Long-term quality of life of testicular cancer survivors differs according to applied adjuvant treatment and tumour type.

PURPOSE: To evaluate the quality of life (QoL) in long-term testicular cancer (TC) survivors. METHODS: QoL was assessed in TC survivors treated between March 1976 and December 2004 (n = 625) using the EORTC-QLQ-C30 questionnaire, including a TC module. The assessment was performed at two time points (2006: response rate: n = 201/625 (32.2%), median follow-up (FU): 12.9 years (range 1.1-30.9); 2017: response rate: n = 95/201 (47.3%), median FU: 26.2 years (range: 13.0-41.2)). TC survivors were grouped according to treatment strategy, tumour entity, clinical stage and prognosis group. Linear and multiple linear regression analyses were performed, with age and time of follow-up as possible confounders. RESULTS: Radiation therapy (RT) compared to retroperitoneal lymph node dissection (RPLND) was associated with a higher impairment of physical function (2017: ß = - 9.038; t(84) = - 2.03; p = 0.045), role function (2017: ß = - 12.764; t(84) = - 2.00; p = 0.048), emotional function (2006: ß = - 9.501; t(183) = - 2.09; p = 0.038) and nausea (2006: ß = 6.679; t(185) = 2.70; p = 0.008). However, RT was associated with a lower impairment of sexual enjoyment (2017: symptoms: ß = 26.831; t(64) = 2.66; p = 0.010; functional: ß = 22.983; t(65) = 2.36; p = 0.021). Chemotherapy (CT), compared to RPLND was associated with a higher impairment of role (2017: ß = - 16.944; t(84) = - 2.62; p = 0.011) and social function (2017: ß = - 19.160; t(79) = - 2.56; p = 0.012), more insomnia (2017: ß = 19.595; t(84) = 2.25; p = 0.027) and greater concerns about infertility (2017: ß = 19.830; t(80) = 2.30; p = 0.024). In terms of tumour type, nonseminomatous germ cell tumour (NSGCT) compared to seminoma survivors had significantly lower impairment of nausea (2006: ß = - 4.659; t(187) = - 2.17; p = 0.031), appetite loss (2006: ß = - 7.554; t(188) = - 2.77; p = 0.006) and future perspective (2006: ß = - 12.146; t(175) = - 2.08; p = 0.039). On the other hand, surviving NSGCT was associated with higher impairment in terms of sexual problems (2006: ß = 16.759; t(145) = 3.51; p < 0.001; 2017: ß = 21.207; t(63) = 2.73; p = 0.008) and sexual enjoyment (2017: ß = - 24.224; t(66) = - 2.76; p = 0.008). CONCLUSIONS: The applied adjuvant treatment and the tumour entity had a significant impact on the long-term QoL of TC survivors, even more than 25 years after the completion of therapy. Both RT and CT had a negative impact compared to survivors treated with RPLND, except for sexual concerns. NSGCT survivors had a lower impairment of QoL compared to seminoma survivors, except in terms of sexual concerns. IMPLICATIONS FOR CANCER SURVIVORS: Implications for cancer survivors are to raise awareness of aspects of long-term and late effects on QoL in TC survivors; offer supportive care, such as psycho-oncological support or lifestyle modification, if a deterioration in QoL is noticed; and avoid toxic treatment without compromising a cure whenever possible.

Course of Vitamin D Levels in Newly Diagnosed Non-Metastatic Breast Cancer Patients over One Year with Quarterly Controls and Substitution.

(1) Background: Vitamin D levels in patients remain inadequately understood, with research yielding inconsistent findings. Breast cancer patients, particularly due to oncological therapies, face an increased risk of osteopenia, which can be exacerbated by a vitamin D deficiency. (2) Methods: The prospective observational "BEGYN-1" study assessed serum 25(OH)D levels at baseline and quarterly thereafter. Clinical, pathological, nutritional, vitamin supplementation, and lifestyle data were recorded. (3) Results: Before treatment, 68.5% of patients were vitamin D deficient (<30 ng/mL), with 4.6% experiencing severe deficiency (<10 ng/mL). The median baseline 25(OH)D levels were 24 ng/mL (range: 4.8 to 64.7 ng/mL). Throughout the study, the median vitamin D levels increased to 48 ng/mL (range: 22.0 to 76.7 ng/mL). Before diagnosis, 16.7% received vitamin D substitution, and 97.8% received vitamin D substitution throughout the year with a median weekly dose of 20,000 IU. It took at least three quarterly assessments for 95% of patients to reach the normal range. A multiple GEE analysis identified associations between 25(OH)D levels and supplementation, season, age, VLDL, magnesium levels, and endocrine therapy. (4) Conclusions: Physicians should monitor 25(OH)D levels before, during, and after oncological therapy to prevent vitamin D deficiency and to adjust substitution individually. While variables such as seasons, age, VLDL, magnesium, diet, and oncological interventions affect 25(OH)D levels, supplementation has the greatest impact.

Neutrophil to lymphocyte ratio and early seizures after ischemic stroke: A case-control study.

BACKGROUND: Early post-stroke seizures (EPSS) are associated with an increased risk of mortality and post-stroke epilepsy. This study aimed to identify potential risk factors for EPSS, focusing on blood parameters, such as the neutrophil-to-lymphocyte ratio (NLR), which is a biomarker for inflammation. METHODS: Patients treated for ischemic stroke between 2017 and 2019 were retrospectively identified. 44 of them had a first epileptic seizure within 7 days after the stroke. They were matched 1:2 for age and sex with controls who had a stroke but no EPSS. Information on demographics, stroke characteristics, and blood parameters were collected on admission. Logistic regression was used to identify variables associated with EPSS and the area under the receiver operating characteristic curve (AUROC) to estimate their predictive accuracy. RESULTS: The NLR value (p = 0.035), National Institutes of Health Stroke Scale (NIHSS) (p = 0.016) and cortical localization of stroke (p = 0.03) were significantly correlated with the occurrence of EPSS in univariate logistic regression. In multivariable logistic regression, after adjusting for age, sex, baseline NIHSS, and stroke localization, the NLR values [adjusted odds ratio 1.097, 95% confidence interval (CI): 1.005-1.197; p = 0.038] were independently associated with the occurrence of EPSS. The AUROC for NLR was 0.639 (95% CI: 0.517-0.761) with 2.98 as the best predictive cut-off value. There was a significant positive relationship between NLR and NIHSS, rS(87) = 0.383, p = <0.001. CONCLUSION: Higher NLR values were associated with increased risk of EPSS. This biomarker appears useful to assess the risk of developing EPSS.

Teaching breaking bad news in a gyneco-oncological setting: a feasibility study implementing the SPIKES framework for undergraduate medical students.

BACKGROUND: It is a crucial task for physicians to deliver life threatening information to patients (breaking bad news; BBN). Many aspects influence these conversations on both sides, patients, and doctors. BBN affects the patient-physician relationship, patients' outcome, and physicians' health. Many physicians are still untrained for this multi-facetted task and feel unprepared and overburdened when facing situations of BBN. Therefore, any faculties should aim to integrate communication skills into their medical curricula as early as possible. The SPIKES protocol is an effective framework to deliver BBN. Aim of this study is to evaluate the feasibility and obstacles of a BBN seminar and its acceptance and learning curve among undergraduate medical students. METHODS: 158 2nd year undergraduate medical students attended a compulsory BBN seminar. The task was to deliver a cancer diagnosis to the patient within a patient - physician role-play in a gyneco-oncological setting before and after a presentation of the SPIKES protocol by the lecturer. The students evaluated important communication skills during these role-plays respectively. Self-assessment questionnaires were obtained at the beginning and end of the seminar. RESULTS: Most students indicated that their confidence in BBN improved after the seminar (p < 0.001). They like the topic BBN to be part of lectures (76%) and electives (90%). Communication skills improved. Lecturer and seminar were positively evaluated (4.57/5). CONCLUSION: The seminar significantly increased confidence and self-awareness in delivering life-threatening news to patients among undergraduate medical students. Important learning aspects of BBN and communication skills could be delivered successfully to the participants within a short time at low costs. The integration of communication skills should be implemented longitudinally into medical curricula starting before clinical education to increase the awareness of the importance of communication skills, to decrease anxiety, stress, and workload for future doctors and- most importantly- to the benefit of our patients.

Size and Morphology of the Anterior and Posterior Cruciate Ligaments at Different Pediatric Age Intervals: An MRI Analysis.

Background: The incidence of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) tears in children and adolescents has increased over the past decade, with increasing numbers of ACL and PCL reconstructions in this patient population. Purpose: To evaluate the size and morphology of both the ACL and the PCL by magnetic resonance imaging (MRI) in different pediatric age groups. Study Design: Cross-sectional study; Level of evidence, 3. Methods: MRI examinations of 127 knees (67 female, 60 male; aged 0-18 years) were analyzed retrospectively. The cohort was split into 6 age subgroups, 1 subgroup for every 3 years (minimum 8 patients per subgroup). The following parameters were measured by 2 independent raters at 2 different time points: ACL length, anteroposterior and mediolateral ACL width, sagittal and coronal ACL inclination, inclination of the intercondylar notch, bicondylar width, notch width, coronal ACL and PCL width, PCL length, and sagittal width of the lateral femoral condyle. The following indices, areas, and volumes were calculated: sagittal width of the lateral femoral condyle/PCL length, ACL area and volume, notch width index, ACL width/notch width, PCL width/notch width, ACL width/bicondylar width, and PCL width/bicondylar width. A correlation analysis was performed for patient age, height, weight, and body mass index (BMI). Results: ACL length was between 18 and 37 mm, and ACL width was between 4 and 6 mm. PCL length ranged between 27 and 43 mm, while PCL width was between 7 and 9 mm. Growth of the cruciate ligaments was the most pronounced between the ages of 4 and 12 years. Correlations with size and weight were strong, while BMI correlated slightly with the measurements. Measurements in female patients were slightly larger than in their male counterparts between the ages of 0 and 6 years, while male patients tended to have larger values starting from ages 7 to 9 years. These values were significantly larger in male patients from the ages of 16 to 18 years (P < .05). Conclusion: This study provides normative data on the morphology of pediatric anatomic features in the knee as a basis for age-appropriate and individualized surgical care of ACL and PCL injuries in children and adolescents.

SNPs in cytochrome P450 genes decide on the fate of individuals with genetic predisposition to Parkinson's disease.

Parkinson's disease (PD) is one of the most frequent neurological diseases affecting millions of people worldwide. While the majority of PD cases are of unknown origin (idiopathic), about 5%-10% are familial and linked to mutations in different known genes. However, there are also people with a genetic predisposition to PD who do not develop the disease. To elucidate factors leading to the manifestation of PD we compared the occurrence of single nucleotide polymorphisms (SNPs) in various cytochrome P450 (P450) genes in people with a genetic predisposition and suffering from PD (GPD) to that of people, who are genetically predisposed, but show no symptoms of the disease (GUN). We used the PPMI (Parkinson's Progression Markers Initiative) database and the gene sequences of all 57 P450s as well as their three redox partners. Corresponding odds ratios (OR) and confidence intervals (CI) were calculated to assess the incidence of the various SNPs in the two groups of individuals and consequently their relation to PD. We identified for the first time SNPs that are significantly (up to 10fold!) over- or under-represented in GPD patients compared to GUN. SNPs with OR > 5 were found in 10 P450s being involved in eicosanoid, vitamin A and D metabolism as well as cholesterol degradation pointing to an important role of endogenous factors for the manifestation of PD clinical symptoms. Moreover, 12 P450s belonging to all P450 substrate classes as well as POR have SNPs that are significantly under-represented (OR < 0.2) in GPD compared to GUN, indicating a protective role of those SNPs and the corresponding P450s regarding disease advancement. To the best of our knowledge our data for the first time demonstrate an association between known PD predisposition genes and SNPs in other genes, shown here for different P450 genes and for their redox partner POR, which promote the manifestation of the disease in familial PD. Our results thus shed light onto the pathogenesis of PD, especially the switch from GUN to GPD and might further help to advance novel strategies for preventing the development or progression of the disease.

Improved awareness of physical activities is associated with a gain of fitness and a stable body weight in breast cancer patients during the first year of antineoplastic therapy: the BEGYN-1 study.

Background: Breast cancer is the most frequent cancer in women. Reduced physical activity and overweight are associated with poor prognosis. Breast cancer patients have a high risk to gain weight, lose muscle mass and reduce physical activity during therapy. Concepts are urgently needed to motivate patients to engage in physical activity. Methods: 110 non-metastatic breast cancer patients were included in the prospective observational BEGYN-1 study. Physiological parameters and body composition were measured before the start of therapy and then quarterly for one year. Patients used a fitness tracker and documented their physical activity in a diary throughout the study. Results: Although the patients were not offered any guided exercise, and despite the restrictions during the COVID-19 pandemic, they increased their physical activity (metabolic equivalent of task (MET) -minutes): p<0.001), physical fitness (decreasing resting heart rate: p=0.001) and did not gain weight (median - 0.4kg) over the course of the study. Conclusion: Improved awareness of physical activity is associated with an increase in physical activity, fitness, and a stable weight during the first year of therapy in breast cancer patients. Counselling at diagnosis should motivate patients to engage in physical activity, wear a fitness tracker and document activities.

Obstetric practice differences between Syrian refugees and non-Syrian nonrefugee gravidae: A retrospective cross-sectional study.

OBJECTIVE: To assess differences in obstetric practices between Syrian war refugees (SRs) and non-Syrian nonrefugees (NSRs) in a tertiary care provider in Germany. METHODS: This was a retrospective study of SRs (n = 356) and NSRs (n = 5836) giving birth between January 2015 and December 2018. Data on medical history, birth mode, complications, and neonatal parameters was extracted. Group differences were evaluated using Mann-Whitney and χ2 test. Logistic regression models were fitted to investigate the association of refugee status with mode of birth in conditions associated with increased risk of cesarean section (CS). RESULTS: SRs had higher rates of adolescent pregnancies (1.7% versus 0.6%, P = 0.020) but fewer maternal diseases compared with NSRs (1.7% versus 3.9%, P = 0.035). The rate of CS was higher in the NSR group (43.9% versus 36%, P = 0.003), as well as the rates of premature rupture of membranes (P = 0.006) and steroid administration for lung maturation (P = 0.012). Cases of umbilical artery pH ≤7.0 were more common in SRs (0.4% versus 1.1%, P = 0.027). Women with previous CS had similar odds of CS in the current pregnancy irrespective of study group (odds ratio, 0.94 [95% confidence interval, 0.50-1.75]). CONCLUSION: SR women had lower rates of CS but higher rates of adolescent pregnancies and neonatal pH ≤7.0 at birth compared with NSR women.

Sex Differences in the Frequencies of B and T Cell Subpopulations of Human Cord Blood.

Cord blood represents a link between intrauterine and early extrauterine development. Cord blood cells map an important time frame in human immune imprinting processes. It is unknown whether the sex of the newborn affects the lymphocyte subpopulations in the cord blood. Nine B and twenty-one T cell subpopulations were characterized using flow cytometry in human cord blood from sixteen male and twenty-one female newborns, respectively. Except for transitional B cells and naïve B cells, frequencies of B cell counts across all subsets was higher in the cord blood of male newborns than in female newborns. The frequency of naïve thymus-negative Th cells was significantly higher in male cord blood, whereas the remaining T cell subpopulations showed a higher count in the cord blood of female newborns. Our study is the first revealing sex differences in the B and T cell subpopulations of human cord blood. These results indicate that sex might have a higher impact for the developing immune system, urging the need to expand research in this area.

The Impact of the Microbiological Vaginal Swab on the Reproductive Outcome in Infertile Women.

BACKGROUND: The thesis on which this paper is based intended to investigate whether the result of the microbiological vaginal swab has an influence on the outcome of the fertility treatment. METHODS: The microbiological vaginal swabs of patients who received fertility treatment at Saarland University Hospital were evaluated. Depending on the microorganisms detected, the swab result was classified as inconspicuous, intermediate, or conspicuous. The SPSS software was used to determine the correlation between the swab result and the outcome of the fertility treatment. RESULTS: Dysbiosis was associated with a worse outcome of fertility treatment. The pregnancy rate with a conspicuous swab was 8.6%, whereas it was 13.4% with an inconspicuous swab. However, this association was not statistically significant. Furthermore, an association of endometriosis with dysbiosis was found. Endometriosis was more frequent with a conspicuous swab result than with an inconspicuous result (21.1% vs. 17.7%), yet the correlation was not statistically significant. However, the absence of lactobacilli was significantly associated with endometriosis (p = 0.021). The association between endometriosis and a lower pregnancy rate was also statistically significant (p = 0.006). CONCLUSION: The microbiological vaginal and cervical swabs can be used as predictors for the success of fertility treatments. Further studies are needed to assess the impact of transforming a dysbiotic flora into a eubiotic environment on the success of fertility treatments.

Prolapse repair for aortic regurgitation in tricuspid aortic valves.

OBJECTIVE: Cusp prolapse is an important cause of aortic regurgitation (AR) in tricuspid aortic valves (TAVs) and can be caused by myxomatous degeneration or cusp fenestration. Long-term data for prolapse repair in TAVs are scarce. We analyzed the results of aortic valve repair in patients with TAV morphology and AR caused by prolapse and compared the results for cusp fenestration and myxomatous degeneration. METHODS: Between October 2000 and December 2020, 237 patients (221 male; 15-83 years) underwent TAV repair for cusp prolapse. Prolapse was associated with fenestrations in 94 (group I) and myxomatous degeneration in 143 patients (group II). Fenestrations were closed using a pericardial patch (n = 75) or suture (n = 19). In myxomatous degeneration, prolapse was corrected by free margin plication (n = 132) or triangular resection (n = 11). Follow-up was 97% complete (cumulatively 1531, mean 6.5, median 5.8 years). Cardiac comorbidities were present in 111 patients (46.8%), and more frequent in group II (P = .003). RESULTS: Ten-year survival was better in group I (I: 84.5%; II: 72.4%; P = .037), and patients without cardiac comorbidities (89.2% vs 67.0%; P = .002). Ten-year freedom from reoperation (P = .778), moderate or greater AR (P = .070), and valve-related complications (P = .977) were similar in both groups. AR at discharge was the only significant predictor for reoperation (P = .042). The type of annuloplasty did not affect repair durability. CONCLUSIONS: Repair of cusp prolapse in TAVs with preserved root dimensions can be performed with acceptable durability, even in the presence of fenestrations.

Adjuvant vs. progression-triggered treatment with gemcitabine in platinum-ineligible high-risk bladder cancer patients: Long-term follow-up of a randomized phase 3 trial.

BACKGROUND: Cisplatin-based chemotherapy (ChT) is the preferred perioperative treatment in muscle-invasive urothelial carcinoma of the urinary bladder (UCUB). Nevertheless, a certain number of patients are ineligible for platinum-based ChT. This trial compared immediate adjuvant vs. delayed gemcitabine ChT at progression in platinum-ineligible patients with high-risk UCUB. METHODS: High-risk platinum-ineligible UCUB patients (n = 115) were randomized 1:1 to adjuvant gemcitabine (n = 59) or gemcitabine at progression (n = 56). Overall survival was analyzed. Additionally, we analyzed progression-free survival (PFS), toxicity and quality of life (QoL). RESULTS: After a median follow-up of 3.0 years (inter quartile range [IQR]: 1.3-11.6), adjuvant ChT did not significantly prolong overall survival (OS) (HR: 0.84; 95% CI: 0.57-1.24; P = 0.375), with 5-year OS of 44.1% (95% CI: 31.2-56.2) and 30.4% (95% CI: 19.0-42.5), respectively. We noted no significant difference in PFS (HR: 0.76; 95% CI: 0.49-1.18; P = 0.218), with 5-year PFS of 36.2% (95% CI: 22.8-49.7) in the adjuvant group and 22.2% (95% CI: 11.5%-35.1%) when treated at progression. Patients with adjuvant treatment showed a significantly worse QoL. The trial was prematurely closed after recruitment of 115 of the planned 178 patients. CONCLUSIONS: There was no statistically significant difference in terms of OS and PFS for patients with platinum-ineligible high-risk UCUB receiving adjuvant gemcitabine compared to patients treated at progression. These findings underline the importance of implementing and developing new perioperative treatments for platinum-ineligible UCUB patients.

Differential nasal swab cytology represents a valuable tool for therapy monitoring but not prediction of therapy response in chronic rhinosinusitis with nasal polyps treated with Dupilumab.

Introduction: Chronic Rhinosinusitis with nasal polyps (CRSwNP) is a common chronic disease with a high impact on patients' quality of life. If conservative and surgical guideline treatment cannot sufficiently control disease burden, biologicals can be considered as a comparably new treatment option that has revolutionized CRSwNP therapy since the first approval of Dupilumab in 2019. With the aim to select patients who benefit from this new treatment and to find a marker for therapy monitoring, we investigated the cellular composition of nasal mucous membranes and inflammatory cells of patients suffering from CRSwNP and undergoing Dupilumab therapy using non-invasive nasal swab cytology. Methods: Twenty CRSwNP patients with the indication for Dupilumab therapy have been included in this prospective clinical study. In total, five study visits were conducted with ambulatory nasal differential cytology using nasal swabs starting with the beginning of therapy and followed by visits every 3 months for 12 months. First, these cytology samples were stained with the May-Grunwald-Giemsa method (MGG) and the percentage of ciliated cells, mucinous cells, eosinophil cells, neutrophil cells, and lymphocytes was analyzed. Secondly, an immunocytochemical (ICC) ECP-staining was performed to detect eosinophil granulocytes. Additionally, during each study visit the nasal polyp score, SNOT20 questionnaire, olfactometry, the total IgE concentration in peripheral blood as well as the eosinophil cell count in peripheral blood were recorded. The change of parameters was evaluated over one year and the correlation between clinical effectiveness and nasal differential cytology was analyzed. Results: In both MGG (p<0.0001) and ICC analysis (p<0.001) a significant decrease of eosinophils was seen under Dupilumab treatment. When patients were divided into a Eo-low- (<21%) and Eo-high- (≥21%) group according to the percentage eosinophils in nasal swab catology in the first study visit, the Eo-high-group showed a greater change of eosinophils over time (Δ17.82) compared to the Eo-low-group (Δ10.67) but, however, no better response to therapy. The polyp score, SNOT20 questionnaire, and total IgE concentration in peripheral blood showed a significant decrease during the observation period (p<0.0001). Discussion: Nasal swab cytology as an easy-to-apply diagnostic method allows detection and quantification of the different cell populations within the nasal mucosa at a given time. The nasal differential cytology showed a significant decrease of eosinophils during Dupilumab therapy and can therefore be used as non-invasvive method for monitoring therapy success of this cost intensive therapy and potentially can allow an optimized individual therapy planning and management for CRSwNP patients. Since the validity of initial nasal swab eosinophil cell count as a predictive biomarker for therapy response was limited in our study, additional studies including larger number of participants will be necessary to further evaluate the potential benefits for clinical practice of this new diagnostic method.

Antimicrobial use in pediatric oncology and hematology in Germany and Austria, 2020/2021: a cross-sectional, multi-center point-prevalence study with a multi-step qualitative adjudication process.

Background: Due to the high risk of severe infection among pediatric hematology and oncology patients, antimicrobial use is particularly high. With our study, we quantitatively and qualitatively evaluated, based on institutional standards and national guidelines, antimicrobial usage by employing a point-prevalence survey with a multi-step, expert panel approach. We analyzed reasons for inappropriate antimicrobial usage. Methods: This cross-sectional study was conducted at 30 pediatric hematology and oncology centers in 2020 and 2021. Centers affiliated to the German Society for Pediatric Oncology and Hematology were invited to join, and an existing institutional standard was a prerequisite to participate. We included hematologic/oncologic inpatients under 19 years old, who had a systemic antimicrobial treatment on the day of the point prevalence survey. In addition to a one-day, point-prevalence survey, external experts individually assessed the appropriateness of each therapy. This step was followed by an expert panel adjudication based upon the participating centers' institutional standards, as well as upon national guidelines. We analyzed antimicrobial prevalence rate, along with the rate of appropriate, inappropriate, and indeterminate antimicrobial therapies with regard to institutional and national guidelines. We compared the results of academic and non-academic centers, and performed a multinomial logistic regression using center- and patient-related data to identify variables that predict inappropriate therapy. Findings: At the time of the study, a total of 342 patients were hospitalized at 30 hospitals, of whom 320 were included for the calculation of the antimicrobial prevalence rate. The overall antimicrobial prevalence rate was 44.4% (142/320; range 11.1-78.6%) with a median antimicrobial prevalence rate per center of 44.5% (95% confidence interval [CI] 35.9-49.9). Antimicrobial prevalence rate was significantly higher (p < 0.001) at academic centers (median 50.0%; 95% CI 41.2-55.2) compared to non-academic centers (median 20.0%; 95% CI 11.0-32.4). After expert panel adjudication, 33.8% (48/142) of all therapies were labelled inappropriate based upon institutional standards, with a higher rate (47.9% [68/142]) when national guidelines were taken into consideration. The most frequent reasons for inappropriate therapy were incorrect dosage (26.2% [37/141]) and (de-)escalation/spectrum-related errors (20.6% [29/141]). Multinomial, logistic regression yielded the number of antimicrobial drugs (odds ratio, OR, 3.13, 95% CI 1.76-5.54, p < 0.001), the diagnosis febrile neutropenia (OR 0.18, 95% CI 0.06-0.51, p = 0.0015), and an existing pediatric antimicrobial stewardship program (OR 0.35, 95% CI 0.15-0.84, p = 0.019) as predictors of inappropriate therapy. Our analysis revealed no evidence of a difference between academic and non-academic centers regarding appropriate usage. Interpretation: Our study revealed there to be high levels of antimicrobial usage at German and Austrian pediatric oncology and hematology centers with a significant higher number at academic centers. Incorrect dosing was shown to be the most frequent reason for inappropriate usage. Diagnosis of febrile neutropenia and antimicrobial stewardship programs were associated with a lower likelihood of inappropriate therapy. These findings suggest the importance of febrile neutropenia guidelines and guidelines compliance, as well as the need for regular antibiotic stewardship counselling at pediatric oncology and hematology centers. Funding: European Society of Clinical Microbiology and Infectious Diseases, Deutsche Gesellschaft für Pädiatrische Infektiologie, Deutsche Gesellschaft für Krankenhaushygiene, Stiftung Kreissparkasse Saarbrücken.

Chronic pain patients and time to sustained acceptable pain scores after major surgery - A retrospective registry analysis.

STUDY OBJECTIVE: We tested the hypothesis that pre-existing chronic pain is associated with prolonged time to reach sustained acceptable pain scores after major surgery. DESIGN: Retrospective study using the German Network for Safety in Regional Anaesthesia and Acute Pain Therapy registry. SETTING: Operating rooms and surgical wards. PATIENTS: 107,412 patients recovering from major surgery who were cared for by an acute pain service. 3.3% of the treatments were in patients who reported chronic pain with functional or psychological impairment. INTERVENTIONS AND MEASUREMENT: We compared time to sustained adequacy of postoperative pain control defined by numeric rating scores <4 at rest and with movement in patients with and without chronic pain using an adjusted cox proportional hazard regression model and Kaplan-Meier analysis. The observation period was censored at 10 days and propensity score matching was used as a sensitivity analysis. MAIN RESULTS: Postoperative pain at rest took significantly longer to resolve in patients with chronic pain than in those without (adjusted hazard ratio HR 1.42, 95% CI 1.36-1.49, P < 0.001). Postoperative pain with movement took even longer to resolve in patients with chronic pain (adjusted HR 1.65, 95%CI 1.56-1.75, P < 0.001). CONCLUSIONS: Patients with chronic pain sustain more surgical pain than those without, and the pain takes longer to resolve. Clinicians providing postoperative pain management should consider the special needs of chronic pain patients.

Prevalence and Relevance of Vitamin D Deficiency in Newly Diagnosed Breast Cancer Patients: A Pilot Study.

(1) Background: Vitamin D plays an important role in many types of cancer. It was the aim of this study to analyze serum 25-hydroxyvitamin D (25(OH)D) levels in newly diagnosed breast cancer patients, and the association with prognostic and lifestyle factors. (2) Methods: 110 non-metastatic breast cancer patients were included in the prospective observational "BEGYN" study at Saarland University Medical Center between September 2019 and January 2021. At the initiation visit, serum 25(OH)D levels were measured. Clinicopathological data on prognosis, nutrition, and lifestyle were extracted from data files and obtained using a questionnaire. (3) Results: Median serum 25(OH)D in breast cancer patients was 24 ng/mL (range 5-65 ng/mL), with 64.8% of patients being vitamin D deficient. 25(OH)D was higher among patients that reported the use of vitamin D supplements (43 ng/mL versus 22 ng/mL; p < 0.001), and in summer compared to other seasons (p = 0.03). Patients with moderate vitamin D deficiency were less likely to have triple negative breast cancer (p = 0.047). (4) Conclusions: Routinely measured vitamin D deficiency is common in breast cancer patients and needs to be detected and treated. However, our results do not support the hypothesis that vitamin D deficiency may be a main prognostic factor for breast cancer.

CDK4/6 Inhibitors in Advanced HR+/HER2 - Breast Cancer: A Multicenter Real-World Data Analysis.

Purpose: CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy are considered standard-of-care for first-line therapy of patients with hormone receptor positive, HER2 negative, advanced breast cancer (HR+/HER2- ABC). Superiority of combination therapy over endocrine monotherapy has been demonstrated in a multitude of randomized controlled trials (RCTs) in phase III and IV. However, RCTs reflect clinical reality only to a limited extent, as narrow inclusion criteria lead to a selected patient collective. Here, we present real-world data (RWD) on CDK4/6i treatment in patients with HR+/HER2- ABC at four certified German university breast cancer centers. Methods: Patients diagnosed with HR+/HER2- ABC who were treated in clinical routine with CDK4/6i between November 2016 and December 2020 at four certified German university breast cancer centers (Saarland University Medical Center, University Medical Center Charité Berlin, University Medical Center Bonn, and University Medical Center Hospital Schleswig-Holstein, Campus Kiel) were identified and enrolled in this retrospective study. Clinicopathological characteristics and clinical outcomes were recorded with particular emphasis on CDK4/6i therapy course [progression-free survival (PFS) following treatment initiation, toxicity, dose reduction, therapy discontinuation, prior and subsequent therapy line]. Results: Data from n = 448 patients were evaluated. The mean patient age was 63 (±12) years. Of these patients, n = 165 (36.8%) were primarily metastasized, and n = 283 (63.2%) had secondary metastatic disease. N = 319 patients (71.3%) received palbociclib, n = 114 patients (25.4%) received ribociclib, and n = 15 patients (3.3%) received abemaciclib, respectively. Dose reduction was performed in n = 132 cases (29.5%). N = 57 patients (12.7%) discontinued the treatment with CDK4/6i due to side effects. N = 196 patients (43.8%) experienced disease progression under CDK4/6i treatment. The median PFS was 17 months. Presence of hepatic metastases and prior therapy lines were associated with shorter PFS, whereas estrogen positivity and dose reduction due to toxicity were positively associated with PFS. Presence of bone and lung metastases, progesterone positivity, Ki67 index, grading, BRCA1/2 and PIK3CA mutation status, adjuvant endocrine resistance, and age did not significantly impact on PFS. Conclusion: Our RWD analysis on CDK4/6i treatment in Germany supports data from RCTs regarding both treatment efficacy and safety of CDK4/6i for treatment of patients with HR+/HER2- ABC. In comparison to data from the pivotal RCTs, median PFS was lower but within the expected range for RWD, which could result from inclusion of patients with more advanced diseases (i.e., higher therapy lines) to our dataset.

Evaluation of Electrochemotherapy with Bleomycin in the Treatment of Colorectal Hepatic Metastases in a Rat Model.

BACKGROUND: The available ablative procedures for the treatment of hepatic cancer have contraindications due to the heat-sink effect and the risk of thermal injuries. Electrochemotherapy (ECT) as a nonthermal approach may be utilized for the treatment of tumors adjacent to high-risk regions. We evaluated the effectiveness of ECT in a rat model. METHODS: WAG/Rij rats were randomized to four groups and underwent ECT, reversible electroporation (rEP), or intravenous injection of bleomycin (BLM) eight days after subcapsular hepatic tumor implantation. The fourth group served as Sham. Tumor volume and oxygenation were measured before and five days after the treatment using ultrasound and photoacoustic imaging; thereafter, liver and tumor tissue were additionally analysed by histology and immunohistochemistry. RESULTS: The ECT group showed a stronger reduction in tumor oxygenation compared to the rEP and BLM groups; moreover, ECT-treated tumors exhibited the lowest levels of hemoglobin concentration compared to the other groups. Histological analyses further revealed a significantly increased tumor necrosis of >85% and a reduced tumor vascularization in the ECT group compared to the rEP, BLM, and Sham groups. CONCLUSION: ECT is an effective approach for the treatment of hepatic tumors with necrosis rates >85% five days following treatment.

[Educating Parents about Fever in Childhood Evaluation of the Effect of an Information Leaflet]. / Aufklärung von Eltern zu Fieber im Kindesalter Evaluation der Wirkung einer Informationsbroschüre.

BACKGROUND: Fever is an important immune reaction of the body in infections and plays a major role in childhood. Fear and uncertainty in dealing with fever are still widespread among parents. Information leaflets on the knowledge and handling of fever in childhood can serve as an educational tool for parents. It has not yet been investigated whether this type of information transfer is a suitable tool for educating parents. METHODS: 16 kindergartens in Saarland were visited. 481 parents of at least one child between the ages of 1 and 7 years answered a questionnaire on knowledge, approach and handling of fever in infections. Subsequently, an information leaflet on fever was handed out. On the following day, the questionnaire was answered again by the 190 parents who had read the information leaflet. The change due to reading the information leaflet was analyzed. RESULTS: 40% of the participants read the information leaflet. 87% mothers and 13% fathers participated in the follow-up survey. 10% of the post-survey respondents had a secondary school diploma and 34% had a university degree. After reading, fever was considered useful significantly more often and febrile convulsions and consequential damage were mentioned significantly less often as a reason for fever reduction. CONCLUSION: Information leaflets on fever can be a complementary tool for education, the short-term effect is confirmed, the sustainability needs to be further evaluated. There is also a need to reach the majority.

Zygote Diameter and Total Cytoplasmic Volume as Useful Predictive Tools of Blastocyst Quality.

Introduction According to the Embryo Protection Act, the selection of embryos with the greatest potential for successful implantation in Germany must be performed in the pronucleus stage. The main aim of this study was to identify morphokinetic parameters that could serve as noninvasive biomarkers of blastocyst quality in countries with restrictive reproductive medicine laws. Materials and Methods The sample comprised 191 embryos from 40 patients undergoing antagonist cycles for intracytoplasmic sperm injection. Blastocysts were cultured in an EmbryoScope chamber and video records were validated to determine the post-injection timing of various developmental stages, cleavage stages, and blastocyst formation. The Gardner and Schoolcraft scoring system was used to characterize blastocyst quality. Results Morphokinetic data showed that the zygote diameter and total cytoplasmic volume were significantly different between good and poor blastocysts quality groups, where zygotes, which formed better blastocyst quality, had smaller diameter and smaller total cytoplasmic volume. Zygotes with more rapid pronuclear disappearance developed in better-quality blastocysts. Differences between good- and poor-quality blastocysts were also observed for late-stage parameters and for the spatial arrangement of blastomere where tetrahedral embryos more frequently forming good-quality blastocyst compare to the non-tetrahedral. Conclusions The study findings could be used to enhance embryo selection, especially in countries with strict Embryo Law Regulations. Further studies, including those in which the implantation potential and pregnancy rate are considered, are warranted to confirm these preliminary results.