Symptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.

Acute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10-17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7-14). The median age for the first ARI episode was 91 days (IQR: 57-128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants.

Cyclic Di-Adenosine Monophosphate: A Promising Adjuvant Candidate for the Development of Neonatal Vaccines.

Underdeveloped immunity during the neonatal age makes this period one of the most dangerous during the human lifespan, with infection-related mortality being one of the highest of all age groups. It is also discussed that vaccination during this time window may result in tolerance rather than in productive immunity, thus raising concerns about the overall vaccine-mediated protective efficacy. Cyclic di-nucleotides (CDN) are bacterial second messengers that are rapidly sensed by the immune system as a danger signal, allowing the utilization of these molecules as potent activators of the immune response. We have previously shown that cyclic di-adenosine monophosphate (CDA) is a potent and versatile adjuvant capable of promoting humoral and cellular immunity. We characterize here the cytokine profiles elicited by CDA in neonatal cord blood in comparison with other promising neonatal adjuvants, such as the imidazoquinoline resiquimod (R848), which is a synthetic dual TLR7 and TLR8 agonist. We observed superior activity of CDA in eliciting T helper 1 (Th1) and T follicular helper (TfH) cytokines in cells from human cord blood when compared to R848. Additional in vivo studies in mice showed that neonatal priming in a three-dose vaccination schedule is beneficial when CDA is used as a vaccine adjuvant. Humoral antibody titers were significantly higher in mice that received a neonatal prime as compared to those that did not. This effect was absent when using other adjuvants that were reported as suitable for neonatal vaccination. The biological significance of this immune response was assessed by a challenge with a genetically modified influenza H1N1 PR8 virus. The obtained results confirmed that CDA performed better than any other adjuvant tested. Altogether, our results suggest that CDA is a potent adjuvant in vitro on human cord blood, and in vivo in newborn mice, and thus a suitable candidate for the development of neonatal vaccines.

Hormonal Contraception. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry Number 015/015, January 2020).

Aims This is an official interdisciplinary guideline published and coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking regions and is backed by numerous professional societies and organizations. The aim of this guideline is to provide an evidence- and consensus-based overview of the diagnostic approach and the management of hormonal contraception based on a systematic evaluation of the relevant literature. Methods To compile this S3-guideline, a systematic search for evidence was carried out in PubMed and the Cochrane Library to adapt existing guidelines and identify relevant reviews and meta-analyses. A structured evaluation of the evidence was subsequently carried out on behalf of the Guidelines Commission of the DGGG, and a structured consensus was achieved based on consensus conferences attended by representative members from the different specialist societies and professions. Recommendations Evidence-based recommendations about the advice given to women requesting contraception were compiled. The guideline particularly focuses on prescribing contraceptives which are appropriate to women's individual needs, take account of her personal circumstances, and have few or no side effects.

Does mean heart dose sufficiently reflect coronary artery exposure in left-sided breast cancer radiotherapy? : Influence of respiratory gating.

PURPOSE: With extensive use of systemic treatment, the issue of cardiac mortality after breast cancer radiation (RT) is still important. The aim of our analysis was to clarify whether the dose to one surrogate parameter (e. g., mean heart dose, as used in most studies) reflects the dose to the other cardiovascular structures especially the left anterior descending artery depending on breathing-adapted RT. PATIENTS AND METHODS: A total of 130 patients who underwent adjuvant RT (50.4 Gy plus boost 9-16 Gy) were evaluated. In all, 71 patients were treated with free-breathing and 59 patients using respiratory monitoring (gated RT). Dosimetric associations were calculated. RESULTS: The mean dose to the heart (Dmean heart) was reduced from 2.7 (0.8-5.2) Gy to 2.4 (1.1-4.6) Gy, the Dmean LAD (left anterior descending artery) decreased from 11.1 (1.3-28.6) Gy to 9.3 (2.2-19.9) Gy with gated RT (p = 0.04). A significant relationship was shown for Dmean heart-Dmean LAD, V25heart-Dmean LAD and Dmax heart-Dmax LAD for gated patients only (p < 0.01). For every 1 Gy increase in Dmean heart, mean LAD doses rose by 3.6 Gy, without gating V25 ≤5 % did not assure a benefit and resulted in Dmean LAD between 1.3 and 28.6 Gy. CONCLUSION: A significant reduction and association of heart and coronary artery (LAD) doses using inspiratory gating was shown. However, in free-breathing plans commonly measured dose constraints do not allow precise estimation of the dose to the coronary arteries.

Predictors of overall satisfaction of cancer patients undergoing radiation therapy.

BACKGROUND: Reporting the experiences and satisfaction of patients, as well as their quality of care scores is an emerging recommendation in health care systems. Many aspects of patients' experience determine their overall satisfaction. The aim of this evaluation was to define the main factors contributing to the satisfaction of patients undergoing radiotherapy in an outpatient setting. PATIENTS AND METHODS: A total of 1,710 patients with a histologically proven cancer, who were treated in our department between 2012 and 2014, were recruited for this prospective evaluation. At the end of therapy, each patient was asked to grade the skills and the care provided by radiation therapists, physicians, and physician's assistants, as well as the overall satisfaction during therapy. Statistical analysis was performed to determine which parameters had the greatest influence on overall satisfaction. RESULTS: Overall satisfaction with the provided care was high with a mean satisfaction score of 1.4. Significant correlations were found between overall satisfaction and each of the following survey items: courtesy, protection of privacy, professional skills and care provided by the radiation therapists and physicians, accuracy of provided information, and cleanliness. Linear regression analysis demonstrated that courteous behavior and the protection of privacy were the strongest predictors for overall satisfaction (P<0.001), followed by care and skills of physicians and radiation therapists. Patients suffering from head and neck cancer expressed lower overall satisfaction. CONCLUSION: Based on our prospectively acquired data, we were able to identify and confirm key factors for patient satisfaction in an outpatient radiooncological cancer center. From these results, we conclude that patients want most importantly to be treated with courtesy, protection of privacy and care.

Optimal treatment for patients with ectopic pregnancies and a history of fertility-reducing factors.

PURPOSE: With most ectopic pregnancy (EP) cases now diagnosed and treated early, a major concern has become future reproductive outcome. The aim of this study was to evaluate long-term reproductive outcome after salpingotomy versus salpingectomy in patients with and without additional fertility-reducing factors. METHODS: As part of a prospective follow-up study, 261 patients underwent laparoscopic management of EP at our institution. History was taken specifically looking at preexisting risk factors for reduced fertility. Patients were then followed with regard to future reproductive events. RESULTS: Of 261 patients, 196 (75%) reported a subsequent desire for pregnancy. 145 patients had undergone salpingotomy and 51 salpingectomy. In patients without prior history of fertility-reducing factors, the subsequent intrauterine pregnancy rates were >90% for both salpingotomy and salpingectomy groups irrespective of the surgical approach. In patients with preexisting fertility-reducing factors, postoperative intrauterine pregnancy rates were 75% in the salpingotomy group, but only 40% in the salpingectomy group (p < 0.05), showing maximal effect for conservative surgery. CONCLUSION: Laparoscopic salpingotomy is of particular benefit for patients with additional fertility-reducing factors desirous of future pregnancy. Reproductive outcome is excellent in patients without such risk factor, irrespective of the surgical approach.

Repeatability of innervation zone identification in the external anal sphincter muscle.

AIMS: Knowledge of the distribution of the innervation zones (IZs) of the external anal sphincter (EAS) may be useful for preventing anal sphincter incompetence during vaginal delivery. A method proposed for the automatic estimation of the distribution of IZs of EAS from high-density surface electromyography (EMG) was evaluated for repeatability in continent volunteers. METHODS: In 13 healthy female subjects (age: 35 +/- 11 years) surface EMG signals were acquired using an anal probe with three circumferential electrode arrays (of 16 contacts each) at different depths within the anal canal (15 mm distance between the centers of adjacent arrays), during four independent experimental sessions. Three maximal voluntary contractions (MVCs) of 10 sec were performed for each session for a total of 12 contractions per subject. Repeatability of the estimation of the distribution of IZ was tested by evaluating the coefficient of multiple correlations (CMC) between the IZ distributions estimated from the signals recorded from each subject. RESULTS: A high repeatability (CMC > 0.8) was found comparing IZ distributions estimated from signals recorded by each array within the same session. A slightly lower value was obtained considering signals recorded during different sessions (CMC > 0.7), but a higher value (CMC > 0.8) was obtained after aligning the estimated IZ distributions. The realignment compensates for the operator's error in repositioning the probe in the same position during different sessions. CONCLUSION: This result justifies clinical studies using high-density surface EMG in routine examinations, providing information about IZs of EAS and assessing the possibilities of preventing neuronal trauma during vaginal delivery.

Asymmetric sphincter innervation is associated with fecal incontinence after anal sphincter trauma during childbirth.

AIMS: Functional asymmetry of pelvic floor innervation has been shown to exist in healthy subjects, and has been proposed to be a predictor of increased risk for fecal incontinence in case of trauma. However, this remains to be shown for different clinical conditions such as traumatic childbirth. METHODS: A conventional surface EMG system was used to assess the innervation of the external anal sphincter. A symmetry index was used to define the relative EMG amplitude asymmetry of the external anal sphincter between 0 (symmetric) and 1 (asymmetric). Three cohorts were studied: 40 nulliparous women in the third trimester (Study 1), 15 primiparous women within 6 months following vaginal delivery without clinically apparent anal sphincter trauma (Study 2), and 50 women after childbirth-related third or fourth degree perineal tear 6-12 months postpartum (Study 3). Furthermore, all women underwent conventional anorectal manometry. RESULTS: Sixteen or forty nulliparous women reported signs of fecal incontinence; however, relative asymmetry was not correlated to symptom severity (P = 0.345), and not to manometric measures (Study 1). In Study 2, Women who had suffered clinically apparent anal sphincter trauma (P = 0.07) tended to have a stronger association between incontinence and asymmetry. In Study 3, 19/50 women reported moderate to severe incontinence. Asymmetry and symptom severity were significantly correlated (P < 0.001). Patients with incontinence had a significantly higher asymmetry score than their continent counterparts. CONCLUSION: Functional asymmetry of anal sphincter innervation is significantly associated with incontinence symptoms, but only after childbirth-related sphincter injuries and therefore, should be regarded as an additional risk factor.