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PURPOSE To evaluate the outcomes and safety of retropupillary iris-claw intraocular lens implantation and associated pars plana vitrectomy. METHODS Multicenter, national audit of 325 eyes (325 patients). Demographics, surgical details, and complications are described. Visual acuity, intraocular pressure, and central retinal thickness assessed by optical coherence tomography were collected at 1, 3, 6, and 12 months after surgery. Kaplan-Meier curves were created to assess the cumulative probability of postoperative visual acuity and intraocular pressure levels, macular edema development, and corneal decompensation. RESULTS The cumulative probability of the final visual acuity ≤0.3 logarithm of the minimum angle of resolution (≥20/40 Snellen) was 75.6% at 12-month follow-up. The probability of intraocular pressure >21, ≥25, and ≥30 mmHg was 48.1%, 33.1%, and 19.0%, and the probability of intraocular pressure-lowering drops was 50.9% at 12 months. Glaucoma surgery was required in 4.3% of the eyes (14/325). The cumulative probability of macular edema was 20.5% at 12 months and was greater in complicated cataract surgery than in intraocular lens-luxation eyes (26% vs. 16.7%, P = 0.04). Corneal transplantation was required in 2.8% of the eyes (9/325). CONCLUSION This study on 325 eyes with aphakia or intraocular lens dislocation managed with the retropupillary iris-claw intraocular lens technique provides clinical outcomes in a real-world scenario, reporting relevant data for patient counseling and preoperative discussions.

Pathogenic mutations in NDUFAF4 have been reported in very few cases. Here we present new data to further delineate the phenotypic spectrum of NDUFAF4 deficiency. We describe two siblings presenting with facial dysmorphia and lactic acidosis in the neonatal period. Later on, they developed fatal early encephalopathy with apneic episodes, irritability, central hypoventilation, liver involvement and hyperammonemia. Abnormality of the cerebral white matter was demonstrated in one case, and cardiomyopathy in the other. Urine organic acid profile showed an increased excretion of lactate, Krebs cycle metabolites and 3-methylglutaconate. Whole-exome sequencing identified a novel homozygous nonsense mutation in NDUFAF4 (c.478G > T; p.Glu160Ter), encoding a mitochondrial complex I assembly factor. The disruptive effect of the mutation was corroborated by the absence of NDUFAF4 expression in patient fibroblasts. OXPHOS assembly studies demonstrated almost undetectable levels of fully assembled complex I and complex I–containing supercomplexes and an abnormal accumulation of SCIII2IV1 supercomplexes. Morphologically, fibroblasts showed rounder mitochondria and a diminished degree of branching of the mitochondrial network. Cellular respiratory capacity in fibroblasts was also markedly reduced. In sum, we provide insights into the physiopathological mechanisms underlying NDUFAF4 deficiency and expand the knowledge about the clinical and biochemical spectrum of this disorder.

The aim of this study was to validate and analyze the psychometric properties of a Spanish version of the Sexual Trafficking Attitudes Scale towards women and girls (STAS). A sample of 204 students from the University of Salamanca (Spain) was used. The exploratory factor analysis and confirmatory factor analysis confirmed a multifactorial structure of six factors (70.1% of variance). The Cronbach’s α internal consistency index obtained for the sample was 0.87 and composite reliability was 0.94. Convergent validity was determined between the full scale and the six dimensions, and divergent between subscales. The Spanish version of the instrument consisted of 25 items, proving to be a reliable and parsimonious measure.

Pre- and postnatal development and variability in discrete vertebral traits have been poorly described in embryonic studies. Numerous authors have reported that these variations are observable only from adolescence; scientific publications on the vertebrae of fetuses and infants are scarce. Thus, the aims of this study were to (1) describe the ontogeny and variability of anatomical variations in the vertebral column of a Spanish infant population and (2) analyze the frequency and relationship between sex, age, and intertrait variables. A total of 4728 vertebrae from 197 skeletons were studied. The age at death ranged from 22 intrauterine weeks to 8 years. Twenty morphological traits related to vertebral column development were analyzed. A descriptive statistical analysis was performed, and the chi-square test was used to measure the relationship between sex, age, and intertrait variables. We observed that 88.32% of skeletons expressed discrete traits along the spine. In fetuses, the double transverse foramen and unclosed transverse process of the axis were the most prevalent traits. In infants older than one year, the appearance of the L5 cleft neural arch, unclosed transverse process of the atlas, and craniocaudal shifts were frequent. A significant result was found between sex and the unclosed transverse process in the axis. The intertrait relationship was significant for all traits that shared the same embryonic structure. Morphological variations became visible following the appearance of ossification centers during the pre- and postnatal periods, and their etiology was associated with embryonic development.

Background In 2019, EWGSOP2 proposed 4 steps to diagnose and assess sarcopenia. We aimed to quantify the prevalence of sarcopenia according to the EWGSOP2 diagnostic algorithm and to assess its applicability in elderly patients on hemodialysis. Methods Prospective study of 60 outpatients on chronic hemodialysis aged 75- to 95-years, sarcopenia was assessed according to the 4-step EWGSOP2: Find: Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls (SARC-F); Assess: grip strength by dynamometry (GSD) and sit to stand to sit 5 (STS5); Confirm: appendicular skeletal muscle mass (ASM) by bioimpedance; Severity: gait speed (GS), Timed-Up and Go (TUG), and Short Physical Performance Battery (SPPB). Results The sequential four steps resulted in a prevalence of confirmed or severe sarcopenia of 20%. Most (97%) patients fulfilled at least one criterion for probable sarcopenia. The sensitivity of SARC-F for confirmed sarcopenia was low (46%). Skipping the SARC-F step increased the prevalence of confirmed and severe sarcopenia to 40% and 37%, respectively. However, 78% of all patients had evidence of dynapenia consistent with severe sarcopenia. Muscle mass (ASM) was normal in 60% of patients, while only 25% had normal muscle strength values (GSD). Conclusions According to the 4-step EWGSOP2, the prevalence of confirmed or severe sarcopenia was low in elderly hemodialysis patients. The diagnosis of confirmed sarcopenia underestimated the prevalence of dynapenia consistent with severe sarcopenia. Future studies should address whether a 2-step EWGSOP2 assessment (Assess-Severity) is simpler to apply and may provide better prognostic information than 4-step EWGSOP2 in elderly persons on hemodialysis.

Refractoriness to induction therapy and relapse after complete remission are the leading causes of death in patients with acute myeloid leukaemia (AML). This study focussed on the prediction of response to standard induction therapy and outcome of patients with AML using a combined strategy of mutational profiling by next-generation sequencing (NGS, n = 190) and ex vivo PharmaFlow testing (n = 74) for the 10 most widely used drugs for AML induction therapy, in a cohort of adult patients uniformly treated according to Spanish PETHEMA guidelines. We identified an adverse mutational profile (EZH2, KMT2A, U2AF1 and/or TP53 mutations) that carries a greater risk of death [hazard ratio (HR): 3·29, P < 0·0001]. A high correlation was found between the ex vivo PharmaFlow results and clinical induction response (69%). Clinical correlation analysis showed that the pattern of multiresistance revealed by ex vivo PharmaFlow identified patients with a high risk of death (HR: 2·58). Patients with mutation status also ran a high risk (HR 4·19), and the risk was increased further in patients with both adverse profiles (HR 4·82). We have developed a new score based on NGS and ex vivo drug testing for AML patients that improves upon current prognostic risk stratification and allows clinicians to tailor treatments to minimise drug resistance.

(1) Sarcopenia is a progressive loss of skeletal muscle mass and strength. The aim of this study was to determine the association of sarcopenia, defined according to the Working Group on Sarcopenia in Older People (EWGSOP2) diagnostic criteria, with mortality at 24 months in very elderly hemodialysis patients. (2) A prospective study was conducted in 60 patients on chronic hemodialysis who were older than 75 years. Sarcopenia was diagnosed according to EWGSOP2 criteria. Additionally, clinical, anthropometric and analytical variables and body composition by bioimpedance were assessed. The date and cause of death were recorded during 2 years of follow-up. (3) Among study participants, 41 (68%) were men, the mean age 81.85 ± 5.58 years and the dialysis vintage was 49.88 ± 40.29 months. The prevalence of probable sarcopenia was 75% to 97%, depending on the criteria employed: confirmed sarcopenia ranged from 37 to 40%, and severe sarcopenia ranged from 18 to 37%. A total of 30 (50%) patients died over 24 months. Sarcopenia probability variables were not related to mortality. In contrast, sarcopenia confirmation (appendicular skeletal muscle mass, ASM) and severity (gait speed, GS) variables were associated with mortality. In multivariate analysis, the hazard ratio (95% confidence interval) for all-cause death was 3.03 (1.14–8.08, p = 0.028) for patients fulfilling ASM sarcopenia criteria and 3.29 (1.04–10.39, p = 0.042) for patients fulfilling GS sarcopenia criteria. (4) The diagnosis of sarcopenia by EWGSOP2 criteria is associated with an increased risk of all-cause death in elderly dialysis patients. Specifically, ASM and GS criteria could be used as mortality risk markers in elderly hemodialysis patients. Future studies should address whether the early diagnosis and treatment of sarcopenia improve outcomes.

Background and Aims The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. Results A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusions Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

Background Well-designed studies assessing the treatment outcome of brain arteriovenous malformations (AVMs) are infrequent and have not consistently included all of the available treatment modalities, making their results not completely generalizable. Moreover, the predictors of poor outcome are not well defined. Methods We performed an observational retrospective study of AVM patients. We included patients with clinical, radiologic, and outcome data, with a minimum follow-up of 1 year. Neurologic outcome was documented using the modified Rankin Scale (mRS) at the AVM diagnosis and 30 days after the treatment. Results There were 117 patients, with equal male/female proportion. The mean follow-up time was 51 months. Treatment distribution in the Spetzler–Martin grades I–III was as follows: 52 (54.6%) surgery, 31 (32.35%) radiosurgery, 2 (0.02%) embolization, and 11 (12%) conservative follow-up. Treatment distribution in Spetzler–Martin grades IV and V was as follows: 4 (20%) surgery, 7 (35%) radiosurgery, and 10 (45%) conservative follow-up. Poor neurologic outcome (mRS ≥ 3) was significantly associated with poor clinical status at diagnosis (Glasgow Coma Scale [GCS] score< 14; odds ratio [OR]: 0.20; 95% confidence interval [CI]: 0.001–0.396; p = 0.010). The rupture of the AVM was associated with poor neurologic outcome. The Lawton–Young Supplementary scale (LYSS) proved to be the most effective in predicting poor outcome. The existence of seizures, treatment-related complications, and conservative treatment was associated with the worsening of the mRS score, whereas the existence of hemorrhage was associated with the likelihood of disability. Conclusion Our results suggest that poor neurologic status at diagnosis, AVM rupture, and conservative treatment were associated with worse outcome. Hemorrhage as initial presentation is related to disability, not with mRS worsening. The LYSS appeared to be the best method to predict outcome.

Severe combined immunodeficiency (SCID), the most severe form of T-cell immunodeficiency, can be screened at birth by quantifying T-cell receptor excision circles (TREC) in dried blood spot (DBS) samples. Early detection of this condition speeds up the establishment of appropriate treatment and increases the patient's life expectancy. Newborn screening for SCID started in January 2017 in Catalonia, the first Spanish and European region to universally include this testing. The results obtained in the first three years and a half of experience (January 2017 - June 2020) are shown here, using EnLite Neonatal TREC kit (Perkin Elmer) with 20 copies/µL as TREC detection cutoff. Of 222,857 newborns screened, 48 tested positive: three patients were diagnosed with SCID (incidence 1:74,285); 17 patients had clinically significant T-cell lymphopenia (non-SCID) with an incidence of 1 in 13,109 newborns; twenty two patients were considered false-positive cases because of an initially normal lymphocyte count with normalization of TREC between 3 and 6 months of life; one case had transient lymphopenia due to an initially low lymphocyte count with recovery in the following months; and five patients are still under study. The results obtained provide further evidence of the benefits of including this disease in newborn screening programs. Even longer follow-up could be necessary to define the exact incidence of SCID in Catalonia.La inmunodeficiencia combinada grave (IDCG) es la forma más grave de inmunodeficiencia primaria, que afecta sobre todo a los linfocitos T, y puede ser detectada al nacer mediante la cuantificación de los círculos de escisión del receptor de linfocitos T (TREC) en una muestra de sangre impregnada en papel (DBS). La detección precoz de esta enfermedad permite establecer de forma temprana un tratamiento adecuado en el paciente, permitiendo así su curación. El cribado neonatal de IDCG comenzó en Cataluña en enero de 2017, siendo la primera región española y europea en incluirla oficial y universalmente en su programa. En el presente trabajo se presentan los resultados obtenidos durante los tres primeros años y medio de experiencia (enero 2017 – junio 2020) empleando el kit EnLite Neonatal TREC (Perkin Elmer), con un cutoff de detección de TREC de 20 copias/µL. De 222.857 recién nacidos analizados, cuarenta y ocho fueron detecciones positivas: tres casos de IDCG (incidencia de 1:74.285); diecisiete casos de linfopenia T no IDCG (incidencia de 1:13.109); veintidós casos falsos positivos (recuento de linfocitos inicialmente normal, con normalización de TREC entre los tres y seis meses de vida); un caso con linfopenia transitoria (con un recuento de linfocitos inicialmente bajo, que se normaliza en los meses siguientes); y cinco pacientes se encuentran todavía en estudio. Los resultados obtenidos aportan evidencias de los beneficios que supone incluir esta enfermedad en los programas de cribado neonatal. Podría ser necesario un seguimiento todavía más prolongado para acabar de definir la incidencia exacta de IDCG en Cataluña.

Patients with life threatening diseases may experience anxiety and depression.To analyze anxiety and depression in Chilean patients with cancer.The Hospital Anxiety and Depression Scale (HADS) was applied to 623 ambulatory and hospitalized patients with cancer (70% women).A low frequency of clinical anxiety (11,7%) and depression (5,3%) was observed. Depression was more common in women, in patients with mid-level education, in unemployed patients and in older people. Anxiety was more common in young and unemployed patients.The frequency of depression and anxiety was low in this group of cancer patients. Women, educated, uneomployed, and older subjects are risk groups for depression. Young and unemployed subjects experience more anxiety.

Purpose To report a case of hypertensive choroidopathy with detailed chorioretinal images obtained using swept source optical coherence tomography. Methods We report the case of a 36-year-old pregnant woman who presented with extensive bilateral exudative retinal detachments (visual acuity of hands movement bilaterally), high blood pressure, and severe alteration of the laboratory test results resulting in the diagnosis of HELLP syndrome. The baby was delivered by emergency cesarean section and the patient was hospitalized in the intensive care unit. Results Two weeks later, exudative retinal detachments improved substantially and bilateral Elschnig spots were present in the posterior fundus. Swept source optical coherence tomography revealed serous retinal detachment, multiple pigmentary epithelial detachments (PEDs), a thickened subfoveal choroid (437 and 466 μm), and fibrinous material between the neurosensory retina and retinal pigment epithelium in the B-scans of both eyes. En face swept source optical coherence tomography allowed a more precise evaluation of the multiple and confluent PEDs. Six weeks later, despite some focal areas of thickened retinal pigment epithelium, the serous retinal detachment, PEDs, and fibrinous material resolved bilaterally and visual acuity and choroidal thickness returned to normal range (361 and 366 μm). En face swept source optical coherence tomography revealed a dramatic improvement of PEDs in terms of extension and distribution. Conclusion Swept source optical coherence tomography detected serous retinal detachment, PEDs, increased subfoveal choroidal thickness, and fibrinous material under the neurosensory retina in the acute phase of hypertensive choroidopathy. En face OCT is useful for monitoring the evolution of confluent PEDs in hypertensive choroidopathy.

High myopia and the subsequent degenerative changes of the retina, choroid, and sclera, known as myopic maculopathy (MM), are a serious visual problem in many Asian countries, and are beginning to be so in the south of Europe, especially in the Mediterranean. It is therefore necessary to carry out genetic and environmental studies to determine the possible causes of this disease. This study aims to verify if the genetic factors that have been most related to Asian populations are also associated in two Spanish cohorts. Eight SNPs from six genes (PAX6, SCO2, CCDC102B, BLID, chromosome 15q14, and COL8A1) along with demographic, ophthalmic and environmental factors were analysed in two cohorts from a total of 365 highly myopic subjects and 177 control subjects. The genetic analysis showed that COL8A1 SNP rs13095226 was associated with the development of choroidal neovascularization (CNV) and also seems to play an important role in the increase of axial length. The SNP rs634990 of chromosome 15q14 also showed a significant association with MM, although this was lost after the Bonferroni correction. Additional demographic and environmental factors, namely age, sex, smoking status, and pregnancy history, were also found to be associated with MM and CNV in this population.

Background: Effectiveness of vedolizumab in real world clinical practice is unknown. Aim: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). Methods: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. Results: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. Conclusions: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.

Intraocular pressure; Intravitreal dexamethasone Pressió intraocular; Dexametasona intravitrea Presión intraocular; Dexametasona intravítrea PURPOSE: To evaluate the long-term cumulative probability of intraocular pressure (IOP) elevation with the intravitreal dexamethasone implant (IDI) when used to treat different indications: diabetic macular edema, uveitis, retinal vein occlusion. METHODS: 705 IDI injections (429 eyes) were assessed and Kaplan-Meier graphs were generated to assess: the probability of different levels of IOP elevation (IOP≥21, ≥25 or ≥35 mmHg), IOP change ≥10 mmHg, initiation of IOP-lowering treatment, glaucoma surgery, IOP change with repeat injections and IOP elevation in eyes with glaucoma and ocular hypertension (OHT). RESULTS: The cumulative probability of IOP ≥21, ≥25 and ≥35 mmHg was 50%-60%, 25%-30% and 6%-7% at 12-24 months, respectively. The probability of initiating IOP-lowering medication was 31%-54% at 12-24 months. Glaucoma and OHT eyes had a higher probability of mild IOP elevation (≥21 mmHg, 65.1%, 75% and 57.8%, p = 0.01), yet a similar moderate (≥25 mmHg, 22.3%, 28% and 30.2%, p = 0.91) and severe elevation of IOP (≥35 mmHg, 3.7%, 7.1% and 4%, p = 0.71) as normal eyes. Glaucoma surgery was required in only 0.9% cases (4/429). At baseline, 8.8% of the treated eyes had glaucoma, 6.7% OHT and 16.9% were already on IOP-lowering medication. CONCLUSIONS: In the long-term (24 months), IOP elevation is common, generally mild (30% IOP, ≥25 mmHg) and well-tolerated, resolving with topical treatment (54%) and rarely requiring surgery (0.9%).

The frequency of mitochondrial diseases (MD) has been scarcely documented, and only a few studies have reported data in certain specific geographical areas. In this study, we arranged a nationwide call in Spain to obtain a global estimate of the number of cases. A total of 3274 cases from 49 Spanish provinces were reported by 39 centres. Excluding duplicated and unsolved cases, 2761 patients harbouring pathogenic mutations in 140 genes were recruited between 1990 and 2020. A total of 508 patients exhibited mutations in nuclear DNA genes (75% paediatric patients) and 1105 in mitochondrial DNA genes (33% paediatric patients). A further 1148 cases harboured mutations in the MT-RNR1 gene (56% paediatric patients). The number of reported cases secondary to nuclear DNA mutations increased in 2014, owing to the implementation of next-generation sequencing technologies. Between 2014 and 2020, excepting MT-RNR1 cases, the incidence was 6.34 (95% CI: 5.71–6.97) cases per million inhabitants at the paediatric age and 1.36 (95% CI: 1.22–1.50) for adults. In conclusion, this is the first study to report nationwide epidemiological data for MD in Spain. The lack of identification of a remarkable number of mitochondrial genes necessitates the systematic application of high-throughput technologies in the routine diagnosis of MD.

Since their separation as independent diagnostics, autism spectrum disorders (ASD) and schizophrenia spectrum disorders (SSD) have been conceptualized as mutually exclusive disorders. Similarities between both disorders can lead to misdiagnosis, especially when it comes to average-IQ adults who were not identified during childhood. The aim of this review was to examine the occurrence of SSD in average-IQ adults with ASD. Electronic and manual searches identified a total of 278 references, of which 10 were included in a meta-analysis. The pooled prevalence of SSD in the total ASD sample was close to 6%, pointing to a high co-occurrence of the two conditions. Further research is needed to determine the factors that predispose members of this population to the emergence of psychotic disorders.

Hepatic encephalopathy (HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events (i.e., portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here, we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment, hyperammonaemia, electroencephalograph alterations, impaired neuropsychological performance, and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE, paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE.

Isolated complex I (CI) deficiency is the most common cause of oxidative phosphorylation (OXPHOS) dysfunction. Whole-exome sequencing identified biallelic mutations in NDUFA8 (c.[293G > T]; [293G > T], encoding for an accessory subunit of CI, in two siblings with a favorable clinical evolution. The individuals reported here are practically asymptomatic, with the exception of slight failure to thrive and some language difficulties at the age of 6 and 9 years, respectively. These observations are remarkable since the vast majority of patients with CI deficiency, including the only NDUFA8 patient reported so far, showed an extremely poor clinical outcome. Western blot studies demonstrated that NDUFA8 protein was strongly reduced in the patients' fibroblasts and muscle extracts. In addition, there was a marked and specific decrease in the steady-state levels of CI subunits. BN-PAGE demonstrated an isolated defect in the assembly and the activity of CI with impaired supercomplexes formation and abnormal accumulation of CI subassemblies. Confocal microscopy analysis in fibroblasts showed rounder mitochondria and diminished branching degree of the mitochondrial network. Functional complementation studies demonstrated disease-causality for the identified mutation as lentiviral transduction with wild-type NDUFA8 cDNA restored the steady-state levels of CI subunits and completely recovered the deficient enzymatic activity in immortalized mutant fibroblasts. In summary, we provide additional evidence of the involvement of NDUFA8 as a mitochondrial disease-causing gene associated with altered mitochondrial morphology, CI deficiency, impaired supercomplexes formation, and very mild progression of the disease.

INTRODUCTION: To compare Engerix-B and Fendrix hepatitisBvirus for primo vaccination in inflammatory bowel disease (IBD). METHODS: Patients with IBD were randomized 1:1 to receive Engerix-B double dose or Fendrix single dose at months 0, 1, 2, and 6. Anti-HBs titers were measured 2 months after the third and fourth doses. Response to vaccination was defined as anti-HBs >= 100 UI/L. Anti-HBs titers were measured 2 months after the third and fourth doses and again at 6 and 12 months after the fourth dose. RESULTS: A total of 173 patients were randomized (54% received Engerix-B and 46% Fendrix). Overall, 45% of patients responded (anti-HBs >= 100 IU/L) after 3 doses and 71% after the fourth dose. The response rate after the fourth dose was 75% with Fendrix vs 68% with Engerix-B (P 5 0.3). Older age and treatment with steroids, immunomodulators, or anti-tumor necrosis factor were associated with a lower probability of response. However, the type of vaccine was not associated with the response. Anti-HBs titer negativization occurred in13% of patients after 6months and 20% after12months. Anti-HBs 100 IU/L after vaccination was the only factor associated with maintaining anti-HBs titers during follow-up. DISCUSSION: We could not demonstrate a higher response rate of Fendrix (single dose) over Engerix-B (double dose). A 4-dose schedule is more effective than a 3-dose regimen. Older age and treatment with immunomodulators or anti-tumor necrosis factors impaired the success. A high proportion of IBD patients with protective anti-HBs titers after vaccination loose them over time. The risk of losing protective anti-HBs titers is increased in patients achieving anti-HBs

INTRODUCTION: Patients with Crohn's disease experiencing endoscopic postoperative recurrence (POR) may benefit from antitumor necrosis factor (TNF) agents but scarce data on this are available. Our aim was to assess the efficacy of anti-TNF in improving mucosal lesions in patients with endoscopic POR. METHODS: Multicenter, retrospective, study of patients with Crohn's disease who underwent therapy with anti-TNF agents for endoscopic POR (Rutgeerts score > i1). Treatment outcomes were assessed by the findings in the last ileocolonoscopy performed after anti-TNF therapy was initiated. Endoscopic improvement and remission were defined as any reduction in the baseline Rutgeerts score and by a Rutgeerts score < i2, respectively. RESULTS: A total of 179 patients were included, 83 were treated with infliximab and 96 with adalimumab. Median time on anti-TNF therapy at the last endoscopic assessment was 31 months (interquartile range, 13-54). Endoscopic improvement was observed in 61%, including 42% who achieved endoscopic remission. Concomitant use of thiopurines and treatment with infliximab were associated with endoscopic improvement (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.04-4.46; P = 0.03, and OR 2.34, 95% CI 1.18-4.62; P < 0.01, respectively) and endoscopic remission (OR 3.16, 95% CI 1.65-6.05; P < 0.01, and OR 2.01, 95% CI 1.05-3.88; P = 0.04, respectively) in the multivariable logistic regression analysis. These results were confirmed in a propensity-matched score analysis. DISCUSSION: In patients with endoscopic POR, anti-TNF agents improve mucosal lesions in almost two-thirds of the patients. In this setting, concomitant use of thiopurines and use of infliximab seem to be more effective in improving mucosal lesions.

Objective:To describe social participation strategies and resilience in the people affected by the 2017 earthquakes in Mexico.Methods:A cross-sectional study was carried out with 1504 participants from Mexico City, State of Mexico, Oaxaca, Chiapas, Puebla, and Morelos in November and December 2017. A nonprobabilistic convenience sampling method was used to recruit voluntary participants who met the inclusion criteria: age 18 or over and residents in damaged states at the time of the earthquakes. Postearthquake social participation strategies were assessed with the formats used in the postearthquake Chilean survey in 2010. The Spanish-validated version of the resilience scale RS-14 was applied for measuring resilience in the Mexican population.Results:The most frequent social participation strategies were related to emotional support and aid supplying water, food, and clothing. The highest resilience was observed in the state of Oaxaca and in Mexico City. Men, people age 40 or over, and people who defined themselves as indigenous were the most resilient.Conclusions:Factors related to resilience were male gender, age over 40, did not participate in activities of help to the community, no household damage, and belonging to an indigenous community.

The objective of this study was to adapt and validate the abbreviated version of the “Autism-Spectrum Quotient” (AQ-Short) in a sample of Spanish native adults. A total of 46 individuals with ASD, 41 ASD-relatives, 17 patients with schizophrenia spectrum disorders and 190 non-clinical adults were administered the Spanish version of the AQ-Short. The results of the confirmatory factorial analysis found two high-order factors (Social Behaviour and Numbers/Patterns) and four subscales (Social Skills, Routines, Switching and Imagination). The reliability analysis showed very good internal structure and test–retest reliability. The AQ-Short also showed moderate convergent validity with ADOS-2. Differences by group were found in the ASD group when compared to other groups. Gender differences were only found in the non-clinical group.

Background Fatigue is a common symptom in patients with inflammatory bowel disease (IBD), and it often persists despite clinical remission. Acupuncture has been shown to be effective for treating fatigue in patients with many chronic diseases. The main objective of the study was to assess the efficacy of electroacupuncture (EAc), compared with sham EAc (ShEAc) or being on a waitlist (WL), for treating fatigue in patients with quiescent IBD in a single-blind randomized trial. Methods Fifty-two patients with IBD in clinical remission and fatigue were randomly assigned to 1 of 3 groups: EAc, ShEAc, or WL. Patients in the EAc and ShEAc groups received 9 sessions over 8 weeks. Fatigue was evaluated with the IBD-validated Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-FS). Results Baseline characteristics were similar in the 3 groups. Both EAc and ShEAc presented improved Functional Assessment of Chronic Illness Therapy-Fatigue Scale scores compared with baseline: the respective improvements were 9.53 (95% confidence intervals, 6.75–12.3, P < 0.001) and 5.46 points (95% confidence intervals, 2.7–9.7, P = 0.015), respectively. No significant changes were observed in the WL group. In the comparison of treatment groups, EAc was nonsignificantly better than ShEAc (EAc, 33.27 and ShEAc, 28.13, P = 0.168); both EAc and ShEAc improved fatigue scores significantly compared to WL (24.5; P = 0.01 and 0.04, respectively). Conclusions Both EAc and ShEAc reduced fatigue scores in IBD patients when compared to WL. No differences were observed between EAc and ShEAc, although the study was not powered to rule out a difference. Acupuncture may offer improvements to patients with few other treatment alternatives. Clinical Trials Org Id: NCT02733276.

Immunosuppressant therapies (IMTs; thiopurines, anti-tumor necrosis factor agents) may influence the immunologic control of cancer and might facilitate the spread and recurrence of cancer. This study assesses the impact of the use of IMTs on the development of incident cancers (recurrent or new) in patients with inflammatory bowel disease (IBD) and a history of malignancy.Patients with IBD included in the ENEIDA registry with a history of cancer without being exposed to IMTs were identified and retrospectively reviewed and compared regarding further treatment with IMTs or not by means of a log-rank test.Overall, 520 patients with previous extracolonic cancer naive to IMTs before the diagnosis of cancer were identified. Of these, 146 were subsequently treated with IMTs (exposed), whereas 374 were not (nonexposed). The proportion of patients with incident cancers was similar in both exposed (16%) and nonexposed (18%) patients (P = 0.53); however, there was more than a 10-year difference in the age at index cancer between these 2 groups. Cancer-free survival was 99%, 98%, and 97% at 1, 2, and 5 years in exposed patients, and 97%, 96%, and 92% at 1, 2, and 5 years in non-exposed patients, respectively (P = 0.03). No differences in incident cancer rates were observed between exposed and nonexposed patients when including only those who were exposed within the first 5 years after cancer diagnosis.In patients with IBD and a history of cancer not related to immunosuppression, the use of IMTs is not associated with an increased risk of new or recurrent cancers even when IMTs are started early after cancer diagnosis.

Describe a time-sparing technique to measure disc-foveal angle (DFA), determine normal values and its role when analyzing paired fundus photographs.DFA was analysed using the software program Keynote v.6.2.2 on 440 fundus photographs (3D OCT 2000, Topcon Corporation, Tokio, Japan) of 20 individuals. The 11 different head positions were determined with the cervical range of motion device (CROM, Performance Attainment Associates). A reproducibility and correlation study between two fundus cameras (OCT 3D-2000 and TRC-50EX, Topcon Corporation, Tokio, Japan) was performed.Mean DFA of the right and left eye was 5.5±3.4° and 8.6±2.9°, with a difference of 3.1° (P=0.001 Wilcoxon signed-rank test) in the upright head position. Mean absolute difference in DFA between eyes was 3.5±2.6°; an increase was seen with increasing head tilt (P=0.000 Wilcoxon signed-rank test). Mean sum of DFA in both eyes was 14.1±5.4°. On head-tilt of 20° and 40° to the right, mean ocular counterrolling (OCR) was 7.1° and 12.2° in the right eye and 7.7° and 12.1° in the left eye. On head-tilt of 20° and 40° to the left, OCR was 4.4° and 8° in the right eye and 4.2° and 8.7° in the left eye (P=0.000 Wilcoxon signed-rank test). The two cameras showed strong correlation and high reproducibility.Our DFA measurement technique is time-sparing and reproducible. Left eye shows higher DFA than right eye. OCR occurs only in the roll plane. This information is of value when analyzing paired fundus photographs.

The pathophysiology of restless legs syndrome (RLS) is complex. Secondary RLS with iron deficiency -which suggests disturbed iron homeostasis- remains to be elucidated.We report the findings from a unique blood donor family with RLS. Three blood donors family members were diagnosed with RLS defined by the International RLS Study Group and without history of neurologic diseases and RLS symptoms in the last 3-5 years (range of blood donation: 10-40 years). The neurological examination and electromyographies were normal. A polisomnography showed disturbed nocturnal sleep with a reduction in sleep efficiency and an increased periodic limbs movement index. The cranial MRI showed brain iron deposits in basal ganglia, substantia nigra, red nuclei and dentate nuclei. Phenotypic and genotypic studies rule out genetic haemochromatosis or iron overload.The abnormal iron accumulation in the basal ganglia indicated a complex iron metabolism disorder of the central nervous system. Further studies are warranted to confirm our findings and its role in the pathophysiology of RLS.Aumento de los depositos cerebrales de hierro en una familia de donantes de sangre con sindrome de piernas inquietas.Introduccion. La fisiopatologia del sindrome de piernas inquietas (SPI) es compleja. El mecanismo a traves del cual la ferropenia favorece el desarrollo del SPI no esta esclarecido, aunque se sugiere la presencia de una alteracion en la homeostasis cerebral del hierro. Casos clinicos. Se presentan los hallazgos inusuales en una familia de donantes de sangre con SPI. Tres miembros de la misma familia fueron diagnosticados de SPI, cumpliendo los criterios definidos por el grupo internacional para el estudio del SPI (International Restless Legs Syndrome Study Group). Todos eran donantes de sangre habituales (rango de donacion: 10-40 años) y los sintomas de SPI tenian un curso de 3-5 años. La exploracion general y neurologica fue normal en todos los casos, asi como los electromiogramas. El estudio fenotipico y genotipico descarto la presencia de hemocromatosis y otras causas geneticas de sobrecarga cerebral de hierro. Los estudios polisomnograficos mostraron sueño nocturno perturbado, con reduccion de su eficiencia, y un aumento del indice de movimientos periodicos de las piernas. La resonancia magnetica craneal evidencio un aumento de los depositos cerebrales de hierro en los ganglios basales, la sustancia negra, el nucleo rojo y los dentados. Conclusion. Este aumento patologico de los depositos cerebrales de hierro sugiere la presencia de un complejo trastorno del metabolismo cerebral del hierro en nuestros pacientes. Futuros estudios deben confirmar estos hallazgos y profundizar en el estudio de su relacion con la fisiopatologia del SPI.

This is the first study to produce a reliable valid measure of the symptoms of Posttraumatic Stress Disorders (PTSD) in Mexico, which has a high incidence of disasters, and has not had a measurement of PTSD frequency in the population. The objective was to analyze the prevalence of PTSD symptoms in persons who experienced the 2017 earthquakes in Mexico. A probabilistic sample of 1539 participants from Mexico City, the State of Mexico, Chiapas, Puebla, Morelos and Oaxaca during November and December of 2017 was screened using the Davidson Trauma Scale (DTS) for symptoms of post-traumatic stress. The prevalence of PTSD symptoms was 34.6%, with greater effects on the inhabitants of Oaxaca, Morelos and Puebla, women, indigenous people and people who experienced damage to their homes (p = 0.001). The DTS had a moderate negative correlation with the RS-14 and a Cronbach's alpha coefficient of 0.957. The confirmatory factor analysis generated four factors that explain 50% of the variance, compatible with a Dysphoria model. We can conclude that one in three people exposed to earthquakes had symptoms of post-traumatic stress.

Background and Aims Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. Methods PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. Results In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50–139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7–19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9–5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1–9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39–53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. Conclusions PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.

Newborn screening; Severe combined immunodeficiency; T-cell receptor excision circles Cribratge de nadons; Immunodeficiència combinada greu; Cercles d'excisió de receptors de cèl·lules T Cribado de recién nacidos; Inmunodeficiencia combinada grave; Círculos de escisión de receptores de células T Severe combined immunodeficiency (SCID), the most severe form of T-cell immunodeficiency, can be screened at birth by quantifying T-cell receptor excision circles (TRECs) in dried blood spot (DBS) samples. Early detection of this condition speeds up the establishment of appropriate treatment and increases the patient's life expectancy. Newborn screening for SCID started in January 2017 in Catalonia, the first Spanish and European region to universally include this testing. The results obtained in the first 2 years of experience are evaluated here. All babies born between January 2017 and December 2018 were screened. TREC quantification in DBS (1.5 mm diameter) was performed with the Enlite Neonatal TREC kit from PerkinElmer (Turku, Finland). In 2018, the retest cutoff in the detection algorithm was updated based on the experience gained in the first year, and changed from 34 to 24 copies/μL. This decreased the retest rate from 3.34 to 1.4% (global retest rate, 2.4%), with a requested second sample rate of 0.23% and a positive detection rate of 0.02%. Lymphocyte phenotype (T, B, NK populations), expression of CD45RA/RO isoforms, percentage and intensity of TCR αβ and TCR γδ, presence of HLA-DR+ T lymphocytes, and in vitro lymphocyte proliferation were studied in all patients by flow cytometry. Of 130,903 newborns screened, 30 tested positive, 15 of which were male. During the study period, one patient was diagnosed with SCID: incidence, 1 in 130,903 births in Catalonia. Thirteen patients had clinically significant T-cell lymphopenia (non-SCID) with an incidence of 1 in 10,069 newborns (43% of positive detections). Nine patients were considered false-positive cases because of an initially normal lymphocyte count with normalization of TRECs between 3 and 6 months of life, four infants had transient lymphopenia due to an initially low lymphocyte count with recovery in the following months, and three patients are still under study. The results obtained provide further evidence of the benefits of including this disease in newborn screening programs. Longer follow-up is needed to define the exact incidence of SCID in Catalonia.

Research suggests that the progressive abandonment of activities in cancer patients are related to depression and worse quality of life. Behavioral activation (BA) encourages subjects to activate their sources of reinforcement and modify the avoidance responses. This study assesses the effectiveness of BA in improving quality of life and preventing emotional disorders during chemotherapy treatment. One sample of lung cancer patients and another of breast cancer patients were randomized into a BA experimental group (E.G.lung/4sess. n = 50; E.G.breast/6sess. n = 33) and a control group (C.G.lung/4sess. n = 40; C.G.breast/6sess. n = 35), respectively. In each session and in follow-ups (3/6/9 months), all participants completed different assessment scales. The results converge to show the effectiveness of BA, encouraging cancer patients to maintain rewarding activities which can activate their sources of day-to-day reinforcement and modify their experience avoidance patterns. BA appears to be a practical intervention which may improve social and role functioning and the emotional state of cancer patients during chemotherapy treatment.

Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules., This study was supported by grants from the Spanish Ministry of Economy, Industry and Competitiveness, Enisa (Empresa Nacional de Innovación, S.A.) and Soprea (Sociedad para la Promoción y Reconversión Económica de Andalucía, S.A.U.).

Introduction: Few recent data on the epidemiology of inflammatory bowel disease (IBD) are available, especially in Southern Europe. Aim: To evaluate the prevalence, incidence and mortality of IBD in Catalonia during the period 2011–2016. Material and methods: Data on the prevalence, incidence and mortality of IBD were obtained from the Catalan Health Surveillance System (CHSS). Crude incidence and prevalence rates were calculated for all the Catalan population. Trends in age-sex-adjusted rates were also estimated, and logistic regression was used to calculate the adjusted mortality odds ratio (OR). Data for Crohn’s disease (CD) and ulcerative colitis (UC) were analyzed separately. Results: The prevalence per 100,000 inhabitants in 2016 was 353.9 for UC and 191.4 for CD. The total number of IBD patients rose from 29543 in 2011 to 40614 in 2016. IBD was associated with significantly elevated adjusted mortality ratios: 1.28 (95% CI: 1.6–1.4) for UC and 1.85 (95% CI: 1.62–2.12) for CD. Conclusions: IBD prevalence is very high and is increasing rapidly in Catalonia. Both CD and UC are associated with significantly higher mortality rates.Key messageCrohn disease and ulcerative colitis present a small but significant increase in mortality compared to non-inflammatory bowel disease.The prevalence of inflammatory bowel disease is increasing rapidly in Catalonia.Data on prevalence and incidence suggest that the number of patients may double in approximately 10 years. Crohn disease and ulcerative colitis present a small but significant increase in mortality compared to non-inflammatory bowel disease. The prevalence of inflammatory bowel disease is increasing rapidly in Catalonia. Data on prevalence and incidence suggest that the number of patients may double in approximately 10 years.

The health status of a population is the conjunction of many biological, political and social factors. The biological representations of diseases are attributed to factors, such as ischemic heart disease, that are attributed to unhealthy lifestyles when individuals have high levels of cholesterol and triglycerides, or lack of physical activity, or to genetic factors while ignoring social factors such as poverty. This study observes how morbidity and mortality of the population could be affected by living conditions.

Objective: To determine the comparative effectiveness of 3 real-practice preventive programs aimed at lowering the relapse risk following a suicide attempt: a single priority appointment with an outpatient psychiatrist, an enhanced contact intervention, and an individual psychotherapy program. Methods: This observational study was conducted in a sample of 1,492 suicide attempters from 3 catchment areas in Madrid, Spain, between 2013 and 2017. Relapse was defined as an emergency department return after a new attempt within a 1-year follow-up. Kaplan-Meier survival functions were obtained by intervention, and Cox proportional hazard regression models were used to estimate unadjusted and adjusted risks of relapse by intervention. Sex- and age-stratified analyses were also conducted. Covariates were age, sex, history of suicide attempts, history of psychiatric disorders, main ICD-10 psychiatric diagnostic groups, medical comorbidities, and family support. Results: A total of 133 subjects (8.9%) relapsed. The psychotherapy group had a lower presence of known risk factors for suicide attempt. Individual psychotherapy and enhanced contact were more effective than a single priority appointment at reducing suicide reattempt, with a 40% lower relapse risk in adjusted models. Results did not differ after sex and age stratification. Conclusions: In a naturalistic clinical setting, patients exposed to individual psychotherapy or an enhanced contact intervention had a similar, lower relapse risk than the single priority appointment group.

Background and objectives The aim of this project is to assess diagnostic reclassification based on molecular data over morphology in a series of glial tumours since the introduction of the 2016 WHO classification of brain tumours. Materials and methods Retrospective review of glial tumours (oligodendrogliomas and astrocytomas) treated in our centre between January 2012 and June 2016 in which a review of diagnosis was performed when molecular studies were added. Statistical analysis included evaluation of variables of epidemiology, morphology and molecular data (mainly IDH mutation and 1p19q codeletion), diagnostic changes after new classification was considered, and clinical impact in cases of diagnostic reclassification. Results From a total of 147 glial tumours reviewed in our centre, molecular diagnosis was obtained in 74 cases (50.3%). Initial diagnosis changed in 23 cases (31%), and 20 (87%) of them had a prior histological diagnosis of oligodendroglioma (69.6% grade ii and 17.4% grade iii ). Only 3 of these 23 cases diagnosis changed from astrocytoma to oligodendroglioma. Among reclassified tumours, there was a common molecular pattern, as findings showed mutant IDH in 16 cases (69.6%) and no codeletion in 20 cases (87%). According to the cell of origin, of the whole group of 27 oligodendrogliomas in our series (reclassified and non-reclassified), 20 cases (74%) became astrocytomas, despite typical oligodendroglial morphology, due to absence of 1p19q codeletion. There was a trend for diagnosis reclassification in younger patients ( p = 0.065, mainly in those with a prior diagnosis of oligodendroglioma, with no statistical differences based on gender or clinical data. Besides, reclassification was more common among tumours with mutant IDH (69.6%), p = 0.003, than those with wild type IDH. In terms of survival, despite receiving different treatments, no significant changes were detected between reclassified and non-reclassified tumours after a mean follow-up of 16 months, partly related to lower grade of these lesions. Conclusions Within the spectrum of the glial tumours treated in our institution, this new classification including molecular genetics over morphological data has provided marked diagnostic changes. These changes appear mainly in tumours previously diagnosed as oligodendrogliomas and in younger patients, with molecular patterns of mutant IDH and 1p19q codeletion. Although diagnosis reclassification may affect clinic, prognosis or therapeutic management of these tumours, deeper and prospective studies on these specific aspects are needed.

Based on the clear neuroanatomical delineation of many neuropathic pain (NP) symptoms, a simple tool for performing a short structured clinical encounter based on the IASP diagnostic criteria was developed to identify NP. This study evaluated its accuracy and usefulness.A case-control study was performed in 19 pain clinics within Spain. A pain clinician used the experimental screening tool (the index test, IT) to assign the descriptions of non-neuropathic (nNP), non-localized neuropathic (nLNP), and localized neuropathic (LNP) to the patients' pain conditions. The reference standard was a formal clinical diagnosis provided by another pain clinician. The accuracy of the IT was compared with that of the Douleur Neuropathique en 4 questions (DN4) and the Leeds Assessment of Neuropathic Signs and Symptoms (LANSS).Six-hundred and sixty-six patients were analyzed. There was a good agreement between the IT and the reference standard (kappa =0.722). The IT was accurate in distinguishing between LNP and nLNP (83.2% sensitivity, 88.2% specificity), between LNP and the other pain categories (nLNP + nNP) (80.0% sensitivity, 90.7% specificity), and between NP and nNP (95.5% sensitivity, 89.1% specificity). The accuracy in distinguishing between NP and nNP was comparable with that of the DN4 and the LANSS. The IT took a median of 10 min to complete.A novel instrument based on an operationalization of the IASP criteria can not only discern between LNP and nLNP, but also provide a high level of diagnostic certainty about the presence of NP after a short clinical encounter.

Background: Depression and anxiety are common in patients with cancer. Aim: To adapt and validate the Hospital Anxiety and Depression Scale (HADS) for adult Chilean cancer patients, and to provide information about their prevalence of anxiety and depression. Material and Methods: Two hundred fifteen patients with cancer answered an adapted version of HADS for Chilean population. The language adjustment of the scale was carried out with the opinions of 10 expert linguists and with a pilot study on 17 cancer patients. The Depression and Anxiety subscales of the DASS-21 were also applied to verify the convergent validity of HADS: Results: The confirmatory factor analysis indicated that the data fits the model of two correlated factors (anxiety and depression), χ2 = 98.608; df = 76;p < 0.05; χ2/df= 1.23, RMSEA = 0.037; CFI = 0.99; TLI = .98. Reliability analysis showed an adequate internal consistency of both subscales (.76 for anxiety and .84 for depression) and the general scale (.87). Correlations between HADS and DASS-21 scores were significant for both anxiety (r =.514, p < 0.001) and depression (r = 0.600, p < 0.001). Prevalence rates were approximately 30% for depression (actual = 12%, possible = 22.8%) and approximately 20% for anxiety (actual = 7%, possible = 8.4%). Conclusions: We conclude that HADS is a reliable and valid instrument for screening clinically relevant anxiety and depression symptoms in Chilean cancer patients.

According to the so-called disconnection hypothesis, the loss of synaptic inputs from the medial temporal lobes (MTL) in Alzheimer's disease (AD) may lead to reduced activity of target neurons in cortical areas and, consequently, to decreased cerebral blood flow (CBF) in those areas. The aim of this study was to assess whether hypoperfusion in parietotemporal and frontal cortices of patients with mild cognitive impairment who converted to AD (MCI-c) and patients with mild AD is associated with atrophy in the MTL and/or microstructural changes in the white matter (WM) tracts connecting these areas. We assessed these relationships by investigating correlations between CBF in hypoperfused areas, mean cortical thickness in atrophied regions of the MTL, and fractional anisotropy (FA) in WM tracts. In the MCI-c group, a strong correlation was observed between CBF of the superior parietal gyri and FA in the parahippocampal tracts (left: r = 0.90, p < 0.0001; right: r = 0.597, p = 0.024), and between FA in the right parahippocampal tract and the right precuneus (r = 0.551, p = 0.041). No significant correlations between CBF in hypoperfused regions and FA in the WM tract were observed in the AD group. These results suggest an association between perfusion deficits and altered WM tracts in prodromal AD, while microvasculature impairments may have a greater influence in more advanced stages. We did not find correlations between cortical thinning in the medial temporal lobes and decreased FA in the WM tracts of the limbic system in either group.

Niemann-Pick type C (NPC) is a progressive neurodegenerative disease characterized by lysosomal/endosomal accumulation of unesterified cholesterol and glycolipids. Recent studies have shown that plasma cholestane-3β,5α,6β-triol (CT) and 7-ketocholesterol (7-KC) could be potential biomarkers for the diagnosis of NPC patients. We aimed to know the sensitivity and specificity of these biomarkers for the diagnosis of NPC compared with other diseases that can potentially lead to oxysterol alterations. We studied 107 controls and 122 patients including 16 with NPC, 3 with lysosomal acid lipase (LAL) deficiency, 8 with other lysosomal diseases, 5 with galactosemia, 11 with cerebrotendinous xanthomatosis (CTX), 3 with Smith-Lemli-Opitz, 14 with peroxisomal biogenesis disorders, 19 with unspecific hepatic diseases, 13 with familial hypercholesterolemia, and 30 with neurological involvement and no evidence of an inherited metabolic disease. CT and 7-KC were analyzed by HPLC-ESI-MS/MS as mono-dimethylglycine derivatives. Levels of 7-KC were high in most of the studied diseases, whereas those of CT were only high in NPC, LAL, and CTX patients. Consequently, although CT is a sensitive biomarker of NPC disease, including those cases with doubtful filipin staining, it is not specific. 7-KC is a very unspecific biomarker.

Aminoglycoside antibiotics, such as gentamicin, may induce premature termination codon (PTC) readthrough and elude the nonsense-mediated mRNA decay mechanism. Because PTCs are frequently involved in lysosomal diseases, readthrough compounds may be useful as potential therapeutic agents. The aim of our study was to identify patients responsive to gentamicin treatment in order to be used as positive controls to further screen for other PTC readthrough compounds. With this aim, fibroblasts from 11 patients affected by 6 different lysosomal diseases carrying PTCs were treated with gentamicin. Treatment response was evaluated by measuring enzymatic activity, abnormal metabolite accumulation, mRNA expression, protein localization, and cell viability. The potential effect of readthrough was also analyzed by in silico predictions. Results showed that fibroblasts from 5/11 patients exhibited an up to 3-fold increase of enzymatic activity after gentamicin treatment. Accordingly, cell lines tested showed enhanced well-localized protein and/or increased mRNA expression levels and/or reduced metabolite accumulation. Interestingly, these cell lines also showed increased enzymatic activity after PTC124 treatment, which is a PTC readthrough-promoting compound. In conclusion, our results provide a proof-of-concept that PTCs can be effectively suppressed by readthrough drugs, with different efficiencies depending on the genetic context. The screening of new compounds with readthrough activity is a strategy that can be used to develop efficient therapies for diseases caused by PTC mutations.

Patients on thiopurine therapy need frequent monitoring to prevent drug adverse events. To describe the structure and main results of a nurse-driven outpatient clinic (NDOC) program for the follow-up of patients receiving treatment with thiopurine immunosuppressants, we retrospectively reviewed patients' clinical charts on thiopurine drugs, azathioprine (AZA), and 6-mercaptopurine. We evaluated the efficacy of the NDOC by comparing the number of physician visits and the adequacy of laboratory controls for each patient before and after inclusion in the program. From January 2006 to December 2008, 179 patients were included. Of these, 102 had received thiopurines for at least 1 year before the start of the NDOC. Mean age was 42 ± 15 years; 83 were female. In all, 137 of the 179 patients (76%) had Crohn disease. AZA was the most frequent drug used (97%). Mean time of follow-up was 2.03 ± 0.9 years. Implementation of this program decreased the number of physician visits per year-from 4.6 ± 1.9 to 2.4 ± 1.3 (p < .001)-and the number of periods longer than 4 months without laboratory control (from 68% to 45%; p = .01). Leucopenia episodes and complications did not differ significantly before and after the start of the NDOC. Nurse-driven follow-up of these patients reduces physician visits while improving tightness of the follow-up.

Background Prognosis of metastatic melanoma is changing due to advances in immunotherapy and targeted therapy. However, management of patients with brain metastases in day-to-day practice continues to be a challenge. Case Report We describe a 40-year-old woman diagnosed with symptomatic brain metastases from cutaneous melanoma and Eastern Cooperative Oncology Group 3. She was treated, off label, with BRAF inhibitor (dabrafenib) + MEK inhibitor (trametinib) and radiotherapy. There was significant, long-lasting, response (17 months), no clinically relevant toxicity, and clear improvement in quality of life. Conclusions This case is an example of real-life application of advances in targeted therapy.

Altres ajuts: This study was funded by Grifols. [...] James T. Becker (Department of Psychiatry, Neurology and Psychology. University of Pittsburgh, Pittsburgh PA, USA) read and commented on an earlier draft of the manuscript. Jordi Bozzo PhD, CMPP (Grifols) is acknowledged for medical writing and editorial assistance in the preparation of the manuscript. Recently, modifications of Aβ levels in CSF and plasma associated with improvement in memory and language functions have been observed in patients with mild-moderate Alzheimer's disease (AD) treated with plasma exchange (PE) with albumin replacement. To detect structural and functional brain changes in PE-treated AD patients as part of a Phase II clinical trial. Patients received between 3 and 18 PE with albumin (Albutein ® 5%, Grifols) or sham-PE (controls) for 21 weeks (divided in one intensive and two maintenance periods) followed by 6-month follow-up. Brain perfusion assessed by SPECT scans using an automated software (NeuroGam ®) and brain structural changes assessed by MRI were performed at weeks 0 (baseline), 21, and 44 (with additional SPECT at weeks 9 and 33). Statistical parametric mapping (voxel-based analysis, SPM) and Z-scores calculations were applied to investigate changes to baseline. 42 patients were recruited (39 evaluable; 37 analyzed: 18 PE-treated; 19 controls). There was a trend toward decreasing hippocampi and total intracranial volume for both patient groups during the study (p < 0.05). After six months, PE-treated patients had less cerebral perfusion loss than controls in frontal, temporal, and parietal areas, and perfusion stabilization in Brodmann area BA38-R during the PE-treatment period (p < 0.05). SPM analysis showed stabilization or absence of progression of perfusion loss in PE-treated patients until week 21, not observed in controls. Mild-moderate AD patients showed decreased brain volume and impairment of brain perfusion as expected for the progression of the disease. PE-treatment with albumin replacement favored the stabilization of perfusion.

This observational study intends to estimate the causal effects of an English as a Medium of Instruction (EMI) program (as predictor) on students Grade Point Average (GPA) (as outcome) at a particular University in Spain by using a Counterfactual Impact Evaluation (CIE). The need to address the crucial question of causal inferences in EMI programs to produce credible evidences of successful interventions contrasts, however, with the absence of experimental or quasi-experimental research and evaluation designs in the field. CIE approach is emerging as a methodologically viable solution to bridge that gap. The program evaluated here consisted in delivering an EMI program in a Primary Education Teacher Training Degree group. After achieving balance on the observed covariates and recreating a situation that would have been expected in a randomized experiment, three matching approaches such as genetic matching, nearest neighbor matching and Coarsened Exact Matching were used to analyze observational data from a total of 1288 undergraduate students, including both treatment and control group. Results show unfavorable effects of the bilingual group treatment condition. Potential interpretations and recommendations are provided in order to strengthen future causal evidences of bilingual education programs’ effectiveness in Higher Education., This work was supported by the Junta de Andalucía-funded Proyecto de Excelencia: “Análisis y Garantía de Calidad de la Educación Superior Plurilingüe en la Educación Superior de Andalucía [Junta de Andalusia-funded Project of Excelence: Analysis and Warrantee of the Quality of Plurilingual Higher Education in Andalucia] (AGCEPESA; Grant Agreement No. P12-SEJ − 1588).

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs.METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring.RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)).CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.Am J Gastroenterol advance online publication, 20 February 2018; doi:10.1038/ajg.2017.501.

The reason cancer pain remains prevalent and hard to classify may be partially explained by the failure to identify neuropathic mechanisms. The objective of this research was to identify the syndromes of cancer pain that may be particularly hard to manage due to their mixed pathophysiology. A series of 384 patients who had cancer of any type, at any stage, and suffered from chronic pain (symptom onset > 3 months) were assessed during a routine return visit in Spain. Medical oncologists indicated the presence and pathophysiology of 33 predefined pain syndromes on a per-patient basis. This information was then measured against clinical, psychosocial, and health care-related data to determine which syndromes pose particular challenges. The mean (standard deviation) age of patients was 61.6 (12.6) years, 49.7% were women. Most (82%) had advanced metastatic disease, 68.7% were on second-line or palliative therapies. The worst syndrome was nociceptive, pure neuropathic, and mixed in 34.6, 26.9, and 38.6% of patients, respectively. Any syndrome could be of mixed pathophysiology. Only 10 syndromes were common (≥ 5% of patients). Syndromes related to malignant bone pain and involvement of chest wall structures were the most frequent. Certain syndromes (including tumor-related bone pain, chemotherapy-induced peripheral neuropathies, paraneoplastic pain syndromes, and malignant neuralgias or injury to cranial nerves) can be particularly challenging when they have a mixed pathophysiology, because the neuropathic component is rarely or unevenly considered. Virtually all cancer pain syndromes can present mixed pathophysiology. Certain syndromes can include neuropathic components that are frequently overlooked.