Adherence to oxygen saturation targets increased in preterm infants when a higher target range and tighter alarm limits were introduced.

AIM: European consensus guidelines published in May 2013 recommended a target peripheral capillary oxygen saturation (SpO2 ) range of 90-95% for preterm infants. These were incorporated into guidelines at the Karolinska University Hospital, Sweden, in November 2013. This study compared clinical practice before and after those local guidelines. METHODS: We included infants who were born between 23 + 0 and 30 + 6 weeks from January 1, 2013 to December, 31 2015 and received intensive care in two Karolinska units. The lower saturation target of 88-92% and alarm limits of 85-95% used before November 2013 were compared to the new higher saturation target of 90-95% and alarm limits of 89-96%. RESULTS: Data from 399 infants were analysed. The mean SpO2 was 92.4% with the higher target (n = 301) and 91.1% with the lower target (n = 98). Using the higher instead of lower target meant that the SpO2 was within the prescribed target range more frequently (51% versus 30%) and the proportion of time with SpO2 >95% was increased by 9% (95% confidence interval 7-11%, p < 0.001). CONCLUSION: The higher saturation target and tighter alarm limits led to higher mean oxygen saturation, increased adherence to the target and increased time with hyperoxaemia.

Life weariness and suicidal thoughts in late life: a national study in Sweden.

OBJECTIVES: This study aimed at investigating the point prevalence of life weariness and suicidal thoughts and their relationship with socio-demographic characteristics in a population of older adults in Sweden. METHOD: Data from 7913 individuals aged 60 years and older were drawn from the Swedish National Study on Aging and Care, a collaborative study in Sweden. Life weariness and suicidal thoughts were measured by one item derived from the Montgomery-Åsberg Depression Rating Scale. A multinomial regression model was used to investigate the relationships of socio-demographic characteristics with life weariness and suicidal thoughts. RESULTS: Living in urban and semi-urban areas, being of advanced age, being divorced and having lower educational levels were related to life weariness. Living in a residential care facility, being widowed or unmarried, being born in a non-Nordic European country and experiencing financial difficulties were related to both life weariness and suicidal thoughts. Sex was found to be unrelated to either life weariness or suicidal thoughts. CONCLUSION: This study found that several socio-demographic variables were associated with life weariness and suicidal thoughts among older adults. Specific attention to older individuals with these characteristics may be warranted as they might be more vulnerable to life weariness and suicidal thoughts.

Cohort study of growth patterns by gestational age in preterm infants developing morbidity.

OBJECTIVES: To examine differences in growth patterns in preterm infants developing major morbidities including retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC) and intraventricular haemorrhage (IVH). STUDY DESIGN: Cohort study of 2521 infants born at a gestational age (GA) of 23-30 weeks from 11 level III neonatal intensive care units in USA and Canada, and 3 Swedish population-based cohorts. OUTCOMES: Birth weight and postnatal weight gain were examined relative to birth GA and ROP, BPD, NEC and IVH development. RESULTS: Among infants with a birth GA of 25-30 weeks, birth weight SD score and postnatal weight were lower in those developing ROP and BPD. Infants developing ROP showed lower growth rates during postnatal weeks 7-9 in the 23-24 weeks GA group, during weeks 4-6 in the 25-26 weeks GA group and during weeks 1-5 in the 27-30 weeks GA group. Infants with BPD born at 27-30 weeks GA showed lower growth rates during postnatal weeks 3-5. Infants with NEC had lower growth rates after postnatal week 6 in all GA groups, with no significant differences in birth weight SD score. IVH was not associated with prenatal or postnatal growth. CONCLUSIONS: In this cohort study of extremely preterm infants, we found that the postnatal growth pattern was associated with morbidities such as ROP, BPD and NEC as well as with gestational age at birth.

Impact of Nutritional Status and Sleep Quality on Hospital Utilisation in the Oldest Old with Heart Failure.

OBJECTIVES: To describe three-year trends in nutritional status and sleep quality and their impact on hospital utilisation in the oldest old (80 +) with heart failure (HF). DESIGN: Single-centred longitudinal observational study. SETTING: South-eastern Sweden. PARTICIPANTS: 90 elderly (80+) with objectively verified HF. MEASUREMENTS: Baseline data from the Mini Nutritional Assessment (MNA) and on sleep quality were collected through structured interviews following the HF diagnosis (n=90) and at a three-year follow-up (n=41). Data on hospital utilisation during the three years following the HF diagnosis were also collected. RESULTS: Nineteen percent of the participants were found to have impaired nutritional status, a condition that increased hospital utilisation by four bed days per year. A majority (85%) had impaired sleep quality, but no impact on hospital utilisation was found. Nutritional status and sleep quality were stable over the three-year period. CONCLUSION: In the oldest old with HF, impaired nutritional status and impaired sleep quality are already common at HF diagnosis. Impaired nutritional status increases hospital utilisation significantly. Therefore, it is of supreme importance to systematically evaluate nutritional status and sleep quality in the oldest old when they are diagnosed with HF, as well as to take action if impairments are present.

Secretion of non-cell-bound phytase by the yeast Pichia kudriavzevii TY13.

AIMS: Mineral deficiencies cause several health problems in the world, especially for populations consuming cereal-based diets rich in the anti-nutrient phytate. Our aim was to characterize the phytate-degrading capacity of the yeast Pichia kudriavzevii TY13 and its secretion of phytase. METHODS AND RESULTS: The phytase activity in cell-free supernatants from cultures with 100% intact cells was 35-190 mU ml(-1) depending on the media. The Km was 0.28 mmol l(-1) and the specific phytase activity 0.32 U mg(-1) total protein. The phytase activity and secretion of extracellular non-cell-bound phytase was affected by the medium phosphate concentrations. Further, addition of yeast extract had a clearly inducing effect, resulting in over 60% of the cultures total phytase activity as non-cell-bound. CONCLUSIONS: Our study reveals that it is possible to achieve high extracellular phytase activity from the yeast P. kudriavzevii TY13 by proper composition of the growth medium. SIGNIFICANCE AND IMPACT OF THE STUDY: TY13 could be a promising future starter culture for fermented foods with improved mineral bioavailability. Using strains that secrete phytase to the food matrix may significantly improve the phytate degradation by facilitating the enzyme-to-substrate interaction. The secreted non-cell-bound phytase activities by TY13 could further be advantageous in industrial production of phytase.

Birth weight is the most important predictor of abnormal retinal vascularisation in moderately preterm infants.

AIM: To find predictors of abnormal retinal vascularisation in moderately to late preterm newborn infants considered to have no risk of developing retinopathy of prematurity. METHODS: Seventy-eight infants (34 girls) were recruited from a longitudinal study of otherwise healthy premature children born at a gestational age of 32 + 0-36 + 6 weeks. Retinal vessel morphology was evaluated at mean postnatal age 7 days. Insulin-like growth factor-I (IGF-I) levels were analysed in umbilical cord blood. RESULTS: Of the 78 infants, 21 (27%) had abnormal retinal vessel morphology; they had significantly lower median (range) birth weight [1850 g, (1190-3260), vs. 2320, (1330-3580), p < 0.0001], shorter birth length [43.0 cm, (38-49), vs. 46.0, (40-50), p < 0.0001] and smaller head circumference [31.0 cm, (27.7-34.0), vs. 32.0, (27.5-36.5), p = 0.003]. They also had significantly lower gestational age [34 + 1 weeks, (32 + 2-35 + 3), vs. 34 + 6, (32 + 2-36 + 6), p = 0.004] and mean ± SD IGF-I levels (24.6 ± 17.0 µg/L vs. 46.7 ± 21.5, p < 0.0001). A higher percentage of these infants were small for gestational age (57.1% vs. 15.8%, p = 0.001), and maternal hypertension/preeclampsia rates were also higher (47.6% vs. 19.3%, p = 0.03). Step-wise logistic regression showed that birth weight was the strongest predictor of abnormal retinal vascularisation (p < 0.0001, odds ratio 0.040, 95% confidence interval 0.007-0.216). CONCLUSION: In this population of moderately to late preterm newborns, birth weight appeared to affect the retinal vascular system.

Urinary bladder control during the first 3 years of life in healthy children in Vietnam--a comparison study with Swedish children.

OBJECTIVES: To study outcomes of early potty training in a population of healthy children with a tradition of early potty training and to compare these findings with a group of children to whom potty training was applied later. SUBJECTS AND METHODS: Mothers and their 47 healthy children in Vietnam participated in this longitudinal study. The voiding pattern and emptying ability were followed by the 4-h voiding observation method from 3 months to 3 years of age. A comparison is made with a group of 57 Swedish children investigated in a similar manner. RESULTS: In the group of Vietnamese children, 89% were on daily potty training at the age of 6 months. At the age of 24 months, potty training was complete for 98%. In the Swedish group, just a few (5%) had started daily potty training by the age of 24 months (p < 0.001). The Vietnamese group had fewer voidings and lower voided volumes than the Swedish group. In the Vietnamese children, bladder emptying could be regarded as having been completed, with no residual urine at 9 months, compared with the Swedish group, which first showed complete emptying at the age of 36 months. CONCLUSION: Potty training performed daily affects the emptying ability positively. In the Vietnamese group, no residual urine was found at the age of 9 months. These results differ significantly from those of the group of Swedish children.

Impact of genomic stability on protein expression in endometrioid endometrial cancer.

BACKGROUND: Genomic stability is one of the crucial prognostic factors for patients with endometrioid endometrial cancer (EEC). The impact of genomic stability on the tumour tissue proteome of EEC is not yet well established. METHODS: Tissue lysates of EEC, squamous cervical cancer (SCC), normal endometrium and squamous cervical epithelium were subjected to two-dimensional (2D) gel electrophoresis and identification of proteins by MALDI TOF MS. Expression of selected proteins was analysed in independent samples by immunohistochemistry. RESULTS: Diploid and aneuploid genomically unstable EEC displayed similar patterns of protein expression. This was in contrast to diploid stable EEC, which displayed a protein expression profile similar to normal endometrium. Approximately 10% of the differentially expressed proteins in EEC were specific for this type of cancer with differential expression of other proteins observed in other types of malignancy (e.g., SCC). Selected proteins differentially expressed in 2D gels of EEC were further analysed in an EEC precursor lesion, that is, atypical hyperplasia of endometrium, and showed increased expression of CLIC1, EIF4A1 and PRDX6 and decreased expression of ENO1, ANXA4, EMD and Ku70. CONCLUSION: Protein expression in diploid and aneuploid genomically unstable EEC is different from the expression profile of proteins in diploid genomically stable EEC. We showed that changes in expression of proteins typical for EEC could already be detected in precursor lesions, that is, atypical hyperplasia of endometrium, highlighting their clinical potential for improving early diagnostics of EEC.

[The early postnatal weight gain as a predictor of retinopathy of prematurity]. / Der frühe postnatale Gewichtsverlauf als Prädiktor einer Frühgeborenenretinopathie.

BACKGROUND: Premature infants are often stressed by the current retinopathy of prematurity (ROP) screening procedure. Additionally, only < 10 % of the screened infants will develop a ROP stadium requiring laser therapy. Therefore the present screening strategy is unsatisfactory. Furthermore, the current guidelines do not take into account postnatal factors. A new method considering postnatal factors is the weight, insulin-like growth factor, neonatal ROP (WINROP) algorithm. This approach is based on the early postnatal weight gain. The aim of this study was to assign the WINROP-algorithm to a preterm population in Switzerland and to analyze its ability for prediction. PATIENTS AND METHODS: In this retrospective study, all preterm infants with a gestational age (GA) < 32 weeks and/or a birth weight (BW) ≤ 1500 g taken care of in the Department of Neonatology at the University Hospital Zurich from January 2003 to December 2008 were included. The weekly postnatal weight gain was analyzed by means of the modified WINROP-algorithm. RESULTS: Altogether 376 preterm infants were analyzed. In 58 infants a "high-risk" alarm was released, thereof eight preterms developed a severe ROP and four of them needed laser therapy. CONCLUSIONS: The high predictive value of the WINROP-algorithm was confirmed in our population of Swiss preterms. This instrument has the potential to simplify the current ROP screening procedure. Accordingly, the amount of ophthalmoscopies could be reduced significantly.

Ophthalmological findings in children and adolescents with Silver-Russell syndrome.

AIM: To evaluate ophthalmological findings in children with Silver-Russell syndrome (SRS). METHODS: An ophthalmological evaluation including visual acuity (VA), refraction, strabismus, near point of convergence (NPC), slit-lamp examination, ophthalmoscopy, axial length measurements and full-field electroretinogram was performed on 18 children with SRS (8 girls, 10 boys; mean age 11.6 years). Fundus photographs were taken for digital image analysis. Data were compared with data on an age- and gender-matched reference group (ref) of school children (n=99). RESULTS: Seventeen out of 18 children with SRS had ophthalmological abnormalities. Best corrected VA of the best eye was <0.1 log of the minimal angle of resolution in 11 children (ref n=98) (p<0.0001), and 11 children had refractive errors (ref n=33) (p=0.05). Anisometropia (≥1 dioptre) was noted in three of the children (ref n=3) (p=0.046). Subnormal stereo acuity and NPC were found in 2/16 (ref=0) (p=0.02). The total axial length in both eyes was shorter compared with that in controls (p<0.006 and p<0.001). Small optic discs were found in 3/16, large cup in 3/16 and increased tortuosity of retinal vessels in 4/13 children with SRS. CONCLUSION: Children with SRS, who are severely intrauterine growth retarded, show significant ophthalmological abnormalities. Based on the present findings, ophthalmological examination is recommended in children with SRS.

A comparison of active management and expectant management of the third stage of labour: a Swedish randomised controlled trial.

OBJECTIVE: to compare blood loss in women actively and expectantly managed in the third stage of labour. DESIGN: randomised controlled trial (RCT). SETTING: two delivery units at a Swedish university hospital. POPULATION: healthy women with normal pregnancies, at gestational age 34-43 weeks, with singleton cephalic presentation and expected vaginal delivery. METHODS: the women were randomly allocated to either active (n = 903) or expectant (n = 899) management of the third stage of labour. MAIN OUTCOME MEASURES: the primary outcome was blood loss > 1000 ml, and secondary outcomes were mean blood loss, duration of third stage, retained placenta, haemoglobin level and blood transfusion. RESULTS: blood loss > 1000 ml occurred in 10% of the actively managed group and 16.8% of the expectantly managed group (P < 0.001). Mean blood loss was 535 ml in the actively managed group and 680 ml in the expectantly managed group (P < 0.001). A prolonged duration of the third stage was associated with increased blood loss. Increased placenta weight was associated with increased blood loss. The haemoglobin level was 118 g/dl in actively managed women and 115/dl in expectantly managed women (P < 0.001) the day after childbirth. The occurrence of retained placenta and the number of blood transfusions did not differ between the groups. CONCLUSIONS: active management of the third stage of labour was associated with less blood loss compared with expectant management. It is reasonable to advocate this regime, especially in primiparous women.

Sleep complaints and their association with comorbidity and health-related quality of life in an older population in Sweden.

OBJECTIVE: The relationship between sleep complaints, comorbidity and health-related quality of life (HRQoL) in advanced age has not been clearly established. The aim of this study is therefore to investigate the presence of sleep complaints and discuss their association with morbidity and the HRQoL among the people aged 60 years and above. METHODS: Data regarding demography, sleep, comorbidity and HRQoL were collected through questionnaires and interviews among 1128 people in Sweden. The Johns Hopkins adjusted clinical groups (ACG®) Case-Mix System 6.0 and the Short-Form Health Survey-12 were used to assess morbidity and HRQoL, respectively. RESULTS: There was a divergence in the number of sleep complaints between those with no morbidity and those who had a high degree of comorbidity. Most of the sleep complaints related to low HRQoL were found among those with a high degree of comorbidity. CONCLUSIONS: People with a high degree of comorbidity appear to be a group with a high risk of having both sleep complaints and a low HRQoL. Thus, this study suggests that even if sleep complaints appear to be difficult to identify and treat successfully, it is important to pay particular attention to those people who suffer from a high degree of comorbidity if their HRQoL is to be maintained.

Differential expression of ANXA6, HSP27, PRDX2, NCF2, and TPM4 during uterine cervix carcinogenesis: diagnostic and prognostic value.

BACKGROUND: Cytology-based diagnostics of squamous cervical cancer (SCC) precursor lesions is subjective and can be improved by objective markers. METHODS: IHC-based analysis of ANXA6, HSP27, peroxiredoxin 2 (PRDX2), NCF2, and tropomyosin 4 (TPM4) during SCC carcinogenesis. RESULTS: Expression of ANXA6, HSP27, PRDX2, and NCF2 in the cytoplasm of dysplastic cells increased from cervical intraepithelial neoplasia 2/3 (CIN2/3) to microinvasive cancer. Invasive SCC showed lower expression of TPM4 than CIN and normal epithelium. CIN2/3 with the highest sensitivity and specificity differed from normal epithelium by cytoplasmic expression of HSP27. Patients with cytoplasmic HSP27 expression in SCC deviating from that observed in normal epithelium had worse relapse-free (P=0.019) and overall (P=0.014) survival. Invasive SCC with the highest sensitivity and specificity differed from normal epithelium by expression of PRDX2 and TPM4 in the cytoplasm, from CIN2/3 by the expression of ANXA6 and TPM4 in the cytoplasm, and from microinvasive SCC by the expression of PRDX2 and ANXA6 in the cytoplasm. The number of sporadic ANXA6+ cells between the atypical cells increased from CIN2/3 to invasive SCC. CONCLUSION: Detection of expression changes of the proteins ANXA6, HSP27, PRDX2, NCF2, and TPM4 in SCC precursor lesions may aid current cytological and pathological diagnostics and evaluation of prognosis.

Early postnatal growth variables are related to morphologic and functional ophthalmologic outcome in children born preterm.

AIM: To evaluate the association between gestational age (GA), early and late postnatal growth variables and ophthalmologic outcome in ex-preterm children. methods: Children (GA < 32 weeks, n = 66), previously examined regarding insulin-like growth factor 1 (IGF-1) serum concentrations in relation to ROP, underwent ophthalmologic examination at median 5.6 years. Weight, height, and head circumference (HC) were measured and expressed as SDS. Growth variables were analysed in relation to ophthalmologic outcome. RESULTS: At follow-up 74% had some ophthalmologic abnormality and 17% had visual impairment. Poor visual acuity was correlated with low GA (r(s) = 0.29, p = 0.019), low weight at 32 weeks (r(s) = 0.30, p = 0.013), and low weight (r(s) = 0.37, p = 0.0025), height (r(s) = 0.41, p = 0.0007) and HC (r(s) = 0.55, p < 0.0001) at follow-up. Hyperopic children (25%) had low neonatal IGF-1 (p = 0.0096) and HC at follow-up (p = 0.022). Poor visual perception was correlated with low early weight (r(s) = 0.38, p = 0.0036) and HC at follow-up (r(s) = 0.39, p = 0.0024). Head circumference at follow-up was correlated with GA (r(s) = 0.40, p = 0.0012), neonatal IGF-1 (r(s) = 0.37, p = 0.0031), and early weight (r(s) = 0.27, p = 0.035). CONCLUSIONS: In very preterm children, early and later postnatal growth is closely related to visual acuity and perception at follow-up. In addition, IGF-1 concentrations and early growth are correlated with head circumference and refraction at follow-up.

New insights into the development of retinopathy of prematurity--importance of early weight gain.

UNLABELLED: Evidence is accumulating that one of the strongest predictors of retinopathy of prematurity (ROP), in addition to low gestational age, is poor weight gain during the first weeks of life. In infants born preterm, the retina is not fully vascularised. The more premature the child, the larger is the avascular area. In response to hypoxia, vascular endothelial growth factor (VEGF) is secreted. For appropriate VEGF-induced vessel growth, sufficient levels of insulin-like growth factor I (IGF-I) in serum are necessary. IGF-I is a peptide, related to nutrition supply, which is essential for both pre- and post-natal general growth as well as for growth of the retinal vasculature. In prematurely born infants, serum levels are closely related to gestational age and are lower in more prematurely born infants. At preterm birth the placental supply of nutrients is lost, growth factors are suddenly reduced and general as well as vascular growth slows down or ceases. In addition, the relative hyperoxia of the extra-uterine milieu, together with supplemental oxygen, causes a regression of already developed retinal vessels. Postnatal growth retardation is a major problem in very preterm infants. Both poor early weight gain and low serum levels of IGF-I during the first weeks/months of life have been found to be correlated with severity of ROP. CONCLUSION: This review will focus on the mechanisms leading to ROP by exploring factors responsible for poor early weight gain and abnormal vascularisation of the eye of the preterm infant.

Differential tissue-specific protein markers of vaginal carcinoma.

The objective was to identify proteins differentially expressed in vaginal cancer to elucidate relevant cancer-related proteins. A total of 16 fresh-frozen tissue biopsies, consisting of 5 biopsies from normal vaginal epithelium, 6 from primary vaginal carcinomas and 5 from primary cervical carcinomas, were analysed using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Of the 43 proteins identified with significant alterations in protein expression between non-tumourous and tumourous tissue, 26 were upregulated and 17 were downregulated. Some were similarly altered in vaginal and cervical carcinoma, including cytoskeletal proteins, tumour suppressor proteins, oncoproteins implicated in apoptosis and proteins in the ubiquitin-proteasome pathway. Three proteins were uniquely altered in vaginal carcinoma (DDX48, erbB3-binding protein and biliverdin reductase) and five in cervical carcinoma (peroxiredoxin 2, annexin A2, sarcomeric tropomyosin kappa, human ribonuclease inhibitor and prolyl-4-hydrolase beta). The identified proteins imply involvement of multiple different cellular pathways in the carcinogenesis of vaginal carcinoma. Similar protein alterations were found between vaginal and cervical carcinoma suggesting common tumourigenesis. However, the expression level of some of these proteins markedly differs among the three tissue specimens indicating that they might be useful molecular markers.

Abnormal optic disc and retinal vessels in children with surgically treated hydrocephalus.

AIMS: To investigate the morphology of the optic disc and retinal vessels in children with surgically treated hydrocephalus. METHODS: A prospective, population-based study was performed in 69 children (median age 9.6 years) with early surgically treated hydrocephalus. All children were examined by ophthalmoscopy. Additionally, optic disc and retinal vessel morphology was evaluated in 55 children by digital image analysis of ocular fundus photographs. RESULTS: Optic atrophy was found in 10 of 69 children (14%). In comparison with a reference group, the median optic-disc area was significantly smaller (p = 0.013) in the children with hydrocephalus. There was no corresponding difference in cup area, so the rim area was significantly smaller in the hydrocephalic children (p = 0.002). Children with hydrocephalus had an abnormal retinal vascular pattern, with significantly straighter retinal arteries and fewer central vessel branching points compared with controls (p<0.001 and p<0.001, respectively). CONCLUSION: Hydrocephalus is associated with subnormal optic disc and rim areas and an abnormal vascular pattern, indicating a pre/perinatal disturbance of the development of these structures. A promising finding is that the frequency of optic atrophy in the present study was lower than previously reported, most likely reflecting improved perinatal care and better regulation of the intracranial pressure.