Efficacy and safety of tirbanibulin 1% ointment in actinic keratoses: Data from two phase-III trials and the real-life clinical practice presented at the European Academy of Dermatology and Venereology Congress 2022.

BACKGROUND: The 31st European Academy of Dermatology and Venereology (EADV) Congress took place between 7th and 10th of September 2022 in Milan, Italy. OBJECTIVES: We report presented clinical data on the efficacy/effectiveness, safety and tolerability of tirbanibulin 1% ointment that has recently been licensed for actinic keratosis (AK) of the face or scalp in adults. METHODS: Summary of presentations given at the EADV Congress. RESULTS: Prof. Pellacani presented two post hoc analyses from two phase-III trials with AK patients (NCT03285477 [N = 351] and NCT03285490 [N = 351]): A descriptive analysis of medical history, concomitant medications, and safety results confirming a favourable profile for tirbanibulin showing that number of baseline AK lesions was not correlated to severity of local skin reactions. The latter analysis showed that cases of tirbanibulin application site pain or pruritus were few, and most were found to be mild. Prof. Kunstfeld reported six real-life clinical cases in Austria showing good tirbanibulin effectiveness, safety and tolerability for the treatment of new or recurring AK lesions. Results demonstrated that after 2- to 4-month follow-up, tirbanibulin was well tolerated and effective in AK patients. Presentations by Dr. Patel confirmed good outcomes and tolerability of tirbanibulin in Olsen grade 1-2 AK (N = 12) and porokeratosis patients (N = 4) treated once daily for 5 consecutive days in the United Kingdom. Furthermore, real-world experience in solid organ transplant recipients (N = 2) demonstrated effectiveness of tirbanibulin in skin field cancerization treatment. A symposium sponsored by Almirall was conducted during the congress in which Dr. Hadshiew and Dr. Lear brought together their clinical experience in Germany and the United Kingdom respectively. Interesting clinical cases of 5 consecutive days of tirbanibulin treatment compared to other treatments were discussed with attendees, as well as current treatment needs of AK patients. CONCLUSIONS: This article provides an overview of presentations and symposium discussions, summarizing key phase-III results and real-life clinical experience with tirbanibulin shared by dermatologists across Europe.

[Postoperative nausea and vomiting-recommendations for its prevention and therapy in paediatric medicine]. / Postoperative Übelkeit und Erbrechen ­ Handlungsempfehlungen zur Prävention und Therapie bei Kindern.

Post-operative nausea and/or vomiting (PONV/POV) are among the biggest problems occurring in the paediatric recovery room and in the course of the following post-operative period. Apart from pain and emergence delirium, PONV is one of the main causes of post-operative discomfort in children. The DGAI Scientific Working Group on Paediatric Anaesthesia already worked out recommendations for the prevention and treatment of PONV in children years ago. These recommendations have now been revised by a team of experts, the current literature has been reviewed, and evidence-based core recommendations have been consented. Key elements of the new recommendations consist of effective individual measures for prevention and therapy, next to the implementation of a fixed dual prophylaxis in the clinical routine applicable to all children ≥ 3 years of age.

Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: an abridged Cochrane network meta-analysis.

Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta-analyses to compare, and rank in terms of efficacy and safety, single anti-emetic drugs and their combinations, including 5-hydroxytryptamine3 , dopamine-2 and neurokinin-1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo-controlled and head-to-head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta-Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class-specific side-effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin-1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18-0.38); ramosetron, 0.44 (0.32-0.59); granisetron, 0.45 (0.38-0.54); dexamethasone, 0.51 (0.44-0.57); and ondansetron, 0.55 (0.51-0.60). It was moderate for fosaprepitant, 0.06 (0.02-0.21) and droperidol, 0.61 (0.54-0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side-effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.

[Anesthesia and intensive care ventilators: differences and usability in COVID-19 patients]. / Anästhesie- und Intensivbeatmungsgeräte: Unterschiede und Nutzbarkeit bei COVID-19-Patienten.

The current coronavirus disease 2019 (Covid-19) pandemia is a highly dynamic situation characterized by therapeutic and logistic uncertainties. Depending on the effectiveness of social distancing, a shortage of intensive care respirators must be expected. Concomitantly, many physicians and nursing staff are unaware of the capabilities of alternative types of ventilators, hence being unsure if they can be used in intensive care patients. Intensive care respirators were specifically developed for the use in patients with pathological lung mechanics. Nevertheless, modern anesthesia machines offer similar technical capabilities including a number of different modes. However, conceptual differences must be accounted for, requiring close monitoring and the presence of trained personnel. Modern transport ventilators are mainly for bridging purposes as they can only be used with 100% oxygen in contaminated surroundings. Unconventional methods, such as "ventilator-splitting", which have recently received increasing attention on social media, cannot be recommended. This review intends to provide an overview of the conceptual and technical differences of different types of mechanical ventilators.

Quo Vadis PCA? A Review on Current Concepts, Economic Considerations, Patient-Related Aspects, and Future Development with respect to Patient-Controlled Analgesia.

This review assesses four interrelating aspects of patient-controlled analgesia (PCA), a long-standing and still widely used concept for postoperative pain management. Over the years, anaesthesiologists and patients have appreciated the benefits of PCA alike. The market has seen new technologies leveraging noninvasive routes of administration and, thus, further increasing patient and staff satisfaction as well as promoting safety aspects. Pharmaceutical research focuses on the reduction or avoidance of opioids, side effects, and adverse events although influence of these aspects appears to be minor. The importance of education is still eminent, and new educational formats are tested to train healthcare professionals and patients likewise. New PCA technology can support the implementation of efficient processes to reduce workload and human errors; however, these new products come with a cost, which is not necessarily reflected through beneficial budget impact or significant improvements in patient outcome. Although first steps have been taken to better recognize the importance of postoperative pain management through the introduction of value-based reimbursement, in most western countries, PCA is not specifically compensated. PCA is still an effective and valued technique for postoperative pain management. Although there is identifiable potential for future developments in various aspects, this potential has not materialized in new products.

[Identification of the epidural space using pressure waveform analysis (CompuFlo® technology): a case series]. / Identifikation des Epiduralraums mithilfe einer Druckkurvenanalyse (CompuFlo®-Technologie): eine Fallserie.

Anesthesiologists commonly perform the loss of resistance technique in order to identify the epidural space during neuraxial procedures; however, this technique is subjective and lacks reliability in certain cases. The so-called CompuFlo® technology provides objective information about the position of the epidural needle by means of a pressure curve and acoustic signals. The technology was introduced several years ago and was evaluated in several trials, which showed promising results. The purpose of the present publication is to report on the first experiences with the CompuFlo® technology in German-speaking countries. A series of 24 epidural procedures using the CompuFlo® device was carried out in routine daily practice. The epidural space was successfully identified in 23 cases. Conversion to the conventional loss of resistance technique was performed during the initial cases in a prolonged procedure. The CompuFlo® technique is considered to be a promising technology, which might help to reduce complications after epidural anesthesia, e.g. postdural puncture headache.

Thermometry of a high temperature high speed micro heater.

A high temperature high-speed tungsten micro heater was fabricated and tested for application in phase change switches to indirectly heat and transform phase change material. Time domain transmissometry was used to measure heater temperature transients for given electrical inputs. Finite element modeling results on heater temperature transients show a good consistency between experiments and simulations with 0.2% mismatch in the best case and 13.1% in the worst case. The heater described in this work can reliably reach 1664 K at a rate of 1.67 × 10(10) K/s and quench to room temperature with a thermal RC time constant (time for T to fall by a factor of e) of less than 40 ns.

The relationship between competencies acquired through Swiss academic sports science courses and the job requirements.

In view of the changes in and growing variety of sports-related occupations, it is highly relevant for educational institutions to know how well the educational contents of their sport science courses meet the professional requirements. This study analyses the relationship between the competencies acquired through academic sports science courses and the requirements of the relevant jobs in Switzerland. The data for this empirical analysis were drawn from a sample of n = 1054 graduates of different academic sport science programmes at all eight Swiss universities. The results show that academic sport science courses primarily communicate sports-specific expertise and practical sports skills. On the other hand, most graduates consider that the acquisition of interdisciplinary competencies plays a comparatively minor role in sport science education, even though these competencies are felt to be an important requirement in a variety of work-related environments and challenges.

Measurement of the radiation dose and assessment of the risk in mammography screening for early detection of cancer of the breast, in Israel.

The mean glandular doses to samples of women attending for mammographic screening are measured routinely at screening centres in Israel. As at present, no detailed and systematic data have been collected regarding the average glandular dose in mammography screening procedures carried out in Israel for the last 20 y. Especially data are lacking related to the glandular dose (GD) involved in mammography with the new digital mammography systems. In this work, partial results of the measurements are presented to asses the radiation dose to the breast and to the glandular tissue within the Israeli national mammography programme updated to year 2009.

Field localization in very small aperture lasers studied by apertureless near-field microscopy.

Localized surface plasmon polaritons (SSPs) have been observed on very small aperture lasers using apertureless near-field microscopy. Fields around multiple apertures are shown to result from interferences of SPP point sources at each aperture and optical fields. The near-field optical pattern around a single aperture indicates the interference of SPPs with their scattered counterparts. Near-field measurements also confirmed a preferred orientation of the rectangular aperture waveguide for the signal localization in very small aperture lasers.

Familial cutaneous mastocytosis.

Cutaneous mastocytosis appears to occur sporadically; however, familial inheritance has been reported in 50 families since the mid-1880s. We report four cases of telangiectasia macularis eruptiva perstans (TMEP) occurring in three generations of a family. Whereas most patients with TMEP manifest in adulthood, all of the members of this family developed initial lesions during childhood. This is the third documented instance of familial mastocytosis affecting members of three generations, and the first report of familial TMEP. Although the inheritance pattern is unknown, the presentation of disease in this family further supports the hypothesis of an autosomal dominant mode of transmission with incomplete penetrance.

Optical field study of near-field optical recording with a solid immersion lens.

The use of a solid immersion lens (SIL) is an important technique for increasing areal density in optical recording. Here an approximate method is presented for analyzing the optical fields in a SIL above a half-space and a SIL above a multilayer recording medium. Both propagating and evanescent components are included in the distribution of fields below the SIL. An approximate closed-form expression is given for the decay of the intensity away from the SIL surface above a half-space. In the case of a SIL above a recording medium the model describes the strong oscillations that are observed in the reflected Kerr rotation and ellipticity as the medium spacing is varied. These oscillations are attributed to standing waves in the propagating field component.

Platelet-derived growth factor-dependent association of the GTPase-activating protein of Ras and Src.

Here we report that the platelet-derived growth factor beta receptor (betaPDGFR) is not the only tyrosine kinase able to associate with the GTPase-activating protein of Ras (RasGAP). The interaction of non-betaPDGFR kinase(s) with RasGAP was dependent on stimulation with platelet-derived growth factor (PDGF) and seemed to require tyrosine phosphorylation of RasGAP. Because the tyrosine phosphorylation site of RasGAP is in a sequence context that is favoured by the Src homology 2 ('SH2') domain of Src family members, we tested the possibility that Src was the kinase that associated with RasGAP. Indeed, Src interacted with phosphorylated RasGAP fusion proteins; immunodepletion of Src markedly decreased the recovery of the RasGAP-associated kinase activity. Thus PDGF-dependent tyrosine phosphorylation of RasGAP results in the formation of a complex between RasGAP and Src. To begin to address the relevance of these observations, we focused on the consequences of the interaction of Src and RasGAP. We found that a receptor mutant that did not activate Src was unable to efficiently mediate the tyrosine phosphorylation of phospholipase Cgamma (PLCgamma). Taken together, these observations support the following hypothesis. When RasGAP is recruited to the betaPDGFR, it is phosphorylated and associates with Src. Once bound to RasGAP, Src is no longer able to promote the phosphorylation of PLCgamma. This hypothesis offers a mechanistic explanation for our previously published findings that the recruitment of RasGAP to the betaPDGFR attenuates the tyrosine phosphorylation of PLCgamma. Finally, these findings suggest a novel way in which RasGAP negatively regulates signal relay by the betaPDGFR.

MEK kinase 1 (MEKK1) transduces c-Jun NH2-terminal kinase activation in response to changes in the microtubule cytoskeleton.

Cell shape change and the restructuring of the cytoskeleton are important regulatory responses that influence the growth, differentiation, and commitment to apoptosis of different cell types. MEK kinase 1 (MEKK1) activates the c-Jun NH2-terminal kinase (JNK) pathway in response to exposure of cells to microtubule toxins, including taxol. MEKK1 expression is elevated 3-fold in mitosis and microtubule toxin-treated cells accumulated at G2/M of the cell cycle. Targeted disruption of MEKK1 expression in embryonic stem cells resulted in the loss of JNK activation and increased apoptosis in response to taxol. Targeted disruption of the MEK kinase 2 gene had no effect on activation of the JNK pathway in response to microtubule toxins demonstrating a specific role of MEKK1 in this response. Cytochalasin D-mediated disruption of actin fibers activates JNK and stimulates apoptosis similarly in MEKK1(-/-) and wild type cells. The results show that MEKK1 is required for JNK activation in response to microtubule but not actin fiber toxins in embryonic stem cells. MEKK1 activation can protect cells from apoptosis in response to change in the integrity of the microtubule cytoskeleton.

Integrated electro-optic lens/scanner in a LiTaO3 single crystal.

We report what we believe to be the first stand-alone integrated electro-optic lens and scanner fabricated on a single crystal of Z-cut LiTaO(3). The independently controlled lens and scanner components consist of lithographically defined domain-inverted regions extending through the thickness of the crystal. A lens power of 0.233 cm(-1) kV(-1) and a deflection angle of 12.68 mrad kV(-1) were observed at the output of the device.

The TAO of MEKK.

Cloning and characterization of MEKK1 in 1993 revealed that in addition to Raf there were other pathways activated by extracellular stimuli that were responsible for ERK activation. Since then, three additional MEKK family members have been cloned adding even further diversity to the regulation of MAPK pathways. The MEKK family members are regulated by a diverse array of extracellular stimuli ranging from growth factors to DNA damaging stimuli and so are important for the cell to sense exposure to various environmental stimuli. One important aspect of MEKK biology is that they can potentially serve in more than one pathway. Regulation of MEKK family members often involves LMWG proteins, phosphorylation and subcellular localization. With regard to at least MEKK1, serine/threonine kinases such as NIK, GLK and HPK1 appear also to be important for regulation. Of the MEKK family members, the biological role of MEKK1 is best characterized and studies have shown that MEKK1 is important in mediating survival vs. apoptosis, possibly via its ability to regulate transcription factors, the expression of death receptors and their ligands. The biological roles of MEKK2, 3 and 4 are under investigation and undoubtedly homologous deletion of these MEKK family members will be invaluable at determining the biological functions of these MEKKs. At present, the MEKK family members are characterized as localized sensors that control cell responses at the level of gene expression, metabolism and the cytoskeleton

Anti-apoptotic versus pro-apoptotic signal transduction: checkpoints and stop signs along the road to death.

The activation of caspases is a final commitment step for apoptosis. It is now evident that signal transduction pathways involving specific protein kinases modulate the apoptotic response. Both pro-apoptotic and anti-apoptotic pathways integrate environmental cues that control the decision to undergo apoptosis. Pro- and anti-apoptotic signal pathways regulate the activation of the caspases. In this review we describe our current understanding of apoptotic signal transduction.

An economic evaluation of the use of rare earth screens to reduce the radiation dose from diagnostic X-ray procedures in Israel.

In Israel the diffusion of rare earth screen technology has been limited. These screens could halve the radiation dose to the patient from diagnostic X-ray radiography, with little managerial effort and without being detrimental to the quality of the diagnostic image. We estimated the total effective dose from diagnostic film radiography capable of reduction by the use of rare earth screens, based on the number of hospital and ambulatory diagnostic X-ray procedures. This number was multiplied by the computed radiation dose per body site for a series of diagnostic procedures. The annual dose was approximately 0.53 mSv per head, approximately half of which could be averted by the introduction of rare earth screen technology. Based on a fatality risk of 3% Sv-1, it is estimated that the adoption of rare earth screen technology might reduce the annual incidence of cancer by some 93 cases, half of which would be fatal after an average latency period of 18.4 years. The cost of purchasing rare earth screens on a nationwide basis is approximately $3.0 million. This cost is outweighed by a saving of $9.6 million in X-ray tube replacement costs over the period 1997-2006. Government legislation enforcing the use of rare earth screens is essential, because of the lack of prestige associated with acquiring rare earth technology, as well as institutional reluctance to accept the external benefits of reduced morbidity and mortality and/or to extend budgetary time horizons.

Paraneoplastic pemphigus occurring in a patient with B-cell non-Hodgkin's lymphoma.

We present the case of a 71-year-old white male with paraneoplastic pemphigus associated with a B-cell non-Hodgkin's lymphoma. Diagnosis of paraneoplastic pemphigus was made by the characteristic findings on immunoprecipitation performed on a serum specimen. Paraneoplastic pemphigus is a severe autoimmune disease comprised of polymorphous mucocutaneous lesions, characteristic laboratory findings, association with one of several types of neoplasms, and a very poor prognosis.