Profiles of autism characteristics in thirteen genetic syndromes: a machine learning approach.

BACKGROUND: Phenotypic studies have identified distinct patterns of autistic characteristics in genetic syndromes associated with intellectual disability (ID), leading to diagnostic uncertainty and compromised access to autism-related support. Previous research has tended to include small samples and diverse measures, which limits the generalisability of findings. In this study, we generated detailed profiles of autistic characteristics in a large sample of > 1500 individuals with rare genetic syndromes. METHODS: Profiles of autistic characteristics based on the Social Communication Questionnaire (SCQ) scores were generated for thirteen genetic syndrome groups (Angelman n = 154, Cri du Chat n = 75, Cornelia de Lange n = 199, fragile X n = 297, Prader-Willi n = 278, Lowe n = 89, Smith-Magenis n = 54, Down n = 135, Sotos n = 40, Rubinstein-Taybi n = 102, 1p36 deletion n = 41, tuberous sclerosis complex n = 83 and Phelan-McDermid n = 35 syndromes). It was hypothesised that each syndrome group would evidence a degree of specificity in autistic characteristics. To test this hypothesis, a classification algorithm via support vector machine (SVM) learning was applied to scores from over 1500 individuals diagnosed with one of the thirteen genetic syndromes and autistic individuals who did not have a known genetic syndrome (ASD; n = 254). Self-help skills were included as an additional predictor. RESULTS: Genetic syndromes were associated with different but overlapping autism-related profiles, indicated by the substantial accuracy of the entire, multiclass SVM model (55% correctly classified individuals). Syndrome groups such as Angelman, fragile X, Prader-Willi, Rubinstein-Taybi and Cornelia de Lange showed greater phenotypic specificity than groups such as Cri du Chat, Lowe, Smith-Magenis, tuberous sclerosis complex, Sotos and Phelan-McDermid. The inclusion of the ASD reference group and self-help skills did not change the model accuracy. LIMITATIONS: The key limitations of our study include a cross-sectional design, reliance on a screening tool which focuses primarily on social communication skills and imbalanced sample size across syndrome groups. CONCLUSIONS: These findings replicate and extend previous work, demonstrating syndrome-specific profiles of autistic characteristics in people with genetic syndromes compared to autistic individuals without a genetic syndrome. This work calls for greater precision of assessment of autistic characteristics in individuals with genetic syndromes associated with ID.

Mucosal Integrity Testing Can Detect Differences in the Rectums of Patients with Inflammatory Bowel Disease Compared to Controls: A Pilot Study.

BACKGROUND: While the pathogenesis of inflammatory bowel disease (IBD) is incompletely understood, disruption of epithelial integrity is suspected to play a prominent role in disease initiation and progression. Currently, there is no convenient way to measure this in vivo. AIMS: Our aim is to determine whether a mucosal integrity (MI) testing device that has been used to measure MI in the esophagus can also be used to measure barrier function in the colon during colonoscopy. METHODS: Mucosal integrity testing was measured in patients with IBD (n = 17) and controls (n = 7) during colonoscopy. During the procedure, an MI catheter was passed down the working channel of the colonoscope and placed along the mucosal wall to measure MI in the rectum, left, transverse, and right colon. In patients with IBD, MI measurements and biopsies were taken in areas which appeared inflamed when present. We then determined if there was a significant difference in MI between patients with IBD and controls. RESULTS: MI was significantly higher in the rectum of patients with IBD (CD and UC combined) versus control colons [767 (618-991) vs. 531 (418-604) ohms, P < 0.01]. There were no significant differences in MI among patients with IBD versus controls in the right, transverse, or left colon. Within the IBD group, there were no significant differences in MI between inflamed versus non-inflamed rectums. There was no correlation between quality of life scores or endoscopic severity with MI, though this study was likely underpowered to detect these differences. CONCLUSION: Rectal MI is significantly higher in patients with IBD versus controls. Future studies are needed to determine how this information can be used clinically.

High-dose vitamin C therapy for symptomatic deficiency in a patient with myasthenia gravis and Crohn's disease.

Vitamin C (ascorbic acid) is an essential water-soluble antioxidant, and deficiency (ie, plasma level <11 µmol/L) can result in scurvy. People at the highest risk for vitamin C deficiency (ie, scurvy) are those with inadequate intake, such as patients with alcohol abuse disorder, malnutrition, psychiatric disorders, restrictive eating habits, and food insecurity, as well as those with malabsorptive syndromes. We present a case of a 26-year-old woman with Crohn's colitis, myasthenia gravis, and juvenile rheumatoid arthritis who presented with frequent bruising, epistaxis, and excessive bleeding from small cuts and who was found to be deficient in vitamin C. Plasma levels initially normalized with oral vitamin C supplementation, but bleeding symptoms eventually returned despite high-dose oral supplementation with 2000 mg daily. She ultimately required routine intravenous supplementation in the home setting for the normalization of levels and the resolution of symptoms. Case reports of vitamin C deficiency typically involve patients with an inadequate intake of vitamin C-containing foods or inadequate absorption. In contrast, our patient reported a regular intake of vitamin C-containing foods, in addition to oral supplementation, but continued to have difficulty maintaining normal vitamin C levels. Scurvy should be considered for any patient with symptoms of bleeding, petechiae, or ecchymosis and, although it can typically be treated with oral vitamin C, intravenous repletion may be necessary in some cases.

Precision nicotine metabolism-informed care for smoking cessation in Crohn's disease: A pilot study.

INTRODUCTION: Smoking is a strong risk factor for disease severity in Crohn's disease (CD) and cessation improves outcomes. The nicotine metabolite ratio (NMR) predicts cessation success with pharmacotherapy: varenicline doubles cessation over nicotine replacement therapy (NRT) for "normal", but not "slow" metabolizers. Varenicline side effects are heightened in slow metabolizers. Methods using NMR to optimize cessation pharmacotherapy have not been evaluated in CD. AIMS: We aim to determine the prevalence of smoking in a CD population and then assess these smokers' attitudes toward a personalized metabolism-informed care (MIC) approach to cessation. METHODS: In this observational study, we surveyed 1098 patients visiting an inflammatory bowel disease center about their smoking history. We then evaluated a subgroup of individuals with CD (n = 32) who participated in a randomized controlled trial of smoking cessation using MIC versus usual care. For MIC, medication selection was informed by the NMR (normal ≥0.31 vs. slow <0.31). The primary outcomes were intervention satisfaction and match rates between NMR and medication choice. RESULTS: The baseline prevalence of smoking in our CD population was 13%. Intervention participants reported high rates of satisfaction (85%) and chose a medication that matched their NMR result more often in the MIC group (100% vs. 64%, p = 0.01). Six of 16 (37.5%) patients prescribed varenicline discontinued due to side effects. CONCLUSION: MIC produced high rates of satisfaction and matching between NMR and medication in CD patients, supporting patient acceptance and feasibility of precision smoking cessation in this population. To reduce smoking in CD, therapies such as MIC are needed to maximize efficacy and minimize side effects.

Serum Polyunsaturated Fatty Acids Correlate with Serum Cytokines and Clinical Disease Activity in Crohn's Disease.

Crohn's disease (CD) has been associated with an increased consumption of n-6 polyunsaturated fatty acid (PUFA), while greater intake of n-3 PUFA has been associated with a reduced risk. We sought to investigate serum fatty acid composition in CD, and associations of fatty acids with disease activity, cytokines, and adipokines. Serum was prospectively collected from 116 CD subjects and 27 non-IBD controls. Clinical disease activity was assessed by the Harvey Bradshaw Index (HBI). Serum fatty acids were measured by gas chromatography. Serum cytokines and adipokines were measured by Luminex assay. Dietary histories were obtained from a subset of patients. Nine serum cytokines and adipokines were increased in CD versus controls. CD subjects had increased percentage serum monounsaturated fatty acids (MUFA), dihomo-gamma linolenic acid (DGLA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and oleic acid, but decreased arachidonic acid (AA) versus controls. The % total n-3 fatty acids and % EPA directly correlated with pro-inflammatory cytokine levels and HBI, whereas the % total n-6 fatty acids were inversely correlated with pro-inflammatory cytokine levels and HBI. CD subjects had increased caloric intake versus controls, but no alterations in total fat or PUFA intake. We found differences in serum fatty acids, most notably PUFA, in CD that correlated both with clinical disease activity and inflammatory cytokines. Our findings indicate that altered fatty acid metabolism or utilization is present in CD and is related to disease activity.

Sarcopenia Is Common in Overweight Patients with Inflammatory Bowel Disease and May Predict Need for Surgery.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with altered body composition, such as low muscle mass, which affects clinical outcomes. Body composition changes in overweight patients with IBD are less understood. The study aim was to determine the prevalence of sarcopenic overweight and obese patients in a cohort of patients with IBD starting new anti-tumor necrosis factor-α therapy and examine differences in response. METHODS: This is a retrospective review of patients with IBD starting a new anti-tumor necrosis factor-α medication that had computed tomography within 3 months of initiation. L3 vertebral slice was used for segmentation of body composition and identification of sarcopenia. CRP, ESR, Harvey Bradshaw Index, albumin, 25-OH vitamin D, and body mass index at anti-tumor necrosis factor-α initiation and at 6 months were collected. Outcomes included hospitalization, need for surgery, or new biological medication. RESULTS: Ninety patients were studied. Forty-one of ninety (45%) were sarcopenic; of these, 17 (41.5%) had a normal body mass index and 8 (19.5%) were overweight/obese. More men were sarcopenic (68% versus 32%, P < 0.001). CRP was higher and albumin lower in sarcopenic subjects. Sarcopenia did not predict outcomes in the cohort but was the only significant predictor of need for surgery in overweight and obese subjects (P = 0.002). CONCLUSIONS: Almost half of our cohort was sarcopenic. Most of these patients are normal or overweight and would not be identified as malnourished by traditional measures. Sarcopenia was a predictor of surgery in patients with a body mass index ≥ 25. Identification of sarcopenia has implications for medical nutrition therapy as typically efforts are focused on underweight patients.

A silver-impregnated antimicrobial dressing reduces hospital costs for pediatric burn patients.

PURPOSE: Since using a novel silver-impregnated antimicrobial dressing (Aquacel Ag, ConvaTec, Princeton, NJ) in our pediatric patients with partial-thickness burns, hospital LOS has been significantly reduced. Here we investigated whether there was concomitant cost-effectiveness of this approach. METHODS: We retrospectively reviewed Burn Registry Data from a large Children's Hospital Burn Unit from January 2005 through August 2005 for inpatients with partial-thickness burns treated with Aquacel Ag. A comparison group was composed of patients from the same period the previous year treated with silver sulfadiazine cream (SSD, Par Pharmaceuticals, Woodcliff, NJ) and matched for age and %TBSA burned. Patients with inhalation injury or full-thickness burns were excluded. Intent-to-treat analysis was limited to patients with less than 22% TBSA burn. Direct costs and total charges were compared statistically after log transformation due to the skewedness of the data. RESULTS: Total charges and direct costs were significantly lower for Aquacel Ag-treated patients (n = 38) than for SSD-treated patients (n = 39) (P = .004 and P < .001, respectively). In addition, Aquacel Ag-treated patients had a shorter LOS than SSD-treated patients. DISCUSSION: These data strongly support our findings that the application of Aquacel Ag reduces hospital LOS which results in a significant cost savings in the care of pediatric patients with partial-thickness burns.

Effective surgical treatment of cubital tunnel syndrome based on provocative clinical testing without electrodiagnostics.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe a method of clinical evaluation for accurate diagnosis of ulnar compression syndrome at the elbow. 2. Evaluate the accuracy and efficacy of the described method in diagnosing surgically correctable nerve entrapment. 3. Present a protocol for conservative management followed by surgical correction. 4. Discuss the results of the method and protocol in two series of patients treated by a single surgeon. BACKGROUND: This study of two patient populations addresses the effectiveness of identifying surgically correctable ulnar nerve compression at the elbow based on provocative clinical testing alone in patients with cubital tunnel syndrome after failure of conservative treatment. METHODS: Twenty-four patients were included in the preliminary study (mean age, 60 years). Three of these patients underwent bilateral procedures. Patients complaining of symptoms in the distribution of the ulnar nerve were tested by elicitation of Tinel's sign and combined flexion and pressure testing at the elbow and wrist. Two-point discrimination was determined. After a failed 6-week trial of conservative therapy, patients underwent anterior submuscular transposition of the ulnar nerve with carpal tunnel release. RESULTS: Postoperatively, the change in two-point discrimination as measured at 6 months was significantly improved, with a mean improvement per digital nerve of 2.52 mm (p < 0.001). Mean time to relief was 7.2 weeks. Complications included one hematoma and one seroma. A total of 26 of the 27 limbs chosen for surgical treatment by provocative clinical testing alone experienced relief of symptoms with anterior submuscular transposition of the ulnar nerve and carpal tunnel release. CONCLUSIONS: This study demonstrates the effectiveness of surgical therapy in patients with lesions identified by clinical examination without electrodiagnostic testing. After the completion of this study, an additional 87 patients were treated (18 bilateral) with cubital tunnel release. The data from these patients confirm the effectiveness of surgical treatment of ulnar entrapment neuropathy based on provocative clinical testing.

QTL analysis of fruit antioxidants in tomato using Lycopersicon pennellii introgression lines.

Antioxidants present in fruits and vegetables may help prevent some chronic diseases such as cancer, arthritis, and heart disease. Tomatoes provide a major contribution to human dietary nutrition because of their widespread consumption in fresh and processed forms. A tomato introgression line population that combines single chromosomal segments introgressed from the wild, green fruited species Lycopersicon pennellii in the background of the domesticated tomato, Lycopersicon esculentum, was used to identify quantitative trait loci (QTL) for nutritional and antioxidant contents. The concentration of ascorbic acid, total phenolics, lycopene and beta-carotene, and the total antioxidant capacity of the water-soluble fraction (TACW) were measured in the ripe fruits. A total of 20 QTL were identified, including five for TACW (ao), six for ascorbic acid (aa), and nine for total phenolics (phe). Some of these QTL (ao6-2, ao6-3, ao7-2, ao10-1, aa12-4, phe6-2, and phe7-4) increased levels as compared to the parental line L. esculentum. For lycopene content, we detected four QTL, but none increased levels relative to L. esculentum. The two QTL (bc6-2 and bc6-3) detected for beta-carotene increased its levels. The traits studied displayed a strong environmental interaction as only 35% of the water-soluble antioxidant QTL (including TACW, ascorbic, and phenolic contents) were consistent over at least two seasons. Also, only two QTL for phenolics were observed when plants were grown in the greenhouse and none was detected for ascorbic or TACW. The analysis demonstrates that the introgression of wild germplasm may improve the nutritional quality of tomatoes; however regulation appears to be complex with strong environmental effects.

Quality of life for patients following total laryngectomy vs chemoradiation for laryngeal preservation.

BACKGROUND: The incorporation of chemotherapy and radiation, either sequentially or concurrently, has been increasingly used for organ preservation in patients with advanced laryngeal cancer. Traditional outcome measures of clinical response such as locoregional control and survival have been similar for patients treated with chemoradiotherapy and those treated with total laryngectomy (TL). The impact of concurrent chemoradiotherapy for laryngeal preservation on the overall quality of life (QOL) of patients has not been clearly evaluated, particularly in direct comparison with TL. OBJECTIVE: To compare the QOL of patients treated with concurrent chemoradiotherapy with those treated with TL. DESIGN: Nonrandomized, retrospective, cross-sectional study. SETTING: Academic tertiary care referral center. METHODS: The study included 42 patients with advanced stage III or IV cancer of the larynx, who were treated with either concurrent chemoradiotherapy or TL with postoperative radiation therapy. Patients had to be without evidence of recurrence and to have completed therapy at least 3 months prior to inclusion in the study. Quality of life was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) in tandem with the head and neck module (EORTC QLQ-H&N35). RESULTS: On the core questionnaire (QLQ-C30), there were no statistically significant differences in the overall QOL score between the 2 groups. Functional subscale analysis revealed a trend for patients in the surgery and radiotherapy group to experience greater difficulties with social functioning (P =.18) relative to the chemoradiation group. On the QLQ-H&N35, surgery patients reported significantly greater difficulties with sensory disturbances (smell and taste, P =.001), use of painkillers (P =.049), and coughing (P =.004). On the other hand, chemoradiation patients reported significantly greater problems with dry mouth (P =.02). CONCLUSIONS: Both chemoradiation and TL affect, albeit differently, the QOL of patients treated for advanced cancer of the larynx. Although these differences can be detected by functional and subscale analysis, the overall QOL scores of both groups seem similar.