Citations

The process of transition from childhood to adulthood is characterised by physical, mental and psychosocial development. Data on the transition and transfer of care in adolescents/young adults with coeliac disease (CD) are scarce. In this paper, 17 physicians from 10 countries (Sweden, Italy, the USA, Germany, Norway, the Netherlands, Australia, Britain, Israel and Denmark) and two representatives from patient organisations (Association of European Coeliac Societies and the US Celiac Disease Foundation) examined the literature on transition from childhood to adulthood in CD. Medline (Ovid) and EMBASE were searched between 1900 and September 2015. Evidence in retrieved reports was evaluated using the Grading of Recommendation Assessment, Development and Evaluation method. The current consensus report aims to help healthcare personnel manage CD in the adolescent and young adult and provide optimal care and transition into adult healthcare for patients with this disease. In adolescence, patients with CD should gradually assume exclusive responsibility for their care, although parental support is still important. Dietary adherence and consequences of non-adherence should be discussed during transition. In most adolescents and young adults, routine small intestinal biopsy is not needed to reconfirm a childhood diagnosis of CD based on European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) or North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) criteria, but a biopsy may be considered where paediatric diagnostic criteria have not been fulfilled, such as, in a patient without biopsy at diagnosis, additional serology (endomysium antibody) has not been performed to confirm 10-fold positivity of tissue transglutaminase antibodies or when a no biopsy strategy has been adopted in an asymptomatic child.

ABSTRACTIntroductionQuantitative EEG features have been identified as surrogates and predictors of cognitive decline/dementia, a common feature of progressive PD. The biochemical correlates for altered quantitative EEG features are unknown. Our primary objective was to test the hypothesis that quantitative EEG measures correlate with cortical levels of phosphorylated α‐synuclein, a modified form of the synaptic protein α‐synuclein, in PD cases, in contrast to other pathology‐associated proteins. A secondary objective was to explore the same correlations among cellular fractions of these proteins.MethodsWe used posterior cingulate cortex autopsy tissue from 44 PD subjects with various degrees of cognitive decline, who had undergone EEG. In this brain region, which is a major hub of the default mode network, biochemical measurements for levels of phosphorylated α‐synuclein, unmodified α‐synuclein, amyloid beta peptide, phosphorylated tau, and key synaptic proteins were analyzed and data correlated with spectral EEG measures.ResultsFindings revealed significant correlations between background rhythm peak frequency and all bandpower values (highest in delta bandpower) with total phosphorylated α‐synuclein, but not any correlation with total α‐synuclein, phosphorylated tau protein, amyloid beta peptide, or synaptic proteins. Certain fractions of synaptosomal‐associated protein 25 showed correlation with some quantitative EEG measures.ConclusionsThese data show an association between increased phosphorylation of α‐synuclein and the abnormal EEG signatures of cognitive decline. Results suggest that quantitative EEG may provide an in vivo approximation of phosphorylated α‐synuclein in PD cortex. This adds to previous evidence that quantitative EEG measures can be considered valid biomarkers of PD cognitive decline. © 2016 International Parkinson and Movement Disorder Society

Background: Clinical misdiagnosis, particularly at early disease stages, is a roadblock to finding new therapies for Lewy body disorders. Biopsy of a peripheral site might provide improved diagnostic accuracy. Previously, we reported, from both autopsy and needle biopsy, a high prevalence of submandibular gland synucleinopathy in Parkinson’s disease (PD). Here, we report on an extension of these studies to subjects with dementia with Lewy bodies (DLB) and other Lewy body disorders in 228 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders. Objective: To provide an estimate of the prevalence of histological synucleinopathy in the submandibular glands of subjects with PD and other Lewy body disorders. Methods: Submandibular gland sections from autopsied subjects were stained with an immunohistochemical method for α-synuclein phosphorylated at serine 129. Included were 146 cases with CNS Lewy-type synucleinopathy (LTS), composed of 46 PD, 28 DLB, 14 incidental Lewy body disease (ILBD), 33 Alzheimer’s disease with Lewy bodies (ADLB) and 2 with progressive supranuclear palsy and Lewy bodies (PSPLB). Control subjects included 79 normal elderly, 15 AD, 12 PSP, 2 conticobasal degeneration (CBD) and 2 multiple system atrophy (MSA). Results: Submandibular gland LTS was found in 42/47 (89%) of the PD subjects, 20/28 (71%) DLB, 4/33 (12%) ADLB and 1/9 (11%) ILBD subjects but none of the 110 control subjects. Conclusions: These results provide support for further clinical trials of in vivo submandibular gland diagnostic biopsy for PD and DLB. An accurate peripheral biopsy diagnosis would assist subject selection for clinical trials and could also be used to verify other biomarkers.

Objective To describe findings and outcomes of 331 bilateral inferior petrosal sinus sampling (BIPSS) procedures performed in 327 patients evaluated for Cushing disease (CD). Materials and methods The radiology department's electronic database was searched to identify all BIPSS procedures (1990–2013). Electronic medical records were used to identify demographics, laboratory, procedural, surgical and pathologic findings. Results A total of 331 BIPSS procedures were performed in 327 patients (254 F, 73 M), mean age 41 (range 7–81) years. The overall technical success rate was 88% for bilateral cannulation, though nearly two-thirds of the technical failures had unilateral sampling that diagnosed CD. Of the 331 BIPSS procedures, 40 were performed without, and 291 with stimulation by Acthrel or desmopressin. Sensitivity was 89–94% for unstimulated BIPSS, 96% for stimulated BIPSS, and 77% for MRI. BIPSS lateralization was accurate in about half of patients, compared with 75% accuracy for MRI. Mean inferior petrosal sinus (IPS):peripheral adrenocorticotropic hormone ratio was 17.3 (SE 1.8) at baseline, and 99.2 (SE 14.8) at 3 min, with decreasing values over time. All patients with follow-up after surgical resection for centralizing BIPSS were reported to be cured, with cortisol levels significantly decreased from 19 to 4 μg/dL (p<0.0001). Complications from BIPSS were rare, including groin hematoma (2.5%), but no thromboembolic complications were seen. Conclusions BIPSS remains the ‘gold standard’ for diagnosing CD. Stimulation with Acthrel or desmopressin is key to increasing specificity. When only one IPS can be successfully cannulated, results may still be diagnostic. BIPSS findings cannot be used to accurately lateralize lesions within the pituitary.

ABSTRACTIntroductionFinding a peripheral tissue biopsy site to diagnose early PD would be of value for clinical care, biomarker validation, and as research enrollment criteria. Whereas autopsy and advanced PD studies suggest that the submandibular gland is an important biopsy site, there are no studies in early PD. The aim of this study was to determine whether needle biopsy of the submandibular gland reveals Lewy type alpha‐synucleinopathy in early PD.MethodsTwenty‐five early PD (duration < 5 years) and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated alpha‐synuclein, reviewed blind to clinical diagnosis, and only nerve element staining was considered positive.ResultsMean (standard deviation) age was 69.5 (8.3) for the PD group, 64.8 (8.0) years for controls, and disease duration 2.6 (1.1) years. Six PD and 1 control subject had inadequate glandular tissue. Positive staining was found in 14 of 19 (74%) PD and 2 of 9 (22%) control subjects. PD‐positive and ‐negative cases did not differ clinically. Adverse events (mainly swelling and bruising) were common (77% of cases), but were minor and transient.ConclusionsSubmandibular gland needle biopsies identified phosphorylated alpha‐synuclein staining in 74% of early PD subjects. False positives may be true false positives or may represent prodromal PD. If confirmed in larger studies with eventual autopsy confirmation, the potential value of submandibular gland biopsies for early PD may be to aid in clinical trial inclusion/exclusion and eventually serve as a gold standard for biomarker studies short of autopsy confirmation. © 2016 International Parkinson and Movement Disorder Society

AbstractBackgroundCachexia is a significant problem in patients with cancer. The effect of cancer on interstitial cells of Cajal (ICC) and neurons of the gastrointestinal tract have not been studied previously. Although supplementation with L‐glutamine 2% may have beneficial effects in cancer‐related cachexia, and be protective of ICC in models of oxidative stress such as diabetes, its effects on ICC in cancer have also not been studied.MethodsTwenty‐eight male Wistar rats were divided into four groups: control (C), control supplemented with L‐glutamine (CG), Walker 256 tumor (WT), and Walker 256 tumor supplemented with L‐glutamine (WTG). Rats were implanted with tumor cells or injected with saline in the right flank. After 14 days, the jejunal tissues were collected and processed for immunohistochemical techniques including whole mounts and cryosections and Western blot analysis.Key ResultsTumor‐bearing rats demonstrate reduced numbers of Myenteric ICC and deep muscular plexus ICC and yet increased Ano1 protein expression and enhanced ICC networks. In addition, there is more nNOS protein expressed in tumor‐bearing rats compared to controls. L‐glutamine treatment had a variety of effects on ICC that may be related to the disease state and the interaction of ICC and nNOS neurons. Regardless, L‐glutamine reduced the size of tumors and also tumor‐induced cachexia that was not due to altered food intake.Conclusions & InferencesThere are significant effects on ICC in the Walker 256 tumor model. Although supplementation with L‐glutamine has differential and complex effects of ICC, it reduces tumor size and tumor‐associated cachexia, which supports its beneficial therapeutic role in cancer.

SummaryInvasive mucormycosis is a rare fungal infection in immunocompromised hosts, but it carries a high mortality rate. Primary gastrointestinal disease is the least frequent form of presentation. Early diagnosis and treatment are critical in the management; however, symptoms are typically non‐specific in gastrointestinal disease, leading to delayed therapy. To describe the clinical presentation, diagnosis, treatment and outcomes of gastrointestinal mucormycosis in immunocompromised hosts, we reviewed all cases of primary gastrointestinal mucormycosis in immunocompromised hosts reported in English literature as well as in our Institution from January 1st 1991 to December 31st 2013 for a total of 31 patients. About 52% of patients underwent solid organ transplant (SOT), while the rest had an underlying haematologic malignancy. Abdominal pain was the most common presenting symptom, followed by gastrointestinal bleeding and fever. Gastric disease was more common in SOT, whereas those with haematologic malignancy presented with intestinal disease (P = 0.002). Although gastrointestinal mucormycosis remains an uncommon condition in immunocompromised hosts, it carries significant morbidity and mortality, particularly in cases with intestinal involvement. A high index of suspicion is of utmost importance to institute early and appropriate therapy and improve outcomes.