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Αλέξανδρος Γ. Σφακιανάκης

Monday, June 13, 2022

Identification of multiple isoforms of glucocorticoid receptor in nasal polyps of patients with chronic rhinosinusitis

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The conventional belief that glucocorticosteroid (GC) acts through a single brand glucocorticoid receptor (GR)α protein has changed dramatically with the discovery of multiple GR isoforms. We aimed to evaluate...
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Total thyroidectomy versus hemithyroidectomy with intraoperative radiofrequency ablation for unilateral thyroid cancer with contralateral nodules: A propensity score matching study

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For unilateral papillary thyroid carcinoma (PTC) patients with contralateral benign nodules, optimal treatment decisions are made according to patient preference and the disease's pathological features. This s...
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Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes

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Abstract
BackgroundAttention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder caused by a combination of genetic and environmental factors and is often thought as an entry point into a negative life trajectory, including risk for comorbid disorders, poor educational achievement or low income. In the present study, we aimed to clarify the causal relationship between ADHD and a comprehensive range of related traits.
Methods
We used genome-wide association study (GWAS) summary statistics for ADHD (n = 53 293) and 124 traits related to anthropometry, cognitive function and intelligence, early life exposures, education and employment, lifestyle and environment, longevity, neurological, and psychiatric and mental health or personality and psychosocial factors available in the MR-Base database (16 067 ≤n ≤766 345). To investigate their causal relationship with ADHD , we used two-sample Mendelian randomization (MR) with a range of sensitivity analyses, and validated MR findings using causal analysis using summary effect estimates (CAUSE), aiming to avoid potential false-positive results.
Results
Our findings strengthen previous evidence of a causal effect of ADHD liability on smoking and major depression, and are consistent with a causal effect on odds of decreased average total household income [odds ratio (OR) = 0.966, 95% credible interval (CrI) = (0.954, 0.979)] and increased lifetime number of sexual partners [OR = 1.023, 95% CrI = (1.013, 1.033)]. We also found evidence for a causal effect on ADHD for liability of arm predicted mass and weight [OR = 1.452, 95% CrI = (1.307, 1.614) and OR = 1.430, 95% CrI = (1.326, 1.539), respectively] and time spent watching television [OR = 1.862, 95% CrI = (1.545, 2.246)], and evidence for a bidirectional effect for age of first sexual intercourse [beta� ��= −0.058, 95% CrI = (−0.072, −0.044) and OR = 0.413, 95% CrI = (0.372, 0.457), respectively], odds of decreased age completed full-time education [OR = 0.972, 95% CrI = (0.962, 0.981) and OR = 0.435, 95% CrI = (0.356, 0.533), respectively] and years of schooling [beta = -0.036, 95% CrI = (−0.048, −0.024) and OR = 0.458, 95% CrI = (0.411, 0.511), respectively].
Conclusions
Our results may contribute to explain part of the widespread co-occurring traits and comorbid disorders across the lifespan of individuals with ADHD and may open new opportunities for developing preventive strategies for ADHD and for negative ADHD trajectories.
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Isolated cerebral toxoplasmosis 17 years post renal transplant

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Extended‐spectrum β‐lactamase‐producing and carbapenem‐resistant Enterobacterales bloodstream infection after solid organ transplantation: recent trends in epidemiology and therapeutic approaches

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Abstract

Background

: Infections caused by multidrug-resistant Gram-negative bacilli (MDR GNB), in particular extended-spectrum β-lactamase-producing (ESBL-E) and carbapenem-resistant Enterobacterales (CRE), pose a major threat in solid organ transplantation (SOT). Outcome prediction and therapy are challenging due to the scarcity of randomized clinical trials (RCTs) or well-designed observational studies focused on this population.

Methods

: Narrative review with focus on the contributions provided by the ongoing multinational INCREMENT-SOT consortium (ClinicalTrials identifier NCT02852902) in the fields of epidemiology and clinical management.

Results

: The Spanish Society of Transplantation (SET), the Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC), and the Spanish Network for Research in Infectious Diseases (REIPI) recently published their recommendations for the management of MDR GNB infections in SOT recipients. We revisit the SET/GESITRA-SEIMC/REIPI document taking into consideration new evidence emerged on the molecular epidemiology, prognostic stratification and treatment of post-transplant ESBL-E and CRE infections. Results derived from the INCREMENT-SOT consortium may support the therapeutic approach to post-transplant bloodstream infection (BSI). The initiatives devoted to spare the use of carbapenems in low-risk ESBL-E BSI or to repurpose existing non-β-lactam antibiotics for CRE in both non-transplant and transplant patients are reviewed, as well as the eventual positioning in the specific SOT setting of recently approved antibi otics.

Conclusion

: Due to the clinical complexity and relative rarity of ESBL-E and CRE infections in SOT recipients, multinational cooperative efforts such as the INCREMENT-SOT Project should be encouraged. In addition, RCTs focused on post-transplant serious infection remain urgently needed.

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A novel nonsense PKD1L1 variant cause heterotaxy syndrome with congenital asplenia in a Han Chinese patient

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Journal of Human Genetics, Published online: 13 June 2022; doi:10.1038/s10038-022-01053-w

A novel nonsense PKD1L1 variant cause heterotaxy syndrome with congenital asplenia in a Han Chinese patient
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Genetics of amyotrophic lateral sclerosis: seeking therapeutic targets in the era of gene therapy

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Journal of Human Genetics, Published online: 13 June 2022; doi:10.1038/s10038-022-01055-8

Genetics of amyotrophic lateral sclerosis: seeking therapeutic targets in the era of gene therapy
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