Health conditions in adults with HIV compared with the general population:A population-based cross-sectional analysis

BACKGROUND: Life expectancy in adults with human immunodeficiency virus (HIV) has increased and managing other health conditions is increasingly important for patients and healthcare planning. The aim of this study was to examine the prevalence and association between different health conditions and HIV status. METHODS: We performed a cross-sectional analysis of adult UK Clinical Practice Research Datalink primary care electronic medical records linked to hospital admissions as of Nov 30, 2015. We examined 47 health condition groups and 304 physical and mental health conditions by HIV status, after adjustment for age, sex, social deprivation status using logistic regression. FINDINGS: There were 964 patients with HIV (61.7% male; 92.8% aged <65 years) and 941,113 non-HIV patients (49.4% male; 75.2% aged <65 years). Condition groups with the greatest prevalence in HIV that were also highly prevalent in adults without HIV included: lipid disorder (41.4% vs 40.2%), and hypertension (19.1% vs 24.6%). Following adjustment, 18 (37.5%) condition groups were more likely in adults with HIV and ten (20.8%) were less likely. Individual conditions that were less likely in adults with HIV included: atrial fibrillation (odds ratio [OR] 0.37 [95% CI 0.20–0.64]) and hypertension (OR_0.78 [0.65–0.94]); rheumatoid arthritis (OR 0.27 [0.05–0.84]); asthma (OR_0.65 (0.53–0.80]); and certain eye diseases such as macular degeneration (OR_0.30 [0.09–0.70]). Meanwhile individual conditions that were more likely included: liver fibrosis, sclerosis, and cirrhosis (OR_3.23 [1.85–5.20]); pulmonary embolism (OR_2.06 [1.15–3.36]); male infertility (OR_2.23 [1.50–3.16]) and female infertility (OR_2.01 [1.34–2.88]); bipolar disorder (OR_2.93 [1.52–5.05]) and depression (OR_1.49 [1.28–1.71]); cervical malignancy (OR_4.64 [1.15–12.15]); and infections. INTERPRETATION: Comorbidity is common in adults with HIV, with physical and mental health conditions spanning a wide spectrum. HIV management should consider multidisciplinary care models to provide optimal patient care. FUNDING: The project was funded by the Bart’s Charity; DRM was funded by a Wellcome Trust Clinical Research Career Development Fellowship; DRM and DMM received funding from the HDR-UK Precision therapeutics programme

Gobierno corporativo y transparencia informativa

Los importantes desarrollos normativos producidos en los últimos años dentro de nuestro Derecho Mercantil y Financiero han intentado reforzar el funcionamiento de los mercados financieros, incorporando leyes que se encaminan a aumentar la transparencia informativa de las entidades emisoras, y por tanto la confianza de los inversores. El importante volumen regulador permite construir un entramado que soporta los requisitos mínimos a facilitar en las cuentas anuales, pero no garantizan la plena transparencia de las empresas. Los estudios realizados permiten evidenciar cómo las cuentas anuales de mejor calidad son aquellas reportadas por empresas de gran tamaño o que presentan un cierto riesgo financiero, descartando otras alternativas. Ello nos permite constatar la dificultad que tienen las empresas de valorar el beneficio real de ser transparentes más allá de las disposiciones legales establecidas, por lo que el regulador debe estar muy despierto actualizando sus normas y reforzando las actividades de control y supervisión ejercidas por los auditores (dentro de una limitación de su responsabilidad)

Absolute and relative handgrip strength as indicators of self-reported physical function and quality of life in breast cancer survivors. The EFICAN study

Background: Although breast cancer (BC) is the most prevalent type of cancer in the world, its high survival rate implies that many people live long after the treatments and face their side effects. The physical function (PF) and health-related quality of life (HRQoL) of people surviving BC decreases significantly, which makes important to identify markers that may be associated with a better health status and prognosis. Previous studies suggest that handgrip strength (HGS) and HGS relative to the body mass index (rHGS) are good indicators of PF and HRQoL in different populations. However, it is unknown whether this applies to BC survivors. This study aimed to evaluate the association of HGS and rHGS with PF and HRQoL in this population. Methods: Sixty female BC survivors participated. Handgrip strength was assessed with a dynamometer. Arm volume was estimated and upper limb impairments, as well as cancer-related fatigue, depression, life satisfaction and HRQoL, were assessed using standardized questionnaires. Results: Higher levels of HGS and rHGS were associated with higher levels of HRQoL, lower cancer-related fatigue, and fewer problems with the affected arm. Conclusions: These results suggest that HGS may be a good indicator of self-reported PF and HRQoL in female BC survivors

ColoLipidGene: Signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients

Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolismrelated genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk groupThis work was supported by Ministerio de Ciencia e Innovación del Gobierno de España (Plan Nacional I + D + i AGL2013–48943-C2–2-R and IPT-2011–1248-060000), Comunidad de Madrid (P2013/ABI-2728. ALIBIRDCM) and European Union Structural Funds. CIBEREHD is funded by the Instituto de Salud Carlos III. This is a collaborative study between the Molecular Oncology Unit of The Institute of Advanced Studies of Madrid IMDEA Food and the Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD

Recommendations for Diagnosis and Treatment of Pseudohypoparathyroidism and Related Disorders : An Updated Practical Tool for Physicians and Patients

Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses. Given the variability of the clinical, radiological, and biochemical presentation, establishment of the molecular diagnosis is of critical importance for patients. It facilitates management, including prevention of complications, screening and treatment of endocrine deficits, supportive measures, and appropriate genetic counselling. Based on the first international consensus statement for these disorders, this article provides an updated and ready-to-use tool to help physicians and patients outlining relevant interventions and their timing. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care.Peer reviewe

Diagnosis and management of pseudohypoparathyroidism and related disorders : first international Consensus Statement

This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders.Peer reviewe

Genetics of Growth Disorders-Which Patients Require Genetic Testing?

The second 360° European Meeting on Growth Hormone Disorders, held in Barcelona, Spain, in June 2017, included a session entitled Pragmatism vs. Curiosity in Genetic Diagnosis of Growth Disorders, which examined current concepts of genetics and growth in the clinical setting, in terms of both growth failure and overgrowth. For patients with short stature, multiple genes have been identified that result in GH deficiency, which may be isolated or associated with additional pituitary hormone deficiencies, or in growth hormone resistance, primary insulin-like growth factor (IGF) acid-labile subunit deficiency, IGF-I deficiency, IGF-II deficiency, IGF-I resistance, and primary PAPP-A2 deficiency. While genetic causes of short stature were previously thought to primarily be associated with the GH-IGF-I axis, it is now established that multiple genetic anomalies not associated with the GH-IGF-I axis can result in short stature. A number of genetic anomalies have also been shown to be associated with overgrowth, some of which involve the GH-IGF-I axis. In patients with overgrowth in combination with an intellectual disability, two predominant gene families, the epigenetic regulator genes, and PI3K/AKT pathway genes, have now been identified. Specific processes should be followed for decisions on which patients require genetic testing and which genes should be examined for anomalies. The decision to carry out genetic testing should be directed by the clinical process, not merely for research purposes. The intention of genetic testing should be to direct the clinical options for management of the growth disorder

Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy

Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability