Lysosomal storage disorders (LSDs) are a heterogenous group of disorders due to genetically determined deficits of lysosomal enzymes. The specific molecular mechanism and disease phenotype depends on ...the type of storage material. Several disorders affect the brain resulting in severe clinical manifestations that substantially impact the expectancy and quality of life. Current treatment modalities for LSDs include enzyme replacement therapy (ERT) and hematopoietic cell transplantation (HCT) from allogeneic healthy donors, but are available for a limited number of disorders and lack efficacy on several clinical manifestations. Hematopoietic stem cell gene therapy (HSC GT) based on integrating lentiviral vectors resulted in robust clinical benefit when administered to patients affected by Metachromatic Leukodystrophy, for whom it is now available as a registered medicinal product. More recently, HSC GT has also shown promising results in Hurler syndrome patients. Here, we discuss possible novel HSC GT indications that are currently under development. If these novel drugs will prove effective, they might represent a new standard of care for these disorders, but several challenges will need to be addresses, including defining and possibly expanding the patient population for whom HSC GT could be efficacious.
In the past recent years, the expanding use of next-generation sequencing has led to the discovery of new cancer predisposition syndromes (CPSs), which are now known to be responsible for up to 10% ...of childhood cancers. As knowledge in the field is in constant evolution, except for a few “classic” CPSs, there is no consensus about when and how to perform germline genetic diagnostic studies in cancer-bearing children. Several clinical screening tools have been proposed to help identify the patients who carry higher risk, with heterogeneous strategies and results. After introducing the main clinical and molecular features of several CPSs predisposing to solid and hematological malignancies, we compare the available clinical evidence on CPS prevalence in pediatric cancer patients and on the most used decision-support tools in identifying the patients who could benefit from genetic counseling and/or direct genetic testing. This analysis highlighted that a personalized stepwise approach employing clinical screening tools followed by sequencing in high-risk patients might be a reasonable and cost-effective strategy in the care of children with cancer.
Epidemiologic, pathophysiologic, and clinical evidences recently revealed the link between upper and lower airways, changing the global pathogenic view of respiratory allergy. The aim of this review ...is to highlight the strong interaction between the upper and lower respiratory tract diseases, in particular allergic rhinitis and asthma.
To analyze the difference in the salivary cortisol response to psychosocial stress between the patients with the first episode of psychosis (FEP) and the control group.
We performed a cross-sectional ...analysis of the baseline measurements of a prospective cohort study conducted from 2015 to 2018 at two Croatian psychiatric hospitals. The study consecutively enrolled 53 patients diagnosed with FEP and 63 healthy controls. The primary outcome was the difference in the changes of salivary cortisol concentration during the stress test. The secondary outcome was the difference in the baseline levels of salivary cortisol between patients with FEP and controls. The tertiary outcome were the correlations of salivary cortisol levels with the results of the Positive and Negative Syndrome Scale for Schizophrenia, Rosenberg Self-Esteem Scale, and the International Personality Item Pool.
Patients with FEP had significantly higher baseline salivary cortisol than controls, but their salivary cortisol increased significantly less during the stress test.
Patients with FEP respond differently to stressful stimuli than controls, as shown by the increased baseline salivary cortisol and blunted cortisol response, possibly indicating a greater vulnerability to psychosocial stress.
•Patients with FEP performed significantly worse than HC in all cognitive domains.•There are differences in the long-term course of domain-specific cognitive deficits.•Treatment can help to improve ...the majority of domain-specific deficits in FEP.•However, despite the improvement, neurocognitive status in FEP was still below HC.•Verbal and executive deficits remained unchanged after 18 months of treatment.
Neurocognitive symptoms exert the most influence on treatment outcomes over the course of schizophrenia, starting from the first-episode of psychosis (FEP) onwards. Our aim was to analyze the neurocognitive status of FEP compared to healthy controls (HC), and its change after 18 months of treatment. We performed a study in a sample of 159 patients with FEP and 100 HC. We followed the patients up for 18 months after initial assessment with a battery of neurocognitive tests. We observed statistically significant improvement in the majority of neurocognitive tests after 18 months, but several tests of specific neurocognitive domains (verbal memory, language functions, executive functions) did not show significant differences between the two assessments. The results for the majority of tests obtained from patients with FEP after 18 months of treatment showed significant deterioration compared with HC. Although our study showed significant improvement of baseline neurocognitive deficits in FEP with treatment, this varied across domains and overall performance remained below that of HC. Thus, while it seems that treatment of FEP may help to delay or restore neurocognitive deterioration, it is unclear whether specific areas of neurocognitive deterioration (e.g. verbal domain) would benefit from more time or specific treatment approaches.
Nodular lymphoid hyperplasia (NLH) is a lymphoproliferative disease caused by non-clonal expansion of lymphoid cells in the gut mucosa. Little is known about the pathogenesis of NLH, which is often ...disregarded as an insignificant or para-physiologic phenomenon. We present the case of a girl with isolated diffuse NLH (extending from the stomach to the rectum) caused by activated PI3Kδ syndrome (APDS) due to the novel p.Glu525Gly variant in
PIK3CD
. The
gain-of-function
effect of the variant was confirmed by demonstration of over activation of the Akt/mTOR pathway in the patient's cells. APDS diagnosis led to treatment with sirolimus, which resulted in the complete remission of NLH and in the prevention of extra intestinal complications. In conclusion, we identify APDS as a novel cause of isolated NLH and suggest that patients with severe pan-enteric NLH should be screened for this disorder that may not be apparent on first-line immunological testing.
To summarize all available evidence from systematic reviews about the impact of stress response in development of first-episode psychosis (FEP) in schizophrenia.
An overview of systematic reviews of ...any type of primary studies was performed. An electronic search of five databases was conducted in February 2017 (CDSR, DARE, Embase, MEDLINE and PsychINFO). Quality of included systematic reviews was assessed using the AMSTAR checklist.
Eight systematic reviews were included. The main findings of the included reviews point out a possible alteration of the stress response in a subgroup of persons with proneness to psychosis. However, the evidence is limited by the inadequate quality of studies, as well as lack of standardization of outcomes and assessment methods.
Given the heterogeneity of current results, there is no solid evidence for uniform alterations of stress response found in persons with FEP in suggestive of schizophrenia that may serve as a marker of vulnerability to stress and possibly proneness to psychotic state in response to daily hassles.
Background: Changes in cerebral hemodynamics have been reported in schizophrenia and proposed as underlying the cognitive
deficits seen in patients. The objective of our study was to compare changes ...of the cerebral blood flow velocity (BFV) during
neurocognitive tasks between the patients with the first episode of psychosis and healthy controls.
Subjects and methods: We recruited 46 patients with the first episode of psychosis (FEP), admitted to the University Hospital
Centre Zagreb during 2016-2017 and 41 control subjects. Transcranial Doppler ultrasonography monitoring of BFV in both middle
cerebral arteries was recorded during 25-minute long neurocognitive assessment with Phonemic Verbal Fluency test, Trial Making
Test B and Stroop test. Between every consecutive test resting periods were recorded.
Results: After the adjustment for age, sex and education by quantile regression, patients with FEP had significantly lower BFV
in middle cerebral arteries during the 3rd (
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