Relapse of Hodgkin's disease revealed by skin involvement

We present a case of a relapse of HL revealed by a skin involvement. A biopsy of the skin lesion showed infiltration by a mixed cellularity and Reed–Sternberg cells. The immunoreactivity was positive for CD30 and CD15. The patient was undergoing ICE protocol with good improvement after three cycles.     

IFNGR2 genetic polymorphism associated with sex-specific paranoid schizophrenia risk

Background: Considering current scientific evidence about the significant role of chronic low grade inflammation in the physiopathology of schizophrenia, it has been hypothesized that changes in pro-inflammatory cytokines such as interferon gamma may have a significant role in the predisposition to schizophrenia.

Aim: This study focuses on identifying whether the functional polymorphism of interferon gamma receptor 2 (IFNGR2) is a risk factor for the development of schizophrenia.

Methods: This study was conducted by the RFLP-PCR on a Tunisian population composed of 225 patients with different sub-types of schizophrenia and 166 controls.

Results: The IFNGR2 (Q64R) polymorphism analysis showed higher frequencies of minor homozygous genotype (RR) and allele (R) in all patients compared to controls (21.8% vs 10.2%; p?=?.006, OR?=?2.54) and (44% vs 34.9%; p?=?.01; OR?=?1.46), respectively. This correlation was confirmed only for males. This study also noted a significant increase of the mutated homozygous (RR) genotype and (R) allele frequencies of IFNGR2 in paranoid schizophrenics compared to controls (31.4% vs 10.2%; p?=?.001; OR?=?3.34 and 47.2% vs 34.9%; p?=?.009; OR?=?1.66, respectively). This increase remains significant after using binary logistic regression to eliminate confounding factors such as age and sex. Additionally, carriers of RR genotype have significant lower scores on the Scale of Assessment of Positive (SAPS) and negative (SANS) symptoms comparatively to the carrier of the QQ?+?QR genotypes, suggesting that the R recessive allele carriers could have milder symptoms.

Conclusion: The IFNGR2Q64R polymorphism is correlated with male sex and paranoid schizophrenia. It is suggested that a chronic neuroinflammation may predispose to the paranoid schizophrenia development in men.     

Decrease of air pollution during lockdown in Tuscany (Italy): An effect on sperm DNA fragmentation?

In March 2020, the Italian government imposed a national lockdown which was almost completely removed in June 2020. Due to the abrupt stop of human activities, emissions of air pollutants decreased. Air pollution is an environmental risk factor for noncommunicable disease and mortality. Emerging evidence also suggests a role in male infertility. In this study, we compared sperm DNA fragmentation (sDF) levels and conventional semen parameters between subjects undergoing sDF determination and routine semen analysis in a single Italian centre, during about 6 months before (N = 119) and after lockdown (N = 105). After lockdown, we found an improvement of sperm progressive motility (48.00[38.50–58.00]% vs. 42.00[33.00–53.00]%) and sDF levels (as total: 24.79[18.33–33.97]% vs. 35.02[25.04–45.73]%, p < .001; brighter: 14.02[10.69–17.93]% vs 18.54[13.58–25.82]%, p < .001 and dimmer sDF: 9.24[5.64–15.78]% vs. 12.24[8.08–19.10]%, p < .01), mirrored by a decrease of leukocyte semen concentration (p < .01). The improvement of sperm motility and DNA quality was maintained after adjusting for leukocyte concentration and several conditions known to affect sperm motility and/or sDF levels. With a significant decrease in air pollution observed in Tuscany during and after lockdown, associated improvement in sperm motility and DNA quality in patients referred to the infertility clinic is suggestive of the potential role of air pollution in male infertility.     

Fear‐potentiated startle response as an endophenotype: Evaluating metrics and methods for genetic applications

The modulation of the startle response (SR) by threatening stimuli (fear‐potentiated startle; FPS) is a proposed endophenotype for disorders of the fearful‐fearlessness spectrum. FPS has failed to show evidence of heritability, raising concerns. However, metrics used to index FPS—and, importantly, other conditional phenotypes that are dependent on a baseline—may not be suitable for the approaches used in genetic epidemiology studies. Here, we evaluated multiple metrics of FPS in a population‐based sample of preadolescent twins (N = 569 from 320 twin pairs, M_age = 11.4) who completed a fear‐conditioning paradigm with airpuff‐elicited SR on two occasions (~1 month apart). We applied univariate and multivariate biometric modeling to estimate the heritability of FPS using several proposed standardization procedures. This was extended with data simulations to evaluate biases in heritability estimates of FPS (and similar metrics) under various scenarios. Consistent with previous studies, results indicated moderate test‐retest reliability (r = 0.59) and heritability of the overall SR (h² = 34%) but poor reliability and virtually no unique genetic influences on FPS when considering a raw or standardized differential score that removes baseline SR. Simulations demonstrated that the use of differential scores introduces bias in heritability estimates relative to jointly analyzing baseline SR and FPS in a multivariate model. However, strong dependency of FPS on baseline levels makes unique genetic influences virtually impossible to detect regardless of methodology. These findings indicate that FPS and other conditional phenotypes may not be well suited to serve as endophenotypes unless such codependency can be disentangled.     

Association of cytokine Th2 gene polymorphisms with autoimmune thyroid diseases in Tunisian population

Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. Th2 cytokines act on the development of AITD. This study was conducted on Tunisian patients with AITD to investigate the association of Th2 cytokine gene polymorphisms and haplotype combination with GD or HT risk. A total of 156 controls, 160 patients with HT and 88 patients with GD were genotyped for IL‐4 rs2243250, IL‐5 rs2069812, IL‐6 rs1800796 and IL‐13 rs1800925 polymorphisms by PCR‐RFLP. The AITD risk was assessed by a logistic regression analysis using the SNP stats statistical program. False‐positive report probability (FPRP) was estimated to evaluate significant findings. IL‐13 rs1800925 was associated with GD, after adjustment for age and gender, in codominant, dominant and allele genetic models (p = .0072; p = .0018; p = .012, respectively). Significant association of the IL‐6 rs1800796C/G genotype with GD was also detected (p = .025). Furthermore, increased risk of HT was still found for IL‐13 rs1800925T allele (p = .039, OR = 1.39) and for IL‐4 rs2243250T/T genotype both in codominant (p = .033, OR = 2.59) and recessive (p = .011, OR = 2.73) models after adjustment for age and gender. Interestingly, haplotype analysis performed on the IL‐4, IL‐5 and IL‐13 genes revealed a high risk of HT with CTT haplotype (p = .008, OR = 2.12). However, the CCT haplotype is a protective factor (OR = 0.36). Patients carrying the CT haplotype with only one minor allele had a moderate risk of HT (OR = 1.56). The FPRP analysis showed that the association of IL‐13 rs1800925 polymorphism with GD and HT and the association of CTT haplotype with HT were noteworthy. In conclusion, the IL‐4, IL‐5, IL‐6 and IL‐13 polymorphism may play a role in susceptibility to GD and HT in the Tunisian population. Furthermore, gene–gene interaction between the IL‐4, IL‐5 and IL‐13 significantly increases the risk of AITD. Further studies with larger numbers of individuals are needed to confirm the results.     

Association between TLR2 polymorphisms (− 196–174 Ins/Del,R677W,R753Q,and P631H) and schizophrenia in a Tunisian population

Since immune dysregulation has been well studied in schizophrenia pathophysiology, recent studies showed a potent role of TLR2 in neuroinflammation process underlying schizophrenia pathogenesis. However, the genetic predisposition is still unclear. Thus, we hypothesized that TLR2 polymorphisms − 196–174 Ins/Del (rs111200466), R753Q (rs5743708), R677W (rs121917864), and P631H (rs5743704) could be involved in schizophrenia predisposition. A case–control study was performed on a Tunisian population composed of 250 healthy controls and 250 patients genotyped by PCR–RFLP. Genotype and allele distribution were evaluated with sex, schizophrenia subtypes, and other clinical features. We also assessed a haplotype analysis for TLR2 polymorphisms with schizophrenia. Our results showed higher ins/del genotype frequency in healthy women compared to patients (p = 0.006; OR = 0.2). In the other hand, logistic regression showed higher ins/del genotype frequency in controls compared to paranoid patients (p = 0.05; OR = 0.48, adjusted). Frequencies of CT and T allele of R677W were significantly higher in patients compared to controls (p < 10⁻⁴, OR = 10.39; p < 10⁻⁴, OR = 4, adjusted, respectively). R753Q polymorphism was exclusively detected in patients (GA + AA = 2.5%) particularly in men with disorganized subtype. P631H did not show any association with schizophrenia. Finally, haplotype analysis showed that InsGTC and delGTC were associated with higher risk of schizophrenia (p = 0.0001, OR = 8.58; p = 0.04, OR = 5.01, respectively). In the Tunisian population, our results suggested that TLR2 R677W could be associated with susceptibility for schizophrenia, while − 196–174 Ins/Del suggested a trend of protection in women. Otherwise, R753Q could have an effect on schizophrenia especially for disorganized subgroup.

     

Proposals for Engaging Patients and Healthcare Professionals in Risk Minimisation from an Analysis of Stakeholder Input to the EU Valproate Assessment Using the Novel Analysing Stakeholder Safety Engagement Tool (ASSET)

Drug Safety - Understanding the impact of regulatory actions for medicines and enablers/barriers for positive health outcomes is fundamental to effective risk minimisation measures (RMM)....     

Value of hematological parameters for predicting patients with severe coronavirus disease 2019: a real-world cohort from Morocco

ObjectiveCoronavirus disease 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus 2. The clinical manifestations and the evolution of patients with COVID-19 are variable. In addition to respiratory involvement, COVID-19 leads to systemic involvement and can affect the hematopoietic system. This study aimed to evaluate the prognostic value of hematological and hemocytometric parameters in predicting the severity of patients with COVID-19.MethodsWe performed a retrospective study at Mohammed VI university Hospital from 1 March to 11 November 2020. We collected demographic characteristics and hematological findings of incident COVID-19 cases.ResultsA total of 245 patients were included in our study. We found that the rate of lymphopenia was significantly reduced in patients who were severely affected by COVID-19. Additionally, the rate of neutrophilia, the neutrophil side fluorescence light signal, monocyte fluorescent intensity, monocyte size, the neutrophil-to-lymphocyte ratio, the platelet-to-lymphocyte ratio, and the lymphocyte-to-monocyte ratio were significantly elevated in patients who were severely affected by COVID-19.ConclusionsThese results are consistent with the literature regarding the predictive value of these markers. A prospective validation in a large population with a longer follow-up is required.