Hip Displacement in MECP2 Disorders: Prevalence and Risk Factors.

BACKGROUND: Methyl-CpG binding protein 2 (MECP2) disorders, including Rett syndrome and MECP2 duplication syndrome, are typified by profound intellectual disability, spasticity, and decline in gross motor function. Unlike scoliosis, linked to disease severity, little has been reported regarding the hip. The aim of this study was to report the prevalence and risk factors of hip displacement (HD) in MECP2 disorders. METHODS: This was a retrospective, comparative study. Children with a genetically confirmed MECP2 disorder were included. The primary outcome measure was the prevalence of HD (migration percentage>30%). Secondary outcomes included age at HD onset, ambulatory status, presence of clinically relevant scoliosis, genetic severity, presence of seizures, and associated comorbidities. Analysis of proportions of categorical variables was performed using χ2 testing (P=0.05). RESULTS: Fifty-six patients (54 Rett syndrome and 2 MECP2 duplication syndrome), diagnosed at 6.6 (SD: 4.7) years, met the inclusion criteria. The prevalence of HD was 36% [onset, 7.7 (SD: 3.8) y]. Risk factors for HD were nonwalker status (P=0.04), scoliosis (P=0.001), and refractory epilepsy (P=0.04). CONCLUSIONS: The prevalence of HD in MECP2 disorders is comparable to cerebral palsy, associated with proxy measures of disease severity. These results can be used to develop hip surveillance programs for MECP2 disorders, allowing for timely management. LEVEL OF EVIDENCE: Level III.

Factors predicting postoperative complications following spinal fusions in children with cerebral palsy scoliosis.

PURPOSE: The purpose of this study was to review the postoperative complications after posterior spinal fusion (PSF) in cerebral palsy (CP) scoliosis and identify the predictive preoperative risk factors. METHODS: All PSFs consecutively performed for CP scoliosis between 2004 and 2013 were reviewed. Preoperative risk score (ORS) and postoperative complications score (POCS) were used as measures of all recorded preoperative risk factors and postoperative complications, respectively. RESULTS: The review included 303 children with a mean age of 14.6 ± 3.0 years. Mean hospitalization was 16 days. Dependence on G-tube feeding was associated with higher POCS (P = 0.027). Postoperative fever, seizures, and septicemia were associated with higher ORS (P < 0.01). Specifically, postoperative pancreatitis and deep wound infections were more common in children with G-tube. CONCLUSION: This study suggests that G-tube dependence is a predictive risk factor of complications after PSF in CP scoliosis. Children with G-tube need special perioperative care. No other specific preoperative risk factor predicted postoperative complications.

Hip Reconstruction in Children With Unilateral Cerebral Palsy and Hip Dysplasia.

BACKGROUND: Highly functioning children with unilateral cerebral palsy (CP) who have hip involvement (type IV hemiplegia) may present with hip dysplasia during their adolescence. The aim of this report is to assess the outcomes of combined femoral and acetabular reconstruction in this population. METHODS: This study is a retrospective review of all patients with unilateral CP, Gross Motor Function Classification System types I and II, who had hip reconstruction for unilateral dysplasia between 1989 and 2013. Clinical variables (pain and hip passive range of motion) were reviewed. Hip morphology was assessed radiographically according to Melbourne Cerebral Palsy Hip Classification System. Three-dimensional gait analyses were also reviewed to evaluate the effect of surgery on these patients' gaits. RESULTS: Twelve patients were included with a mean age at surgery of 14 years (range, 7 to 19 y) and follow-up mean of 4 years (range, 1 to 8 y). Nine hips were improved according to Melbourne Cerebral Palsy Hip Classification System. Migration percentage decreased significantly (P<0.001) from 45% (30% to 86%) to 15% (0% to 28%). Neck shaft angle decreased (P<0.001) from 144 degrees (range, 129 to 156 degrees) to 125 degrees (range, 114 to 139 degrees). Tonnis angle and Sharp angle also decreased significantly. All patients were pain free at the last visit. Overall level of gait function as measured by Gait Deviation Index and Gait Profile Score [78 (61 to 89) and 12 (8 to 16), respectively] for all patients was maintained without significant changes. CONCLUSIONS: In hemiplegic type IV CP, with high functional level (Gross Motor Function Classification System I and II), hip dysplasia is a rare occurrence during adolescent years. Combined hip reconstruction improves hip morphology, relieves pain, and maintains a high level of function. LEVEL OF EVIDENCE: Level IV-therapeutic study.

Prophylactic methylprednisolone to reduce inflammation and improve outcomes from one lung ventilation in children: a randomized clinical trial.

BACKGROUND: One lung ventilation (OLV) results in inflammatory and mechanical injury, leading to intraoperative and postoperative complications in children. No interventions have been studied in children to minimize such injury. OBJECTIVE: We hypothesized that a single 2-mg·kg(-1) dose of methylprednisolone given 45-60 min prior to lung collapse would minimize injury from OLV and improve physiological stability. METHODS: Twenty-eight children scheduled to undergo OLV were randomly assigned to receive 2 mg·kg(-1) methylprednisolone (MP) or normal saline (placebo group) prior to OLV. Anesthetic management was standardized, and data were collected for physiological stability (bronchospasm, respiratory resistance, and compliance). Plasma was assayed for inflammatory markers related to lung injury at timed intervals related to administration of methylprednisolone. RESULTS: Three children in the placebo group experienced clinically significant intraoperative and postoperative respiratory complications. Respiratory resistance was lower (P = 0.04) in the methylprednisolone group. Pro-inflammatory cytokine IL-6 was lower (P = 0.01), and anti-inflammatory cytokine IL-10 was higher (P = 0.001) in the methylprednisolone group. Tryptase, measured before and after OLV, was lower (P = 0.03) in the methylprednisolone group while increased levels of tryptase were seen in placebo group after OLV (did not achieve significance). There were no side effects observed that could be attributed to methylprednisolone in this study. CONCLUSIONS: Methylprednisolone at 2 mg·kg(-1) given as a single dose prior to OLV provides physiological stability to children undergoing OLV. In addition, methylprednisolone results in lower pro-inflammatory markers and higher anti-inflammatory markers in the children's plasma.

Rectus femoris transfer improves stiff knee gait in children with spastic cerebral palsy.

BACKGROUND: Stiff knee gait is common among children with ambulatory cerebral palsy (CP). When surgery is indicated, rectus femoris transfer as a primary treatment enhances knee range of motion, reduces time to peak knee flexion, increases peak knee flexion, and reduces toe drag. QUESTIONS/PURPOSES: We determined whether (1) distal rectus femoris transfer improved knee range of motion, time to peak knee flexion, peak knee flexion, and toe drag in children with CP diagnosed with stiff knee gait; and (2) patients in some subgroups (eg, those with relatively high knee range of motion compared with those with low knee range of motion before rectus femoris transfer) had greater improvement in these parameters. METHODS: We retrospectively reviewed gait data from 56 patients (99 limbs) preoperatively, short-term, and long-term. Subgroup analyses were performed to determine whether patients with high knee range of motion relative to those with low or moderate knee range of motion improved differentially after rectus femoris transfer. The minimum followup was 7 years (mean ± SD, 10 ± 2 years; range, 7-13 years). RESULTS: The mean peak knee flexion increased from baseline to short-term and to long-term followup. Patients with low peak knee flexion had the greatest improvement of peak knee flexion after rectus femoris transfer relative to the moderate and high peak knee flexion subgroups. Similarly, the greatest improvement after rectus femoris transfer for knee range of motion occurred in the low knee range of motion subgroup relative to moderate and high subgroups. Rectus femoris transfer improved mean time to peak knee flexion at short-term and long-term followup compared with baseline. Likewise, there was a decrease in toe drag at short- and long-term after rectus femoris transfer. CONCLUSION: Distal rectus femoris transfer selectively improved peak knee flexion, toe drag, and reduced time to peak knee flexion in ambulatory children with CP with stiff knee gait. LEVEL OF EVIDENCE: Level IV, therapeutic study. See guidelines for authors for a complete description of levels of evidence.

Subtalar fusion in cerebral palsy patients: results of a new technique using corticocancellous allograft.

BACKGROUND: Valgus deformity of the hindfoot in cerebral palsy (CP) patients is common and causes functional deterioration and shoe fitting problems together with skin ulcerations. Our aims in this study are, to present an intra-articular technique of subtalar fusion using allograft and internal fixation to achieve stabilization and second to report the results and clinical outcome of a series of intra-articular subtalar arthrodesis performed in CP children. METHODS: We performed a retrospective review of radiographs and medical records of 145 children with CP who underwent intra-articular subtalar fusion from January 1994 to December 2004. The subtalar joint was fixed through the anterior facet with a cannulated screw whereas the anterior aspect of the calcaneus was parallel to the anterior aspect of the head of the talus. Tricortical iliac crest allograft was placed into the sinus tarsi and the denuded posterior facet area. Results are grouped as good, satisfactory, and poor according to the radiographic and clinical outcomes. RESULTS: The mean age at the time of surgery was 12.7 years (range: 5 to 20 y) and the average follow-up was 4.8 years (range: 2 to 11 y). Good results were obtained in 242 feet (96%). Satisfactory results were obtained in 6 feet (2%) which were painless pseudoarthrosis of subtalar joint in 2 feet and screw removal was required in 4 feet because of pain. Nonunion of thesubtalar joint together with recurrence of deformity was observed in 5 feet (2%) which is accepted as poor result and required revision surgery. No deep infections, implant failure, allograft failure were observed in a mean of 4.8 years. CONCLUSIONS: Our described technique of intra-articular subtalar joint fusion is safe and reliable in CP children with high rate of satisfactory results. LEVEL OF EVIDENCE: Therapeutic studies-Level IV.

Single-event multilevel surgery in cerebral palsy: Value added by a co-surgeon.

ABSTRACT: The aim of this study was to compare outcomes for single-event multilevel surgery (SEMLS) in cerebral palsy (CP) performed by 1 or 2 attending surgeons.A retrospective review of patients with CP undergoing SEMLS was performed. Patients undergoing SEMLS performed by a single senior surgeon were compared with patients undergoing SEMLS by the same senior surgeon and a consistent second attending surgeon. Due to heterogeneity of the type and quantity of SEMLS procedures included in this study, a scoring system was utilized to stratify patients to low and high surgical burden. The SEMLS events scoring less than 18 points were categorized as low burden surgery and SEMLS scoring 18 or more points were categorized as high burden surgery. Operative time, estimated blood loss, hospital length of stay, and operating room (OR) utilization costs were compared.In low burden SEMLS, 10 patients had SEMLS performed by a single surgeon and 8 patients had SEMLS performed by 2 surgeons. In high burden SEMLS, 10 patients had SEMLS performed by a single surgeon and 12 patients had SEMLS performed by 2 surgeons. For high burden SEMLS, operative time was decreased by a mean of 69 minutes in cases performed by 2 co-surgeons (P = 0.03). Decreased operative time was associated with an estimated savings of $2484 per SEMLS case. In low burden SEMLS, a trend toward decreased operative time was associated for cases performed by 2 co-surgeons (182 vs 221 minutes, P = 0.11). Decreased operative time was associated with an estimated savings of $1404 per low burden SEMLS case. No difference was found for estimated blood loss or hospital length of stay between groups in high and low burden SEMLS.Employing 2 attending surgeons in SEMLS decreased operative time and OR utilization cost, particularly in patients with a high surgical burden. These findings support the practice of utilizing 2 attending surgeons for SEMLS in patients with CP.Level of Evidence: Level III.

Complications of intrathecal baclofen pump therapy in pediatric patients.

BACKGROUND: The aim of this study was to investigate and evaluate complications of intrathecal baclofen (ITB) pump implantation and maintenance in children with cerebral palsy. METHODS: We reviewed our entire consecutive series of pediatric patients treated with ITB between 1997 and 2006 at our hospital. There were 174 patients with a diagnosis of cerebral palsy, 8 with mixed dystonia, 2 with athetosis, and 3 with pure dystonia. During follow-up, 8 deaths occurred with no evidence of pump or catheter malfunction in any way contributing to the cause of death. Acute infection within 60 days of the surgery and late infection rates were calculated on the basis of number of incidents and incidents/follow-up patient years, respectively. Independently, a blinded caregiver phone questionnaire was completed in 92 cases. RESULTS: There were 316 surgical procedures; 161 were initial ITB pump implants at our institution. The average age at initial implant was 12 years, with an average follow-up of 3 years, 2 months. There were 80 planned replacement procedures (46 battery expirations and 3 planned pump replacements during posterior spinal fusion, 26 catheter replacements for posterior spinal fusion, and 5 reinsertions). There were 78 procedures in 57 patients related to complications, and the acute infection rate was 4.0%. The probability of developing a late infection was 1.0% per year of follow-up. On the basis of the follow-up questionnaire, 81% of parents/caregivers were satisfied with the treatment, and 87% would recommend ITB therapy. CONCLUSIONS: ITB therapy is a safe and effective treatment for severe spasticity in the pediatric population, but does have a 31% rate of complications requiring surgical management over a 3-year treatment period. Parents and caregivers have a high rate of satisfaction and most would recommend the treatment to others.

Implication of Vaginal and Cesarean Section Delivery Method in Black-White Differentials in Infant Mortality in the United States: Linked Birth/Infant Death Records, 2007-2016.

Racial/ethnic disparities in infant mortality (IM) continue to persist in the United States, with Black/African Americans (AA) being disproportionally affected with a three-fold increase in mortality compared to Whites. Epidemiological data have identified maternal characteristics in IM risk such as preeclampsia, eclampsia, maternal education, smoking, maternal weight, maternal socioeconomic status (SES), and family structure. Understanding the social gradient in health including implicit bias, as inherent in the method of labor and delivery and the racial heterogeneity, may facilitate intervention mapping in narrowing the Black-White IM risk differences. We aimed to assess the temporal/racial trends and the methods of delivery, mainly vaginal vs. cesarean section (C-section) as an exposure function of IM. The United States linked birth/infant death records (2007-2016) were used with a cross-sectional ecological design. The analysis involved chi squared statistic, incidence rate estimation by binomial regression model, and period percent change. Of the 40,445,070 births between 2007 and 2016, cumulative mortality incidence was 249,135 (1.16 per 1000). The IM rate was highest among Black/AA (11.41 per 1000), intermediate among Whites (5.19 per 1000), and lowest among Asian /Pacific Islanders (4.24 per 1000). The cumulative incidence rate difference, comparing vaginal to cesarean procedure was 1.73 per 1000 infants, implying excess IM with C-section. Compared to C-section, there was a 31% decreased risk of IM among mothers with vaginal delivery, rate ratio (RR) = 0.69, 95% confidence interval (CI): 0.64-0.74. Racial disparities were observed in the method of delivery associated with IM. Black/AA mothers with vaginal delivery had a 6% decreased risk of IM compared to C-section, RR = 0.94, 95% CI: 0.92-0.95, while Whites with vaginal delivery had a 38% decrease risk of IM relative to C-section, RR= 0.68, 95% CI: 0.67-0.69, p < 0.001. Infant mortality varied by race, with Black/AA disproportionally affected, which is explained in part by labor and delivery procedures, suggestive of reliable and equitable intrapartum assessment of Black/AA mothers during labor, as well as implicit bias marginalization in the healthcare system.

Black-White Risk Differentials in COVID-19 (SARS-COV2) Transmission, Mortality and Case Fatality in the United States: Translational Epidemiologic Perspective and Challenges.

BACKGROUND: Social and health inequities predispose vulnerable populations to adverse morbidity and mortality outcomes of epidemics and pandemics. While racial disparities in cumulative incidence (CmI) and mortality from the influenza pandemics of 1918 and 2009 implicated Blacks with survival disadvantage relative to Whites in the United States, COVID-19 currently indicates comparable disparities. We aimed to: (a) assess COVID-19 CmI by race, (b) determine the Black-White case fatality (CF) and risk differentials, and (c) apply explanatory model for mortality risk differentials. METHODS: COVID-19 data on confirmed cases and deaths by selective states health departments were assessed using a cross-sectional ecologic design. Chi-square was used for CF independence, while binomial regression model for the Black-White risk differentials. RESULTS: The COVID-19 mortality CmI indicated Blacks/AA with 34% of the total mortality in the United States, albeit their 13% population size. The COVID-19 CF was higher among Blacks/AA relative to Whites; Maryland, (2.7% vs. 2.5%), Wisconsin (7.4% vs. 4.8%), Illinois (4.8% vs. 4.2%), Chicago (5.9% vs. 3.2%), Detroit (Michigan), 7.2% and St. John the Baptist Parish (Louisiana), 7.9%. Blacks/AA compared to Whites in Michigan were 15% more likely to die, CmI risk ratio (CmIRR) = 1.15, 95% CI, 1.01-1.32. Blacks/AA relative to Whites in Illinois were 13% more likely to die, CmIRR = 1.13, 95% CI, 0.93-1.39, while Blacks/AA compared to Whites in Wisconsin were 51% more likely to die, CmIRR = 1.51, 95% CI, 1.10-2.10. In Chicago, Blacks/AA were more than twice as likely to die, CmIRR = 2.24, 95% CI, 1.36-3.88. CONCLUSION: Substantial racial/ethnic disparities are observed in COVID-19 CF and mortality with Blacks/AA disproportionately affected across the United States.

[Knee capsulotomy for fixed knee flexion contracture]. / Kalici diz fleksiyon kontraktüründe kapsülotomi.

OBJECTIVES: This study aimed to assess the results of knee capsulotomy for correcting fixed knee flexion contracture in children with cerebral palsy (CP). METHODS: Thirty-five children (20 boys, 15 girls; mean age 13.5+/-2.5 years) with CP underwent posterior knee capsulotomy for 59 knees. Eleven patients had diplegia, one patient had hemiplegia, and 23 patients had quadriplegia. There were two community ambulators (3 knees), 19 household ambulators (33 knees), and 14 nonambulators (23 knees). Posterior knee capsulotomy was combined with hamstring lengthening (50 knees, 84.8%), rectus femoris transfer (10 knees, 17%), Achilles tendon lengthening (12 knees, 20.3%), and posterior cruciate ligament release (eight knees, 13.6%). The mean follow-up was 3.5+/-1.7 years. RESULTS: Fixed knee flexion contracture significantly improved from 26.5+/-15.4 degrees to 17.0+/-15.5 degrees after posterior knee capsulotomy (p<0.0001). The mean improvement was 9.5 degrees. Popliteal angle significantly improved from 70.6+/-18.7 degrees to 48.2+/-19.9 degrees (p<0.0001). Ankle dorsiflexion did not differ significantly. At the end of follow-up, 38 knees (64.4%) had improved knee flexion contracture and 21 knees (35.6%) had recurrent flexion contracture (failure). Age and male gender were significantly associated with failure rate (adjusted odds ratio 0.78, 95% CI: 0.62-0.99 and 12.1, 95% CI: 2.37-61.7, respectively). Complications included transient sciatic nerve palsy in seven knees (11.9%), and wound dehiscence in two knees (3.4%). Revision was required in two knees (3.4%), and posterolateral corner reconstruction in one knee (1.7%). CONCLUSION: Posterior knee capsulotomy is another option for the treatment of knee contracture in CP, resulting in a significant decrease in knee contracture with acceptable complications. However, failure rate is higher in boys, patients who are marginal ambulators, and in younger age group.

DNA Methylation of Candidate Genes (ACE II, IFN-γ, AGTR 1, CKG, ADD1, SCNN1B and TLR2) in Essential Hypertension: A Systematic Review and Quantitative Evidence Synthesis.

Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor dysregulation, leading to impaired gene expression and abnormal protein synthesis. Stressful environments such as social adversity, isolation, sustained social threats, physical inactivity, and highly methylated diets predispose individuals to molecular level alterations such as aberrant epigenomic modulations that affect homeostasis and hemodynamics. With cardiovascular disease as the leading cause of mortality in the US and blacks/African Americans being disproportionately affected by hypertension (HTN) which contributes substantially to these deaths, reflecting the excess mortality and survival disadvantage of this sub-population relative to whites, understanding the molecular events, including epigenomic and socio-epigenomic modulations, is relevant to narrowing the black-white mortality risk differences. We aimed to synthesize epigenomic findings in HTN namely (a) angiotensin-converting enzyme 2 (ACE II) gene, (b) Toll-like receptor 2 (TLR2) gene, (c) interferon γ (IFN-γ) gene, and (d) Capping Actin Protein, Gelosin-Like (CAPG) gene, adducin 1(ADD1) gene, (e) Tissue inhibitor of metalloproteinase 3 (TIMP3), (f) mesoderm specific transcript (MEST) loci, (g) sodium channel epithelial 1 alpha subunit 2 (SCNN1B), (h) glucokinase (CKG) gene (i) angiotensin II receptor, type1 (AGTR1), and DNA methylation (mDNA). A systematic review and quantitative evidence synthesis (QES) was conducted using Google Scholar and PubMed with relevant search terms. Data were extracted from studies on: (a) Epigenomic modulations in HTN based on ACE II (b) TLR2, (c) IFN-γ gene, (d) CAPG, ADD1, TIMP3, MEST loci, and mDNA. The random-effect meta-analysis method was used for a pooled estimate of the common effect size, while z statistic and I^2 were used for the homogeneity of the common effect size and between studies on heterogeneity respectively. Of the 642 studies identified, five examined hypermethylation while seven studies assessed hypomethylation in association with HTN. The hypermethylation of ACE II, SCNN1B, CKG, IFN-γ gene, and miR-510 promoter were associated with hypertension, the common effect size (CES) = 6.0%, 95% CI, -0.002-11.26. In addition, the hypomethylation of TLR2, IFN-γ gene, ADD1, AGTR1, and GCK correlated with hypertension, the CES = 2.3%, 95% CI, -2.51-7.07. The aberrant epigenomic modulation of ACE II, TLR2, IFN-γ, AGTR1, and GCK correlated with essential HTN. Transforming the environments resulting from these epigenomic lesions will facilitate early intervention mapping in reducing HTN in the US population, especially among socially disadvantaged individuals, particularly racial/ethnic minorities.

Aberrant Epigenomic Modulation of Glucocorticoid Receptor Gene (NR3C1) in Early Life Stress and Major Depressive Disorder Correlation: Systematic Review and Quantitative Evidence Synthesis.

Early life stress (ELS) induced by psychological trauma, child maltreatment, maternal separation, and domestic violence predisposes to psycho-behavioral pathologies during adulthood, namely major depressive disorder (MDD), anxiety, and bipolar affective disorder. While environmental data are available in illustrating this association, data remain to be established on the epigenomic underpinning of the nexus between ELS and MDD predisposition. Specifically, despite the observed aberrant epigenomic modulation of the NR3C1, a glucocorticoid receptor gene, in early social adversity and social threats in animal and human models, reliable scientific data for intervention mapping in reducing social adversity and improving human health is required. We sought to synthesize the findings of studies evaluating (a) epigenomic modulations, mainly DNA methylation resulting in MDD following ELS, (b) epigenomic modifications associated with ELS, and (c) epigenomic alterations associated with MDD. A systematic review and quantitative evidence synthesis (QES) were utilized with the random effect meta-analytic procedure. The search strategy involved both the PubMed and hand search of relevant references. Of the 1534 studies identified through electronic search, 592 studies were screened, 11 met the eligibility criteria for inclusion in the QES, and 5 examined ELS and MDD; 4 studies assessed epigenomic modulation and ELS, while 2 studies examined epigenomic modulations and MDD. The dense DNA methylation of the 1F exon of the NR3C1, implying the hypermethylated region of the glucocorticoid receptor gene, was observed in the nexus between ELS and MDD, common effect size (CES) = 14.96, 95%CI, 10.06-19.85. With respect to epigenomic modulation associated with child ELS, hypermethylation was observed, CES = 23.2%, 95%CI, 8.00-38.48. In addition, marginal epigenomic alteration was indicated in MDD, where hypermethylation was associated with increased risk of MDD, CES = 2.12%, 95%CI, -0.63-4.86. Substantial evidence supports the implication of NR3C1 and environmental interaction, mainly DNA methylation, in the predisposition to MDD following ELS. This QES further supports aberrant epigenomic modulation identified in ELS as well as major depressive episodes involving dysfunctional glucocorticoid-mediated negative feedback as a result of allostatic overload. These findings recommend prospective investigation of social adversity and its predisposition to the MDD epidemic via aberrant epigenomic modulation. Such data will facilitate early intervention mapping in reducing MDD in the United States population.

Implication of Spiritual Network Support System in Epigenomic Modulation and Health Trajectory.

With challenges in understanding the multifactorial etiologies of disease and individual treatment effect heterogeneities over the past four decades, much has been acquired on how physical, chemical and social environments affect human health, predisposing certain subpopulations to adverse health outcomes, especially the socio-environmentally disadvantaged (SED). Current translational data on gene and adverse environment interaction have revealed how adverse gene-environment interaction, termed aberrant epigenomic modulation, translates into impaired gene expression via messenger ribonucleic acid (mRNA) dysregulation, reflecting abnormal protein synthesis and hence dysfunctional cellular differentiation and maturation. The environmental influence on gene expression observed in most literature includes physical, chemical, physicochemical and recently social environment. However, data are limited on spiritual or religious environment network support systems, which reflect human psychosocial conditions and gene interaction. With this limited information, we aimed to examine the available data on spiritual activities characterized by prayers and meditation for a possible explanation of the nexus between the spiritual network support system (SNSS) as a component of psychosocial conditions, implicated in social signal transduction, and the gene expression correlate. With the intent to incorporate SNSS in human psychosocial conditions, we assessed the available data on bereavement, loss of spouse, loneliness, social isolation, low socio-economic status (SES), chronic stress, low social status, social adversity (SA) and early life stress (ELS), as surrogates for spiritual support network connectome. Adverse human psychosocial conditions have the tendency for impaired gene expression through an up-regulated conserved transcriptional response to adversity (CTRA) gene expression via social signal transduction, involving the sympathetic nervous system (SNS), beta-adrenergic receptors, the hypothalamus-pituitary-adrenal (HPA) axis and the glucocorticoid response. This review specifically explored CTRA gene expression and the nuclear receptor subfamily 3 group C member 1 (NR3C1) gene, a glucocorticoid receptor gene, in response to stress and the impaired negative feedback, given allostatic overload as a result of prolonged and sustained stress and social isolation as well as the implied social interaction associated with religiosity. While more remains to be investigated on psychosocial and immune cell response and gene expression, current data on human models do implicate appropriate gene expression via the CTRA and NR3C1 gene in the SNSS as observed in meditation, yoga and thai-chi, implicated in malignant neoplasm remission. However, prospective epigenomic studies in this context are required in the disease causal pathway, prognosis and survival, as well as cautious optimism in the application of these findings in clinical and public health settings, due to unmeasured and potential confoundings implicated in these correlations.

Risk factors for pancreatitis after posterior spinal fusion in children with cerebral palsy.

This study reports on the prevalence and risk factors of acute pancreatitis after posterior spinal fusion for cerebral palsy scoliosis. Pancreatitis diagnosis was based on elevated amylase or lipase above three times the upper normal limit. Perioperative data were compared between patients with and without pancreatitis. We included 300 patients; 55% developed acute pancreatitis. Gastrostomy dependence was more common in the pancreatitis group (P=0.048). Perioperative data were similar between groups. Patients with pancreatitis had longer duration of hospitalization (19 vs. 13 days, P<0.001). Acute pancreatitis is common after cerebral palsy scoliosis surgery. Gastrostomy dependence increases its risk. Although no mortality was reported, hospital stay was longer.

Factors affecting femoral varus osteotomy in cerebral palsy: a long-term result over 10 years.

The present study was conducted to review the long-term results of femoral varus osteotomy with/without pelvic osteotomy of spastic cerebral palsy. We also evaluated the spastic hip score with following factors: migration index of Reimer's, Shenton's line, shape of the femoral head, shape of the roof of the acetabulum, and presence of windblown effect. Of the 31 children (61 hips) reviewed, 49 hips (80%) had satisfactory outcomes after 10 years of follow-up. Twelve hips showed unsatisfactory outcomes with recurrent dislocation or significant osteoarthritis. A low preoperative spastic hip score was more indicative of a better outcome.

Soft-tissue releases to treat spastic hip subluxation in children with cerebral palsy.

BACKGROUND: Spastic hip subluxation and dislocation are common problems in children with cerebral palsy. Soft-tissue releases have proved to be beneficial in the prevention of spastic hip dislocation. A protocol for treatment based on patient age, hip abduction, and hip migration percentage was established in 1988. The purpose of this study was to assess the outcome in sixty-five children treated according to this protocol and followed for a minimum of eight years. METHODS: The medical records and radiographs of sixty-five children, from an original series of seventy-four patients, who met the inclusion criteria were available for review. Forty-seven children had spastic quadriplegia and were unable to walk; eighteen children had spastic diplegia and were able to walk independently or with assistive devices. The mean age at the time of the surgery was 4.4 years. Open adductor tenotomy and psoas muscle recession or iliopsoas tenotomy were performed on 129 hips, which were followed for a mean of 10.8 years. The mean age at the time of follow-up was fifteen years. Hips were grouped according to the hip migration percentage preoperatively, at one year postoperatively, and at the time of final follow-up. The final outcome for the patient was defined according to the worse hip. An analysis was performed to identify potential factors influencing outcome. RESULTS: Thirty-two patients (49%) had a good result, eleven (17%) had a fair result, three (4%) had a poor result, and nineteen (30%) had a failure. The mean hip migration percentage was 34% preoperatively and 18% at the time of final follow-up. Nineteen patients required subsequent osseous reconstructive procedures, and eleven required repeat soft-tissue releases. The migration percentage at one year postoperatively was the most predictive of the final outcome (p = 0.001). Patients who had been able to walk preoperatively had a better long-term outcome (p = 0.01). Neither the preoperative hip migration percentage nor the age at surgery significantly affected the outcome. CONCLUSIONS: Soft-tissue release was effective for long-term prevention of hip dislocation in 67% (forty-three) of sixty-five children with spastic hip subluxation. Two preoperative factors that were related to a favorable outcome were a spastic diplegic pattern of involvement and the ability to walk. The hip migration percentage at one year postoperatively was a good predictor of final outcome.

Correction of sagittal plane spinal deformities with unit rod instrumentation in children with cerebral palsy.

BACKGROUND: To our knowledge, there have been no previous studies addressing the indications for and the results of treatment of patients with cerebral palsy and concomitant kyphosis or lordosis without scoliosis. The purpose of the present study was to identify the indications for and the results of treatment of patients with cerebral palsy who have a spinal curve deformity solely in the sagittal plane. METHODS: We conducted a retrospective review of the data on all patients with cerebral palsy who had a sagittal plane spinal deformity but no coronal plane deformity, had undergone posterior spinal fusion with unit rod instrumentation at our institution, and had been followed for at least two years. Medical records and radiographs were reviewed for symptoms, type and magnitude of deformity, age at surgery, duration of surgery, nutritional status, complications, and concomitant medical problems. RESULTS: Twenty-four patients--ten boys and fourteen girls--were identified. Eight patients had a hyperlordotic deformity, fourteen had a hyperkyphotic deformity, and two exhibited both. Surgical indications included severe seating problems that could not be rectified with wheelchair modifications (eighteen patients), severe back pain (four patients), superior mesenteric artery syndrome that was refractory to conservative treatment (two patients), and a hyperlordotic deformity with a loss of bowel and bladder control (one patient). It was found that specific technical concerns had to be addressed when the unit rod instrumentation was used. The mean preoperative hyperkyphotic curve of 93.8 degrees was corrected to a mean of 35.8 degrees postoperatively and was a mean of 34.8 degrees at the last visit. The mean preoperative hyperlordotic curve of 91.8 degrees was corrected to a mean of 43.6 degrees postoperatively and was a mean of 48.6 degrees at the last visit. All patients with seating problems and back pain had improvement or resolution of the problem after the surgery. The superior mesenteric artery syndromes, losses of bowel and bladder function, and malnutrition all resolved completely after the surgery. CONCLUSIONS: Patients with cerebral palsy and a severe sagittal plane deformity (> or = 70 degrees ) can be treated successfully with posterior spinal fusion with use of unit rod instrumentation. Indications for treatment include loss of sitting ability or balance, back pain, loss of bowel or bladder function, and superior mesenteric artery syndrome that is unresponsive to medical management.