Surgical fusion of early onset severe scoliosis increases survival in the child with rett syndrome: A population based study

Introduction. Rett Syndrome is a rare genetic neurodevelopmental disorder usually affecting females. Scoliosis is a common comorbidity and spinal fusion may be recommended if severe. Little is known about long term outcomes. We examined the impact of spinal fusion on survival and risk of severe lower respiratory tract infection (LRTI) in Rett Syndrome. Methods Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry of Rett Syndrome cases established in 1993, and the Australian Institute of Health and Welfare National Death Index database. An extended Cox regression model was used to estimate the effect of spinal surgery on survival in females who developed severe scoliosis (Cobb angle > 45 degrees). Generalized estimating equation modelling was used to estimate the effect of spinal surgery on the odds of developing severe LRTI. Results Severe scoliosis was identified in 140 cases (60.3%) of whom slightly fewer than half (48.6%) developed scoliosis prior to eight years of age. Scoliosis surgery was performed in 98 (69.0%) of those at a median age of 13 years 3 months (IQR 11 years 5 months – 14 years 10 months). After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (HR 0.30, 95% CI 0.12, 0.74, P = 0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06, 0.52, P = 0.002). Spinal fusion was not associated with reduction in the occurrence of a severe LRTI overall (OR 0.60, 95%CI 0.27, 1.33, P=0.206) but was associated with a large reduction in odds of severe LRTI among those with early onset scoliosis (OR 0.32, 95%CI 0.11, 0.93, P=0.036). Conclusion With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome.

A systematic review of axillary web syndrome (AWS)

Introduction Axillary web syndrome (AWS) can result in early post-operative and long-term difficulties following lymphadenectomy for cancer and should be recognised by clinicians. This systematic review was conducted to synthesise information on AWS clinical presentation and diagnosis, frequency, natural progression, grading, pathoaetiology, risk factors, symptoms, interventions and outcomes. Methods Electronic searches were conducted using Cochrane, Pubmed, MEDLINE, CINAHL, EMBASE, AMED, PEDro and Google Scholar until June 2013. The methodological quality of included studies was determined using the Downs and Black checklist. Narrative synthesis of results was undertaken. Results Thirty-seven studies with methodological quality scores ranging from 11 to 26 on a 28-point scale were included. AWS diagnosis relies on inspection and palpation; grading has not been validated. AWS frequency was reported in up to 85.4 % of patients. Biopsies identified venous and lymphatic pathoaetiology with five studies suggesting lymphatic involvement. Twenty-one studies reported AWS occurrence within eight post-operative weeks, but late occurrence of greater than 3 months is possible. Pain was commonly reported with shoulder abduction more restricted than flexion. AWS symptoms usually resolve within 3 months but may persist. Risk factors may include extensiveness of surgery, younger age, lower body mass index, ethnicity and healing complications. Low-quality studies suggest that conservative approaches including analgesics, non-steroidal anti-inflammatory drugs and/or physiotherapy may be safe and effective for early symptom reduction. Conclusions AWS appears common. Current evidence for the treatment of AWS is insufficient to provide clear guidance for clinical practice. Implications for Cancer Survivors Cancer survivors should be informed about AWS. Further investigation is needed into pathoaetiology, long-term outcomes and to determine effective treatment using standardised outcomes.

Molecular mimicry: Can epitope mimicry induce autoimmune disease?

Mimicry of host antigens by infectious agents may induce cross-reactive autoimmune responses to epitopes within host proteins which, in susceptible individuals, may tip the balance of immunological response versus tolerance toward response and subsequently lead to autoimmune disease. Epitope mimicry may indeed be involved in the pathogenesis of several diseases such as post-viral myocarditis or Chagas disease, but for many other diseases in which it has been implicated, such as insulin-dependent diabetes mellitis or rheumatoid arthritis, convincing evidence is still lacking. Even if an epitope mimic can support a cross-reactive T or B cell response in vitro, its ability to induce an autoimmune disease in vivo will depend upon the appropriate presentation of the mimicked host antigen in the target tissue and, in the case of T cell mimics, the ability of the mimicking epitope to induce a proliferative rather than anergizing response upon engagement of the MHC-peptide complex with the T cell receptor. B cell presentation of mimicking foreign antigen to T cells is a possible mechanism for instigating an autoimmune response to self antigens that in turn can lead to autoimmune disease under particular conditions of antigen presentation, secondary signalling and effector cell repertoire. In this review evidence in support of epitope mimicry is examined in the light of the necessary immunological considerations of the theory.

Prospective external validation of an accelerated (2-h) acute coronary syndrome rule-out process using a contemporary troponin assay

Background: Recently there have been efforts to derive safe, efficient processes to rule out acute coronary syndrome (ACS) in emergency department (ED) chest pain patients. We aimed to prospectively validate an ACS assessment pathway (the 2-Hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker (ADAPT) pathway) under pragmatic ED working conditions. Methods: This prospective cohort study included patients with atraumatic chest pain in whom ACS was suspected but who did not have clear evidence of ischaemia on ECG. Thrombolysis in myocardial infarction (TIMI) score and troponin (TnI Ultra) were measured at ED presentation, 2 h later and according to current national recommendations. The primary outcome of interest was the occurrence of major adverse cardiac events (MACE) including prevalent myocardial infarction (MI) at 30 days in the group who had a TIMI score of 0 and had presentation and 2-h TnI assays <99th percentile. Results: Eight hundred and forty patients were studied of whom 177 (21%) had a TIMI score of 0. There were no MI, MACE or revascularization in the per protocol and intention-to-treat 2-h troponin groups (0%, 95% confidence interval (CI) 0% to 4.5% and 0%, 95% CI 0% to 3.8%, respectively). The negative predictive value (NPV) was 100% (95% CI 95.5% to 100%) and 100% (95% CI 96.2% to 100%), respectively. Conclusions: A 2-h accelerated rule-out process for ED chest pain patients using electrocardiography, a TIMI score of 0 and a contemporary sensitive troponin assay accurately identifies a group at very low risk of 30-day MI or MACE.

Limited utility of exercise stress testing in the evaluation of suspected acute coronary syndrome in patients aged less than 40 years with intermediate risk features

Objective National guidelines for management of intermediate risk patients with suspected acute coronary syndrome, in whom AMI has been excluded, advocate provocative testing to final risk stratify these patients into low risk (negative testing) or high risk (positive testing suggestive of unstable angina). Adults less than 40 years have a low pretest probability of acute coronary syndrome. The utility of exercise stress testing in young adults with chest pain suspected of acute coronary syndrome who have National Heart Foundation intermediate risk features was evaluated Methods A retrospective analysis of exercise stress testing performed on patients less than 40 years was evaluated. Patients were enrolled on a chest pain pathway and had negative serial ECGs and cardiac biomarkers before exercise stress testing to rule-out acute coronary syndrome. Chart review was completed on patients with positive stress tests. Results The 3987 patients with suspected intermediate risk acute coronary syndrome underwent exercise stress testing. One thousand and twenty-seven (25.8%) were aged less than 40 years (age 33.3 ± 4.8 years). Four of these 1027 patients had a positive exercise stress test (0.4% incidence of positive exercise stress testing). Of those, three patients had subsequent non-invasive functional testing that yielded a negative result. One patient declined further investigations. Assuming this was a true positive exercise stress test, the incidence of true positive exercise stress testing would have been 0.097% (95% confidence interval: 0.079–0.115%) (one of 1027 patients). Conclusions Routine exercise stress testing has limited value in the risk stratification of adults less than 40 years with suspected intermediate risk of acute coronary syndrome

Efficacy and feasibility of a tele-health intervention for acute coronary syndrome patients with depression: Results of the 'MoodCare' randomized controlled trial

Background Depression is common after a cardiac event, yet there remain few approaches to management that are both effective and scalable. Purpose We aimed to evaluate the 6-month efficacy and feasibility of a tele-health program (MoodCare) that integrates depression management into a cardiovascular disease risk reduction program for acute coronary syndrome patients with low mood. Methods A two-arm, parallel, randomized design was used comprising 121 patients admitted to one of six hospitals for acute coronary syndrome. Results Significant treatment effects were observed for Patient Health Questionnaire 9 (PHQ9) depression (mean difference [change] = −1.8; p = 0.025; effect size: d = 0.36) for the overall sample, when compared with usual medical care. Results were more pronounced effects for those with a history of depression (mean difference [change] = −2.7; p = 0.043; effect size: d = 0.65). Conclusions MoodCare was effective for improving depression in acute coronary syndrome patients, producing effect sizes exceeding those of some face-to-face psychotherapeutic interventions and pharmacotherapy. (Trial Registration Number: ACTRN1260900038623.)

Spatiotemporal transmission dynamics of hemorrhagic fever with renal syndrome in China, 2005-2012

Background Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by many serotypes of hantaviruses. In China, HFRS has been recognized as a severe public health problem with 90% of the total reported cases in the world. This study describes the spatiotemporal dynamics of HFRS cases in China and identifies the regions, time, and populations at highest risk, which could help the planning and implementation of key preventative measures. Methods Data on all reported HFRS cases at the county level from January 2005 to December 2012 were collected from Chinese Center for Disease Control and Prevention. Geographic Information System-based spatiotemporal analyses including Local Indicators of Spatial Association and Kulldorff's space-time scan statistic were performed to detect local high-risk space-time clusters of HFRS in China. In addition, cases from high-risk and low-risk counties were compared to identify significant demographic differences. Results A total of 100,868 cases were reported during 2005–2012 in mainland China. There were significant variations in the spatiotemporal dynamics of HFRS. HFRS cases occurred most frequently in June, November, and December. There was a significant positive spatial autocorrelation of HFRS incidence during the study periods, with Moran's I values ranging from 0.46 to 0.56 (P<0.05). Several distinct HFRS cluster areas were identified, mainly concentrated in northeastern, central, and eastern of China. Compared with cases from low-risk areas, a higher proportion of cases were younger, non-farmer, and floating residents in high-risk counties. Conclusions This study identified significant space-time clusters of HFRS in China during 2005–2012 indicating that preventative strategies for HFRS should be particularly focused on the northeastern, central, and eastern of China to achieve the most cost-effective outcomes.

Partial epilepsy syndrome in a Gypsy family linked to 5q31.3-q32

PURPOSE The restricted genetic diversity and homogeneous molecular basis of Mendelian disorders in isolated founder populations have rarely been explored in epilepsy research. Our long-term goal is to explore the genetic basis of epilepsies in one such population, the Gypsies. The aim of this report is the clinical and genetic characterization of a Gypsy family with a partial epilepsy syndrome. METHODS Clinical information was collected using semistructured interviews with affected subjects and informants. At least one interictal electroencephalography (EEG) recording was performed for each patient and previous data obtained from records. Neuroimaging included structural magnetic resonance imaging (MRI). Linkage and haplotype analysis was performed using the Illumina IVb Linkage Panel, supplemented with highly informative microsatellites in linked regions and Affymetrix SNP 5.0 array data. RESULTS We observed an early-onset partial epilepsy syndrome with seizure semiology strongly suggestive of temporal lobe epilepsy (TLE), with mild intellectual deficit co-occurring in a large proportion of the patients. Psychiatric morbidity was common in the extended pedigree but did not cosegregate with epilepsy. Linkage analysis definitively excluded previously reported loci, and identified a novel locus on 5q31.3-q32 with an logarithm of the odds (LOD) score of 3 corresponding to the expected maximum in this family. DISCUSSION The syndrome can be classified as familial temporal lobe epilepsy (FTLE) or possibly a new syndrome with mild intellectual deficit. The linked 5q region does not contain any ion channel-encoding genes and is thus likely to contribute new knowledge about epilepsy pathogenesis. Identification of the mutation in this family and in additional patients will define the full phenotypic spectrum.

Physical activity cost in children following an acquired brain injury : a comparative study

Background: Alterations in energy expenditure during activity post head injury has not been investigated due primarily to the difficulty of measurement. Objective: The aim of this study was to compare energy expenditure during activity and body composition of children following acquired brain injury (ABI) with data from a group of normal controls. Design: Energy expenditure was measured using the Cosmed K4b2 in a group of 15 children with ABI and a group of 67 normal children during rest and when walking and running. Mean number of steps taken per 3 min run was also recorded and body composition was measured. Results: The energy expended during walking was not significantly different between both groups. A significant difference was found between the two groups in the energy expended during running and also for the number of steps taken as children with ABI took significantly less steps than the normal controls during a 3 min run. Conclusions: Children with ABI exert more energy per activity than healthy controls when controlled for velocity or distance. However, they expend less energy to walk and run when they are free to choose their own desirable, comfortable pace than normal controls. © 2003 Elsevier Ltd. All rights reserved.

Target acquired: Progress and promise of targeted therapeutics in the treatment of prostate cancer

Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient’s disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

Characterization of an Evolutionarily Conserved Metallophosphoesterase That Is Expressed in the Fetal Brain and Associated with the WAGR Syndrome

Among the human diseases that result from chromosomal aberrations, a de novo deletion in chromosome 11p13 is clinically associated with a syndrome characterized by Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR). Not all genes in the deleted region have been characterized biochemically or functionally. We have recently identified the first Class III cyclic nucleotide phosphodiesterase, Rv0805, from Mycobacterium tuberculosis, which biochemically and structurally belongs to the superfamily of metallophosphoesterases. We performed a large scale bioinformatic analysis to identify orthologs of the Rv0805 protein and identified many eukaryotic genes that included the human 239FB gene present in the region deleted in the WAGR syndrome. We report here the first detailed biochemical characterization of the rat 239FB protein and show that it possesses metallophosphodiesterase activity. Extensive mutational analysis identified residues that are involved in metal interaction at the binuclear metal center. Generation of a rat 239FB protein with a mutation corresponding to a single nucleotide polymorphism seen in human 239FB led to complete inactivation of the protein. A close ortholog of 239FB is found in adult tissues, and biochemical characterization of the 239AB protein demonstrated significant hydrolytic activity against 2',3'-cAMP, thus representing the first evidence for a Class III cyclic nucleotide phosphodiesterase in mammals. Highly conserved orthologs of the 239FB protein are found in Caenorhabditis elegans and Drosophila and, coupled with available evidence suggesting that 239FB is a tumor suppressor, indicate the important role this protein must play in diverse cellular events.

Tarsal tunnel syndrome: A narrative literature review

Background Tarsal tunnel syndrome is classified as a focal compressive neuropathy of the posterior tibial nerve or one of its associated branches individually or collectively. The tunnel courses deep to fascia, the flexor retinaculum and within the abductor hallucis muscle of the foot/ankle. The condition is rare and regularly under-diagnosed leading to a range of symptoms affecting the plantar margins of the foot. There are many intervention strategies for treating tarsal tunnel syndrome with limited robust evidence to guide the clinical management of this condition. The role of conservative versus surgical interventions at various stages of the disease process remains unclear, and there is a need for a structured, step-wise approach in treating patients with this syndrome based on derived empirical evidence. This narrative review attempts to scrutinize the literature to date by clarifying initial presentation, investigations and definitive treatment for the purpose of assisting future informed clinical decision and prospective research endeavours. Process The literature searches that have been incorporated in compiling a rigorous review of this condition have included: the Cochrane Neuromuscular Group's Specialized Register (Cochrane Library 2013), the databases of EMBASE, AMED, MEDLINE, CINAHL, Physiotherapy evidence database (PEDRO), Biomed Central, Science Direct and Trip Database (1972 to the present). Reference listings of located articles were also searched and scrutinized. Authors and experts within the field of lower-limb orthopaedics were contacted to discuss applicable data. Subject-specific criteria searches utilizing the following key terms were performed across all databases: tarsal tunnel syndrome, tibial neuralgia, compression neuropathy syndromes, tibial nerve impingement, tarsal tunnel neuropathy, entrapment tibial nerve, posterior tibial neuropathy. These search strategies were modified with differing databases, adopting specific sensitivity-searching tools and functions unique to each. This search strategy identified 88 journal articles of relevance for this narrative literature review. Findings This literature review has appraised the clinical significance of tarsal tunnel syndrome, whilst assessing varied management interventions (non-surgical and surgical) for the treatment of this condition in both adults and children. According to our review, there is limited high-level robust evidence to guide and refine the clinical management of tarsal tunnel syndrome. Requirements for small-scaled randomized controlled trials in groups with homogenous aetiology are needed to analyse the effectiveness of specific treatment modalities. Conclusions It is necessary that further research endeavours be pursued for the clinical understanding, assessment and treatment of tarsal tunnel syndrome. Accordingly, a structured approach to managing patients who have been correctly diagnosed with this condition should be formulated on the basis of empirical evidence where possible.

Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377)

In Pediatric AIDS Clinical Trials Group 377, antiretroviral therapy-experienced children were randomized to 4 treatment arms that included different combinations of stavudine, lamivudine (3TC), nevirapine (Nvp), nelfinavir (Nfv), and ritonavir (Rtv). Previous treatment with zidovudine (Zdv), didanosine (ddI), or zalcitabine (ddC) was acceptable. Drug resistance ((R)) mutations were assessed before study treatment (baseline) and at virologic failure. Zdv(R), ddI(R), and ddC(R) mutations were detected frequently at baseline but were not associated with virologic failure. Children with drug resistance mutations at baseline had greater reductions in virus load over time than did children who did not. Nvp(R) and 3TC(R) mutations were detected frequently at virologic failure, and Nvp(R) mutations were more common among children receiving 3-drug versus 4-drug Nvp-containing regimens. Children who were maintained on their study regimen after virologic failure accumulated additional Nvp(R) and 3TC(R) mutations plus Rtv(R) and Nfv(R) mutations. However, Rtv(R) and Nfv(R) mutations were detected at unexpectedly low rates.

Factors potentiating the risk of sudden infant death syndrome associated with the prone position

Background. In several studies the sudden infant death syndrome (SIDS) has been significantly associated with sleeping in the prone position. It is not known how the prone position increases the risk of SIDS. Methods. We analyzed data from a case-control study (58 infants with SIDS and 120 control infants) and a prospective cohort study (22 infants with SIDS and 213 control infants) in Tasmania. Interactions were examined in matched analyses with a multiplicative model of interaction. Results. In the case-control study, SIDS was significantly associated with sleeping in the prone position, as compared with other positions (unadjusted odds ratio, 4.5; 95 percent confidence interval, 2.1 to 9.6). The strength of this association was increased among infants who slept on natural-fiber mattresses (P = 0.05), infants who were swaddled (P = 0.09), infants who slept in heated rooms (P = 0.006), and infants who had had a recent illness (P = 0.02). These variables had no significant effect on infants who did not sleep in the prone position. A history of recent illness was significantly associated with SIDS among infants who slept prone (odds ratio, 5.7; 95 percent confidence interval, 1.8 to 19) but not among infants who slept in other positions (odds ratio, 0.83). In the cohort study, the risk of SIDS was greater among infants who slept prone on natural-fiber mattresses (odds ratio, 6.6; 95 percent confidence interval, 1.3 to 33) than among infants who slept prone on other types of mattresses (odds ratio, 1.8). Conclusions. When infants sleep prone, the elevated risk of SIDS is increased by each of four factors: the use of natural-fiber mattresses, swaddling, recent illness, and the use of heating in bedrooms.

Lavage treatment of distal intestinal obstruction syndrome in children with cystic fibrosis

The efficacy, adverse reactions, and long-term effects of intestinal lavage treatment with a balanced electrolyte solution (Golytely) was evaluated in patients with cystic fibrosis and distal intestinal obstruction syndrome. Twenty-two patients with cystic fibrosis (mean age 21.8 years, range 14 to 34 years, 15 boys or men) who sough medical attention because of abdominal pain and a mass in the right iliac fossa received Golytely, 5.6 ± 1.9 L (mean ± 1 SD), either orally (n = 14) or via nasogastric tube (n = 8) during 5.6 ± 2.4 hours. No serious side effects occurred. Serum electrolyte values remained within normal limits. Body weight did not change significantly. Minor adverse reactions included bloating (n = 12), nausea (n = 8), vomiting (n = 1), and chills (n = 3). All but one patient reported impressive relief of symptoms and remained pain free for an average of 3 months (range 1 to 19 months). Symptoms of abdominal pain and radiologic signs of fecal impaction assessed before and after lavage both decreased significantly (P < .0001). During follow-up (mean 15.2 months, range 4 to 26 months), 11 patients required a total of 38 (range one to nine) additional doses of Golytely. Seven patients drank the solution at home (21 treatments); only two patients chose a nasogastric tube. In ten patients with symptoms of recurrent distal intestinal obstruction syndrome prior to institution of therapy, duration of hospitalization was significantly reduced by this treatment (5.1 ± 7.6 v 2.3 ± 6.3 hospital days per annum, P < .02). It is concluded that intestinal lavage is a well-accepted, safe, and effective therapy for distal intestinal obstruction syndrome in patients with cystic fibrosis.