curative treatment. Main risk factors were female gender, severe thrombocytopenia, and decreased fibrinogen. Patients with subsequent ICH also had laboratory signs of liver dysfunction.
Conclusions: Intracranial hemorrhage remains a potentially deadly complication with notable incidence despite prophylactic platelet substitution, suggesting that additional prophylactic interventions may be required to further reduce the frequency of ICH in high-risk patients. Unrecognized genetic factors may simultaneously predispose to AML and platelet dysfunction with ICH.
During the last 30 years, our understanding of the development and diversification of postganglionic sympathetic neurons has dramatically increased. In parallel, the list of target structures has been critically extended from the cardiovascular system and selected glandular structures to metabolically relevant tissues such as white and brown adipose tissue, lymphoid tissues, bone, and bone marrow. A critical question now emerges for the integration of the diverse sympathetic neuron classes into neural circuits specific for these different target tissues to achieve the homeostatic regulation of the physiological ends affected.
Efficacy of platelet-rich fibrin in promoting the healing of extraction sockets: a systematic review
(2021)
Purpose: To address the focused question: in patients with freshly extracted teeth, what is the efficacy of platelet-rich fibrin (PRF) in the prevention of pain and the regeneration of soft tissue and bone compared to the respective control without PRF treatment?
Methods: After an electronic data search in PubMed database, the Web of Knowledge of Thomson Reuters and hand search in the relevant journals, a total of 20 randomized and/or controlled studies were included.
Results: 66.6% of the studies showed that PRF significantly reduced the postoperative pain, especially in the first 1–3 days after tooth extraction. Soft tissue healing was significantly improved in the group of PRF compared to the spontaneous wound healing after 1 week (75% of the evaluated studies). Dimensional bone loss was significantly lower in the PRF group compared to the spontaneous wound healing after 8–15 weeks but not after 6 months. Socket fill was in 85% of the studies significantly higher in the PRF group compared to the spontaneous wound healing.
Conclusions: Based on the analyzed studies, PRF is most effective in the early healing period of 2–3 months after tooth extraction. A longer healing period may not provide any benefits. The currently available data do not allow any statement regarding the long-term implant success in sockets treated with PRF or its combination with biomaterials. Due to the heterogeneity of the evaluated data no meta-analysis was performed.
Purpose: To test for differences in cancer-specific mortality (CSM) rates in Hispanic/Latino prostate cancer patients according to treatment type, radical prostatectomy (RP) vs external beam radiotherapy (EBRT).
Methods: Within the Surveillance, Epidemiology, and End Results database (2010–2016), we identified 2290 NCCN (National Comprehensive Cancer Network) high-risk (HR) Hispanic/Latino prostate cancer patients. Of those, 893 (39.0%) were treated with RP vs 1397 (61.0%) with EBRT. First, cumulative incidence plots and competing risks regression models tested for CSM differences after adjustment for other cause mortality (OCM). Second, cumulative incidence plots and competing risks regression models were refitted after 1:1 propensity score matching (according to age, PSA, biopsy Gleason score, cT-stage, cN-stage).
Results: In NCCN HR patients, 5-year CSM rates for RP vs EBRT were 2.4 vs 4.7%, yielding a multivariable hazard ratio of 0.37 (95% CI 0.19–0.73, p = 0.004) favoring RP. However, after propensity score matching, the hazard ratio of 0.54 was no longer statistically significant (95% CI 0.21–1.39, p = 0.2).
Conclusion: Without the use of strictest adjustment for population differences, NCCN high-risk Hispanic/Latino prostate cancer patients appear to benefit more of RP than EBRT. However, after strictest adjustment for baseline patient and tumor characteristics between RP and EBRT cohorts, the apparent CSM benefit of RP is no longer statistically significant. In consequence, in Hispanic/Latino NCCN high-risk patients, either treatment modality results in similar CSM outcome.
Introduction: The estimation of age-at-death of unidentified cadavers is a central aspect of the identification process. With increasing age, the incidence of glomerulosclerosis and the thickness of the carotid wall have been observed to also increase. This correlation has been demonstrated in various international histological studies. The aim of our study was to assess whether these correlations also apply to a Western European population.
Methodology: In this retrospective observational study, kidney and common carotid artery samples from 216 cases autopsied at the Institute of Legal Medicine at the Justus-Liebig University in Giessen, Germany, were examined. Only cases with available tissue samples from both body sides were included. Exclusion criteria were poor sample quality and an age younger than 21 years. After histological processing, the tissue samples were assessed and digitally evaluated. Regression and classification analyses were used to investigate the correlation between age-at-death and intima-media thickness and age-at-death and the incidence of renal glomerular sclerosis.
Results: Of the 216 autopsy cases, 183 were included for evaluation. Analysis of the carotid artery segments showed a strong correlation (Pearson correlation coefficient r = 0.887) between the intima-media-complex thickness and chronological age. Classification of the glomerulosclerotic incidence showed a correlation of 37.7–43.1% with the predicted age group.
Discussion: Both the intima-media thickness and the proportion of sclerotic glomeruli can be used to estimate age in Western European cadavers. On the basis of these results, both methods are suited to supplement other already established methods for age-at-death estimation in the identification of an unknown cadaver.
Purpose: To evaluate the efficacy of alternative or adjunctive measures to conventional non-surgical or surgical treatment of peri-implant mucositis and peri-implantitis.
Material and methods: Prospective randomized and nonrandomized controlled studies comparing alternative or adjunctive measures, and reporting on changes in bleeding scores (i.e., bleed0ing index (BI) or bleeding on probing (BOP)), probing depth (PD) values or suppuration (SUPP) were searched.
Results: Peri-implant mucositis: adjunctive use of local antiseptics lead to greater PD reduction (weighted mean difference (WMD) = − 0.23 mm; p = 0.03, respectively), whereas changes in BOP were comparable (WMD = − 5.30%; p = 0.29). Non-surgical treatment of peri-implantitis: alternative measures for biofilm removal and systemic antibiotics yielded higher BOP reduction (WMD = − 28.09%; p = 0.01 and WMD = − 17.35%; p = 0.01, respectively). Surgical non-reconstructive peri-implantitis treatment: WMD in PD amounted to − 1.11 mm favoring adjunctive implantoplasty (p = 0.02). Adjunctive reconstructive measures lead to significantly higher radiographic bone defect fill/reduction (WMD = 56.46%; p = 0.01 and WMD = − 1.47 mm; p = 0.01), PD (− 0.51 mm; p = 0.01) and lower soft-tissue recession (WMD = − 0.63 mm; p = 0.01), while changes in BOP were not significant (WMD = − 11.11%; p = 0.11).
Conclusions: Alternative and adjunctive measures provided no beneficial effect in resolving peri-implant mucositis, while alternative measures were superior in reducing BOP values following non-surgical treatment of peri-implantitis. Adjunctive reconstructive measures were beneficial regarding radiographic bone-defect fill/reduction, PD reduction and lower soft-tissue recession, although they did not improve the resolution of mucosal inflammation.
Die vorliegende Übersicht zum Biomarker „Lipoprotein(a) – Lp(a)“ wird im Rahmen der Serie Diagnostika des Zentralblatts für Arbeitsmedizin, Arbeitsschutz und Ergonomie publiziert, die sich mit dem immer häufigeren Gebrauch der Bestimmung von spezifischen Markern bei sog. Manager-Vorsorgen und Check-up-Untersuchungen beschäftigt. Lipoprotein(a), Lp(a), eignet sich grundsätzlich nicht für solche Vorsorgen, sondern ist ein Marker zur Risikoabschätzung der peripheren arteriellen Verschlusskrankheit. Hier zeigt dieser eine hohe Sensitivität und Spezifität, wobei der Marker aber auf keinen Fall als Screeningparameter zur Frühdiagnostik eingesetzt werden sollte.