University of Missouri Women's and Children's Hospital

Abstract Heterogeneity within the autism diagnosis obscures the genetic basis of the disorder and impedes our ability to develop effective treatments. We found that by using two readily available tests, autism can be divided into two subgroups, “essential autism” and “complex autism,” with different outcomes and recurrence risks. Complex autism consists of individuals in whom there is evidence of some abnormality of early morphogenesis, manifested by either significant dysmorphology or microcephaly. The remainder have “essential autism.” From 1995 to 2001, 260 individuals who met DSM‐IV criteria for autistic disorder were examined. Five percent (13/260) were microcephalic and 16% (41/260) had significant physical anomalies. Individually, each trait predicted a poorer outcome. Together they define the “complex autism” subgroup, comprising 20% (46/233) of the total autism population. Individuals with complex autism have lower IQs ( P = 0.006), more seizures ( P = 0.0008), more abnormal EEGs (46% vs. 30%), more brain abnormalities by MRI (28% vs. 13%). Everyone with an identifiable syndrome was in the complex group. Essential autism defines the more heritable group with higher sib recurrence (4% vs. 0%), more relatives with autism (20% vs. 9%), and higher male to female ratio (6.5:1 vs. 3.2:1). Their outcome was better with higher IQs ( P = 0.02) and fewer seizures ( P = 0.0008). They were more apt to develop autism with a regressive onset (43% vs. 23%, P = 0.02). Analysis of the features predictive of poor outcome (IQ < 55, functionally non‐verbal) showed that microcephaly was 100% specific but only 14% sensitive; the presence of physical anomalies was 86% specific and 34% sensitive. The two tests combined yielded 87% specificity, 47% sensitivity, and an odds ratio of 4.8:1 for poor outcome. Separating essential from complex autism should be the first diagnostic step for children with autism spectrum disorders as it allows better prognostication and counseling. Definition of more homogeneous populations should increase power of research analyses. © 2005 Wiley‐Liss, Inc.

In an effort to delineate more homogeneous autism subgroups for genetic study, we evaluated 133 consecutive individuals referred to the University of Missouri Autism Center. Each index case underwent a diagnostic evaluation, including a clinical morphology examination, laboratory studies, brain MRI, EEG, and collection of historical, medical, and family data. The 71% (94/133) who fulfilled DSM-IV and CARS autism diagnostic criteria were included in this study. Six of 94 were diagnosed with a known genetic disorder. Of the remaining 88 with apparently "idiopathic autism," 58% (51/88) were phenotypically normal, 22% (19/88) were clearly abnormal, and for 20% (18/88) the clinical morphology examination was equivocal. The percentage of phenotypically abnormal individuals is higher than generally thought and disagrees with the perception that children with autism are usually normally formed. The phenotypically abnormal individuals were 10 times more likely to be diagnosed with a known genetic syndrome (21% vs. 2%) and were more than twice as likely (29% vs. 14%) to have structurally abnormal brain MRIs than the phenotypically normal propositi. Moreover, the male to female ratio correlated with the presence of physical anomalies. The total study group had a male to female ratio of 4.2:1; the morphologically normal subgroup, defined on the basis of a normal physical examination, had a sex ratio of 7.5:1 and the normal subgroup, defined on the basis of both a normal physical examination and a structurally normal brain by MRI had a 23:1 sex ratio. For the phenotypically abnormal subgroup, the sex ratio was 1.7:1. Since differences in sex ratio are presumably a reflection of differences in genetic constitution, we postulate that the phenotypically normal subgroup of individuals with "idiopathic autism" is genetically different from the phenotypically abnormal individuals and that differences in the sex ratio in different autism populations is one indicator of a population's genetic heterogeneity.

BACKGROUND: Anterior vertebral body tethering (VBT) is an early treatment option for progressive scoliosis in pediatric patients, allowing for continued deformity correction during normal growth. We report postoperative radiographic and clinical outcomes for patients treated with VBT. METHODS: This clinical and radiographic retrospective review of 31 consecutive patients included an analysis of preoperative, perioperative, and postoperative details, including the Lenke classification; Cobb angle measurements of the proximal thoracic, main thoracic, and lumbar curves; the sagittal profile; and skeletal maturity. Successful outcomes were defined by a residual curve of ≤30° in skeletally mature patients who did not undergo a posterior spinal fusion (PSF). RESULTS: Of the 31 patients treated, 29 met the inclusion criteria, and 2 were lost to follow-up. The mean patient age (and standard deviation) at the time of the surgical procedure was 12.7 ± 1.5 years (range, 10.2 to 16.7 years), with most patients classified as Risser grade 0 or 1 (52%) and Sanders stage 3 (32%). A mean of 7.2 ± 1.4 vertebral levels were instrumented, with a minimum preoperative Cobb angle of 42°. At the latest follow-up, 27 patients had reached skeletal maturity (Sanders stage ≥7) and 20 patients exhibited a curve magnitude ≤30°, for a success rate of 74%. A suspected broken tether occurred at ≥1 level in 14 patients (48%). Two patients underwent PSF and 4 had tether revision. The overall revision rate was 21% (6 of 29). CONCLUSIONS: This study shows the success and revision rates as well as the impact of a suspected broken tether on the procedural success of VBT. Despite our patient population being slightly more mature at the time of the surgical procedure compared with previous studies, we had a higher success rate and a lower revision rate. A PSF was avoided in 93% of patients, indicating that VBT may be a reliable treatment option for adolescent scoliosis in skeletally immature individuals. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

CD1d and CD1d-restricted natural killer T (NKT) cells serve as a natural bridge between innate and adaptive immune responses to microbes. CD1d downregulation is utilized by a variety of microbes to evade immune detection. We demonstrate here that CD1d is downregulated in human papillomavirus (HPV)-positive cells in vivo and in vitro. CD1d immunoreactivity was strong in HPV-negative normal cervical epithelium but absent in HPV16-positive CIN1 and HPV6-positive condyloma lesions. We used two cell lines for in vitro assay; one was stably CD1d-transfected cells established from an HPV-negative cervical cancer cell line, C33A (C33A/CD1d), and the other was normal human vaginal keratinocyte bearing endogenous CD1d (Vag). Flow cytometry revealed that cell surface CD1d was downregulated in both C33A/CD1d and Vag cells stably transfected with HPV6 E5 and HPV16 E5. Although the steady-state levels of CD1d protein decreased in both E5-expressing cell lines compared to empty retrovirus-infected cells, CD1d mRNA levels were not affected. Confocal microscopy demonstrated that residual CD1d was not trafficked to the E5-expressing cell surface but colocalized with E5 near the endoplasmic reticulum (ER). In the ER, E5 interacted with calnexin, an ER chaperone known to mediate folding of CD1d. CD1d protein levels were rescued by the proteasome inhibitor, MG132, indicating a role for proteasome-mediated degradation in HPV-associated CD1d downregulation. Taken together, our data suggest that E5 targets CD1d to the cytosolic proteolytic pathway by inhibiting calnexin-related CD1d trafficking. Finally, CD1d-mediated production of interleukin-12 from the C33A/CD1d cells was abrogated in both E5-expressing cell lines. Decreased CD1d expression in the presence of HPV E5 may help HPV-infected cells evade protective immunological surveillance.

Here, we examine the potential effect of the COVID-19 pandemic on future birth rates. This highly contagious disease originated in China, and rapidly spread worldwide, leading to extensive lockdown policies being implemented globally with the aim of containing the infection rates and its serious attendant consequences. Based on previous extant literature, this paper overviews the potential demographic consequences of the current progressively widespread epidemic on conception and fertility as driven by the data obtained during similar prior incidents. In general, epidemics manifest a common pattern as far as their impact on population, which is remarkably similar to natural disasters, i.e., a steep decline in birth rates followed by gradual increases and then followed by a baby boom. Additionally, we have also depicted how economic conditions, mental health, fear, and mortality may also influence future birth rates.

Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray-based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P = 6.08 × 10(-7) ), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1.

Background and Purpose— Few studies have examined the epidemiology of stroke in pregnancy, despite the high associated burden of death and disability. We aimed to quantify the incidence, temporal trends, risk factors, and case fatality associated with stroke and cerebrovascular disease in pregnancy. Methods— All antepartum, peripartum, and postpartum hospitalizations and readmissions within 42 days of delivery in Canada (except Quebec) were obtained from the Canadian Institute of Health Information for the years 2003 to 2016. We assessed temporal trends in stroke and quantified associated risk factors using logistic regression. Results— Five hundred twenty-four stroke cases were identified among 3 907 262 deliveries (13.4 per 100 000). The majority of cases were hemorrhagic strokes (307 cases, 58.6%) and most occurred in the postpartum period (270 cases, 51.5%). The case fatality rate was 7.4%. Stroke incidence rose from 10.8 per 100 000 in 2003 to 2004 to 16.6 per 100 000 deliveries in 2015 to 2016 ( P =0.002). Risk factors for stroke included older maternal (age ≥40 years; adjusted odds ratio [AOR], 1.7; 95% CI, 1.1–2.6), preeclampsia (AOR, 7.1; 95% CI, 5.3–9.6), eclampsia (AOR, 65.9; 95% CI, 43.6–99.6), maternal congenital heart disease (AOR, 38.1; 95% CI, 22.1–65.8), connective tissue disorders (AOR, 12.6; 95% CI, 6.1–26.9), sepsis (AOR, 7.6; 95% CI, 3.6–16.2), severe postpartum hemorrhage (AOR, 4.7; 95% CI, 2.8–8.0), and thrombophilia (AOR, 4.2; 95% CI, 1.5–12.1). Conclusions— The rising incidence of stroke in pregnancy, especially during the postpartum period, and its strong association with hypertensive disorders of pregnancy (especially preeclampsia) suggest that follow-up of severe hypertensive patients is required after delivery.

OBJECTIVES: Insufficient sleep affects circadian hormonal profiles and inflammatory markers and may modulate attention, executive functioning and decision-making. Medical professionals and specifically resident physicians, who are involved in long-term nightshift schedules during their post-graduate training, are prone to acute and chronic sleep deprivation and disruption, putting them at risk for making medical errors. The aim of the study was to evaluate the impact of chronic and acute-on-chronic sleep deprivation and disruption among residents on selected physiological and cognitive measures. METHODS: Thirty-three medical and surgical residents were evaluated twice - at baseline and after a 26-hour shift. Eighteen young attending physicians who did not engage in nightshift schedules served as controls and were evaluated once. Measures included morning cortisol and high-sensitivity C-reactive protein (hs-CRP), computerised tests of attention and behaviour, the Behaviour Rating Inventory of Executive Function, a risk-taking questionnaire and the Pittsburgh Sleep Quality Index. RESULTS: Residents, but not attendings, reported chronic sleep disruption and deprivation. Residents at baseline exhibited reduced morning cortisol levels and elevated hs-CRP levels, compared to attendings. Residents at baseline had impaired global executive function compared to attendings. A nightshift with acute sleep deprivation further reduced residents' executive function. Residents at baseline and after a nightshift demonstrated increased impulsivity and slower processing time than attendings. Residents and attendings did not differ in risk-taking tendencies which were assessed in a separate cohort. CONCLUSIONS: In a real-life setting, resident physicians exhibit increased low-grade systemic inflammation (hs-CRP) and impaired HPA-axis function. Their chronic sleep curtailment is associated with greater impulsivity, slower cognitive processing, and impaired executive function. Future research is warranted to understand how improving working schedule by increasing sleep duration may minimise the short-term and potential long-term risks to physicians in training.

Current models of necrotizing enterocolitis (NEC) propose that intraluminal microbes destroy intestinal mucosa and activate an inflammatory cascade that ends in necrosis. We suggest an alternate hypothesis wherein NEC is caused by injury to Paneth cells (PCs) in the intestinal crypts. PCs are specialized epithelia that protect intestinal stem cells from pathogens, stimulate stem cell differentiation, shape the intestinal microbiota, and assist in repairing the gut. Our novel model of NEC uses neonatal mice and ablates PCs followed by enteral infection. We contrast this model with other animal examples of NEC and the clinical disease. Selective destruction of PCs using dithizone likely releases tumor necrosis factor-α and other inflammatory mediators. We propose that this event produces inflammation in the submucosa, generates platelet-activating factor, and induces a coagulopathy. The role of PCs in NEC is consistent with the onset of disease in preterm infants after a period of PC-related maturation, the central role of PCs in crypt-related homeostasis, the anatomic location of pneumatosis intestinalis close to the crypts, and the proximity of PCs to occluded blood vessels that cause coagulation necrosis of the intestinal villi. We offer this hypothesis to promote new thoughts about how NEC occurs and its potential prevention.

IMPORTANCE: Clinical practice guidelines for managing infants and children hospitalized for bronchiolitis recommend only obtaining intermittent or "spot check" pulse oximetry readings for those who show clinical improvement. The effect of such monitoring is currently unknown. OBJECTIVE: To determine the effect of intermittent vs continuous pulse oximetry monitoring on hospital length of stay among nonhypoxemic infants and young children hospitalized for bronchiolitis. DESIGN, SETTING, AND PARTICIPANTS: Randomized, parallel-group, superiority clinical trial of otherwise healthy infants and children 2 years of age or younger hospitalized for bronchiolitis during the period from 2009 to 2014 at 1 of 4 children's hospitals in the United States. Parents or guardians were blinded to allocation assignment until informed consent was obtained; study personnel and outcome assessors were not. INTERVENTIONS: Patients were randomly assigned to undergo continuous or intermittent pulse oximetry monitoring (ie, pulse oximetry measurements were obtained along with a scheduled check of vital signs or for clinical suspicion of deterioration) during hospitalization when oxygen saturation levels were 90% or higher. MAIN OUTCOMES AND MEASURES: Length of hospital stay was the primary outcome. Secondary outcome measures included duration of supplemental oxygen use and rate of escalation of care (defined as transfer to an intensive care unit). RESULTS: A total of 449 infants and young children were screened for inclusion; 288 infants and young children were excluded, resulting in 161 patients who were enrolled in the study (80 patients underwent continuous monitoring, and 81 patients intermittent). The mean length of stay did not differ based on pulse oximetry monitoring strategy (48.9 hours [95% CI, 41.3-56.5 hours] for continuous monitoring vs 46.2 hours [95% CI, 39.1-53.3 hours] for intermittent monitoring; P = .77). The rates of escalation of care and duration of supplemental oxygen use did not differ between groups. CONCLUSIONS AND RELEVANCE: Intermittent pulse oximetry monitoring of nonhypoxemic patients with bronchiolitis did not shorten hospital length of stay and was not associated with any difference in rate of escalation of care or use of diagnostic or therapeutic measures. Our results suggest that intermittent pulse oximetry monitoring can be routinely considered in the management of infants and children hospitalized for bronchiolitis who show clinical improvement. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01014910.

BACKGROUND: There is limited evidence on the clinical characteristics of SARS-CoV-2 infection in Latin America. We present findings from a nationwide study in Argentina. RESEARCH QUESTION: What is disease severity measures and risk factors are associated with admission to an intensive care unit and mortality? STUDY DESIGN AND METHODS: Data were extracted from the COVID-19 database of the Integrated Argentina Health Information System, encompassing the period of March 3rd to October 2nd, 2020, using a standardized case report form that included information on contact history, clinical signs and symptoms, and clinical diagnosis. Information was collected at the initial site of care and follow-up conducted through calls by the regional healthcare authorities. A confirmed case of COVID-19 was defined as having a positive result through sequencing or real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. RESULTS: RT-PCR testing was positive in 738,776 cases. Complete datasets were available for analysis in 207,079 cases. Mean age was 42.9±18.8 years, 50.0% were males. Frequent co-existing conditions included hypertension (19.2%), diabetes (9.7%), asthma (6.1%) and obesity (5.2%). Most common symptoms included fever (58.5%), cough (58.0%), headache (45.4%), and sore throat (42.1%). Death or ICU admission were independently associated with older age, male, coma, dyspnea or tachypnea, and seizures, with underlying co-morbidities such as immunodeficiency, chronic renal failure, and liver disease showing the strongest effects. INTERPRETATION: Most cases of COVID-19 diagnosed in Argentina were mild and had a favorable outcome, but fatality rates were relatively elevated. Risk factors for adverse outcome included older age, male sex, coma and seizures, and the concurrent presence of several morbidities. These data may be useful for healthcare providers and healthcare policy makers of low-middle income and Latin American countries to guide decisions toward optimized care during the pandemic.

IMPORTANCE: Evidence-based treatments that achieve optimal energy intake and improve growth in preschool-aged children with cystic fibrosis (CF) are a critical need. OBJECTIVE: To test whether behavioral and nutritional treatment (intervention) was superior to an education and attention control treatment in increasing energy intake, weight z (WAZ) score, and height z (HAZ) score. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial included 78 children aged 2 to 6 years (mean age, 3.8 years) with CF and pancreatic insufficiency (intervention, n = 36 and control, n = 42). The study was conducted at 7 CF centers between January 2006 and November 2012; all 78 participants who met intent-to-treat criteria completed through follow-up. INTERVENTIONS: Behavioral intervention combined individualized nutritional counseling targeting increased energy intake and training in behavioral child management skills. The control arm provided education and served as a behavioral placebo controlling for attention and contact frequency. Both treatments were delivered in person or telehealth (via telephone). Sessions occurred weekly for 8 weeks then monthly for 4 months (6 months). Participants then returned to standard care for 1 year, with 12-month follow-up thereafter. MAIN OUTCOMES AND MEASURES: Changes in energy intake and WAZ score were examined from pretreatment to posttreatment (6 months) and change in HAZ score was assessed pretreatment to follow-up (18 months). Covariates included sex, Pseudomonas aeruginosa status at baseline, and treatment modality (in person vs telehealth). RESULTS: At baseline, mean (SD) energy intake was 1462 (329) kcals/d, WAZ score was -0.44 (0.81), and HAZ score was -0.55 (0.84). From pretreatment to posttreatment, the intervention increased daily energy intake by 485 calories vs 58 calories for the control group (adjusted difference, 431 calories; 95% CI, 282 to 581; P < .001) and increased the WAZ score by 0.12 units vs 0.06 for the control (adjusted difference, 0.09; 95% CI, -0.06 to 0.24; P = .25). From pretreatment to follow-up, the intervention increased the HAZ score by 0.09 units vs -0.02 for the control (adjusted difference, 0.14 units; 95% CI, 0.001 to 0.27; P = .049). Measured treatment integrity and credibility were high for both groups. CONCLUSIONS AND RELEVANCE: Behavioral and nutritional intervention improved energy intake and HAZ score outcomes but not WAZ score outcomes. Our results provide evidence that behavioral and nutritional treatment may be efficacious as a nutritional intervention for preschoolers aged 2 to 6 years with CF and pancreatic insufficiency. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00241969.

BACKGROUND: Dengue fever shows a broad range of clinical presentations worldwide. Here we report on our clinical findings during the 2019 dengue outbreak in one of the largest tertiary care hospitals in Dhaka, the capital of Bangladesh. METHODS: A total of 747 suspected dengue cases (553 confirmed and 194 probable) were interviewed with a pro forma case record form. Statistical analyses were conducted using SPSS 20.0. Ethical clearance was obtained from the Dhaka Medical College. RESULTS: The mean age of the dengue cases was 27 y and approximately two-thirds were male. Positive tests for NS1 and anti-dengue immunoglobulin M antibody were present in 91.9% and 59.4% of the cases, respectively. Thrombocytopenia was present in 69% of cases and fever was present in 99.1% of cases. Gastrointestinal (GI) features, including anorexia and/or vomiting (69.4%), abdominal pain (39.8%) and diarrhoea (25.6%), were more prevalent than typical rash and pain symptoms. Hypotension was present in approximately one-quarter of patients (25.4%). Probable and confirmed dengue cases have shown similar clinical characteristics and laboratory findings. CONCLUSIONS: The 2019 outbreak of dengue fever in Bangladesh was characterized by increased presentation with GI features. Recognition of this trend would permit early diagnosis and proper management of patients.

"Effort" thrombosis is a unique form of subclavian and axillary vein thrombosis because it is the result of an unusual variant of the thoracic outlet syndrome. Another cause of subclavian vein thrombosis is local compression from trauma, tumor, or development anomalies; a third is intimal damage from indwelling central venous catheters. This is a case report of "effort" thrombosis of the subclavian vein in a competitive swimmer. A recently developed technique of local infusion of low-dose streptokinase therapy is used for clot lysis. Early diagnosis is essential for effective thrombus dissolution with streptokinase. The rationale, risk, and method of streptokinase administration are discussed. Since "effort" thrombosis is secondary to thoracic outlet syndrome (TOS), decompression of the thoracic outlet by removal of the first rib after clot lysis is recommended.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway collapse during sleep resulting in impaired blood gas exchange, namely intermittent hypoxia (IH) and hypercapnia, fragmented sleep (SF), increased oxidative stress and systemic inflammation. Among a myriad of potential associated morbidities, OSA has been particularly implicated as mechanistically contributing to the prevalence and severity of cardiovascular diseases (CVD). However, the benefits of continuous positive airway pressure (CPAP), which is generally employed in OSA treatment, to either prevent or improve CVD outcomes remain unconvincing, suggesting that the pathophysiological mechanisms underlying the incremental CVD risk associated with OSA are not clearly understood. One of the challenges in development of non-invasive diagnostic assays is the ability to identify clinically and mechanistically relevant biomarkers. Circulating extracellular vesicles (EVs) and their cargos reflect underlying changes in cellular homeostasis and can provide insights into how cells and systems cope with physiological perturbations by virtue of the identity and abundance of miRNAs, mRNAs, proteins, and lipids that are packaged in the EVs under normal as well as diseased states, such as OSA. EVs can not only provide unique insights into coordinated cellular responses at the organ or systemic level, but can also serve as reporters of the effects of OSA in CVD, either by their properties enabling regeneration and repair of injured vascular cells or by damaging them. Here, we highlight recent progress in the pathological CVD consequences of OSA, and explore the putative roles of EVs in OSA-associated CVD, along with emerging diagnostic and therapeutic opportunities. The reviews of this paper are available via the supplemental material section.

Mowat-Wilson syndrome (MWS) is characterized by moderate to severe intellectual disability and distinctive facial features in association with variable structural congenital anomalies/clinical features including congenital heart disease, Hirschsprung disease, hypospadias, agenesis of the corpus callosum, short stature, epilepsy, and microcephaly. Less common clinical features include ocular anomalies, craniosynostosis, mild intellectual disability, and choanal atresia. These cases may be more difficult to diagnose. In this report, we add 28 MWS patients with molecular confirmation of ZEB2 mutation, including seven with an uncommon presenting feature. Among the "unusual" patients, two patients had clinical features of charge syndrome including choanal atresia, coloboma, cardiac defects, genitourinary anomaly (1/2), and severe intellectual disability; two patients had craniosynostosis; and three patients had mild intellectual disability. Sixteen patients have previously-unreported mutations in ZEB2. Genotype-phenotype correlations were suggested in those with mild intellectual disability (two had a novel missense mutation in ZEB2, one with novel splice site mutation). This report increases the number of reported patients with MWS with unusual features, and is the first report of MWS in children previously thought to have CHARGE syndrome. These patients highlight the importance of facial gestalt in the accurate identification of MWS when less common features are present.

BACKGROUND: The treatment of metastatic melanoma remains unsatisfactory despite encouraging results with biotherapy and combination chemotherapy. Combining these two modalities may improve outcomes for such patients. METHODS: Patients who were eligible for this study had metastatic melanoma and were in good medical condition. The following regimen was used: dacarbazine 220 mg/m2 and cisplatin 25 mg/m2 administered intravenously (i.v.) daily x 3 days every 3 weeks, carmustine 150 mg/m2 i.v. every 6 weeks, tamoxifen 10 mg administered orally twice a day, and interferon-alpha2b 3.0 thousandths of an International Unit (mIU)/m2 administered subcutaneously on Days 1, 3, and 5 of each week a patient was on study. Patients were analyzed for toxicity, tumor response, and survival. Because of severe toxicity, partway through the trial the regimen was modified as follows: dacarbazine and cisplatin were given at the same dose every 4 weeks, and carmustine was reduced to 100 mg/m2 every 8 weeks. RESULTS: Forty-two patients with a median age of 61 years were enrolled. Twenty had liver metastases and 18 had lung metastases. Forty patients were evaluable for toxicity, 17 at the original dose and 23 at the new dose; of these, 35 were evaluable for response. Hematologic toxicity was severe at the original dose: 10 patients had a nadir < 500/microL, 10 had platelets < 25,000/microL, and 2 discontinued treatment because of toxicity. At the reduced dose, 5 had a nadir absolute neutrophil count < 500, and 10 had platelets < 25,000. Of the 35 patients evaluable for response, there were 10 partial responses (29%) and 2 minimal responses. Median duration of disease control was 4 months. Median survival was 8.9 months. One partial and one minimal responder were removed from the study because they experienced toxicity while still responding. CONCLUSIONS: The addition of interferon-alpha to this chemohormonal therapy regimen greatly increased toxicity without improving the response rate or survival for patients with metastatic melanoma.

OBJECTIVES: The principal aim was to investigate the feasibility of assessing mother-infant interactions at discharge and at 6 months infant corrected age in singletons born before 32 weeks of gestation. The secondary aims were to describe these interactions and their disorders, explore the association between maternal emotional state and the interactions, and assess the relationship between disordered interactions and infant social withdrawal behaviour. METHODS: OLIMPE is an ancillary study of the population-based study EPIPAGE 2, which recruited preterm neonates in France in 2011. 163 dyads participated at discharge and 148 at 6 months. Interactions were observed with the Attachment During Stress (ADS) scale, which includes two behavioural subscales, for the mother (m-ADS) and her infant (i-ADS). Two professionals independently completed the ADS scales for one third of the observations. Maternal emotional state was assessed using self-administered questionnaires of depression, anxiety, and stress. Infant's social withdrawal behaviour at 6 months was measured by the Alarm Distress Baby scale. RESULTS: At discharge, 15.3% of the m-ADS scales and 43.3% of the i-ADS scales had at least one unobserved component. At 6 months, all items on both scales were noticeable in >90% of the dyads. Reliability, estimated by the kappa coefficient, ranged between 0.39 and 0.76 at discharge, and between 0.21 and 0.69 at 6 months. Disordered interactions were indicated on 48.6% of the m-ADS scales and 36.5% of the i-ADS scales at discharge. At 6 months, these rates were 32.6% and 26.0%. Disordered interactions at 6 months were associated with identified disorder at discharge. Insecure infant attachment was not influenced by maternal mental health but was strongly associated with infant social withdrawal behaviour. CONCLUSIONS: The ADS scale can be used to screen for early interaction disorders after premature birth and may help to target dyads that would most benefit from early intervention.

OBJECTIVE: To determine the efficacy of transcutaneous carbon dioxide tension measurement during high-risk neonatal transport. STUDY DESIGN: This was a prospective, randomized comparative study. Infants transported from hospitals more than 30 miles away from our center and who required respiratory intervention were enrolled. Alternating transports used a transcutaneous CO2/O2 monitor. Ventilation parameters and end transport blood gas values served as primary endpoints for the study. RESULTS: Infants with transcutaneous carbon dioxide tension monitoring were more likely to have decreased ventilator peak pressures during transport than neonates not monitored (-1.5 cm H2O vs + 0.6 cm H2O; p = 0.04). Monitored neonates were more likely to arrive at the tertiary center with a more normal pH and a CO2 tension between 35 and 45 mm Hg (4.7 to 6.0 kPa) than nonmonitored infants (p = 0.03 and p = 0.01, respectively). The stabilization times before transport were not significantly prolonged by the use of the transcutaneous monitor. CONCLUSIONS: Transcutaneous monitoring of CO2 tension improves short-term respiratory outcome in neonates receiving mechanical ventilation during transport.

Adult Wilms' tumor is a rare and aggressive malignancy. Despite multimodality therapy for all stages of disease, the majority of patients develop fatal metastases. Little information is available on effective salvage therapy. The current report describes a 38-year-old man who had Stage I disease. Pulmonary metastases developed after radical nephrectomy and tumor bed irradiation while receiving adjuvant chemotherapy. He achieved a complete remission lasting 8 months with a combination chemotherapy regimen of cyclophosphamide, vinblastine, dactinomycin, and cisplatin. After isolated pulmonary relapse, he received whole-lung irradiation and remained disease-free 4.5 years after diagnosis. The previously reported results of therapy in metastatic or unresectable adult Wilms' tumor are reviewed, and the current case of effective salvage therapy is documented.