Spontaneous Preterm Birth: Is Prevention with Aspirin Possible?

Background The rate of preterm births in Germany is 8.6%, which is very high compared to other European countries. As preterm birth contributes significantly to perinatal morbidity and mortality rates, the existing prevention strategies need to be optimized and expanded further. About ⅔ of all women with preterm birth have preterm labor or premature rupture of membranes. They are bracketed together under the term “spontaneous preterm birth” as opposed to iatrogenic preterm birth, for example as a consequence of preeclampsia or fetal growth retardation. Recent studies suggest that low-dose aspirin does not just reduce the rate of iatrogenic preterm births but can also further reduce the rate of spontaneous preterm births. This review article presents the current state of knowledge. Method A selective literature search up until April 2020 was done in PubMed, using the terms “randomized trial”, “randomized study”, “spontaneous preterm birth”, and “aspirin”. Results Secondary analyses of prospective randomized studies on the prevention of preeclampsia with low-dose aspirin show that this intervention also significantly reduced the rate of spontaneous preterm births in both high-risk and low-risk patient populations. The results of the ASPIRIN trial, a prospective, randomized, double-blinded multicenter study carried out in six developing countries, also point in this direction, with the figures showing that the daily administration of 81 mg aspirin starting before 14 weeks of gestation lowered the preterm birth rate of nulliparous women without prior medical conditions by around 11% (11.6 vs. 13.1%; RR 0.89; 95% CI: 0.81 – 0.98, p = 0.012). Conclusion Further studies on this issue are urgently needed. If these confirm the currently available results, then it would be worth discussing whether general aspirin prophylaxis for all pregnant women starting at the latest in 12 weeks of gestation is indicated. Key words: spontaneous preterm birth, iatrogenic preterm birth, prevention, preeclampsia, aspirin     

Follow-up in gastrointestinal cancer

Follow-up after curative treatment of patients with gastrointestinal cancers aims to detect recurrent disease and to provide curative treatment to prolong overall survival if possible. This, however, has only been shown for colorectal cancers. Regular visits including testing of carcinoembryonic antigen and appropriate staging has been shown to enable curative treatment even in relapse. For other gastrointestinal cancers, positive effects of regular follow-up visits on survival have not been shown so far. This is mostly also due to lacking curative treatment strategies in case of relapse. In these cases, follow-up is recommended for providing palliative treatment, detecting recurrence for quality issues, treating complications or symptoms due to relapse, and providing psychological support. This review will give a brief overview about the current follow-up issues in colorectal, esophagogastric, and pancreatic cancers, as these are clinically the most relevant.     

Capsaicin‐induced neurogenic inflammation in the skin in patients with symptoms induced by odorous chemicals

Background: Intradermal injection of capsaicin induces the axonal release of neuropeptides, vasodilatation and flare, e.g. neurogenic inflammation. The spatial profile of neurogenic inflammation in the skin has been studied in various experimental models. Polarization spectroscopy imaging introduced recently may be used for the quantitative assessment of the temporal profile of neurogenic inflammation expressed as erythema intensity. Purpose: In the present study, we aimed to compare capsaicin‐induced erythema intensity with the flare area in patients with symptoms induced by odorous chemicals, thereby comparing the temporal and spatial profiles of neurogenic inflammation. Methods: Sixteen patients fulfilling Cullen's criteria for multiple chemical sensitivity (MCS) and 15 eczema (EC) patients with airway symptoms elicited by odorous chemicals were compared with 29 age‐matched, healthy controls. Participants were administered two intradermal injections of capsaicin 3.3 and 33 μM. Erythema intensity was measured by polarization spectroscopy imaging and flare response was quantified by visual inspection. Results: Erythema intensity and flare area did not differ between patients and controls, and they were not correlated. Erythema intensity and flare area showed a dose‐dependent increase (P<0.05). Erythema intensity increased with age at 3.3 μM but not at 33 μM capsaicin, whereas the flare area increased with age at both concentrations (P<0.05). Conclusion: Capsaicin‐induced erythema intensity and visual flare were normal in patients with MCS and EC patients with airway symptoms from odorous chemicals. Polarized light spectroscopy was a useful method for the measurement of the rapid temporal changes in erythema of experimental reactions.     

Roland Kuhn—100th Birthday of an Innovator of Clinical Psychopharmacology

On the occasion of his 100th birthday this letter is to pay tribute to Swiss psychiatrist and psychopharmacologist Roland Kuhn (1912–2005), who established the antidepressant effects of imipramine starting in 1956. Since until now only monoaminergic-based antidepressants such as this substance found their way into psychopharmacological therapy, one can say that Kuhn established the lead antidepressant substance and has hence fundamentally changed clinical psychiatry and care for the mentally ill.     

Lack of in vitro constitutive activity for four previously reported TSH receptor mutations identified in patients with nonautoimmune hyperthyroidism and hot thyroid carcinomas

Objective Constitutively activating mutations (CAMs) of the TSHR are the major cause for nonautoimmune hyperthyroidism. Re‐examination of constitutive activity previously determined in CHO cell lines recently demonstrated the caveats for the in vitro determination of constitutive TSHR activity, which leads to false positive conclusions regarding the molecular origin of hyperthyroidism or hot thyroid carcinomas. Design Mutations L677V and T620I identified in hot thyroid carcinomas were previously characterized in CHO and in 3T3‐Vill cell lines, respectively, stably expressing the mutant without determination of TSHR expression. F666L identified in a patient with hot thyroid nodules, I691F in a family with nonautoimmune hyperthyroidism and F631I identified in a hot thyroid carcinoma were not characterized for their in vitro function. Therefore, we decided to (re)evaluate the in vitro function of these five TSHR variants by determination of cell surface expression, and intracellular cAMP and inositol phosphate levels and performed additionally linear regression analyses to determine basal activity independently from the mutant’s cell surface expression in COS‐7 and HEK_GT cells. Results and Conclusions Only one (F631I) of the five investigated TSHR variants displayed constitutive activity for G_αs signalling and showed correlation with the clinical phenotype. The previous false classification of T620I and L677V as CAMs is most likely related to the fact that both mutations were characterized in cell lines stably expressing the mutated receptor construct without assessing the respective receptor number per cell. Other molecular aetiologies for the nonautoimmune hyperthyroidism and/or hot thyroid carcinomas in these three patients and one family should be elucidated.