Growth in Children with Cerebral Palsy during five years after Selective Dorsal Rhizotomy: a practice-based study

Background: Overweight is reported as a side effect of SDR. The aims were to study the development of weight, height and body mass index (BMI) during five years after SDR. Methods: This prospective, longitudinal and practice-based study included all 56 children with CP spastic diplegia undergoing SDR from the start in March 1993 to April 2003 in our hospital. The preoperative Gross Motor Function Classification System (GMFCS) levels were I-II in 17, III in 15, IV-V in 24 children. Median age at SDR was 4.3 years (range 2.4-7.4 years). Weight and height/recumbent length were measured. Swedish growth charts for typically developing children generated weight, height and BMI z-scores for age and gender. Results: The preoperative median z-scores were for height-1.92 and for body mass index (BMI)-0.22. Five years later, the median BMI z-score was increased by + 0.57 (p + 2 SD) increased (p < 0.05). Baseline BMI and age at the start of follow-up influenced the BMI change during the five years (p < 0.001 and p < 0.05 respectively). The individual growth was highly variable, but a tendency towards increasing stunting with age was seen in severe gross motor dysfunction (GMFCS levels IV-V) and the opposite, a slight catch-up of height in children with walking ability (GMFCS levels I-III). Conclusions: These are the first available subtype-and GMFCS-specific longitudinal growth data for children with CP spastic diplegia. Their growth potential according to these data should be regarded as a minimum, as some children were undernourished. It is unknown whether the spasticity reduction through SDR increased the weight gain velocity, or if the relative weight increase was part of the general "obesity epidemic". For some children the weight increase was highly desirable. In others, it resulted in overweight and obesity with risk of negative health effects. Weight and height should be monitored to enable early prevention of weight aberrations also causing problems with mobility, activity and participation

CREB-Induced Inflammation Is Important for Malignant Mesothelioma Growth

Malignant mesothelioma (MM) is an aggressive tumor with no treatment regimen. Previously we have demonstrated that cyclic AMP response element binding protein (CREB) is constitutively activated in MM tumor cells and tissues and plays an important role in MM pathogenesis. To understand the role of CREB in MM tumor growth, we generated CREB-inhibited MM cell lines and performed in vitro and in vivo experiments. In vitro experiments demonstrated that CREB inhibition results in significant attenuation of proliferation and drug resistance of MM cells. CREB-silenced MM cells were then injected into severe combined immunodeficiency mice, and tumor growth in s.c. and i.p. models of MM was followed. We observed significant inhibition in MM tumor growth in both s.c. and i.p. models and the presence of a chemotherapeutic drug, doxorubicin, further inhibited MM tumor growth in the i.p. model. Peritoneal lavage fluids from CREB-inhibited tumor-bearing mice showed a significantly reduced total cell number, differential cell counts, and pro-inflammatory cytokines and chemokines (IL-6, IL-8, regulated on activation normal T cell expressed and secreted, monocyte chemotactic protein-1, and vascular endothelial growth factor). In vitro studies showed that asbestos-induced inflammasome/inflammation activation in mesothelial cells was CREB dependent, further supporting the role of CREB in inflammation-induced MM pathogenesis. In conclusion, our data demonstrate the involvement of CREB in the regulation of MM pathogenesis by regulation of inflammation

Use of manual and powered wheelchair in children with cerebral palsy: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Mobility is important for the cognitive and psychosocial development of children. Almost one third of children with cerebral palsy (CP) are non-ambulant. Wheelchairs can provide independent mobility, allowing them to explore their environment. Independent mobility is vital for activity and participation and reduces the dependence on caregivers. The purpose of this study was to describe the use of manual and powered wheelchair indoors and outdoors in relation to the degree of independent wheelchair mobility or need for assistance in a total population of children with CP.</p> <p>Methods</p> <p>A cross-sectional study was performed including all children aged 3-18 years with CP living in southern Sweden during 2008. Data was extracted from a register and health care programme for children with CP (CPUP). There were a total of 562 children (326 boys, 236 girls) in the register. Information on the child's use of manual and powered wheelchair indoors and outdoors and the performance in self-propelling or need for assistance were analysed related to age, CP subtype and gross motor function.</p> <p>Results</p> <p>Wheelchairs for mobility indoors were used by 165 (29%) of the 562 children; 61 used wheelchair for independent mobility (32 using manual only, 12 powered only, 17 both) and 104 were pushed by an adult. For outdoor mobility wheelchairs were used by 228 children (41%); 66 used a wheelchair for independent mobility (18 using manual only, 36 powered only, 12 both) and 162 were pushed. The use of wheelchair increased with age and was most frequent in the spastic bilateral and dyskinetic subtypes. Most powered wheelchairs were operated by children at GMFCS level IV.</p> <p>Conclusion</p> <p>In this total population of children with CP, aged 3-18 years, 29% used a wheelchair indoors and 41% outdoors. A majority using manual wheelchairs needed adult assistance (86%) while powered wheelchairs provided independent mobility in most cases (86%). To achieve a high level of independent mobility, both manual and powered wheelchairs should be considered at an early age for children with impaired walking ability.</p

Sitting and standing performance in a total population of children with cerebral palsy: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Knowledge of sitting and standing performance in a total population of children with cerebral palsy (CP) is of interest for health care planning and for prediction of future ability in the individual child. In 1994, a register and a health care programme for children with CP in southern Sweden was initiated. In the programme information on how the child usually sits, stands, stands up and sits down, together with use of support or assistive devices, is recorded annually.</p> <p>Methods</p> <p>A cross-sectional study was performed, analysing the most recent report of all children with CP born 1990-2005 and living in southern Sweden during 2008. All 562 children (326 boys, 236 girls) aged 3-18 years were included in the study. The degree of independence, use of support or assistive devices to sit, stand, stand up and sit down was analysed in relation to the Gross Motor Function Classification System (GMFCS), CP subtype and age.</p> <p>Result</p> <p>A majority of the children used standard chairs (57%), could stand independently (62%) and could stand up (62%) and sit down (63%) without external support. Adaptive seating was used by 42%, external support to stand was used by 31%, to stand up by 19%, and to sit down by 18%. The use of adaptive seating and assistive devices increased with GMFCS levels (p < 0.001) and there was a difference between CP subtypes (p < 0.001). The use of support was more frequent in preschool children aged 3-6 (p < 0.001).</p> <p>Conclusion</p> <p>About 60% of children with CP, aged 3-18, use standard chairs, stand, stand up, and sit down without external support. Adding those using adaptive seating and external support, 99% of the children could sit, 96% could stand and 81% could stand up from a sitting position and 81% could sit down from a standing position. The GMFCS classification system is a good predictor of sitting and standing performance.</p

Long-Term Health Outcomes in Children Born to Mothers with Diabetes: A Population-Based Cohort Study

BACKGROUND: To examine whether prenatal exposure to parental type 1 diabetes, type 2 diabetes, or gestational diabetes is associated with an increased risk of malignant neoplasm or diseases of the circulatory system in the offspring. METHODS/PRINCIPAL FINDINGS: We conducted a population-based cohort study of 1,781,576 singletons born in Denmark from 1977 to 2008. Children were followed for up to 30 years from the day of birth until the onset of the outcomes under study, death, emigration, or December 31, 2009, whichever came first. We used Cox proportional hazards model to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for the outcomes under study while adjusting for potential confounders. An increased risk of malignant neoplasm was found in children prenatally exposed to maternal type 2 diabetes (HR = 2.2, 95%CI: 1.5-3.2). An increased risk of diseases of the circulatory system was found in children exposed to maternal type 1 diabetes (HR = 2.2, 95%CI: 1.6-3.0), type 2 diabetes (HR = 1.4, 95%CI: 1.1-1.7), and gestational diabetes (HR = 1.3, 95%CI: 1.1-1.6), but results were attenuated after excluding children with congenital malformations. An increased risk of diseases of the circulatory system was also found in children exposed to paternal type 2 diabetes (HR = 1.5, 95%CI: 1.1-2.2) and the elevated risk remained after excluding children with congenital malformations. CONCLUSIONS: This study suggests that susceptibility to malignant neoplasm is modified partly by fetal programming. Diseases of the circulatory system may be modified by genetic factors, other time-stable family factors, or fetal programming

Prevalence of hip dislocation among children with cerebral palsy in regions with and without a surveillance programme: a cross sectional study in Sweden and Norway

<p>Abstract</p> <p>Background</p> <p>Hip dislocation is a serious complication among children with cerebral palsy (CP). The aim of this study was to compare the prevalence of hip dislocation among children with CP in an area providing regular care with an area providing hip surveillance services.</p> <p>Methods</p> <p>This is a cross-sectional study in seven Norwegian counties providing regular care and one Swedish healthcare region where a hip surveillance programme was introduced in 1994. Data were provided by the Norwegian Cerebral Palsy Register and the CP Register in Southern Sweden. Children born 1996 - 2003 with moderate to severe CP, defined as Gross Motor Classification System (GMFCS) levels III - V, were included. In all, 119 Norwegian and 136 Swedish children fulfilled the criteria. In Norway, data on hip operations and radiographs of the hips were collected from medical records, while these data are collected routinely in the Swedish register. The hip migration percentage was measured on the recent radiographs. Hip dislocation was defined as a migration percent of 100%.</p> <p>Results</p> <p>The proportion of children at GMFCS levels III - V was 34% in the Norwegian and 38% in the Swedish population. In the Norwegian population, hip dislocation was diagnosed in 18 children (15.1%; CI: 9.8 - 22.6) compared with only one child (0.7%; 95% CI: 0.01 - 4.0) in Southern Sweden (p = < 0.001). Hip surgery was performed in 53 (44.5%) of the Norwegian children and in 43 (32%) of the Swedish children (p = 0.03). The total number of hip operations was 65 in Norway and 63 in Sweden. Norwegian children were first operated at a mean age of 7.6 years (SD: 2.9) compared with 5.7 years (SD: 2.3) in Sweden (p = 0.001).</p> <p>Conclusions</p> <p>The surveillance programme reduced the number of hip dislocations and the proportion of children undergoing hip surgery was lower. However, with the surveillance programme the first operation was performed at a younger age. Our results strongly support the effectiveness of a specifically designed follow-up programme for the prevention of hip dislocation in children with CP.</p

Well-being of children with chronic illness. A population-based study in a Swedish primary care district

According to a previous study, 8% of all children in Dalby primary care district were chronically ill. The impact of the illness on the children's well-being was investigated using parental questionnaires. No difference in socio-demographic variables was found between responders (70%) and non-responders. The study comprised 98 index and 168 control children. Comfort and well-being in school and pre-school were lower among the index than among the control children and lower among the index children in normal compared with special schools. According to the parents many teachers had insufficient knowledge of disorders/handicaps. Children with a physical disability more often had special remedial education compared with healthy children. The chronically ill children were bullied more often, had fewer contacts with peers and more emotional problems than the control group. Improved knowledge of chronic childhood disorders/disabilities and recognition of the psychosocial consequences at school/pre-school and in the child health services is advocated

Genomic alterations in ovarian endometriosis and subsequently diagnosed ovarian carcinoma

STUDY QUESTION: Can the alleged association between ovarian endometriosis and ovarian carcinoma be substantiated by genetic analysis of endometriosis diagnosed prior to the onset of the carcinoma? SUMMARY ANSWER: The data suggest that ovarian carcinoma does not originate from ovarian endometriosis with a cancer-like genetic profile; however, a common precursor is probable. WHAT IS KNOWN ALREADY: Endometriosis has been implicated as a precursor of ovarian carcinoma based on epidemiologic studies and the discovery of common driver mutations in synchronous disease at the time of surgery. Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are the most common endometriosis-associated ovarian carcinomas (EAOCs). STUDY DESIGN, SIZE, DURATION: The pathology biobanks of two university hospitals in Sweden were scrutinized to identify women with surgically removed endometrioma who subsequently developed ovarian carcinoma (1998-2016). Only 45 archival cases with EAOC and previous endometriosis were identified and after a careful pathology review, 25 cases were excluded due to reclassification into non-EAOC (n = 9) or because ovarian endometriosis could not be confirmed (n = 16). Further cases were excluded due to insufficient endometriosis tissue or poor DNA quality in either the endometriosis, carcinoma, or normal tissue (n = 9). Finally 11 cases had satisfactory DNA from all three locations and were eligible for further analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Epithelial cells were collected from formalin-fixed and paraffin-embedded (FFPE) sections by laser capture microdissection (endometrioma n = 11) or macrodissection (carcinoma n = 11) and DNA was extracted. Normal tissue from FFPE sections (n = 5) or blood samples collected at cancer diagnosis (n = 6) were used as the germline controls for each included patient. Whole-exome sequencing was performed (n = 33 samples). Somatic variants (single-nucleotide variants, indels, and copy number alterations) were characterized, and mutational signatures and kataegis were assessed. Microsatellite instability and mismatch repair status were confirmed with PCR and immunohistochemistry, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: The median age for endometriosis surgery was 42 years, and 54 years for the subsequent ovarian carcinoma diagnosis. The median time between the endometriosis and ovarian carcinoma was 10 (7-30) years. The data showed that all paired samples harbored one or more shared somatic mutations. Non-silent mutations in cancer-associated genes were frequent in endometriosis; however, the same mutations were never observed in subsequent carcinomas. The degree of clonal dominance, demonstrated by variant allele frequency, showed a positive correlation with the time to cancer diagnosis (Spearman's rho 0.853, P &lt; 0.001). Mutations in genes associated with immune escape were the most conserved between paired samples, and regions harboring these genes were frequently affected by copy number alterations in both sample types. Mutational burdens and mutation signatures suggested faulty DNA repair mechanisms in all cases. LARGE SCALE DATA: Datasets are available in the supplementary tables. LIMITATIONS, REASONS FOR CAUTION: Even though we located several thousands of surgically removed endometriomas between 1998 and 2016, only 45 paired samples were identified and even fewer, 11 cases, were eligible for sequencing. The observed high level of intra- and inter-heterogeneity in both groups (endometrioma and carcinoma) argues for further studies of the alleged genetic association. WIDER IMPLICATIONS OF THE FINDINGS: The observation of shared somatic mutations in all paired samples supports a common cellular origin for ovarian endometriosis and ovarian carcinoma. However, contradicting previous conclusions, our data suggest that cancer-associated mutations in endometriosis years prior to the carcinoma were not directly associated with the malignant transformation. Rather, a resilient ovarian endometriosis may delay tumorigenesis. Furthermore, the data indicate that genetic alterations affecting the immune response are early and significant events. STUDY FUNDING/COMPETING INTEREST(S): The present work has been funded by the Sjöberg Foundation (2021-01145 to K.S.; 2022-01-11:4 to A.S.), Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965552 to K.S.; 40615 to I.H.; 965065 to A.S.), Swedish Cancer Society (21-1848 to K.S.; 21-1684 to I.H.; 22-2080 to A.S.), BioCARE-A Strategic Research Area at Lund University (I.H. and S.W.-F.), Mrs Berta Kamprad's Cancer Foundation (FBKS-2019-28, I.H.), Cancer and Allergy Foundation (10381, I.H.), Region Västra Götaland (A.S.), Sweden's Innovation Agency (2020-04141, A.S.), Swedish Research Council (2021-01008, A.S.), Roche in collaboration with the Swedish Society of Gynecological Oncology (S.W.-F.), Assar Gabrielsson Foundation (FB19-86, C.M.), and the Lena Wäpplings Foundation (C.M.). A.S. declares stock ownership and is also a board member in Tulebovaasta, SiMSen Diagnostics, and Iscaff Pharma. A.S. has also received travel support from EMBL, Precision Medicine Forum, SLAS, and bioMCC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.CC BY-NC 4.0 DeedPublished: 09 March 2024Correspondence address: Karin Sundfeldt, Department of Obstetrics and Gynecology, Sahlgrenska Center for Cancer Research, Institute of Clinical Sciences, Sahlgrenska Academyat University of Gothenburg, SE-405 30 Gothenburg, Sweden. E-mail: [email protected] (K.S.) https://orcid.org/0000-0002-7135-3132;Division of Oncology,Department of Clinical Sciences Lund, Lund University, SE-223 81 Lund, Sweden. E-mail: [email protected] (I.H.) https://orcid.org/0000-0002-6840-3The present work has been funded by the Sjöberg Foundation (2021-01145 to K.S.; 2022-01-11:4 to A.S.), Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965552 to K.S.; 40615 to I.H.; 965065 to A.S.), Swedish Cancer Society (21-1848 to K.S.; 21-1684 to I.H.; 22-2080 to A.S.), BioCARE—a strategic research area at Lund University (I.H. and S.W.-F.), Mrs Berta Kamprad’s Cancer Foundation (FBKS-2019-28, I.H.), Cancer and Allergy Foundation (10381, I.H.), Region Västra Götaland (A.S.), Sweden’s Innovation Agency (2020-04141, A.S.), Swedish Research Council (2021- 01008, A.S.), Roche in collaboration with the Swedish Society of Gynecological Oncology (S.W.-F.), Assar Gabrielsson Foundation (FB19-86, C.M.), and the Lena Wäpplings Foundation (C.M.).</p