Health-related quality of life of adults with spinal muscular atrophy: insights from a nationwide patient registry in Germany.

PURPOSE: Spinal muscular atrophy (SMA) is a rare, autosomal-recessive disease characterized by progressive muscular atrophy and weakness resulting in substantial disability and short life expectancy. The objective of this cross-sectional study was to assess health-related quality of life (HRQoL) of adults with SMA in Germany in the era of disease-modifying therapy. METHODS: Adults with SMA were recruited via the German national TREAT-NMD SMA patient registry. HRQoL was measured using the EQ-5D-5L, the Health Utilities Index Mark III (HUI), and the Short Form (36) Health Survey (SF-36). Estimates were stratified by current best motor function of the lower limb and trunk (i.e., non-sitter, sitter, and walker) and SMA type (i.e., type I, II, and III). RESULTS: A total of 82 adults with SMA (mean age: 42 years, 51% female) self-completed the study questionnaire. The mean EQ-5D-5L utility was estimated at 0.5135 (range across subgroups: 0.31-0.99), mean EQ-VAS at 69.71 (64.67-90.00), mean HUI-derived utility at 0.3171 ( - 0.02-0.96), mean SF-6D utility at 0.6308 (0.58-0.65), and mean SF-36 Physical Component Summary and Mental Health Component Summary scores at 33.78 (9.92-53.10) and 53.49 (21.02-72.25), respectively. CONCLUSIONS: We show that adults with SMA experience considerable impairment across a wide range of health dimensions, including mobility, dexterity, pain, and emotional well-being. However, our results exhibit non-trivial variability across clinical subgroups and HRQoL measures. These data contribute to our understanding of the subjective impact of living with a severely debilitating neuromuscular disease, such as SMA.

Ultrasound-guided determination demonstrates influence of age, sex and type of sport on medial femoral condyle cartilage thickness in children and adolescents.

PURPOSE: To analyse the reliability of ultrasound-guided measurement of the cartilage thickness at the medial femoral condyle in athletically active children and adolescents before and after mechanical load in relation to age, sex and type of sport. METHODS: Three successive measurements were performed in 157 participants (median/min-max age: 13.1/6.0-18.0 years, 106 males) before and after mechanical load by squats at the same site of the medial femoral condyle by defined transducer positioning. Test-retest reliability was examined using Cronbach's α $\alpha $ calculation. Differences in cartilage thickness were analysed with respect to age, sex and type of practiced sports, respectively. RESULTS: Excellent reliability was achieved both before and after mechanical load by 30 squats with a median cartilage thickness of 1.9 mm (range: 0.5-4.8 mm) before and 1.9 mm (0.4-4.6 mm) after mechanical load. Male cartilages were thicker (p < 0.01) before (median: 2.0 mm) and after (2.0 mm) load when compared to female cartilage (before: 1.6 mm; after: 1.7 mm). Median cartilage thickness was about three times higher in karate athletes (before: 2.3 mm; after: 2.4 mm) than in sports shooters (0.7; 0.7 mm). Cartilage thickness in track and field athletes, handball players and soccer players were found to lay in-between. Sport type related thickness changes after mechanical load were not significant. CONCLUSION: Medial femoral condyle cartilage thickness in childhood correlates with age, sex and practiced type of sports. Ultrasound is a reliable and simple, pain-free approach to evaluate the cartilage thickness in children and adolescents. LEVEL OF EVIDENCE: Level III.

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.

Inpatient Rsv-Management 2016-2022: Epidemiology and Adherence to A Bronchiolitis Treatment Standard at a German University Children's Hospital.

BACKGROUND: This study analyzes the RSV season 2021/2022 in a referral children's hospital, compares the epidemiology and illness severity with RSV-infected inpatients from 2016 to 2020 and audits the adherence to our internal therapy standard for RSV bronchiolitis. MATERIAL AND METHODS: Inpatients with rtPCR-confirmed RSV infection (Jan. 2016 to Jan. 2022). RESULTS: The audit comprises 306 RSV inpatients, on average 50 hospitalizations per year; in 03/2020, a rapid RSV Season-Offset was observed. In the winter season 2020/2021, no patient with RSV was hospitalized. Beginning in July, we noticed a rapid increase of RSV-admissions (most cases in Sept./Oct, duration until Dec. 2021; n=53). In 2021-2022, a significant larger share needed PICU admission (9.4% vs 3.2%, p=0.040). Adherence to the internal guidance was low; only 11.8% (n=36) of all patients received supportive treatment without inhalative or systemic medications, 37% of all patients received antibiotics. CONCLUSIONS: This audit confirms the strong impact of public preventive measures directed against SARS-CoV-2 transmission on RSV epidemiology. Few weeks after easing public COVID-19 restrictions (summer 2021), RSV inpatient cases rapidly increased, lasting until Dec. 2021. The audit of bronchiolitis management revealed surprisingly low adherence to the internal guidance, despite a face-to-face educational session with the attending pediatricians in Oct. 2021. Low adherence resulted in an unnecessary exposure of RSV patients to systemic medications of questionable benefit including antibiotics.

Different populations of A(H1N1)pdm09 viruses in a patient with hemolytic-uremic syndrome.

Respiratory viral infections may have different impacts ranging from infection without symptoms to severe disease or even death though the reasons are not well characterized. A patient (age group 5-15 years) displaying symptoms of hemolytic uremic syndrome died one day after hospitalization. qPCR, next generation sequencing, virus isolation, antigenic characterization, resistance analysis was performed and virus replication kinetics in well-differentiated airway cells were determined. Autopsy revealed hemorrhagic pneumonia as major pathological manifestation. Lung samples harbored a large population of A(H1N1)pdm09 viruses with the polymorphism H456H/Y in PB1 polymerase. The H456H/Y viruses replicated much faster to high viral titers than upper respiratory tract viruses in vitro. H456H/Y-infected air-liquid interface cultures of differentiated airway epithelial cells did reflect a more pronounced loss of ciliated cells. A different pattern of virus quasispecies was found in the upper airway samples where substitution S263S/F (HA1) was observed. The data support the notion that viral quasispecies had evolved locally in the lung to support high replicative fitness. This change may have initiated further pathogenic processes leading to rapid dissemination of inflammatory mediators followed by development of hemorrhagic lung lesions and fatal outcome.

Self-Reported Health-Related Quality of Life of Children with Spinal Muscular Atrophy: Preliminary Insights from a Nationwide Patient Registry in Germany.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare, severely debilitating neuromuscular disease characterized by a wide spectrum of progressive muscular atrophy and weakness. OBJECTIVES: The objective of this pilot study was to estimate self-assessed health-related quality of life (HRQoL) of children with SMA. METHODS: Children with SMA were recruited via the German national TREAT-NMD SMA patient registry and asked to self-complete the following rating-scales: KIDSCREEN-27, KINDL, the PedsQL 3.0 Neuromuscular Module (PedsQL 3.0 NMM), EQ-5D-5L, and the Health Utilities Index (HUI). Estimates were stratified by current best motor function of the lower limb and trunk (i.e., non-sitter, sitter, and walker) and SMA type (i.e., type I, II, and III). RESULTS: In total, 17 children with SMA (mean age: 9.88 years, SD: 4.33 years, range: 5-16 years; 59% female) participated in the study. Across examined strata, the mean KIDSCREEN-27 total score was estimated at between 48.24 and 83.81; the mean KINDL total score at between 60.42 and 76.73; the mean PedsQL 3.0 NMM total score at between 58.00 and 83.83; the mean EQ-5D-5L utility at between 0.31 and 0.99; and the mean HUI-derived utility at between -0.02 and 0.96. CONCLUSIONS: The results from this pilot study show that German children with SMA, despite significant physical disability, have surprisingly good HRQoL as assessed using KIDSCREEN-27. Yet, many reside in health states associated with low utility. The disease burden was generally higher among non-sitters compared with walkers, and SMA type I compared with type III, but more research is needed to further delineate this variability. Our preliminary findings contribute to the understanding of HRQoL in pediatric patients with SMA and should be helpful to inform the design of future studies of this patient population.

Detection of volatile organic compounds in headspace of Klebsiella pneumoniae and Klebsiella oxytoca colonies.

Introduction: Early diagnosis of infections and sepsis is essential as adequate therapy improves the outcome. Unfortunately, current diagnostics are invasive and time-consuming, making diagnosis difficult, especially in neonatology. Novel non-invasive analytical methods might be suitable to detect an infection at an early stage and might even allow identification of the pathogen. Our aim is to identify specific profiles of volatile organic compounds (VOCs) of bacterial species. Methods: Using multicapillary column-coupled ion mobility spectrometry (MCC/IMS), we performed headspace measurements of bacterial cultures from skin and anal swabs of premature infants obtained during weekly screening for bacterial colonization according to KRINKO. We analyzed 25 Klebsiella pneumoniae (KP) cultures on MacConkey (MC) agar plates, 25 Klebsiella oxytoca (KO) cultures on MC agar and 25 bare MC agar plates as a control group. Results: Using MCC/IMS, we identified a total of 159 VOC peaks. 85 peaks allowed discriminating KP and bare MC agar plates, and 51 peaks comparing KO and bare MC agar plates and 6 peaks between KP and KO (significance level of p < 0.05 after Bonferroni post hoc analysis), respectively. Peaks P51 (n-Decane) and P158 (Phenylethyl Alcohol), showed the best sensitivity/specificity/ positive predictive value/negative predictive value of 99.9% each (p < 0.001) for KP. P158 showed the best sensitivity/specificity/positive predictive value/negative predictive value of 99.9% each (p < 0.001) for KO. Comparing KP and KO, best differentiation was enabled using peaks P72, P97 and P16 with sensitivity/specificity/positive predictive value/negative predictive value of 76.0%, 84.0%, 82.6%, 77.8%, respectively (p < 0.05). Discussion: We developed a method for the analysis of VOC profiles of bacteria. Using MCC/IMS, we demonstrated that VOCs derived from bacteria are clearly distinguishable from a bare agar plate. Characteristic peaks obtained by MCC/IMS are particularly suitable for the species-specific identification and differentiation of KP and KO. Thus, MCC/IMS might be a useful tool for in vitro diagnostics. Future studies must clarify whether similar patterns of VOCs can be detected in vivo in patients that are colonized or infected with KP or KO to enable rapid and accurate diagnosis of bacterial colonization.

Prediction of movement difficulties at 5 years from parent report at 2 years in children born extremely preterm.

AIM: To assess the predictive validity of parent-reported gross motor impairment (GMI) at age 2 years to detect significant movement difficulties at age 5 years in children born extremely preterm. METHOD: Data were from 556 children (270 males, 286 females) born at less than 28 weeks' gestation in 2011 to 2012 in 10 European countries. Parent report of moderate/severe GMI was defined as walking unsteadily or unable to walk unassisted at 2 years corrected age. Examiners assessed significant movement difficulties (score ≤ 5th centile on the Movement Assessment Battery for Children, Second Edition) and diagnoses of cerebral palsy (CP) were collected by parent report at 5 years chronological age. RESULTS: At 2 years, 66 (11.9%) children had moderate/severe GMI. At 5 years, 212 (38.1%) had significant movement difficulties. Parent reports of GMI at age 2 years accurately classified CP at age 5 years in 91.0% to 93.2% of children. Classification of moderate/severe GMI at age 2 years had high specificity (96.2%; 95% confidence interval 93.6-98.0) and positive predictive value (80.3%; 68.7-89.1) for significant movement difficulties at age 5 years. However, 74.5% of children with significant movement difficulties at 5 years were not identified with moderate/severe GMI at age 2 years, resulting in low sensitivity (25.1%; 19.4-31.5). INTERPRETATION: This questionnaire may be used to identify children born extremely preterm who at age 2 years have a diagnosis of CP or movement difficulties that are likely to have a significant impact on their functional outcomes at age 5 years.

Motivations for Adolescent COVID-19 Vaccination: A Comparative Study of Adolescent and Caregiver Perspectives in Germany.

Given the crucial role of vaccination in halting the COVID-19 pandemic, it is imperative to understand the factors that motivate adolescents to get vaccinated. We surveyed adolescents and their accompanying guardians scheduled to receive a COVID-19 vaccination (Comirnaty) in an urban region in Germany in mid-2021 regarding their motivation for getting vaccinated and collected data on their sociodemographic characteristics, medical history, vaccination status, and any history of COVID-19 infection in the family. We also queried information strategies related to the SARS-CoV-2 pandemic. Motivations for getting vaccinated were similar among adolescents and their parents. The primary reasons for vaccination were protection against SARS-CoV-2-related illness and gaining access to leisure facilities. This was not influenced by gender, health status, migration background, or the presence of chronic or acute diseases. The percentage of parents who had received SARS-CoV-2 immunization and the proportion of parents with a high level of education were higher among study participants than in the general population. Adolescents were especially willing to be vaccinated if they came from a better educational environment and had a high vaccination rate in the family. Emphasizing the importance of vaccination among all segments of the population and removing barriers to vaccines may lead to an ameliorated acceptance of COVID-19 vaccines.

Serum cytokines MCP-1 and GCS-F as potential biomarkers in pediatric inflammatory bowel disease.

BACKGROUND: Inflammatory bowel diseases (IBDs) with the subtypes ulcerative colitis (UC) and Crohn disease (CD), are chronic autoimmune inflammatory disorders of the gastrointestinal tract. Cytokines are associated with the development and progression in pediatric IBD. We measured cytokine levels in pediatric IBD patients to assess their potential function as biomarkers in disease assessment. METHOD: In this prospective cohort study, we enrolled 33 children with IBD. All patients were in stable remission for 3 months on enrollment. Patients who developed a relapse within six months after enrollment were classified as relapsers. Blood sampling was performed at enrolment and for relapsers in relapse and post-relapse. Serum concentrations of 14 cytokines, chemokines and growth factors (IL-1α, IL-1ß, IL-6, IL-12p40, IP-10, TNF-α, IFN-γ, IL-10, IL-8, MIP-1α, MCP-1, MCP-3, G-CSF, GM-CSF) were measured simultaneously using multiplex bead-based sandwich immunoassay on Luminex 100 system. RESULTS: MCP-1 was significantly higher in CD patients compared to UC patients at each disease stage: stable remission (P<0.048), unstable remission (P<0.013), relapse (P<0.026) and post-relapse (P<0.024). G-CSF was significantly increased in UC patients developing a relapse and in post-relapse stage compared to UC patients in remission (P<0.02 and p<0.03, respectively). CONCLUSION: MCP-1 showed potential as a diagnostic biomarker in CD patients independent of disease activity as it was able to discriminate between subtypes of pediatric IBD. In UC patients, G-CSF was significantly elevated in relapsers indicating its use and role as a potential prognostic biomarker.

Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin.

BACKGROUND: Peripheral facial palsy (PFP) is a common neurologic symptom which can be triggered by pathogens, autoimmunity, trauma, tumors, cholesteatoma or further local conditions disturbing the peripheral section of the nerve. In general, its cause is often difficult to identify, remaining unknown in over two thirds of cases. As we have previously shown that the quantity and quality of pathogen-specific T cells change during active infections, we hypothesized that such changes may also help to identify the causative pathogen in PFPs of unknown origin. METHODS: In this observational study, pathogen-specific T cells were quantified in blood samples of 55 patients with PFP and 23 healthy controls after stimulation with antigens from varicella-zoster virus (VZV), herpes-simplex viruses (HSV) or borrelia. T cells were further characterized by expression of the inhibitory surface molecule CTLA-4, as well as markers for differentiation (CD27) and proliferation (Ki67). Pathogen-specific antibody responses were analyzed using ELISA. Results were compared with conventional diagnostics. RESULTS: Patients with PFP were more often HSV-seropositive than controls (p = 0.0003), whereas VZV- and borrelia-specific antibodies did not differ between groups. Although the quantity and general phenotypical characteristics of antigen-specific T cells did not differ either, expression of CTLA-4 and Ki67 was highly increased in VZV-specific T cells of 9 PFP patients, of which 5 showed typical signs of cutaneous zoster. In the remaining 4 patients, a causal relationship with VZV was possible but remained unclear by clinical standard diagnostics. A similar CTLA-4- and Ki67-expression profile of borrelia-specific T cells was also found in a patient with acute neuroborreliosis. DISCUSSION: In conclusion, the high prevalence of HSV-seropositivity among PFP-patients may indicate an underestimation of HSV-involvement in PFP, even though HSV-specific T cell characteristics seem insufficient to identify HSV as a causative agent. In contrast, striking alterations in VZV- and borrelia-specific T cell phenotype and function may allow identification of VZV- and borrelia-triggered PFPs. If confirmed in larger studies, antigen-specific immune-phenotyping may have the potential to improve specificity of the clinical diagnosis.

Apgar Score and Neurodevelopmental Outcomes at Age 5 Years in Infants Born Extremely Preterm.

Importance: The Apgar score is used worldwide as an assessment tool to estimate the vitality of newborns in their first minutes of life. Its applicability to estimate neurodevelopmental outcomes in infants born extremely preterm (EPT; <28 weeks' gestation) is not well established. Objective: To investigate the association between the Apgar score and neurodevelopmental outcomes in infants born EPT. Design, Setting, and Participants: This cohort study was conducted using data from the Effective Perinatal Intensive Care in Europe-Screening to Improve Health in Very Preterm Infants in Europe (EPICE-SHIPS) study, a population-based cohort in 19 regions of 11 European countries in 2011 to 2012. Clinical assessments of cognition and motor function at age 5 years were performed in infants born EPT and analyzed in January to July 2023. Exposures: Apgar score at 5 minutes of life categorized into 4 groups (0-3, 4-6, 7-8, and 9-10 points). Main Outcomes and Measures: Cognitive and motor outcomes were assessed using the Wechsler Preschool and Primary Scale of Intelligence test of IQ derived from locally normed versions by country and the Movement Assessment Battery for Children-Second Edition. Parents additionally provided information on communication and problem-solving skills using the Ages and Stages Questionnaire, third edition (ASQ-3). All outcomes were measured as continuous variables. Results: From the total cohort of 4395 infants born EPT, 2522 infants were live born, 1654 infants survived to age 5 years, and 996 infants (478 females [48.0%]) followed up had at least 1 of 3 outcome measures. After adjusting for sociodemographic variables, perinatal factors, and severe neonatal morbidities, there was no association of Apgar score with IQ, even for scores of 3 or less (ß = -3.3; 95% CI, -10.5 to 3.8) compared with the score 9 to 10 category. Similarly, no association was found for ASQ-3 (ß = -2.1; 95% CI, -24.6 to 20.4). Congruent results for Apgar scores of 3 or less were obtained for motor function scores for all children (ß = -4.0; 95% CI, -20.1 to 12.1) and excluding children with a diagnosis of cerebral palsy (ß = 0.8, 95% CI -11.7 to 13.3). Conclusions and Relevance: This study found that low Apgar scores were not associated with longer-term outcomes in infants born EPT. This finding may be associated with high interobserver variability in Apgar scoring, reduced vitality signs and poorer responses to resuscitation after birth among infants born EPT, and the association of more deleterious exposures in the neonatal intensive care unit or of socioeconomic factors with greater changes in outcomes during the first 5 years of life.

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.

[Update Perioperative Antibiotic Prophylaxis in Neonatology]. / Update Perioperative Antibiotikaprophylaxe in der Neonatologie.

This narrative review discusses basic principles of the perioperative antibiotic prophylaxis (PAP) in premature and at term newborns and refers to some particularities concerning the indication and dosing issues. Although this is a vulnerable patient population, the spectrum of activity should not be unnecessarily broad and the regular PAP must not be prolonged beyond 24 hours.

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.

Controlled prospective study on ultrasound simulation training in fetal echocardiography: FESIM II.

PURPOSE: To analyze the learning curves of ultrasound novices in fetal echocardiography during structured simulation-based ultrasound training (SIM-UT) including a virtual, randomly moving fetus. METHODS: 11 medical students with minimal (< 10 h) prior obstetric ultrasound experience underwent 12 h of structured fetal echocardiography SIM-UT in individual hands-on sessions during a 6-week training program. Their learning progress was assessed with standardized tests after 2, 4, and 6 weeks of SIM-UT. Participants were asked to obtain 11 fetal echocardiography standard planes (in accordance with ISUOG and AHA guidelines) as quickly as possible. All tests were carried out under real life, examination-like conditions on a healthy, randomly moving fetus. Subsequently, we analyzed the rate of correctly obtained images and the total time to completion (TTC). As reference groups, 10 Ob/Gyn physicians (median of 750 previously performed Ob/Gyn scans) and 10 fetal echocardiography experts (median of 15,000 previously performed Ob/Gyn scans) were examined with the same standardized tests. RESULTS: The students showed a consistent and steady improvement of their ultrasound performance during the training program. After 2 weeks, they were able to obtain > 95% of the standard planes correctly. After 6 weeks, they were significantly faster than the physician group (p < 0.001) and no longer significantly slower than the expert group (p = 0.944). CONCLUSION: SIM-UT is highly effective to learn fetal echocardiography. Regarding the acquisition of the AHA/ISUOG fetal echocardiography standard planes, the students were able to reach the same skill level as the expert group within 6 weeks.

Serum vascular endothelial growth factor is a potential biomarker for acute mountain sickness.

Background: Acute mountain sickness (AMS) is the most common disease caused by hypobaric hypoxia (HH) in high-altitude (HA) associated with high mortality when progressing to high-altitude pulmonary edema (HAPE) and/or high-altitude cerebral edema (HACE). There is evidence for a role of pro- and anti-inflammatory cytokines in development of AMS, but biological pathways and molecular mechanisms underlying AMS remain elusive. We aimed to measure changes in blood cytokine levels and their possible association with the development of AMS. Method: 15 healthy mountaineers were included into this prospective clinical trial. All participants underwent baseline normoxic testing with venous EDTA blood sampling at the Bangor University in United Kingdom (69 m). The participants started from Beni at an altitude of 869 m and trekked same routes in four groups the Dhaulagiri circuit in the Nepali Himalaya. Trekking a 14-day route, the mountaineers reached the final HA of 5,050 m at the Hidden Valley Base Camp (HVBC). Venous EDTA blood sampling was performed after active ascent to HA the following morning after arrival at 5,050 m (HVBC). A panel of 21 cytokines, chemokines and growth factors were assessed using Luminex system (IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-1ra, sIL-2Rα, IFN-γ, TNF-α, MCP-1, MIP-1α, MIP-1ß, IP-10, G-CSF, GM-CSF, EGF, FGF-2, VEGF, and TGF-ß1). Results: There was a significant main effect for the gradual ascent from sea-level (SL) to HA on nearly all cytokines. Serum levels for TNF-α, sIL-2Rα, G-CSF, VEGF, EGF, TGF-ß1, IL-8, MCP-1, MIP-1ß, and IP-10 were significantly increased at HA compared to SL, whereas levels for IFN-γ and MIP-1α were significantly decreased. Serum VEGF was higher in AMS susceptible versus AMS resistant subjects (p < 0.027, main effect of AMS) and increased after ascent to HA in both AMS groups (p < 0.011, main effect of HA). Serum VEGF increased more from SL values in the AMS susceptible group than in the AMS resistant group (p < 0.049, interaction effect). Conclusion: Cytokine concentrations are significantly altered in HA. Within short interval after ascent, cytokine concentrations in HH normalize to values at SL. VEGF is significantly increased in mountaineers suffering from AMS, indicating its potential role as a biomarker for AMS.

Controlled Prospective Study on the Use of Systematic Simulator-Based Training with a Virtual, Moving Fetus for Learning Second-Trimester Scan: FESIM III.

OBJECTIVES: To analyze the feasibility of structured ultrasound simulation training (SIM-UT) in teaching second-trimester ultrasound screening using a high-end simulator with a randomly moving fetus. METHODS: This was a prospective, controlled trial. A trial group of 11 medical students with minimal obstetric ultrasound experience underwent 12 hours of structured SIM-UT in individual hands-on sessions within 6 weeks. Learning progress was assessed with standardized tests. Performance after 2, 4, and 6 weeks of SIM-UT was compared with two reference groups ((A) Ob/Gyn residents and consultants, and (B) highly skilled DEGUM experts). Participants were asked to acquire 23 2nd trimester planes according to ISUOG guidelines in a realistic simulation B-mode with a randomly moving fetus as quickly as possible within a 30-minute time frame. All tests were analyzed regarding the rate of appropriately obtained images and the total time to completion (TTC). RESULTS: During the study, novices were able to improve their ultrasound skills significantly, reaching the physician level of the reference group (A) after 8 hours of training. After 12 hours of SIM-UT, the trial group performed significantly faster than the physician group (TTC: 621±189 vs. 1036±389 sec., p=0.011). Novices obtained 20 out of 23 2nd trimester standard planes without a significant time difference when compared to experts. TTC of the DEGUM reference group remained significantly faster (p<0.001) though. CONCLUSION: SIM-UT on a simulator with a virtual, randomly moving fetus is highly effective. Novices can obtain standard plane acquisition skills close to expert level within 12 hours of self-training.

Postnatal growth restriction and neurodevelopment at 5 years of age: a European extremely preterm birth cohort study.

OBJECTIVE: To investigate whether extrauterine growth restriction (EUGR) during the neonatal hospitalisation by sex among extremely preterm (EPT) infants is associated with cerebral palsy (CP) and cognitive and motor abilities at 5 years of age. STUDY DESIGN: Population-based cohort of births <28 weeks of gestation with data from obstetric and neonatal records and parental questionnaires and clinical assessments at 5 years of age. SETTING: 11 European countries. PATIENTS: 957 EPT infants born in 2011-2012. MAIN OUTCOMES: EUGR at discharge from the neonatal unit was defined as (1) the difference between Z-scores at birth and discharge with <-2 SD as severe, -2 to -1 SD as moderate using Fenton's growth charts (Fenton) and (2) average weight-gain velocity using Patel's formula in grams (g) per kilogram per day (Patel) with <11.2 g (first quartile) as severe, 11.2-12.5 g (median) as moderate. Five-year outcomes were: a CP diagnosis, intelligence quotient (IQ) using the Wechsler Preschool and Primary Scales of Intelligence tests and motor function using the Movement Assessment Battery for Children, second edition. RESULTS: 40.1% and 33.9% children were classified as having moderate and severe EUGR, respectively, by Fenton and 23.8% and 26.3% by Patel. Among children without CP, those with severe EUGR had lower IQ than children without EUGR (-3.9 points, 95% Confidence Interval (CI)=-7.2 to -0.6 for Fenton and -5.0 points, 95% CI=-8.2 to -1.8 for Patel), with no interaction by sex. No significant associations were observed between motor function and CP. CONCLUSIONS: Severe EUGR among EPT infants was associated with decreased IQ at 5 years of age.