[Influence of the Corona pandemic on cardiovascular risk factors - Data from 1775 participants of the ELITE study before and during the Corona pandemic]. / Einfluss der Corona-Pandemie auf kardiovaskuläre Risikofaktoren ­ Daten von 1775 Teilnehmern der ELITE Studie vor und während der Corona Pandemie.

BACKGROUND: The COVID-19 pandemic and its interventions have led to a deficit in medical care and changes in people's lifestyles, which has consequently changed cardio- and cerebrovascular primary and secondary prevention. The existing data are mainly based on surveys. In addition to the problem of the accuracy of self-assessments, the pandemic per se and the massive public reporting may have biased the data.Only a few publications have compared data collected before the pandemic with results during the pandemic. The ELITE study has regularly monitored risk factors (RF) and psychosocial parameters (stress, depression, well-being, diet, brain performance, exercise) in over 5000 participants for years. From this study, data were analyzed from 1775 individuals collected before the onset and again during the pandemic (06/05/2020-25/01/2022). Thus, baseline values were unaffected by the pandemic. RESULTS: As expected, both improvements and worsening of the collected parameters were found. Blood pressure and depressive symptoms worsened significantly more often, with women more frequently affected. Weight and stress levels also increased more often than they improved. Only physical activity showed a slight increase. 24.1 % showed only deteriorations and no improvements in these parameters. In contrast, 19.6 % showed improvements exclusively. In the group with only worsening, there was a significant increase in individuals with the risk factors (RF) hypertension, obesity, elevated LDL cholesterol, nicotine, and diabetes mellitus. This resulted in an increase in individuals with 2 or more RF. In contrast, the number of individuals with 2 and more RF decreased in the group with only improvements. Strikingly, individuals with risk factors improved more frequently. CONCLUSION: A not insignificant part of the population experienced significant worsening of RF during the pandemic. This particularly affected blood pressure and depressive symptoms, and more often women.

The granulation tissue preservation technique in regenerative periodontal surgery-a randomized controlled clinical trial.

OBJECTIVES: To investigate if the application of the granulation tissue preservation technique (GTPT) in regenerative therapy of infrabony periodontal defects results in more clinical attachment level (CAL) gain and more radiographic bone gain (RBG) than the conventional resective approach 12 months after surgery. MATERIALS AND METHODS: Forty patients exhibiting at least one infrabony defect with a probing pocket depth (PPD) ≥6 mm and a radiographic infrabony component (INFRAX-ray ) ≥3 mm were randomly treated with the GTPT (test group) or the double-flap approach with resection of the defect-filling granulation tissue (control group). Enamel matrix derivatives were applied in both groups. Clinical and radiographic parameters were recorded at baseline (t0), 6 months (t1), and 12 months (t2) after surgery. The primary outcome variable was CAL gain between t0 and t2. RESULTS: When all patients were considered, ΔCALt0-t2 did not differ significantly between the two groups (p = .160). Significant PPD reduction (test group: 4.38 ± 1.36 mm; control group: 4.06 ± 2.38 mm), CAL gain (test group: 3.75 ± 1.24 mm; control group: 2.88 ± 2.09 mm), and RBG (test group: 3.06 ± 1.74 mm; control group: 3.27 ± 2.19 mm) were achieved at t2 in both groups. Using multivariate linear regression, PPDt0 and group were identified as variables with the greatest influence on ΔCALt0-t2 . PPDt0 and INFRAX-ray were identified as variables with the greatest influence on RBGt0-t2 . Patients with a defect angle >22° showed significantly more CAL gain in the test group (t0-t1: 3.08 ± 1.38 mm; t0-t2: 3.62 ± 0.96 mm) than in the control group (t0-t1: 1.77 ± 1.54 mm; t0-t2: 2.18 ± 1.83 mm). CONCLUSIONS: Regarding all patients, the study failed to show significant differences between the test and control groups. However, the GTPT appears to lead to more CAL gain in noncontaining infrabony defects.

Regular Exercise is Associated with a More Favorable Cardiovascular Risk Profile, Better Quality of Life, Less Depression and Less Psychological Stress.

INTRODUCTION: It is well documented that insufficient physical activity (PA) contributes substantially to cardiovascular diseases. The number of physically active people in Germany is still too low. METHODS: In ELITE study in Germany, 4602 participants are regularly examined for cardiovascular risk factors (CVRF). The aim is to motivate participants to improve their CVRF through individual recommendations and regular follow-up. Here, the PA data are presented in correlation with CVRF at baseline. A feature of this presentation is that the usual CVRF but also the effects on psychosocial factors were recorded simultaneously. RESULTS: Participants were divided into 3 groups based on their PA: 1. frequent exercise (FE): daily to 2-3x per week (41.4%), 2. moderate exercise (ME): 1x/week to 2x/month (28.8%), 3. rarely exercise (RE): 1x/month to not at all (29.8%). Age did not differ in the 3 groups. The most common CVRF was arterial hypertension, which decreased significantly with an increase in PA. Diabetes, nicotine, and increased BMI were also significantly less frequent in group 1. Antihypertensives were taken less frequently in this group 1. Less physically active participants were significantly more likely to have 3 or more additional CVRF. While group 1 consumed more fruit (64%) and considerably less pork, in group 2 and 3 only 58.3% and 50.3% respectively included fruit in their diet. FE also had a favorable effect on stress, depression and general well-being, all of which were significantly better in group 1. CONCLUSION: Results confirm the beneficial influences of exercise on known CVRF and on psychosocial parameters. The prevalence of several CVRF per person at low levels of sport is of particular concern, as these participants would benefit most. During a 5-year follow-up, participants will receive intensive education on the need to increase PA. It remains to be seen how successful the effort will be.

Relationship between Lipoprotein(a) and cardiovascular risk factors-data from 4602 participants of the ELITE study.

Lipoprotein(a) (Lp(a)) is becoming increasingly important as an independent risk factor for cardiovascular disease. Since no effective therapy currently exists other than lipid apheresis, the recommendation remains to optimally adjust all other cardiovascular risk factors (CVRF). In a Northwest German population study, the frequency of elevated Lp(a) levels and all other CVRF was investigated. The aim was to investigate whether individuals with elevated Lp(a) levels were also more likely to have other CVRFs. To date, 4602 individuals have been enrolled in the study, and blood pressure, weight, lipids, diabetes, medications, and pre-existing conditions were recorded in addition to Lp(a). In addition, questionnaires assessed physical activity, psychological stress, depression, and brain dysfunction. All participants received detailed individual recommendation about their CVRF and its treatment. In the further follow-up of 5 years, it will be examined how persons with elevated Lp(a) implemented these recommendations in comparison with participants without elevated Lp(a). The first group Lp(a) <75 nmol/L consisted of 3550 (80.2%), the Lp(a) 75-120 nmol/L group of 341 (7.4%) and the Lp(a) >120 nmol/L of 538 (11.7%). 81.6% of all participants had one or more CVRF. Age, sex, and prevalence of hypertension, diabetes, smoking, obesity, and exercise did not differ among the 3 groups. As expected, LDL-Cholesterol was significantly elevated in the Lp(a) >120 nmol/L group despite significantly more frequent use of statins. Significantly more often hypertensive patients were found in the Lp(a) >120 nmol/L group who were inadequately controlled by medication and significantly less often persons without further CVRF. No differences existed in the frequency of psychological stress, depression, and mild cognitive impairment. CVRF occur with comparable frequency in individuals with elevated Lp(a) levels. However, individuals with Lp(a) above 120 nmol/L were more likely to have poorly controlled blood pressure, elevated LDL-C, and less likely to have no other risk factors. This underlines that in case of Lp(a) elevation all further CVRF should be intensively adjusted, especially in case of strongly elevated values >120 nmol/L. However, these recommendations have not been adequately implemented in clinical care in this population to date.

Football beats hypertension: results of the 3F (Fit&Fun with Football) study.

OBJECTIVES: Football as the most popular sport could improve insufficient physical activity in patients with cardiovascular risk factors. A modified 'healthy' football training format could motivate hypertensive patients to return to sport and improve risk factors. METHODS: The 3F study: 'Fit and Fun with Football' a prospective interventional study with 1 year follow-up. Football group: n = 103, structured 'health'-football training (1×/week, 90 min) led by Deutscher Fußball Bund-licensed football coaches. Hypertensive patients at least 45 years who have not exercised for several years were compared with a control group (n = 105). PRIMARY STUDY OBJECTIVE: Reduction of office (OBP) and/or 24-h ambulatory blood pressure (BP) monitoring (ABPM) and/or reduction of number or dosage of antihypertensive medication. MAIN RESULTS: OBP values decreased significantly in the football group from 142.6/87.9 to 130.8/81.8 mmHg (P < 0.001), in the control group the values increased slightly (NS). ABPM values decreased significantly in the football group, while a slight increase was found in the control group. At the end of the study, the mean values in the football group of both OPB (P < 0.001) and ABPM (systolic P < 0.001, diastolic P = 0.017) were significantly lower than in the control group. Significantly more people in the football group were able to reduce antihypertensive patients than in the control group (football group:16, control group:6), while more participants in the control group intensified antihypertensive therapy (football group:3, control group:14) (P < 0.001). Among the secondary endpoints, there was a weight loss of 3 kg in the football group and an increase of 1.7 kg in the control group (P < 0.001). CONCLUSION: Offering modified 'healthy' football-training to middle-aged hypertensive patients can lead to better BP control and a reduction of antihypertensive medication. Therefore, the offer of 'health football' should be established and supported by clubs, insurances and authorities.

Influence of individualized prevention recommendations after one year on the control of hypertension in 3,868 follow-up participants of the ELITE study.

OBJECTIVES: The ELITE study (German acronym for "Nutrition, lifestyle and individual information for prevention of heart attack, stroke and dementia") prospectively collects data on hypertension, cardiovascular risk factors (RF), dietary habits, physical activity, cognitive function, and quality of life in North-West Germany, which will then be improved through targeted individual information. The aim of the study is to improve the health of the participants in the long term and to identify reasons for a lack of implementation of prevention measures. METHODS: Of 4,602 included subjects, 3,868 could be studied so far at one-year follow-up. Blood pressure (BP) was measured according to the guidelines at admission and blood pressure history, premedication, sports behaviour and BMI were recorded by means of questionnaires and compared with the data collected in the follow-up examination after one year. RESULTS: The participants were evaluated in 4 groups (G): G1 - normotensive patients (n = 1,558), G2 - controlled hypertensive patients (n = 502), G3 - untreated uncontrolled hypertensive patients (n = 1,080), G4 - treated uncontrolled hypertensive patients (n = 728). In G1 blood pressure (RR) remained unchanged from 126.3/77.8 to 127.8/78.5, in G2 there was a significant (p < 0.001) RR increase from 128.1/77.0 to 134.9/79.8. In G3 and G4 RR decreased significantly (p < 0.001) from 149.9/90.0 to 143.5/86.9 and from 153.1/87.5 to 146.2 84.1 mmHg, respectively. In G3 and G4, RR decreased in 56.1% and 56.3% of subjects and increased in 18% and 21%, respectively. In contrast, RR increase was found more frequently in G1 and G2 (34.3% and 51%, respectively), and RR decrease less frequently (25.4 and 20.7%, respectively). The main reasons for RR decrease were weight loss, more exercise, and more antihypertensives. Frequently, improved compliance and dietary changes were given as reasons. As expected, the opposite often led to RR increase. CONCLUSION: 56% of the hypertensive participants succeeded in lowering their blood pressure, whereas there was a significant increase in blood pressure, especially in those who were well controlled with antihypertensives. This underlines the need to further motivate normotensive patients to maintain their normotension. The results show that the combination of individual written education and lifestyle interventions are an effective tool for the public health sector to combat hypertension. In our participants, lifestyle interventions have a significant impact on BP change. It should be noted critically that there are still too many patients who have not been reached.

Influence of cardiovascular risk factors on arterial hypertension and mild cognitive impairment in 4602 participants of the ELITE study.

BACKGROUND: In ELITE (Ernährung, Lebensstil und individuelle Information zur Verhinderung von Herzinfarkt, Schlaganfall und Demenz; german for: Nutrition, Lifestyle and Individual Information for the Prevention of Heart Attack, Stroke and Dementia) data on cardiovascular risk factors, cognitive function and quality of life are prospectively collected, which will be improved through targeted individual information. The aim is to improve the health of the participants and identify the reasons for the lack of implementation. METHODS: Risk factors of 4602 participants were linked to (controlled) hypertension and mild cognitive impairment (MCI). Blood pressure was measured according to the guidelines and the DEMTECT- test was used to detect MCI. RESULTS: The most common risk factor was hypertension (60%). Hypertensive patients were older (56.1 and 44.7 years), had a higher BMI (28 and 24.8 kg/m), frequently physical inactive (26 and 32.4%), diabetes (9.3 and 1.3%), higher LDL (134.7 and 124.1 mg/dl), higher triglycerides (169.6 and 124.8 mg/dl) and lower HDL (57.9 and 65.5 mg/dl) compared with normotensives (P < 0.001). Controlled hypertensive patients are less common men (46.1 and 52.1%, P < 0.001), have a lower BMI (28.3 and 29.1 kg/m, P < 0.001), lower LDL (129.0 and 135.6 mg/dl, P = 0.004) and lower triglycerides (162.5 and 182.3 mg/dl, P = 0.001) compared with treated uncontrolled hypertensive patients. Antihypertensives per person (2.015; 2.017) do not differ. The prevalence of MCI is highly significantly associated with the number of risk factors. in participants without risk factors, the prevalence is 3.9%, in participants with 4 risk factors, 16.3%. In hypertensive patients, the frequency is 11.8% compared with 4.8% for normotensives (P < 0.001). The occurrence of MCI depends significantly from age, blood pressure and diabetes CONCLUSION:: The frequency of MCI is highly significantly associated with the number of cardiovascular risk factors, regardless of age. The prevalence was particularly high among hypertensive patients, which is not often described. The occurrence of MCI depends significantly from age, blood pressure and diabetes. The metabolic syndrome and lack of exercise complicate blood pressure control.

Outcomes of Noninvasively Treated Idiopathic Toe Walkers.

Idiopathic toe walking (ITW) causes a common problem in pediatric orthopaedics. In the literature, numerous treatment options have been reported, but consensus about the management of ITW is still missing. The aim of the current study was to evaluate conservative treatment with pyramidal insoles. A total of 193 patients underwent conservative treatment between January 2010 and June 2013. Mean age at the beginning of the treatment was 7.75 ± 0.23 years (range 2.0-17.0 years). For all patients, demographic data, comorbid diseases, passive range of motion (ROM), persistent toe walking, and performed operations were retrospectively evaluated. Following operative treatment was defined failure. Eight (4.15%) patients underwent Achilles tendon lengthening operation after mean therapy time of 2.72 years (range 0.1-7.0 years), 174 cases were treated successfully (90.16%). In 50 cases, toe walking suspended completely after mean therapy time of 2.83 years. In cases of failure, patients were older at diagnosis and at the beginning of the treatment. Mean passive ROM increased over the time. In cases of failure, ROM decreased from the first to the second examination. Conservative treatment of ITW using pyramidal insoles can be effective. Ankle dorsiflexion significantly improved in the patients who were successfully treated. Therapy should start early. A decrease of ROM under therapy should lead to critical revisal of individual therapy. Levels of Evidence: Therapeutic, level IV: Case series.

Intrapartum Care Working Patterns of Midwives: The Long Road to Models of Care in Germany.

INTRODUCTION: Midwifery models of care help to enhance perinatal health outcomes, women's satisfaction, and continuity of care. Despite the ubiquitous presence of certified midwives at births in Germany, no research has investigated the diversity of midwives' practice patterns. Describing the variety of working patterns through which midwives provide intrapartum care may contribute to improving the organisation of midwifery services. METHODS: This cross-sectional survey took place in the region of Hannover and Hildesheim, Germany. Midwives attending births and practicing in hospitals and/or out-of-hospital were able to participate. Midwives who did not attend births were excluded. We assessed midwives' scope of services, practice locations, employment patterns, continuity of care, midwife-led births, and midwives' level of agreement with core values of midwifery care. The response rate of the survey was 32.7 % (69/211). RESULTS: We found that midwifery care services can be described according to midwives' employment patterns. The majority of midwives were employed in a hospital to provide intrapartum care (74.2 %, n = 49), and most also independently offered one or more antenatal and/or postpartum service/s. Only 25.8 % (n = 17) of midwives offered their services independently (laborist model of care). Independent midwives attended births in all three possible settings: hospital, free-standing birth centres and home. Significantly more independent midwives than employed midwives offered antenatal care and lactation consulting. Compared to employed midwives, significantly more independent midwives provided antenatal, intrapartum, and postpartum care to the same women, were more likely to know women before labour, and to offer one-to-one care during labour. DISCUSSION: The most common practice pattern among surveyed midwives was 'employment in a hospital' for provision of intrapartum care with additional postpartum and few antenatal services provided on an independent basis. Midwives who worked solely independently reported more continuity and one-to-one intrapartum care with women. Most midwives did not work in patterns that offered continuity of care or consistently provide one-to-one care. Future research should assess whether women in Germany desire more services similar to caseload midwifery.

[Outcomes of Planned Out-of-Hospital and Low-Risk Hospital Births in Lower Saxony]. / Outcomes geplanter außerklinischer und klinischer Low-Risk Geburten in Niedersachsen.

Introduction Internationally, there is debate on the safety of different birth settings inside and outside of hospitals. Low-risk women in Germany can choose where they give birth, and out-of-hospital births are especially necessary in regions lacking infrastructure. To date, national studies are required. Materials and Methods We investigated planned out-of-hospital (OH) and hospital births in Lower Saxony, Germany, in 2005. Women with a singleton fetus in the vertex position were included once they reached 34+0 gestational weeks. 1 273 out of 4 424 births were included via risk assessment. Outcomes were compared using Pearson's chi-squared test, the Mann-Whitney test, and logistic regression. Results 152 (36.6%) nulliparae (NP) and 263 (63.4%) multiparae (MP) gave birth out of hospital, 439 (51.2%) nulliparae and 419 (48.8%) multiparae in a hospital. 10.1% of women whose care started outside of the hospital needed a transfer to the hospital. Women who planned OH were older and had a higher level of education. Women without a migration background displayed an increased rate of out-of-hospital birth. A higher proportion received their antenatal care from midwives rather than medical doctors. Induction of labor was less likely for women with planned out-of-hospital births, as were other intrapartum interventions. In hospital births, fetal monitoring was more likely performed via cardiotocograph instead of intermittent auscultation. Duration of labor was significantly longer in OH births (median: NP: 9.01 h vs. 7.38 h; MP: 4.53 h vs. 4.25 h). Nulliparae had more spontaneous births out-of-hospital (94.7%) than in hospital (73.6%). There was no difference in adverse fetal outcomes, blood loss, and severe perineal lacerations. The perineum was less frequently intact in hospital births. Retained placenta was more often documented in out-of-hospital births. Conclusions In an out-of-hospital setting, fewer interventions were performed, spontaneous births occurred more often, and there was no difference in neonatal outcomes. OH birth appears reasonably safe with thorough pre-labor risk assessment and good transfer management. Some beneficial aspects of OH birth care (like continuity of care and restriction of routine interventions) could be adopted by hospital labor wards, leading to a higher rate of vaginal births and improved care.

Late radiation side effects, cosmetic outcomes and pain in breast cancer patients after breast-conserving surgery and three-dimensional conformal radiotherapy : Risk-modifying factors.

BACKGROUND AND PURPOSE: The purpose of this work was to identify parameters influencing the risk of late radiation side effects, fair or poor cosmetic outcomes (COs) and pain in breast cancer patients after breast-conserving therapy (BCT) and three-dimensional conformal radiotherapy (3D-CRT). PATIENTS AND METHODS: Between 2006 and 2013, 159 patients were treated at the Hannover Medical School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain were assessed by multivariate analysis. RESULTS: LENT-SOMA grade 1-4 toxicity was observed as follows: fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe breast pain, and 21.4 % complained about moderate or severe pain in the arm or shoulder. In multivariate analysis, axillary clearing (AC) was significantly associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 % confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36), a ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C (OR 5.34, p = 0.029, 95 % CI 1.2-24.12). A ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C were the parameters significantly associated with an unfavourable CO (OR 3.19, p = 0.019, 95 % CI 1.2-8.4). Concerning chronic breast pain, we found a trend related to the prescribed radiation dose including boost (OR 1.077, p = 0.060, 95 % CI 0.997-1.164). Chronic shoulder or arm pain was statistically significantly associated with lymphoedema of the arm (OR 3.9, p = 0.027, 95 % CI 1.17-13.5). CONCLUSION: Chronic arm and breast oedema were significantly influenced by the extent of surgery (AC). Ptotic and large breasts were significantly associated with unfavourable COs and chronic breast oedema. Late toxicities exclusive breast pain were not associated with radiotherapy parameters.

A Fluorescence-Based Assay for Proteinuria Screening in Larval Zebrafish (Danio rerio).

Analysis of genes compromising the glomerular filtration barrier in rodent models using transgenic or knockdown approaches is time- and resource-consuming and often leads to unsatisfactory results. Therefore, it would be beneficial to have a selection tool indicating that your gene of interest is in fact associated with proteinuria. Zebrafish (Danio rerio) is a rapid screening tool to study effects in glomerular filtration barrier integrity after genetic manipulation. We use either injection of high-molecular-weight dextrans or a transgenic fluorescent fish line [Tg(l-fabp:DBP:EGFP)] expressing a vitamin D-binding protein fused with eGFP for indirect detection of proteinuria. A loss of high-molecular-weight proteins from the circulation of the fish into the urine can be identified by monitoring fluorescence intensity in the zebrafish eye. Paired with an optimized analysis method, this assay provides an effective screening solution to detect filtration barrier damage with proteinuria before moving to a mammalian system.

Dermoglandular rotation flaps for breast-conserving therapy: aesthetic results, patient satisfaction, and morbidity in comparison to standard segmentectomy.

We compared a dermoglandular rotation flap (DGR) in the upper inner, lower inner, and upper outer quadrant regarding similar aesthetic results, patient satisfaction, and comfort after breast-conserving therapy with standard segmentectomy (SE). Between 2003 and 2011, 69 patients were treated with breast-conserving surgery using DGR for cancers with high tumor-to-breast volume ratios or skin resection in the three above mentioned quadrants; 161 patients with tumors in the same quadrants were treated with SE. The outcome of the procedures was assessed at least 7 months after completed radiation therapy using a patient and breast surgeon questionnaire and the BCCT.core software. Symmetry, visibility of the scars, the position of the nipple-areola complex, and the appearance of the treated breast were each assessed on a scale from 1 to 4 by an expert panel and by the patients. Univariate and multivariate analysis were used to evaluate the relationship between patient-, tumor-, and treatment-dependent factors and patient satisfaction. 94.2% of the patients with rotation flaps and 83.5% of the patients with lumpectomy were very satisfied with the cosmetic appearance of their breast. Younger patient age was significantly associated with a lower degree of satisfaction. DGR provides good cosmetic results compared with SE and shows high patient satisfaction despite longer scarring and higher median resection volume.

L-arginine/NO pathway is altered in children with haemolytic-uraemic syndrome (HUS).

The haemolytic uraemic syndrome (HUS) is the most frequent cause of acute renal failure in childhood. We investigated L-arginine/NO pathway in 12 children with typical HUS and 12 age-matched healthy control subjects. Nitrite and nitrate, the major NO metabolites in plasma and urine, asymmetric dimethylarginine (ADMA) in plasma and urine, and dimethylamine (DMA) in urine were determined by GC-MS and GC-MS/MS techniques. Urinary measurements were corrected for creatinine excretion. Plasma nitrate was significantly higher in HUS patients compared to healthy controls (P = 0.021), whereas urine nitrate was borderline lower in HUS patients compared to healthy controls (P = 0.24). ADMA plasma concentrations were insignificantly lower, but urine ADMA levels were significantly lower in the HUS patients (P = 0.019). Urinary DMA was not significantly elevated. In HUS patients, nitrate (R = 0.91) but not nitrite, L-arginine, or ADMA concentrations in plasma correlated with free haemoglobin concentration. Our results suggest that both NO production and ADMA synthesis are decreased in children with typical HUS. We hypothesize that in the circulation of children with HUS a vicious circle between the L-arginine/NO pathway and free haemoglobin-mediated oxidative stress exists. Disruption of this vicious circle by drugs that release NO and/or sulphydryl groups-containing drugs may offer new therapeutic options in HUS.

Long-term health-related quality of life after complex and/or complicated esophageal atresia in adults and children registered in a German patient support group.

BACKGROUND: Health-related quality of life (HRQoL) after esophageal atresia (EA) repair is postulated to be good. However, little is known about the long-term results after repair of complex and/or complicated EA regarding HRQoL. We investigated long-term HRQoL after delayed anastomosis, esophageal replacement, major revisions, or multiple dilatations in patients registered in a support group. METHODS: Patients registered in the German patient support group database (KEKS) were enrolled and allocated to subgroups according to surgical treatment and age. HRQoL was evaluated using validated questionnaires (GIQLI, WHO-5, KIDSCREEN27). RESULTS: Complete follow-up (mean 14.5 ± 9.8 years) was available for 90/92 patients. Patients were allocated to subgroups delayed anastomosis (n=28), esophageal replacement (n=27), major revisions (n=15), and multiple dilatations (n=20). Adult patients presented with impaired well-being according to WHO-score and gastrointestinal function (GIQLI). In contrast, HRQoL of children was comparable to controls in most KIDSCREEN27-dimensions. Delayed anastomosis was associated with most-favourable HRQoL. Regarding physical well-being, these children scored significantly better than controls [64.01 ± 10.40 vs. 52.36 ± 8.73;p=0.0011], children after replacement [51.40 ± 5.70;p=0.008], revisions [52.04 ± 6.97;p=0.026], and multiple dilatations [50.22 ± 9.67,p=0.04]. CONCLUSIONS: HRQoL after complex and/or complicated EA is excellent in children registered in a patient support group. In adults, disease-specific symptoms negatively affect HRQoL. Our data indicate that saving the esophagus may achieve the best HRQoL.

Cardiovascular effects of a proprietary l-methadone/fenpipramide combination (Polamivet) alone and in addition to acepromazine in healthy Beagle dogs.

OBJECTIVE: To determine the cardiovascular effects of a proprietary l-methadone/fenpipramide combination (Polamivet) alone and in addition to acepromazine in dogs. STUDY DESIGN: Prospective, randomized, experimental crossover study. ANIMALS: Five adult healthy Beagle dogs (one male and four females, weighing 12.8-16.4 kg). METHODS: Dogs were instrumented for haemodynamic measurements whilst anaesthetized with isoflurane. Three hours after recovery dogs received 0.025 mg kg(-1) acepromazine (AP) or saline (SP) IM followed by 0.5 mg kg(-1) L-methadone/ 0.025 mg kg(-1) fenpipramide IV after 30 minutes. Cardiac output using thermodilution, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (MPAP), pulmonary artery occlusion pressure (PAOP), haemoglobin concentration, arterial and mixed-venous blood gas analysis were measured and sedation evaluated at baseline (BL), 30 minutes after acepromazine or saline IM (A/S), 5 minutes after L-methadone/fenpipramide IV application (35), every 15 minutes for 1 hour (50, 65, 80, 95 minutes) and every hour until baseline cardiac output was regained. Standard cardiovascular parameters were calculated. Data were analyzed by repeated measures anova and paired t-tests with p < 0.05 considered significant. RESULTS: Baseline measurements did not differ. Cardiac index decreased after acepromazine administration in treatment AP (p = 0.027), but was not significantly influenced after l-methadone/fenpipramide injection in either treatment. In both treatments heart rate did not change significantly over time. Stroke volume index increased after A/S in both treatments (p = 0.049). Systemic vascular resistance index, MAP, CVP, MPAP, and pulmonary vascular resistance index did not change significantly after either treatment and did not differ between treatments. Dogs were deeply sedated in both treatments with a longer duration in treatment AP. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs the dose of l-methadone/fenpipramide used in this study alone and in combination with acepromazine induced deep sedation without significant cardiovascular changes.

Aneuploidy screening during pregnancy by a three-dimensional Advanced First Trimester Screening model: description of the AFS-3D algorithm.

BACKGROUND: A novel screening method for fetal aneuploidies was developed, in which nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A), and free-ß human chorionic gonadotropin (free-ß hCG) are placed into a three-dimensional scatter plot. Likelihood ratios are directly inferred from the ratio of already observed healthy and diseased fetuses. This method is called 'Three-dimensional Advanced First trimester Screening' (AFS-3D). It was aimed to develop and test a new algorithm based on the results of previous studies. METHODS: A new static-sized sphere model was developed. Several scaling factors of the axes and the optional application of the modifications 'simulation' (SIM) and 'empty sphere positive' were tested on 15,227 data sets. An additional examination was performed on a second collective (n = 458). RESULTS: The application of the new AFS-3D model with static-sized spheres, a re-sampled ∆NT axis by a scaling factor of 0.125, and the application of SIM and Empty Box Positive resulted in a marked improvement of the test performance (area under curve, AUC = 0.9668). Analogous results (AUC = 0.9807) were found for the second test collective. CONCLUSIONS: This novel approach is promising and should be tested on a larger, independent collective.

In vivo monitoring of natural killer cell-dependent clearance of lung metastasis using dynamic positron emission tomography.

Immunohistological methods indicated a rapid onset of cellular defence shortly after seeding of mammary adenocarcinoma cells into the lungs of F344 rats. The purpose of the present study was to monitor natural killer (NK) cell-mediated effects on tumour cell clearance in vivo, in this model of lung metastasis using dynamic positron-emission tomography (dPET). MADB106 breast cancer cells were labelled with 2'-[(18)F]-2'-deoxy-D-glucose (FDG) then injected intravenously, after the F344 rats had been anaesthetized and placed in a PET scanner. NK cell-depleted and sham-treated control rats were investigated in parallel. The radioactivity per region of interest (ROI) over the lungs peaked at 60 s past injection and was followed by a slow decline over the observation time of 40 min in both groups. Statistical analysis using a linear mixed model revealed that release of radioactivity from tumour cells or tumour cell disintegration was significantly slower in animals after depletion of NK cells compared with controls. There was no significant tumour cell homing in organs other than the lungs. Early kinetics of tumour cells after injection were defined. PET with FDG was shown to be an adequate method to further investigate novel options for using cellular host defence mechanisms in cancer patients.

Apoptosis in extracorporeal preserved inguinal fat flaps of the rat.

Fat cells are fragile cells with a short life span outside the body. Ways to reduce cell death in a biochemical way are almost unknown due to scarce information on the type of cellular death that is induced in fat tissue. This study was designed to investigate the apoptotic pathways of fat tissue in a permanent perfusion bioreactor system with the Hannover preservation solution and the Eurocollins solution in fat flaps of rats. In Lewis rats, the inguinal adipofascial flaps were elevated bilaterally and placed in a bioreactor at 37°C. To detect caspases 3, 8, 9 and 12, immunofluorescence stains of fat tissue specimen were analysed at several time points after preservation of flaps were placed in Hannover solution and Eurocollins solution for 10 days. An additional visual assessment of viability by a calcein based life/dead test was performed. It revealed a superior viability of the adipose tissue preserved in Hannover solution. Immunofluorescence staining demonstrated that apoptotic pathways via mitochondria, endoplasmatic reticulum and death receptors were activated, as Caspases 8, 9 and 12 were detected. Caspase 3 as an effector in the common apoptotic pathway was detected as well. Adipose tissue preserved at 37°C ex vivo in a bioreactor system undergoes apoptosis. Immunofluorescence examination of the fat tissue preserved ex vivo revealed that apoptotic pathways via mitochondria, endoplasmatic reticulum and death receptors are being activated. Significantly less activation of Caspase 3, 8, 9 and 12 in flaps preserved in Hannover solution in comparison to Eurocollins was found, supporting the anti apoptotic characteristics of Hannover solution. Based on these findings, further research to modify the apoptotic pathways to ameliorate viability of fat tissue can be performed.

Biopsy-controlled liver fibrosis staging using the enhanced liver fibrosis (ELF) score compared to transient elastography.

BACKGROUND AND AIMS: Chronic liver diseases are characterized by inflammatory and fibrotic liver injuries that often result in liver cirrhosis with its associated complications such as portal hypertension and hepatocellular carcinoma. Liver biopsy still represents the reference standard for fibrosis staging, although transient elastography is increasingly used for non-invasive monitoring of fibrosis progression. However, this method is not generally available and is associated with technical limitations emphasizing the need for serological biomarkers staging of liver fibrosis. The enhanced liver fibrosis (ELF) score was shown to accurately predict significant liver fibrosis in different liver diseases, although extracellular matrix components detected by this score may not only mirror the extent of liver fibrosis but also inflammatory processes. METHODS: In this prospective biopsy-controlled study we evaluated the utility of the ELF score in comparison to transient elastography to predict different stages of fibrosis in 102 patients with chronic liver diseases. RESULTS: Both techniques revealed similar area under receiver operating characteristic curve values for prediction of advanced fibrosis stages. Compared to transient elastography, the ELF score showed a broader overlap between low and moderate fibrosis stages and a stronger correlation with inflammatory liver injury. CONCLUSIONS: Both the ELF score as well as transient elastography allowed for high quality fibrosis staging. However, the ELF score was less discriminative in low and moderate fibrosis stages and appeared more strongly influenced by inflammatory liver injury. This should be considered when making clinical interpretations on the basis of ELF score values.