Associations between patient-reported late effects and systemic cytokines in long-term survivors of head and neck cancer treated with radiotherapy.

PURPOSE: Head and neck cancer (HNC) treatment may lead to late effects and impaired health-related quality of life of survivors. Knowledge on long-term late effects after radiotherapy (RT) and potential underlying biological mechanisms is lacking. We assessed the prevalence of xerostomia, dysphagia, and chronic fatigue (CF) in HNC survivors ≥ 5 years post-RT, and examined associations between pro-inflammatory cytokines and late effects. METHODS: In a cross-sectional study, 263 HNC survivors treated between 2007 and 2013 were enrolled. They completed validated questionnaires assessing xerostomia and dysphagia (the EORTC QLQ-H&N35), and CF (the Fatigue Questionnaire), and underwent blood sampling and clinical examination. Pro-inflammatory cytokines were analyzed in 262 survivors and 100 healthy age- and gender-matched controls. RESULTS: Median time since treatment was 8.5 years. The proportions of survivors reporting xerostomia, dysphagia, and CF were 58%, 31%, and 33%, respectively, with a preponderance of females. We found no significant associations between IL-6, IL-8, IP-10, TARC, TNF, or ENA-78 and the three late effects. The odds of having elevated levels of IL-6 and IP-10 were significantly higher in the survivors compared to the controls. CONCLUSIONS: More than one-third of long-term HNC survivors experienced xerostomia, dysphagia, and CF. Persistent inflammation, with elevated systemic cytokines, was not associated with these late effects, although HNC survivors had higher levels of some cytokines than the controls. IMPLICATIONS FOR CANCER SURVIVORS: This study provides new knowledge on late effects that can serve as grounds for informing patients with HNC about risk of late effects more than 5 years after RT.

Assessment of clinical factors affecting outcome of myasthenia gravis.

INTRODUCTION/AIMS: In myasthenia gravis (MG) therapy, achieving Myasthenia Gravis Foundation of America minimal manifestation (MM) or better status is proposed as a desirable target. However, this level of control is often not achieved and clinical factors affecting prognosis remain unclear. METHODS: Participants were 104 consecutive patients with MG who visited Osaka Medical College Hospital. We retrospectively assessed the association of clinical and laboratory features at baseline with prognosis. Eighty patients who achieved MM or better status were classified as the good outcome group and the remaining 24 patients were classified as the poor outcome group. RESULTS: The rate of dysphagia at baseline was significantly higher in the poor outcome group than in the good outcome group (P = .002). The levels of serum total protein and albumin at baseline were both significantly lower in the poor outcome group than in the good outcome group (P = .036 and P = .014, respectively). In addition, Controlling Nutritional Status scores at baseline were significantly higher in the poor outcome group than in the good outcome group (P = .043). Multivariate analysis using a Cox proportional hazards model showed that dysphagia (hazard ratio [HR], 6.92; 95% confidence interval [CI], 1.49-40.31) and hypoalbuminemia (HR, 2.57; 95% CI, 1.04-6.57) at baseline were risk factors that predicted prognosis. DISCUSSION: These findings suggest that dysphagia and hypoalbuminemia at baseline are associated with outcomes and are predictive risk factors for poorer outcomes in patients with MG.

Biochemical parameters in determination of nutritional status in amyotrophic lateral sclerosis.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder without effective treatment. Progressive dysphagia, depression, and hypermetabolism may lead to malnutrition. The aim of the present study was to analyze the potential utility of readily available, relatively inexpensive, and rapid strategy for using laboratory parameters to assess nutritional status of ALS patients. METHODS: This study included 203 patients with ALS. The analysis of inflammatory parameters: C Reactive Protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), lymphocytes number (LN), and fibrinogen concentration (FC) was followed by nutritional markers: serum concentration of albumin (ALB), prealbumin (PALB), transferrin (TRNF), and creatinine (CREA), which were correlated with demographic and clinical parameters: body mass index (BMI), ALS phenotype, disease duration, diagnosis delay, and functional and respiratory assessment. RESULTS: Nearly 20% of patients had biochemical features of inflammation. Among patients without inflammation (n = 163), a decreased serum TRNF concentration was found in 84% of cases, PALB in 39%, ALB in 25%, and CREA in 53%. The median of PALB was the highest in patients with PMA (23.5 mg/dL) and the lowest in PBP (16.6 mg/dL) (p < 0.05). The CREA concentration correlated with the BMI (r = 0.25; p < 0.01), while PALB and TRNF significantly varied depending on the severity of dysphagia. Patients with dysphagia qualified to enteral nutrition showed significantly decreased concentration of PALB, triglycerides, as well as reduced forced vital capacity, BMI, and functional status. CONCLUSIONS: CREA, PALB, ALB, and TNFR are easily accessible, accurate, and low-cost parameters useful in assessment of the nutritional status in ALS.

Effects of Fluoxetine on Poststroke Dysphagia: A Clinical Retrospective Study.

BACKGROUND: To investigate whether fluoxetine improves poststroke dysphagia and to detect the potential relationship between serum brain-derived neurotrophic factor (BDNF) levels and fluoxetine effects. METHODS: In this retrospective study, 159 stroke patients who met our study criteria were included. In total, 110 patients were placed in the control group, and 49 patients were placed in the fluoxetine group. Demographic and clinical characteristics of the patients were collected for the baseline assessment. Functional independence measure scores and American speech-language-hearing association/functional communication measures scores for swallowing were collected to evaluate the patients' swallowing function. Patients' serums were collected at weeks 1 and 3 after admission, and serum BDNF levels were measured by enzyme-linked immunosorbent assay. T test, chi-squared test, and general linear model analysis were performed to determine the differences between the two groups. RESULTS: A significantly higher improvement of swallowing function was observed in the fluoxetine group compared with that of the control group (P = .023). In addition, a general linear model analysis showed that the treatment of fluoxetine has a statistically significant effect on swallowing improvement after adjustment of swallowing score on admission, stroke types, and interval between the onset of stroke and admission (P = .022, R2 = .46, adjusted R2 = .446). There is no significant difference in the change of serum BDNF levels in the two groups (P = .269). CONCLUSIONS: This study suggests that treatment with fluoxetine in stroke patients with dysphagia may improve swallowing function. A placebo-controlled, randomized clinical trial is warranted to confirm this finding.

SERUM ELECTROLYTES AND OUTCOME IN PATIENTS UNDERGOING ENDOSCOPIC GASTROSTOMY.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a gold standard for long term enteral feeding. Neurologic dysphagia and head/neck cancer are the most common indications for PEG as they can lead to protein-energy malnutrition and serum electrolyte abnormalities, with potential negative impact on metabolic balance. Refeeding syndrome may also be related with severe electrolyte changes in PEG-fed patients and contribute to poor prognosis. OBJECTIVE: This study aims to evaluate the changes in serum concentrations of the main electrolytes and its possible association with the outcome. METHODS: Retrospective study of patients followed in our Artificial Nutrition Clinic, submitted to PEG from 2010 to 2016, having head/neck cancer or neurologic dysphagia, who died under PEG feeding. Serum electrolytes (sodium, potassium, chlorine, magnesium, calcium and phosphorus) were evaluated immediately before the gastrostomy procedure. Survival after PEG until death was recorded in months. RESULTS: We evaluated 101 patients, 59 with electrolyte alterations at the moment of the gastrostomy. Sodium was altered in 32 (31.7%), magnesium in 21 (20.8%), chlorine in 21 (20.8%), potassium in 14 (13.8%), calcium in 11 (10.9 %) and phosphorus in 11 (10.9%). The survival of patients with low sodium (<135 mmol/L) was significantly lower when compared to patients with normal/high values, 2.76 months vs 7.80 months, respectively (P=0.007). CONCLUSION: Changes in serum electrolytes of patients undergoing PEG were very common. More than half showed at least one abnormality, at the time of the procedure. The most frequent was hyponatremia, which was associated with significantly shorter survival, probably reflecting severe systemic metabolic distress.

Eletrólitos séricos e prognóstico em doentes submetidos a gastrostomia endoscópica / Serum electrolytes and outcome in patients undergoing endoscopic gastrostomy

ABSTRACT BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a gold standard for long term enteral feeding. Neurologic dysphagia and head/neck cancer are the most common indications for PEG as they can lead to protein-energy malnutrition and serum electrolyte abnormalities, with potential negative impact on metabolic balance. Refeeding syndrome may also be related with severe electrolyte changes in PEG-fed patients and contribute to poor prognosis. OBJECTIVE: This study aims to evaluate the changes in serum concentrations of the main electrolytes and its possible association with the outcome. METHODS: Retrospective study of patients followed in our Artificial Nutrition Clinic, submitted to PEG from 2010 to 2016, having head/neck cancer or neurologic dysphagia, who died under PEG feeding. Serum electrolytes (sodium, potassium, chlorine, magnesium, calcium and phosphorus) were evaluated immediately before the gastrostomy procedure. Survival after PEG until death was recorded in months. RESULTS: We evaluated 101 patients, 59 with electrolyte alterations at the moment of the gastrostomy. Sodium was altered in 32 (31.7%), magnesium in 21 (20.8%), chlorine in 21 (20.8%), potassium in 14 (13.8%), calcium in 11 (10.9 %) and phosphorus in 11 (10.9%). The survival of patients with low sodium (<135 mmol/L) was significantly lower when compared to patients with normal/high values, 2.76 months vs 7.80 months, respectively (P=0.007). CONCLUSION: Changes in serum electrolytes of patients undergoing PEG were very common. More than half showed at least one abnormality, at the time of the procedure. The most frequent was hyponatremia, which was associated with significantly shorter survival, probably reflecting severe systemic metabolic distress.

RESUMO CONTEXTO: A gastrostomia endoscópica percutânea (PEG) é a via de eleição preferencial para a nutrição entérica de longa duração. A disfagia neurológica e as neoplasias cervico-faciais constituem as principais indicações para PEG por poderem conduzir a desnutrição energético-proteica e alterações hidroeletrolíticas, com potencial impacto negativo no equilíbrio metabólico. A síndrome de realimentação pode também estar associada a alterações hidroeletrolíticas graves em doentes alimentados por PEG e contribuir para um mau prognóstico. OBJETIVO: Avaliar as alterações das concentrações séricas dos principais eletrólitos e a eventual associação entre os valores séricos alterados e o prognóstico dos doentes gastrostomizados. Métodos - Estudo retrospetivo realizado em doentes seguidos na Consulta de Nutrição Artificial do Hospital Garcia de Orta, propostos e submetidos a PEG, de 2010 a 2016 e que faleceram sob nutrição por PEG. Consideraram-se os valores séricos dos iões em estudo avaliados imediatamente antes do procedimento endoscópico de gastrostomia, obtidos por consulta do processo clínico. A sobrevida, após a realização da PEG até à morte foi registrada em meses. RESULTADOS: Avaliaram-se 101 doentes. A sobrevida média pós-gastrostomia foi 6,55 meses. Destes, 59 apresentaram alterações de alguns iões no momento da realização da PEG. O sódio estava alterado em 31 (30,6%), magnésio em 20 (19,8%), cloro em 19 (18,8%), potássio em 14 (13,8%), cálcio em 10 (9,9%) e o fósforo em 9 (8,9%). Quando comparada a sobrevida dos doentes com valores de sódio baixo (<135 mmol/L) com a dos doentes com valores normais/elevados, esta foi 2,76 meses vs 7,80 meses, respectivamente (P=0,007). CONCLUSÃO: As alterações dos eletrólitos séricos nos doentes submetidos a PEG foram muito frequentes, com mais de metade dos doentes a apresentarem pelo menos uma alteração aquando da realização do procedimento. A alteração mais frequente foi a hiponatrémia, associando-se a pior prognóstico com sobrevida significativamente mais curta, refletindo provavelmente um grave compromisso metabólico sistêmico.

Therapeutic efficacy of neuromuscular electrical stimulation and electromyographic biofeedback on Alzheimer's disease patients with dysphagia.

To study the therapeutic effect of neuromuscular electrical stimulation and electromyographic biofeedback (EMG-biofeedback) therapy in improving swallowing function of Alzheimer's disease patients with dysphagia.A series of 103 Alzheimer's disease patients with dysphagia were divided into 2 groups, among which the control group (n = 50) received swallowing function training and the treatment group (n = 53) received neuromuscular electrical stimulation plus EMG-biofeedback therapy. The mini-mental state scale score was performed in all patients along the treatment period. Twelve weeks after the treatment, the swallowing function was assessed by the water swallow test. The nutritional status was evaluated by Mini Nutritional Assessment (MNA) as well as the levels of hemoglobin and serum albumin. The frequency and course of aspiration pneumonia were also recorded.No significant difference on mini-mental state scale score was noted between 2 groups. More improvement of swallowing function, better nutritional status, and less frequency and shorter course of aspiration pneumonia were presented in treatment group when compared with the control group.Neuromuscular electrical stimulation and EMG-biofeedback treatment can improve swallowing function in patients with Alzheimer's disease and significantly reduce the incidence of adverse outcomes. Thus, they should be promoted in clinical practice.

Measurement of Oxygen Desaturation Is Not Useful for the Detection of Aspiration in Dysphagic Stroke Patients.

BACKGROUND: Dysphagia is one of the most dangerous symptoms of acute stroke. Various screening tools have been suggested for the early detection of this condition. In spite of conflicting results, measurement of oxygen saturation (SpO2) during clinical swallowing assessment is still recommended by different national guidelines as a screening tool with a decline in SpO2 ≥2% usually being regarded as a marker of aspiration. This paper assesses the sensitivity of SpO2 measurements for the evaluation of aspiration risk in acute stroke patients. METHODS: Fifty acute stroke patients with moderate to severe dysphagia were included in this study. In all patients, fiberoptic endoscopic evaluation of swallowing (FEES) was performed according to a standardised protocol. Blinded to the results of FEES, SpO2 was monitored simultaneously. The degree of desaturation during/after swallows with aspiration was compared to the degree of desaturation during/after swallows without aspiration in a swallow-to-swallow analysis of each patient. To minimise potential confounders, every patient served as their control. RESULTS: In each subject, a swallow with and a swallow without aspiration were analysed. Overall, aspiration seen in FEES was related to a minor decline in SpO2 (mean SpO2 without aspiration 95.54 ± 2.7% vs. mean SpO2 with aspiration 95.28 ± 2.7%). However, a significant desaturation ≥2% occurred only in 5 patients during/after aspiration. There was no correlation between aspiration/dysphagia severity or the amount of aspirated material and SpO2 levels. CONCLUSIONS: According to this study, measurement of oxygen desaturation is not a suitable screening tool for the detection of aspiration in stroke patients.

Serum zinc evolution in dysphagic patients that underwent endoscopic gastrostomy for long term enteral feeding.

BACKGROUND AND OBJECTIVES: Patients undergoing endoscopic gastrostomy (PEG) present with protein-energy malnutrition (PEM) but little is known about zinc status. Our aim was to evaluate serum zinc, its relationship with serum proteins and with the nature of the underlying disorder, during the first 3 months of PEG feeding. METHODS AND STUDY DESIGN: Prospective observational study during a 3-month period after gastrostomy. Data was collected at initial PEG procedure (T0), after 4 (T1) and 12 weeks (T3). Initial evaluation included: age, gender, disorder causing dysphagia, Neurological Dysphagia (ND) or Head and Neck Cancer (HNC), NRS-2002, BMI, albumin, transferrin, zinc. At T1 and T3, a blood sample was collected for zinc, albumin, transferrin. Serum zinc evaluation was performed with ICP-AES - Inductively Coupled Plasma-Atomic Emission Spectroscopy. Patients were fed with homemade meals. RESULTS: A total of 146 patients (89 males), 21-95 years were studied: HNC-56, ND-90 and low BMI in 78. Initial low zinc in 122; low albumin in 77, low transferrin in 94; low values for both proteins in 66. Regarding the serum protein evolution, their levels increase T0-T3, most patients reaching normal values. zinc has a slower evolution, most patients still displaying low zinc at T3. Significant differences between the 3 moments for zinc (p=0.011), albumin (p<0.0001) and transferrin (p=0.014). CONCLUSION: PEG patients are prone to PEM and zinc deficiency. Most patients present decreased zinc, suggesting that zinc deficiency is common in PEG candidates and is not corrected during 3 months of enteral feeding. Zinc deficiency should be expected and teams taking care of PEG patients should use zinc supplementation.

Detailed Histologic Evaluation of Eosinophilic Esophagitis in Pediatric Patients Presenting with Dysphagia or Abdominal Pain and Comparison of the Histology between the Two Groups.

EoE in children presents with four main symptoms. Most common symptoms exhibited by our clinic population are dysphagia (D) and abdominal pain (AP). Despite similar treatments, we found in an earlier study that the outcomes between these two groups were different. Therefore, we investigated if there exist any histological differences between these groups that could further our knowledge of EoE. Aim. To compare esophageal histology in detail, apart from the eosinophil count, between EoE-D and EoE-AP. Method. Biopsies of patients with EoE-D and EoE-AP were reevaluated for 10 additional histological criteria, in addition to the eosinophil count. Results. Both groups had 67 patients; peak mean eosinophil was 33.9 and 31.55 for EoE-D and EoE-AP (p < 0.05). Eosinophilic microabscesses, superficial layering of eosinophils, and epithelial desquamation were twice as common and significant in EoE-D group than EoE-AP. Eosinophil distribution around rete pegs was also significantly higher in EoE-D group. The remaining criteria were numerically higher in EoE-D, but not significant, with the exception of rete peg elongation. Conclusion. EoE-D patients have significantly higher eosinophils compared to EoE-AP, and the level of inflammation as seen from eosinophil microabscesses, superficial layering, desquamation, and the distribution around rete pegs is significantly higher.

Eosinophilic Esophagitis in Children and Adolescents with Abdominal Pain: Comparison with EoE-Dysphagia and Functional Abdominal Pain.

Aim. Compare EoE-AP with EoE-D for clinical, endoscopy (EGD), histology and outcomes and also with FAP-N. Method. Symptoms, physical findings, EGD, histology, symptom scores, and treatments were recorded for the three groups. Cluster analysis was done. Results. Dysphagia and abdominal pain were different in numbers but not statistically significant between EoE-AP and EoE-D. EGD, linear furrows, white exudates were more in the EoE-D and both combined were significant (p < 0.05). EoE-D, peak and mean eosinophils (p 0.06) and eosinophilic micro abscesses (p 0.001) were higher. Follow-Up. Based on single symptom, EoE-AP had 30% (p 0.25) improvement, EoE-D 86% (p < 0.001) and similar with composite score (p 0.57 and <0.001, resp.). Patients who had follow-up, EGD: 42.8% with EoE-AP and 77.8% with EoE-D, showed single symptom improvement and the eosinophil count fell from 38.5/34.6 (peak and mean) to 31.2/30.4 (p 0.70) and from 43.6/40.8 to 25.2/22.8 (p < 0.001), respectively. FAP-N patients had similar symptom improvement like EoE-D. Cluster Analysis. EoE-AP and FAP-N were similar in clinical features and response to treatment, but EoE-D was distinctly different from EoE-AP and FAP-N. Conclusion. Our study demonstrates that EoE-AP and EoE-D have different histology and outcomes. In addition, EoE-AP has clinical features similar to the FAP-N group.

Serum trace elements in dysphagic gastrostomy candidates before endoscopic gastrostomy for long term enteral feeding.

BACKGROUND & AIMS: Patients who underwent endoscopic gastrostomy (PEG) present protein-energy malnutrition, but little is known about Trace Elements (TE), Zinc (Zn), Copper (Cu), Selenium (Se), Iron (Fe), Chromium (Cr). Our aim was the evaluation of serum TE in patients who underwent PEG and its relationship with serum proteins, BMI and nature of underlying disorder. METHODS: A prospective observational study was performed collecting: patient's age, gender, underlying disorder, NRS-2002, BMI, serum albumin, transferrin and TE concentration. We used ferrozine colorimetric method for Fe; Inductively Coupled Plasma-Atomic Emission Spectroscopy for Zn/Cu; Furnace Atomic Absorption Spectroscopy for Se/Cr. The patients were divided into head and neck cancer (HNC) and neurological dysphagia (ND). RESULTS: 146 patients (89 males), 21-95 years: HNC-56; ND-90. Low BMI in 78. Low values mostly for Zn (n = 122) and Fe (n = 69), but less for Se (n = 31), Cu (n = 16), Cr (n = 7); low albumin in 77, low transferrin in 94 and 66 with both proteins low. Significant differences between the groups of underlying disease only for Zn (t140.326 = -2,642, p < 0.01) and a correlation between proteins and TE respectively albumin and Zn (r = 0.197, p = 0.025), and albumin and Fe (r = 0.415, p = 0.000). CONCLUSIONS: When gastrostomy was performed, patients display low serum TE namely Zn, but also Fe, less striking regarding others TE. It was related with prolonged fasting, whatever the underlying disease. Low proteins were associated with low TE. Teams taking care of PEG-patients should use Zn supplementation and include other TE evaluation as part of the nutritional assessment of PEG candidates.

Metabolic disturbances in patients with cerebral palsy and gastrointestinal disorders.

Under nutrition and growth failure are common findings in children with cerebral palsy (CP) and neurologically impairments. Electrolyte and micronutrient abnormalities have also been documented. Gastrointestinal (GI) diseases like gastro esophageal reflux disease (GERD), feeding difficulties and constipation have been associated with increased frequency of these derangements. The goal of this study was to determine the prevalence of malnutrition, metabolic and electrolyte abnormalities in pediatric patients with cerebral palsy and gastrointestinal disorders. A retrospective review of 172 medical records was performed out of which 45 subjects did not have any GI problem, 69 patients had constipation and 58 patients either had GERD, esophagitis, gastrostomy and feeding difficulties. Data collected included: weight, length and body mass index, pre-albumin, albumin, vitamin D, potassium, chloride, bicarbonate, calcium, magnesium (Mg), phosphorus. The results demonstrate a significant difference (p = 0.0126) in the values of albumin in children with CP with GI disorders vs. those without. Additionally, a significant difference (p = 0.0129) was found in Mg levels between CP children with constipation vs. GERD/esophagitis/feeding issues/gastrostomy. Results suggest that children with CP and GI disorders have decreased levels of albumin, but normal pre-albumin. The mechanism for this is not completely clear and although we acknowledge importance of nutritional intake for albumin level support, other mechanisms such as low grade chronic inflammation and increased gut and vascular permeability may play a role. The lower levels of Mg in children with CP and constipation could be secondary to the use of laxatives. Further prospective studies looking at nutritional protein intake, gut and vascular permeability and laxative use in this patient population are important for future optimization of health care management.

Utility of a Noninvasive Serum Biomarker Panel for Diagnosis and Monitoring of Eosinophilic Esophagitis: A Prospective Study.

OBJECTIVES: Noninvasive biomarkers would be valuable for diagnosis and monitoring of eosinophilic esophagitis (EoE). The aim of this study was to determine the utility of a panel of serum biomarkers for the diagnosis and management of EoE. METHODS: We conducted a prospective cohort study of consecutive adults undergoing outpatient esophagogastroduodenoscopy. Incident cases of EoE were diagnosed per consensus guidelines; controls had gastroesophageal reflux disease (GERD) or dysphagia and did not meet the EoE criteria. EoE cases were treated with topical steroids and had repeat endoscopy. Pre- and post-treatment serum samples were analyzed in a blinded manner for interleukin (IL)-4, IL-5, IL-6, IL-9, IL-13, transforming growth factor (TGF)-α, TGF-ß, tumor necrosis factor-α, eotaxin-1, -2, and -3, thymic stromal lymphopoietin (TSLP), major basic protein, and eosinophil-derived neurotoxin. Cases and controls were compared at baseline, and pre- and post-treatment assays were compared in cases. RESULTS: A total of 61 incident EoE cases and 87 controls were enrolled; 51 EoE cases had post-treatment serum analyzed. There were no significant differences in any of the biomarkers between EoE cases and controls at baseline. IL-13 and eotaxin-3 for cases and controls were 85 ± 160 vs. 43 ± 161 pg/ml (P=0.12) and 41 ± 159 vs. 21 ± 73 (P=0.30). There were no significant differences in assay values among cases before and after treatment. There were also no differences after stratification by atopic status or treatment response. CONCLUSIONS: A panel of inflammatory factors known to be associated with EoE pathogenesis were not increased in the serum, nor were they responsive to therapy. None of these biomarkers are likely candidates for a serum test for EoE. Histologic analysis for diagnosis and management of EoE continues to be necessary, and novel, less invasive, biomarkers are needed.

Homozygosity in the ApoE 4 polymorphism is associated with dysphagic symptoms in older adults.

Apolipoprotein E (ApoE) is the most well-described genetic risk factor for Alzheimer's disease and nonpathological cognitive decline. While possession of the E2 allele may have protective properties, substantial research evidence suggests the E4 allele increases the risk of cognitive degeneration. As neurodegenerative processes are implicated in swallowing dysfunction, we hypothesized that the presence of ApoE 4 would be predictive of dysphagia symptoms in older adults. Eight hundred members of a genetically well characterized community dwelling elderly cohort received the Sydney oropharyngeal dysphagia questionnaire via mail. Cognitive function was also measured using the modified Telephone Interview of Cognitive Status (TiCS-m) and depression with the Geriatric Depression Score (GDS). ApoE allele was genotyped on blood samples from all subjects and data analyzed using standard statistical software (SPSS version 16). Completed questionnaire response rate was 79% (23.5% men, 76.5% women; mean age 81 ± 5 years; range 69-98 years). Possession of one or more of the ApoE 4 and 2 alleles was found in 23.5% and 16%, respectively. Swallowing score was significantly related to GDS (rho 0.133, P < 0.001**) and age (rho 0.107, P < 0.007**) but not general cognitive function as measured by TICS-m. Self-reported swallowing function was not significantly associated with heterozygosity of any allele or homozygosity for E2 or E3 alleles. Although infrequent (1.1% of all subjects) ApoE E4 homozygosity was significantly associated with higher swallowing scores compared to all other allele combinations (P = 0.033) and while attenuated, was still predicted in multivariate regression modeling (B = 0.812; SE = 0.323; P = 0.012). We report the association between ApoE 4 homozygous genotype and self-reported oropharyngeal dysphagia symptoms in community-dwelling older adults. As this association is weakened by the multivariate analysis and the population frequency of ApoE 4 allele homozygosity is low, this finding while intriguing requires replication in larger independent cohorts.

Feeding impairments associated with plasma sterols in Smith-Lemli-Opitz syndrome.

OBJECTIVE: To quantitatively evaluate feeding impairment in children with Smith-Lemli-Opitz syndrome (SLOS) and to correlate feeding impairment with clinical and biochemical indices of disease severity. STUDY DESIGN: The study subjects were 26 children with SLOS ranging in age from 0.4 to 19 years. Clinical severity was measured using an existing scoring system. We created a tool to quantitatively evaluate feeding. Plasma sterol concentrations were measured, and statistical associations (correlations) with feeding scores were calculated. RESULTS: Oral hyposensitivity or hypersensitivity, adverse behaviors, and risk for dysphagia were seen in ∼65% of the children with SLOS. Thirteen of the 26 children experienced failure to thrive, and 10 children required gastrostomy. Plasma concentration of 7-dehydrocholesterol, as a measure of severity, was correlated with total feeding score and oral function subcategory score (P < .001) and less so with oral structure score, adverse behaviors, or dysphagia. Correlations with cholesterol concentrations were less statistically significant. A plasma 7-dehydrocholesterol concentration >0.24 mmol/L or cholesterol concentration <1.95 mmol/L was predictive of gastrostomy tube use. Feeding impairments may improve with age. CONCLUSION: Feeding impairment is common and complex in patients with SLOS. Our findings confirm that oral sensitivities, adverse feeding behaviors, and risk of oral phase dysphagia are amenable to quantitative evaluation and analysis. Feeding difficulties in children with SLOS are correlated with plasma sterol concentrations, suggesting a link between the biochemical severity of SLOS and feeding function. These findings expand the behavioral phenotype of SLOS and begin to provide insight into the biological causes of feeding difficulties.