The Transcription Factors SOX9 and SOX10 Are Vitiligo Autoantigens in Autoimmune Polyendocrine Syndrome Type I

Vitiligo is common in the hereditary disorder autoimmune polyendocrine syndrome type I (APS I). Patients with APS I are known to have high titer autoantibodies directed against various tissue-specific antigens. Using sera from APS I patients for immunoscreening of a cDNA library from human scalp, we identified the transcription factors SOX9 and SOX10 as novel autoantigens related to this syndrome. Immunoreactivity against SOX9 was found in 14 (15%) and against SOX10 in 20 (22%) of the 91 APS I sera studied. All patients reacting with SOX9 displayed reactivity against SOX10, suggesting shared epitopes. Among the 19 patients with vitiligo, 12 (63%) were positive for SOX10 (p0.0001). Furthermore, three of 93 sera from patients with vitiligo unrelated to APS I showed strong reactivity against SOX10, which may indicate a more general role of SOX10 as an autoantigen in vitiligo

Visual and ocular findings in children with fetal alcohol spectrum disorders (FASD): validating the FASD Eye Code in a clinical setting

Objective Fetal alcohol spectrum disorders (FASD) is an umbrella term covering a spectrum of medical conditions caused by prenatal alcohol exposure. The FASD Eye Code is a new complementary ophthalmological diagnostic tool created to corroborate the complex FASD diagnosis. The aim of this work was to validate the FASD Eye Code by testing it on a second group of children diagnosed with FASD in a clinical setting.Methods and analysis A clinical study was carried out in a group of 21 children (13 males, 8 females, mean age 13.3 years) investigated for suspected FASD and a healthy sex-matched and age-matched control group (n=21). The participants underwent a detailed ophthalmological examination including visual perception problems (VPPs) assessment. Clinical examination results were compiled, and total scores were calculated according to the FASD Eye Code protocol (range 4–16).Results The median total score in the FASD group was 8. Eight individuals in the FASD group and none of the controls obtained a total score of ≥9 corresponding to 38% sensitivity and 100% specificity with an area under the curve of 0.90. A cut-off total score of ≥8 showed 52% sensitivity and 95% specificity. One individual in the FASD group versus 12 controls had a total score of 4, representing normal findings. No significant difference between the two groups regarding VPPs was seen.Conclusion The FASD Eye Code can be used as a complementary diagnostic tool for FASD to assist in diagnosis and to detect ophthalmological abnormalities in individuals with suspected FASD

Parental longevity and prognosis in elderly patients with aggressive non-Hodgkin's lymphoma

In general, elderly patients with aggressive non-Hodgkin's lymphoma (NHL) have a less favourable prognosis than younger patients. Established predictors of prognosis in NHL are less discriminatory in the elderly, which is why there is a need for additional markers giving guidance on treatment decisions and prediction of outcome. The expected length of life of an individual in the general population is intimately associated with that of his/her parents. The aim of this study was to test the hypothesis that parental longevity is associated with improved outcome also among elderly patients with aggressive NHL and thus serves as an easily accessible non-disease associated prognostic factor. A total of 220 patients ( > 60 years) with aggressive NHL with a median age of 71 years (range 60-86) were included. Patients were randomized to receive CHOP or CNOP (doxorubicin replaced with mitoxantrone) chemotherapy with or without the addition of granulocyte colony-stimulating factor. The median follow-up time was 56 (19-89) months. Parental data regarding age at death were available through parish offices for 425 (97%) parents. Relative risk (RR) of death (disease-specific and all-cause) associated with parental lifespan was assessed using Cox proportional hazards regression analyses, with adjustment for sex, age, prognostic index, symptoms, and calendar period of diagnosis. Maternal lifespan below (versus above) median was associated with a borderline significant reduced disease-specific (adjusted RR of death from NHL = 1.5; 95% confidence interval 1.0-2.1) and overall survival. The effect of maternal lifespan was somewhat more pronounced in patients receiving CHOP than CNOP treatment. Paternal lifespan below the median was associated with a borderline significant increased disease-specific (adjusted RR of death from NHL = 0.8 [0.5-1.0]) and overall survival. Combined, maternal, and paternal lifespan had little impact on survival. These effects were true also when CHOP and CNOP treated patients were analysed separately. Maternal and paternal lifespan may predict survival in NHL, but with opposing effects. At present parental age appears not to be a clinically useful predictor of prognosis in the elderly with aggressive NHL

Response to splenectomy is durable after a certain point in time in adult patients with chronic immune thrombocytopenic purpura

Splenectomy may lead to a good response in 60-80% of adult patients with corticosteroid refractory idiopathic thrombocytopenic purpura (ITP) but, the long-term response to splenectomy still remains less well defined. We assessed the long-term efficacy and safety of splenectomy in adult patients with chronic ITP. A cohort of 59 splenectomised ITP patients (M/F = 25/34; median age 39 yr; range 14-75) were followed up for a median of 18 yr (range 2-32). No life-threatening surgical complications were observed. The overall response rate was 78% with 59% complete remission (CR) and 19% partial remission (PR). CR and PR patients were younger than non-responding patients at time of diagnosis (median age: 36 yr vs 48 yr, P = 0.03) and at splenectomy (median age: 38 yr vs 51 yr, P = 0.02). Among the 46 responding patients, eventually 17 had relapse. No disease progression occurred after 12.1 and 7.3 yr for patients in CR or PR, respectively. One case of fatal septicaemia was recorded. We conclude that splenectomy is an effective and safe treatment in adult patients with chronic ITP failing to respond to corticosteroid treatment and importantly, our findings support the view that response to splenectomy is durable after a certain point in time

Response to Splenectomy Is Durable after a Certain Point in Time in Adult ITP Patients

Abstract Background. Splenectomy is the recommended treatment in adult patients with immune thrombocytopenic purpura (ITP) who fail to respond to corticosteroid treatment or who require unacceptably high doses to maintain a safe platelet level. For these patients splenectomy may produce a good response in 60–80% of patients. However, the observation time after splenectomy has in most published studies been relatively short. Thus, the true long-term response to splenectomy still remains less well defined. The efficacy and safety of splenectomy were assessed in a cohort of adult ITP patients followed for a very long period of time. Patients and methods. The study included 59 ITP patients (M/F=25/34, median age at splenectomy; 39 yrs, range 14–75 yrs). The median time from diagnosis to splenectomy was 5.5 mos (range 0.4–199 mos). Criteria used to define response to splenectomy were: CR; platelet count >150 x 109/l lasting ≥4 weeks, PR; platelet count ≥50–150 x 109/l lasting ≥4 weeks and, NR; failure to achieve platelet counts ≥50 x 109/l. The criterion for relapse in CR/PR patients was a decrease in platelet counts to <50 x 109/l. Results. The median follow-up time after splenectomy was 18 yrs (range 2–32 yrs). No serious surgical complications occurred. The overall response rate was 78% with 59% CR and 19% PR. CR and PR patients were younger than NR patients at time of diagnosis (median age: 36 yrs vs 48 yrs, p=0.03) and at splenectomy (median age: 38 yrs vs 51 yrs, p=0.02). Among the 46 responding patients 17 eventually relapsed. A plateau in the progression free survival curve was identified after 12.1 and 7.3 years for patients in CR or PR, respectively. Figure Figure At follow-up, 5 of 17 patients relapsing after splenectomy were in CR. Bacteremia was recorded in two patients during a total of 1023 patient years at risk. Conclusions We conclude that splenctomy is an effective and safe treatment in adult patients with chronic ITP failing to respond to corticosteroid treatment. The complication rate was low and our findings support the view that response to splenectomy is durable after a certain point in time

Cardiovascular risk factors in gout, psoriatic arthritis, rheumatoid arthritis and ankylosing spondylitis: a cross-sectional survey of patients in Western Sweden

Objectives We aimed to compare traditional (trad) cardiovascular risk factors (CVRFs) among patients with gout, psoriatic arthritis (PsA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS) stratified by sex.Methods A survey was sent to patients with gout (n=1589), PsA (n=1200), RA (n=1246) and AS (n=1095). Patients were retrieved from Sahlgrenska University Hospital, the hospitals of Uddevalla and Skövde, and 12 primary care centres in Western Sweden. The prevalence of self-reported trad-CVRFs was compared between diagnoses by age standardisation with the 2018 population of Sweden as the standard population.Results In total, 2896 (56.5%) of 5130 patients responded. Hypertension was the most frequently found comorbidity, reported by 65% of patients with gout, 41% with PsA, 43% with RA and 29% with AS. After age standardisation, women and men with gout had significantly more obesity (body mass index ≥30 kg/m2), hypertension, diabetes, hyperlipidaemia and multiple trad-CVRFs, compared with those with PsA, RA and AS. Obesity was significantly more common in PsA than in RA. In women, obesity, hypertension and multiple trad-CVRFs were more frequently reported in PsA than in RA and AS, whereas similar prevalence of CVRFs and coexistence of multiple trad-CVRFs were found in men with PsA, RA and AS.Conclusions Women and men with gout had the highest prevalence of trad-CVRFs. Differences in occurrence of CVRFs by sex were found in patients with PsA, RA and AS. In women, patients with PsA had higher occurrence of trad-CVRFs than those with RA and AS, whereas in men the distribution of CVRFs was similar in PsA, RA and AS

Short-term glucocorticoids reduce risk of chronic NSAID and analgesic use in early methotrexate-treated rheumatoid arthritis patients with favourable prognosis: subanalysis of the CareRA randomised controlled trial

Objective To explore non-steroidal anti-inflammatory drug (NSAID) and analgesic use in early rheumatoid arthritis (eRA) patients with a favourable risk profile initiating methotrexate (MTX) with or without glucocorticoid (GC) bridging.Methods Patients with eRA (≤1 year) and favourable risk profile (no erosions, negative rheumatoid factor and anticitrullinated protein antibodiesor low disease activity) in the 2-year CareRA trial were randomised to MTX 15 mg with a step-down GC scheme (COBRA Slim), or MTX without oral GCs, Tight-Step-Up (TSU). Used analgesics were recorded, including frequency, start/end date and indication. Chronic intake (≥90 consecutive days in trial) of NSAIDs, acetaminophen, opioids including tramadol and antidepressants for the indication of musculoskeletal (MSK) pain was considered. Treatments were compared using χ2 and analysis of variance with Holm’s correction for multiple testing.Results In total, 43 patients were randomised to COBRA Slim and 47 to TSU. At study inclusion, 33/43 (77%) of patients in the COBRA Slim and 32/47 (68%) in the TSU arm had been using analgesics (p=0.5). During the trial, 67 NSAID and analgesics were used for MSK pain in 26/43 (60%) COBRA Slim patients of which 9/43 (21%) daily chronically (DC), while 107 NSAID and analgesics were used in 43/47 (92%) TSU patients, of which 25/47 (53%) DC. The total number of patients on NSAID and analgesics at any time during the study (p&lt;0.01) and chronically (p=0.01) was significantly different between treatment arms. Number of patients on DC NSAIDs was also significantly different (p&lt;0.01) between COBRA Slim 6/43 (14%) and TSU 19/47 (40%).Conclusion In eRA patients considered to have a favourable prognosis, initial oral GC bridging resulted in lower chronic NSAID and analgesic use.Trial registration number NCT01172639

Mild intellectual disability and ADHD; a comparative study of school age children's adaptive abilities

Aim: To compare adaptive functioning in children with mild intellectual disability (MID) with that of children with attention-deficit/hyperactivity disorder (ADHD). Methods: Thirty-three children with MID were contrasted with 27 children with ADHD with regard to adaptive functioning as measured by the Adaptive Behaviour Assessment System (ABAS-II). The group with MID was population-based, and the group with ADHD was considered representative of a clinically referred group with that diagnosis. The two groups were subdivided into those = 12 years. Results: The group with ADHD had lower adaptive functioning, but differences were not significant at total group levels. In children 12 years or older, the group with ADHD had significantly lower adaptive functioning. Conclusion: Older children with ADHD had poorer adaptive functioning than those with MID, a finding which should be of interest to school and other authorities mapping out education and intervention plans for children with special needs

The visual ecology of a deep-sea fish, the escolar Lepidocybium flavobrunneum (Smith, 1843)

Escolar (Lepidocybium flavobrunneum, family Gempylidae) are large and darkly coloured deep-sea predatory fish found in the cold depths (more than 200 m) during the day and in warm surface waters at night. They have large eyes and an overall low density of retinal ganglion cells that endow them with a very high optical sensitivity. Escolar have banked retinae comprising six to eight layers of rods to increase the optical path length for maximal absorption of the incoming light. Their retinae possess two main areae of higher ganglion cell density, one in the ventral retina viewing the dorsal world above (with a moderate acuity of 4.6 cycles deg), and the second in the temporal retina viewing the frontal world ahead. Electrophysiological recordings of the flicker fusion frequency (FFF) in isolated retinas indicate that escolar have slow vision, with maximal FFF at the highest light levels and temperatures (around 9 Hz at 23°C) which fall to 1-2 Hz in dim light or cooler temperatures. Our results suggest that escolar are slowly moving sit-and-wait predators. In dim, warm surface waters at night, their slow vision, moderate dorsal resolution and highly sensitive eyes may allow them to surprise prey from below that are silhouetted in the downwelling light