Onset Of Type Research Articles

Insight into the possible aetiologies of Blount's disease: a systematic review of the literature.

Blount's disease or bowed leg deformity, is a unilateral or bilateral growth deformity of the medial proximal tibia that leads to a tibial varus deformity. A distinction can be made in an early and late onset type. The disease seems to have a predisposition for certain descends. Since the first publication of Blount's disease, different hypotheses on the aetiology are proposed but no consensus exists. The objective of this study is to provide an overview of the available hypotheses on the aetiology of Blount's disease since its first description and assessment of the available level of evidence, the quality of evidence and the occurrence of bias supporting these individual hypotheses. A systematic search according to the PRISMA statement was conducted using PubMed, MEDLINE, EMBASE and the Cochrane Library using a broad combination of terminology to ascertain a complete selection. Proper MESH search criteria were formulated and the bibliographic search was limited to English and Dutch language articles. Articles with no mention of aetiology or a disease related to Blount's were excluded. Level of evidence and types of bias were assessed. Thirty-two articles that discuss the aetiology of Blount's disease were selected. A variety of hypotheses was postulated in these articles with most research in the field of increased mechanical pressure (obesity, early walking age) and race (descend). Blount's disease most likely has a multifactorial origin with influence of genetic and racial predisposition, increased mechanical pressure on the growth plate as a consequence of obesity or early walking age and possibly also nutrition. However, the exact aetiology remains unclear, the probable explanation is that multifactorial factors are all contributing to the development of Blount's disease. Histological research has shown that a disorganization of bone and cartilage structures on the medial side of the proximal tibial physis is present in patients with Blount's disease. Based on the available evidence on the aetiology of Blount's disease, we conclude that it is multifactorial. Most papers focus only on one hypotheses of Blount's disease occurrence and all are characterized as low level of evidence. There seems to be a preference for certain descends. Further research on especially genetic predisposition is needed to provide more insight in this factor of Blount's disease.

1047 Changes in Liver Fibrosis Scores in Patients With New Onset Type 2 Diabetes on Triple Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy: Year Two Results

INTRODUCTION: Patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) are at higher risk of developing advanced fibrosis. Certain diabetes medications such as pioglitazone and GLP1 agonists have shown some efficacy against NAFLD in small clinical trials. The Durability of Combination Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy in New Onset T2DM trial is an ongoing interventional trial assessing the effects of two different approaches to treating T2D (ClinicalTrials.gov Identifier: NCT01107717). The aim of the current study was to evaluate the effects of these two approaches on liver fibrosis scores after two years of treatment. METHODS: Newly diagnosed, drug-naïve T2DM patients were enrolled into the study. Medical history, clinical characteristics were obtained, and blood was drawn for the measurement of plasma glucose concentration, HbA1c, CBC, and blood chemistries. Subjects were randomized to receive in an open label fashion an initial combination therapy with metformin (2000 mg) plus pioglitazone (45 mg) and exenatide 10 µg BID (triple therapy) or sequential addition of metformin followed by sulfonylurea and insulin (conventional therapy) to maintain HbA1c < 6.5%. Subjects were seen every 3 months for follow-up visits and at 2 years all baseline measurements were repeated. Liver fibrosis scores that were calculated included AST/ALT ration, APRI, FIB-4 and NFS. RESULTS: Baseline characteristics are listed in Table 1; patients were well matched. Liver fibrosis scores at baseline and at 2 years are listed in Table 2. To compare the effect of each therapy on liver fibrosis scores, the ratio between the 2-year values of liver fibrosis scores to the baseline values was compared amongst the two treatment groups with ANOVA. Both therapies significantly reduced liver fibrosis scores but no significant difference was noted between the two treatment arms. CONCLUSION: In this randomized trial in patients with new-onset T2D, good control of HbA1c was associated with reduction in liver fibrosis scores at 2 years but the use of pioglitazone and GLP1 agonist did not have an added benefit over conventional therapy. The effects of longer duration of treatment are currently being evaluated in addition to assessment of fibrosis by Fibroscan and MR elastography.

311 Retrospective Analysis of Patients Receiving Immune Checkpoint Inhibitors Presenting to the Emergency Department

The use of immune checkpoint inhibitors (ICIs) in the treatment of cancer is rapidly expanding. ICIs may cause a wide range of autoimmune toxicities referred to as immune-related adverse effects (irAEs). There is sparse literature regarding why patients on ICI go to the emergency department (ED). In this study, we aim to describe why patients on ICIs go to the ED, whether or not ED providers consider an irAE in the differential diagnoses, and the subsequent management of the irAEs. We performed a retrospective review of all patients receiving an ICI who presented to a tertiary care ED between May 1, 2017 and April 30, 2018. Data including ED chief complaint, diagnosis, treatment, and disposition were collected along with baseline characteristics and diagnosis at the time of outpatient oncology follow-up. We report descriptive statistics summarizing the characteristics of the cohort. There were 97 ED visits identified among 66 unique patients identified. IrAE was diagnosed in 16 (16.3%) cases. The most common ED chief complaint within this group was gastrointestinal symptoms (abdominal pain, diarrhea, or nausea and vomiting) which accounted for 10 cases (62.5%). Other chief complaints included 2 cases (12.5%) of dyspnea, 2 cases (12.5%) of hyperglycemia, 1 case (6.25%) of chest tightness/pressure, and 1 case (6.25%) of dizziness. Among the 16 confirmed irAE cases, the most common irAE diagnosed was colitis, identified in 9 cases (56.3%). Other irAEs diagnosed included 2 cases (12.5%) of new onset type 1 diabetes mellitus, 2 cases (12.5%) of pancreatitis, 1 case (6.25%) of pneumonitis, 1 case (6.25%) of myasthenia gravis, and 1 case (6.25%) of adrenal insufficiency. ED providers documented consideration of an irAE in the differential diagnoses in 14.4% of total ED visits. Among cases with confirmed irAE, ED providers considered an irAE in the differential diagnoses in 43.8% of visits. Two patients with irAEs (12.5%) received corticosteroids during their stay in the ED, and 10 patients (62.5%) required hospital admission. Among patients on ICIs presenting for emergency care, irAEs were infrequently considered and were ultimately diagnosed at a rate of 16%. Gastrointestinal symptoms were the most common chief complaint for these patients. Colitis was the most common irAE diagnosed. Patients with irAE were rarely treated with corticosteroids during their ED visit. Large, multi-center prospective studies are needed to better understand the presentation and subsequent management of patients on ICIs who seek emergency care.

Differences in age and comorbidities of stroke patients from the galilee according to sex and ethnicity Shahien Radi, Ryder Chen and Zarka Salman

Studies done on stroke demonstrated great variance in the rate of hospitalization, age of onset, mortality, and comorbidity between different ethnicities and sexes. The patient’s population at the Northern part of Israel includes distinct groups of different ethnicities, including Jews and Arabs. There is currently scarcity of studies that characterize these groups in relation to risk factors, age of onset and mortality. The purpose of the current study was to characterize differences in comorbidities and age of onset of stroke between different ethnicities. Data was collected from discharge letters of stroke patients admitted to Department of Neurology at Ziv hospital between 2010-2015. 964 patients were included, 64.2% Jews, 7.7% Moslems, 1.7% Christians, 22.5% Druze and 3.9% Bedouins. 61% male and 39% female. The study groups were divided according to ethnicities and sexes. The average age of onset for stroke was 63 for Arabs versus 67 for Jews and 67 for men versus 71 for women. The Jewish population had a higher prevalence of ischemic heart disease, vascular diseases and malignancy, where in the Arab population metabolic diseases, including diabetes, obesity and dyslipidemia were more common. Women were found to have a higher prevalence of atrial fibrillation, endocrine disorders and hematologic diseases, while men were more likely to smoke and consume alcohol. This study showed differences in age of onset and comorbidity type between different ethnicities and sexes regarding to stroke. The results may be a corner stone in constructing a tailored prevention programs.

Cardiovascular risk factors from diagnosis in children with type 1 diabetes mellitus: a longitudinal cohort study

BackgroundFor childhood onset type 1 diabetes (T1D), the pathogenesis of atherosclerosis is greatly accelerated and results in early cardiovascular disease (CVD) and increased mortality. However, cardioprotective interventions in this age...

127 - Poor Sleep, Increased Stress, and Complications in Youth With Type 2 Diabetes (T2D)

Youth onset type 2 diabetes (T2D) disproportionally affects families with fewer resources. The relationship stress and disrupted sleep patterns have on developing T2D related complications remains to be determined.

Maternal vs paternal diabetes: The parental history is different in younger onset versus older onset type 2 diabetes

BackgroundA number of previous studies exploring family history of type 2 diabetes have reported a predominance of maternal diabetes. These studies have not explicitly compared parental history of diabetes across the spectrum of disease onset from youth to later adulthood. MethodsFamily history data from 11,467 patients with type 2 diabetes were extracted from the RPA Diabetes Centre database. Parental histories of diabetes were compared across a range of age of diagnosis strata (15-<30, 30-<40, 40-<50, 50-<60 and 60-<70 years). For the young-onset group (diagnosed between 15 and 30 years of age), associations between parental history of diabetes and the presence of cardio-metabolic risk factors and diabetic complications were also explored. ResultsFor the total cohort and within each age of diagnosis strata, more individuals reported maternal history than paternal history of diabetes. The young-onset group demonstrated the highest prevalence of any parental history of diabetes (60.7%), the highest combined maternal and paternal history (15.8%) and the smallest differential between maternal (25.1%) and paternal (19.7%) history of diabetes. Within the young-onset group, no significant association between parental history and cardio-metabolic risk factors or diabetic complications were identified after a median of 15.0 years of diabetes exposure. ConclusionOverall, our results demonstrate a consistent maternal excess of diabetes which could be consistent with an underlying epigenetic effect. However, the differential between maternal and paternal history is significantly lower in the young-onset group. Earlier emergence of type 2 diabetes may therefore reflect a different interaction and impact of genetic and environmental factors.

A Comprehensive Examination of Percutaneous Endoscopic Gastrostomy and Its Association with Amyotrophic Lateral Sclerosis Patient Outcomes.

There is literature discord regarding the impact of percutaneous endoscopic gastrostomy (PEG), or “feeding tube”, on amyotrophic lateral sclerosis (ALS) outcomes. We assess one of the largest retrospective ALS cohorts to date (278 PEG users, 679 non-users). Kruskal–Wallis and Kaplan–Meier analysis compared cohort medians and survival duration trends. A meta-analysis determined the aggregate associative effect of PEG on survival duration by combining primary results with 7 published studies. Primary results (p < 0.001) and meta-analysis (p < 0.05) showed PEG usage is associated with an overall significant increase in ALS survival duration, regardless of onset type. Percent predicted forced vital capacity (FVC %predict) ≥50 at PEG insertion significantly increases survival duration (p < 0.001); FVC %predict ≥60 has the largest associative benefit (+6.7 months, p < 0.05). Time elapsed from ALS onset until PEG placement is not predictive (p > 0.05). ALSFRS-R survey assessment illustrates PEG usage does not slow functional ALS pathology (p > 0.05), but does stabilize weight and/or body mass index (BMI) (p < 0.05). Observed clinical impression of mood (CIM), was not impacted by PEG usage (p > 0.05). Overall results support PEG as a palliative intervention for ALS patients with ≥50 FVC %predict at PEG insertion.

Pioneering studies on monogenic central precocious puberty.

Pubertal timing in humans is determined by complex interactions including hormonal, metabolic, environmental, ethnic, and genetic factors. Central precocious puberty (CPP) is defined as the premature reactivation of the hypothalamic-pituitary-gonadal axis, starting before the ages of 8 and 9 years in girls and boys, respectively; familial CPP is defined by the occurrence of CPP in two or more family members. Pioneering studies have evidenced the participation of genetic factors in pubertal timing, mainly identifying genetic causes of CPP in sporadic and familial cases. In this context, rare activating mutations were identified in genes of the kisspeptin excitatory pathway (KISS1R and KISS1 mutations). More recently, loss-of-function mutations in two imprinted genes (MKRN3 and DLK1) have been identified as important causes of familial CPP, describing novel players in the modulation of the hypothalamic-pituitary-gonadal axis in physiological and pathological conditions. MKRN3 mutations are the most common cause of familial CPP, and patients with MKRN3 mutations present clinical features indistinguishable from idiopathic CPP. Meanwhile, adult patients with DLK1 mutations present high frequency of metabolic alterations (overweight/obesity, early onset type 2 diabetes and hyperlipidemia), indicating that DLK1 may be a novel link between reproduction and metabolism. Arch Endocrinol Metab. 2019;63(4):438-44.

Distinct two different ages associated with clinical profiles of acute onset type 1 diabetes in Chinese patients

There are abundant variations in the phenotypes and genetics of type 1 diabetes (T1D) patients across different races. This study aimed to assess differences between juvenile acute onset (JAO) and adult acute onset in Chinese T1D patients. Seven hundred and fifty-one acute onset T1D patients were divided into two groups by the patient onset age as follows: the juvenile acute onset group (≤20years, JAO group) and the adult acute onset group (>20years, AAO group). Clinical characteristics, islet autoantibodies, and HLA class II haplotypes and genotypes were compared between these two groups. In comparison with AAO patients, JAO patients had significantly lower relative weights and lower triglyceride levels (P<.001, P<.01, respectively) but higher frequency of ketoacidosis (P<.001), higher daily insulin dosage (Pc <.001), higher HbA1c (Pc <.05), and higher HDL-cholesterol levels (Pc <.01). The JAO group showed a higher prevalence of IA-2A, ZnT8A, and multiple autoantibodies than that in the AAO group (P<.001, P<.01, P<.001, respectively). Haplotypes for DRB1*0301-DQA1*03-DQB1*0201, DR3, DR4, DR9, and DR3/DR9 genotypes are highly associated with JAO susceptibility, whereas only DR3 and DR9 genotypes confer risk for AAO. In the JAO group but not the AAO group, DR3 is related to ZnT8A, and DR3/DR9 is related to IA-2A and multiple autoantibodies. These observations suggest that JAO patients markedly differ from AAO patients in their clinical manifestations and genetics in the Chinese T1D population. Notably, the DR3/DR9 genotype can facilitate the appearance of IA-2A or multiple autoantibodies in JAO patients.

Inequalities in glycemic control in childhood onset type 2 diabetes in England and Wales-A national population-based longitudinal study.

Not much is known about glycaemic-control trajectories in childhood-onset type 2 diabetes (T2D). We investigated characteristics of children and young people (CYP) with T2D and inequalities in glycemic control. We studied 747 CYP with T2D, <19 years of age in 2009-2016 (from the total population-based National Pediatric Diabetes Audit [>95% diabetes cases in England/Wales]). Linear mixed-effects modeling was used to assess socioeconomic and ethnic differences in longitudinal glycated hemoglobin (HbA1c ) trajectories during 4 years post-diagnosis (3326 HbA1c data points, mean 4.5 data points/subject). Self-identified ethnicity was grouped into six categories. Index of Multiple Deprivation (a small geographical area-level deprivation measure) was grouped into SES quintiles for analysis. Fifty-eight percent were non-White, 66% were female, and 41% were in the most disadvantaged SES quintile. Mean age and HbA1c at diagnosis were 13.4 years and 68 mmol/mol, respectively. Following an initial decrease between diagnosis and end of year 1 (-15.2 mmol/mol 95%CI, -19.2, -11.2), HbA1c trajectories increased between years 1 and 3 (10 mmol/mol, 7.6, 12.4), followed by slight gradual decrease subsequently (-1.6 mmol/mol, -2, -1.1). Compared to White CYP, Pakistani children had higher HbA1c at diagnosis (13.2 mmol/mol, 5.6-20.9). During follow-up, mixed-ethnicity and Pakistani CYP had poorer glycemic control. Compared to children in the most disadvantaged quintile, those in the most advantaged had lower HbA1c at diagnosis (-6.3 mmol, -12.6, -0.1). Differences by SES remained during follow-up. Mutual adjustment for SES and ethnicity did not substantially alter the above estimates. About two-thirds of children with childhood-onset T2D were non-White, female adolescents, just under half of whom live in the most disadvantaged areas of England and Wales. Additionally, there are substantial socioeconomic and ethnic inequalities in diabetes control.

Adverse childhood events and risk of diabetes onset in the 1979 National longitudinal survey of youth cohort

BackgroundType 2 diabetes is a major public health problem with considerable personal and societal costs. Adverse childhood experiences (ACE) are associated with a number of serious and chronic health problems in adulthood, but these experiences have not been adequately studied in relation to diabetes in a US national sample. The association between ACE and poor health can be partially explained by greater risky health behaviors (RHB) such as smoking, heavy alcohol use, or obesity. Few studies have examined ACE in relation to adult onset Type 2 diabetes mellitus (T2DM) taking into account the role of RHB. Using longitudinal data from a representative US population sample followed over 30 years, this study examines the impact of ACE on the risk of diabetes onset.MethodsData from the 1982 to 2012 waves of the 1979 National Longitudinal Survey of Youth were analyzed, spanning ages 14 to 56. Bivariate and discrete-time survival models were used to assess the relationships between ACE and RHB including smoking, alcohol use, and obesity, and subsequent onset of diabetes.ResultsT2DM was reported by almost 10% of participants. Over 30% of women and 21% of men reported 2+ ACE events. Women reporting 2–3 or 4+ ACE events were more likely to develop diabetes with the mean number of ACE events being greater in those with diabetes compared to without (1.28 vs.1.05, p < .0001). For men there was no significant association between ACE and diabetes onset. For women, ACE was associated with heavy drinking, current smoking, and obesity. For men, ACE was associated with being underweight and daily smoking. In multivariate discrete-time survival models, each additional ACE increased risk of T2DM onset (ORadj = 1.14; 95% CI 1.02–1.26) for women but not for men. The relationship in women was attenuated when controlling for body mass index (BMI).ConclusionACE predicted diabetes onset among women, though this relationship was attenuated when controlling for BMI. Being overweight or obese was significantly more common among women with a history of ACE, which suggests BMI may be on the pathway from ACE to diabetes onset for women.

Increasing burden of type 2 diabetes in Navajo youth: The SEARCH for diabetes in youth study.

SEARCH has recently reported that both prevalence and incidence of youth onset type 2 diabetes (YT2D) increased among most US race/ethnic groups in the early 2000s. This study reports on the incidence (2002-2013) and prevalence (2001, 2009) of YT2D in the Navajo Nation among youth age < 20 years from 2001 to 2013. SEARCH sought to identify prevalent YT2D cases in 2001 (N = 75) and 2009 (N = 70) and all incident YT2D cases in three periods: 2002 to 2005 (N = 53), 2006 to 2009 (N = 68), and 2010 2013 (N = 90) in Navajo Nation. Denominators were based on the active Indian Health Service user population for eligible health care facilities. Prevalence (per 100 000) and period-specific incidence rates (per 100 000 person-years) were computed for youth aged 10 to 19 years. Changes in prevalence were tested with a two-sided skew-corrected inverted score test, while changes in incidence were tested with Poisson regression. YT2D prevalence was high but stable in 2001 and 2009, overall [146.6 (116.8, 184.0) vs 141.5 (112.0, 178.8), P = .65) and in all subgroups. In contrast, incidence rates increased particularly between the second and third periods overall and in most subgroups by age and by sex. These data confirm the high burden of YT2D among Navajo youth and suggest an increasing risk in more recent years. However, recent improvements in obesity reduction in this population demonstrate optimism for potential reductions in YT2D in Navajo Nation.

Painless jaundice with pancreatic mass in 79-year-old man receiving bortezomib for relapsed multiple myeloma

<b>Objective</b> To investigate whether pre-eclampsia is more common in first pregnancies solely because fewer affected women, who presumably have a higher risk of recurrence, go on to have subsequent pregnancies....

Impact of Interethnic Difference of Collateral Angioarchitectures on Prevalence of Hemorrhagic Stroke in Moyamoya Disease.

Fragile, dilated moyamoya vessels are the main source of hemorrhagic stroke in moyamoya disease (MMD). However, the prevalence of hemorrhagic stroke largely differs between Asian and western countries, although the underlying pathophysiology has not been clarified. To systematically analyze the difference of collateral angioarchitectures between Japanese and European Caucasians with MMD. This study included 71 patients with MMD, including Japanese (n=41) and European Caucasians (n=30). Using preoperative cerebral angiography, the developments of lenticulostriate artery (LSA), anterior choroidal artery (AChoA), posterior communicating artery (PcomA), and posterior choroidal artery (PChoA) were precisely evaluated, and ethic difference was analyzed in terms of patients' age and the onset type. Cerebral angiography demonstrated that the marked dilatation of AChoA and PChoA were significantly more remarkable in Japanese than in European Caucasians (P=.004 and P=.002, respectively). Ageing advanced the dilatation and extension of PChoA and PcomA, and diminished the development of LSA in Japanese patients (P<.001, P=.03, and P=.03, respectively). European Caucasian patients did not have the specific dilated pattern like Japanese patients. The marked dilatation of PChoA and PcomA is considered a powerful predictive marker of hemorrhage in MMD. Collateral channels spontaneously shift from the anterior to posterior circulation in Japanese patients during ageing but not in European Caucasian patients. These different dilation patterns of the collateral pathway may be associated with an ethnic difference of the clinical onset type in MMD.

NEONATAL SEPSIS AND IDENTIFICATION OF RISK FACTORS: STUDY IN AVBRH HOSPITAL SAWANGI

Introduction: India has the highest incidence of clinical sepsis i.e.17,000/ 1,00,000 live births. In Neonatal sepsis septicaemia, pneumonia, meningitis, osteomyelitis, arthritis and urinary tract infections can be included. Mortality in the neonatal period each year account for 41% (3.6 million) of all deaths in children under 5 years and most of these deaths occur in low income countries and about one million of these deaths are due to infectious causes including neonatal sepsis, meningitis, and pneumonia. In early onset neonatal sepsis (EOS) Clinical features are non-specific and are inefficient for identifying neonates with early-onset sepsis. Culture results take up to 48 hours and may give false-positive or low-yield results because of the antenatal antibiotic exposure. Reviews of risk factors has been used globally to guide the development of management guidelines for neonatal sepsis, and it is similarly recommended that such evidence be used to inform guideline development for management of neonatal sepsis.&#x0D; Material and Methods: This study was carried out using institution based cross section study . The total number neonates admitted in the hospital in given study period was 644, of which 234 were diagnosed for neonatal sepsis by the treating pediatrician based on the signs and symptoms during admission. The data was collected: Sociodemographic characteristics; maternal information; and neonatal information for neonatal sepsis like neonatal age on admission, sex, gestational age, birth weight, crying immediately at birth, and resuscitation at birth.&#x0D; Results: Out of 644 neonates admitted 234 (36.34%) were diagnosed for neonatal sepsis by the paediatrician based on the signs and symptoms during admission. Of the 234 neonates, 189 (80.77%) infants were in the age range of 0 to 7 days (Early onset sepsis) while 45 (19.23%) were aged between 8 and 28 days (Late onset sepsis). Male to female ratio in our study was 53.8% and 46% respectively. Out of total 126 male neonates 91(72.2%) were having early onset sepsis while 35 (27.8%) were late onset type. Out of total 108 female neonates 89(82.4%) were having early onset sepsis while 19 (17.6%) were late onset type. Maternal risk factors were identified in 103(57.2%) of early onset sepsis cases while in late onset sepsis cases were 11(20.4%). Foul smelling liquor in early onset sepsis and in late onset sepsis was 10(5.56%) and 2 (3.70%) respectively. In early onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 21(11.67%), 19 (10.56%), 20(11.11%) and 33 (18.33%) cases respectively. In late onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 2 (3.70%), 1(1.85%), 3 (5.56%) and 3 (5.56%) cases respectively.&#x0D; Conclusion: Maternal risk identification may help in the early identification and empirical antibiotic treatment in neonatal sepsis and thus mortality and morbidity can be reduced.

Measurements of Recovery and Predictors of Outcome in an Untreated Chronic Fatigue Syndrome Sample

The current study examined a large cohort of untreated Chronic Fatigue Syndrome patients at initial assessment and at specific time points over a three-year period. Methods used in previous studies to assess patient health, were validated and used to assess recovery and improvement. Possible predictors of outcome would then be identified by assessing improvements in health status at specific follow-up points. The illness was also assessed in terms of recovery and improvement by using health related and psychosocial measures together with the aetiology of the illness. These were further used to investigate possible mechanisms influencing or predicting recovery or improvement. Two-hundred and twenty-six patients completed wide ranging questionnaires at initial assessment and again six and eighteen months and three years later. A current state of health score was used to measure recovery over time and analyses conducted to investigate the relationship between this and other health related measures. Regression analyses were conducted to assess predictors of improvement and recovery. Spontaneous recovery rates in the untreated patient at three-year follow-up were low (6%). The data suggested, however, that illness length, symptom severity and health status have an important role in recovery. Although there was no evidence to suggest an association between illness onset type and subsequent recovery or psychopathology scores at initial assessment and recovery, regression analyses did indicate that levels of anxiety, cognitive difficulties and social support at initial assessment predict a positive outcome. The state of health measure was validated as a method of accurately assessed the health status of patients and was used as an indicator of improvement and recovery within this group. Spontaneous recovery in the patient group was associated with several factors measured at initial assessment. However, further studies are necessary to more fully identify the factors which affect recovery or improvement and to investigate the exact nature of the mechanisms involved. The present study shows that spontaneous recovery of CFS patients is rare. Treatment or management is essential, and the efficacy of different approaches must be assessed.

Characteristics of Moyamoya Disease Based on National Registry Data in Japan.

Background and Purpose- A public registration system for intractable diseases was started in Japan in 1972 to investigate the etiology and pathogenesis of intractable diseases while reducing out-of-pocket medical expenses on patients. The goal of this study was to investigate the epidemiology and clinical characteristics of Moyamoya disease using data from applications submitted to this system between 2004 and 2008. Methods- In addition to demographic factors such as onset age and family history, we evaluated clinical presentation type, imaging findings, clinical symptoms, and functioning in activities of daily living (ADL). Results- Of 3859 cases for which applications were submitted, 2545 were confirmed to meet the diagnostic criteria after data cleansing. Onset age showed a bimodal distribution, and Moyamoya disease had a higher incidence in women than in men. The presence of occlusion and infarction in the proximal region of the anterior cerebral artery was more frequent in pediatric cases than adult cases. Our findings also indicated that 23% of patients required assistance with ADL. Cerebral infarction (odds ratio [OR], 12.5; 95% CI, 3.55-44.66), seizure (OR, 7.44; 95% CI, 1.29-42.96), and sensory disorders (OR, 5.23; 95% CI, 1.15-23.75) were identified as significant predictors of impaired ADL in pediatric cases 3 years after the initial application. Moderate ADL function (OR, 11.59; 95% CI, 5.29-25.39) and intellectual disabilities (OR, 4.38; 95% CI, 1.58-12.17) at the time of the application were identified as significant prognostic factors in adults. Conclusions- The results of this study indicated that characteristics of Moyamoya disease such as onset type, symptoms, and imaging abnormalities differ with onset age. Prognostic analyses suggested that pediatric cases with good ADL but with infarct type onset, seizure, or sensory disorders might have a subsequent decline in ADL.

Serum metabolomics analysis and establishment of diagnostic model of pancreatic cancer associated diabetes

Objective To establish the diagnostic model based on detection of serum biomarkers in pancreatic cancer (PC) associated diabetes. Methods From June 2013 to July 2014, at Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 30 patients diagnosed with PC companied with new onset diabetic mellitus and 30 patients with new onset type 2 diabetic mellitus, were enrolled. Serum samples were examined by liquid chromatography-mass spectrometry (LC-MS) for metabolomics analysis. Orthogonal partial least square (OPLS) was performed for raw data analysis to obtain the differentially expressed metabolites between two groups. The first 15 cases of each group were taken as training samples and the left as validation samples. The model was established using logistic regression via stepwise differentially expressed metabolites and clinical data input in training samples. The diagnostic efficiency of the model was verified in validating samples. Results Ten differentially expressed metabolites were identified in PC companied with new onset diabetic mellitus group and new onset type 2 diabetic mellitus group. The differentially expressed metabolites identified in positive ion mode were 3-ketosphingosine, arachidonoyl dopamine, phosphatidylethanolamine (18∶2), ubiquinone-1 and valine. The differentially expressed metabolites identified in negative ion mode were C16 sphingosine-1-phosphate, keto palmitic acid, isoleucine, N-succinyl-L-diaminopimelic acid and uridine. The diagnostic model was established in training samples: p=e(Xβ)/(1+ e(Xβ)), (Xβ)=-158.975-1.891 (age)+ 0.309 (phosphatidylethanolamine 18∶2)+ 1.035 (C16 sphingosine-1-phosphate)+ 0.084 (isoleucine)+ 1.114 5 (N-succinyl-L-diaminopimelic acid). The area under curve (AUC) of receiver operating characteristic (ROC) of this model was 0.982 in validation samples, the sensitivity and specificity were both 93.3%. Conclusion Serum metabolomics-based diagnostic approach is a promising method for screening PC from new onset diabetic mellitus. Key words: Pancreatic neoplasms; Diabetes mellitus; Serum metabolomics

Peptidase inhibitor 16 identifies a human regulatory T-cell subset with reduced FOXP3 expression over the first year of recent onset type 1 diabetes.

CD4+ T-cell subsets play a major role in the host response to infection, and a healthy immune system requires a fine balance between reactivity and tolerance. This balance is in part maintained by regulatory Tcells (Treg), which promote tolerance, and loss of immune tolerance contributes to autoimmunity. As the Tcells which drive immunity are diverse, identifying and understanding how these subsets function requires specific biomarkers. From a human CD4 Tconv/Treg cell genome wide analysis we identified peptidase inhibitor 16 (PI16) as a CD4 subset biomarker and we now show detailed analysis of its distribution, phenotype and links to Treg function in type 1 diabetes. To determine the clinical relevance of Pi16 Treg, we analysed PI16+ Treg cells from type 1 diabetes patient samples. We observed that FOXP3 expression levels declined with disease progression, suggesting loss of functional fitness in these Treg cells in Type 1 diabetes, and in particular the rate of loss of FOXP3 expression was greatest in the PI16+ve Treg. We propose that PI16 has utility as a biomarker of functional human Treg subsets and may be useful for tracking loss of immune function in vivo. The ability to stratify at risk patients so that tailored interventions can be applied would open the door to personalised medicine for Type 1 diabetes.