Haematopoietic Stem Cell Transplantation in Adolescents and Young Adults With Acute Lymphoblastic Leukaemia: Special Considerations and Challenges

Adolescents and young adults (AYAs) represent a challenging group of acute lymphoblastic leukaemia (ALL) patients with specific needs. While there is growing evidence from comparative studies that this age group profits from intensified paediatric-based chemotherapy, the impact and optimal implementation of haematopoietic stem cell transplantation (HSCT) in the overall treatment strategy is less clear. Over recent years, improved survival rates after myeloablative allogeneic HSCT for ALL have been reported similarly for AYAs and children despite differences in transplantation practise. Still, AYAs appear to have inferior outcomes and an increased risk of treatment-related morbidity and mortality in comparison with children. To further improve HSCT outcomes and reduce toxicities in AYAs, accurate stratification and evaluation of additional or alternative targeted treatment options are crucial, based on specific molecular and immunological characterisation of ALL and minimal residual disease (MRD) assessment during therapy. Age-specific factors such as increased acute toxicities and poorer adherence to treatment as well as late sequelae might influence treatment decisions. In addition, educational, social, work, emotional, and sexual aspects during this very crucial period of life need to be considered. In this review, we summarise the key findings of recent studies on treatment approach and outcomes in this vulnerable patient group after HSCT, turning our attention to the different approaches applied in paediatric and adult centres. We focus on the specific needs of AYAs with ALL regarding social aspects and supportive care to handle complications as well as fertility issues. Finally, we comment on potential areas of future research and concisely debate the capacity of currently available immunotherapies to reduce toxicity and further improve survival in this challenging patient group.

Is the Clinical Course of Non-Arteritic Ischemic Optic Neuropathy Associated with Oxidative Damage and the Dynamics of the Antioxidant Response?

Purpose: Oxidative stress is known to be a decisive factor in the wide etiopathogenesis of optic neuropathy. This study aimed to comprehensively evaluate the interaction of optic neuropathy’s clinical course with systemic oxidative damage and antioxidant response dynamics in a large series.Methods: This case-controlled clinical study included 33 non-arteritic anterior ischemic optic neuropathy patients and 32 healthy individuals. Extensive systemic oxidation profiles were statistically compared between the two groups, and correlations between the clinical and biochemical data in the patient group were analyzed.Results: Vitamin E and MDA levels were significantly higher in the patient group. Significant correlations were observed in the analyses between clinical findings and oxidative stress parameters. Correlations between vitamin E and intraocular pressure, between B12 and cup-to-disc ratio, between antioxidant glutathione and SOD enzyme systems, and between uric acid and age were found to be very significant. As significant correlations were found in either clinical and biochemical data or in oxidative stress parameters, correlations between vitamin E and cholesterol, MDA was found to be very significant. Conclusions: This study not only supplies significant information regarding oxidative damage and antioxidant response in NAION, but also points out the specific interactions of neuromodulators, like vitamin E, in intracellular signaling pathways and regulation mechanisms. A better reading of these connections may help improve diagnosis, follow-ups and treatment criteria and strategies.

Enzalutamide in metastatic castration-resistant prostate cancer, real-world data

Objective: Androgen deprivation therapy (ADT) is used alone or in combination with docetaxel or androgen inhibitors in the initial treatment of metastatic prostate cancer (PC) (mPC). Enzalutamide is an androgen receptor inhibitor that is used orally and plays a role in different steps of the androgen receptor (AR) signal pathway. The aim of this study is to determine the real life data of patients using enzalutamide for metastatic PC. Material and Methods: The 118 patients from a totally 6 centers using enzalutamide treatment were included in this retrospective analysis. Clinical information of patients was recorded from patient files or automation records. Results: Median OS was 71 months, and median PFS was five months (4,1 – 5,9 months). There was no association of Gleason score with OS and PFS (p = 0.5 and p = 0.4, respectively). Although those who were metastatic at the time of diagnosis lived longer than those who developed metastases later, the difference was not statistically significant (p = 0.9). Likewise, there was no relationship between the time of metastasis development and PFS (p = 0.2). There was no difference in OS and PFS between patients with visceral metastasis and those without (p = 0.3, p = 0.5, respectively). Conclusion: Enzalutamide is an effective and safe agent in accordance with the literature in the patient group included in this study, although some patients may have an unresponsiveness to enzalutamide or develop progression under the enzalutamide treatment. More studies are needed to understand which patient group can benefit more from enzalutamide.

Patients’, pharmacists’, and prescribers’ attitude toward using blockchain and machine learning in a proposed ePrescription system: online survey

Objective To evaluate the attitudes of the parties involved in the system toward the new features and measure the potential benefits of introducing the use of blockchain and machine learning (ML) to strengthen the in-place methods for safely prescribing medication. The proposed blockchain will strengthen the security and privacy of the patient’s prescription information shared in the network. Once the ePrescription is submitted, it is only available in read-only mode. This will ensure there is no alteration to the ePrescription information after submission. In addition, the blockchain will provide an improved tracking mechanism to ensure the originality of the ePrescription and that a prescriber can only submit an ePrescription with the patient’s authorization. Lastly, before submitting an ePrescription, an ML algorithm will be used to detect any anomalies (eg, missing fields, misplaced information, or wrong dosage) in the ePrescription to ensure the safety of the prescribed medication for the patient. Methods The survey contains questions about the features introduced in the proposed ePrescription system to evaluate the security, privacy, reliability, and availability of the ePrescription information in the system. The study population is comprised of 284 respondents in the patient group, 39 respondents in the pharmacist group, and 27 respondents in the prescriber group, all of whom met the inclusion criteria. The response rate was 80% (226/284) in the patient group, 87% (34/39) in the pharmacist group, and 96% (26/27) in the prescriber group. Key Findings The vast majority of the respondents in all groups had a positive attitude toward the proposed ePrescription system’s security and privacy using blockchain technology, with 72% (163/226) in the patient group, 70.5% (24/34) in the pharmacist group, and 73% (19/26) in the prescriber group. Moreover, the majority of the respondents in the pharmacist (70%, 24/34) and prescriber (85%, 22/26) groups had a positive attitude toward using ML algorithms to generate alerts regarding prescribed medication to enhance the safety of medication prescribing and prevent medication errors. Conclusion Our survey showed that a vast majority of respondents in all groups had positive attitudes toward using blockchain and ML algorithms to safely prescribe medications. However, a need for minor improvements regarding the proposed features was identified, and a post-implementation user study is needed to evaluate the proposed ePrescription system in depth.

Midbrain injury in patients with subarachnoid hemorrhage: a diffusion tensor imaging study

We investigated the characteristics of midbrain injuries in patients with spontaneous subarachnoid hemorrhage (SAH) by using diffusion tensor imaging (DTI). Twenty-seven patients with SAH and 25 healthy control subjects were recruited for this study. Fractional anisotropy (FA) and mean diffusivity (MD) data were obtained for four regions of the midbrain (the anterior ventral midbrain, posterior ventral midbrain, tegmentum area, and tectum) in 27 hemispheres that did not show any pathology other than SAH. The mean FA and MD values of the four regions of the midbrain (anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum) of the patient group were significantly lower and higher than those of the control group, respectively (p < 0.05). The mean FA values of the patient group were significantly different among the anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum regions (ANOVA; F = 3.22, p < 0.05). Post hoc testing showed that the mean FA value of the anterior ventral midbrain was significantly lower than those of the posterior ventral midbrain, tegmentum, and tectum (p < 0.05); in contrast, there were no differences in mean FA values of the posterior ventral midbrain, tegmentum, and tectum (p > 0.05). However, differences were not observed among four regions of the midbrain (anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum) in the mean MD values. We detected evidence of neural injury in all four regions of the midbrain of patients with SAH, and the anterior ventral midbrain was the most severely injured among four regions of the midbrain. Our results suggest that a pathophysiological mechanism of these neural injuries might be related to the occurrence of a subarachnoid hematoma.

Evaluation of Diagnostic Performance of MDCT Coronary Angiography in Comparison with Conventional Coronary Angiography

Background: Coronary artery disease is now becoming increasingly prevalent than before especially in younger age groups. We in the current study tried to evaluate the potential of 128 slice MDCT coronary angiography for the detection of stenotic coronary lesions by comparing the results of computed tomographic coronary angiography to a gold standard set by Conventional coronary angiography. Methods: A total of n=30 patients with clinically suspected Coronary artery disease. They were evaluated with 128 Slice CT Scanner (PHILIPS INGENUITY) and conventional coronary angiography. All patients were examined with a 128 slice MDCT scanner (Philips Ingenuity 128 slice Netherlands) using standard cardiac CT protocol. Gantry rotation time was 400 ms with a half sector acquisition protocol and multisector reconstruction permitting an effective temporal resolution between 50 and 200 ms depending on patient heart rate. Results: In the n=30 Patients included in the study with CCA, the n=450 coronary segments included in the study were found to contain a total number of n=138 stenoses among them non-significant stenoses. The accuracy of MDCT detection of coronary stenoses greater than 50% diameter of vessel lumen is about 94.78. When raising the threshold for stenosis from 50% to 70% of the vessel lumen, so that only hemodynamic relevant stenoses enter the evaluation, the sensitivity decreases from 88%. The MDCT detection in the patient group with heart rates below 60 beats per minute higher values for sensitivity 93% and specificity 97% were observed, compared to sensitivity 87% and specificity 93% of the patient group with heart rates above 60 beats per minute. Conclusion:The present study revealed that a high negative predictive value (98.08%)suggests that 128- Slice MDCT coronary angiography is a good screening modality for evaluation of patients with mild to intermediate-risk factors who might otherwise require invasive angiography.

BARRIERS TO THE USE OF METHYLPHENIDATE IN PAEDIATRIC NEURO-ONCOLOGY SERVICES

Background The increasing effectiveness of childhood cancer treatment has resulted in a greater number of children surviving previously incurable central nervous system tumours. This growing population of survivors report significant treatment-related difficulties, including attentional impairment associated with poor long-term intellectual development, academic attainment, and health-related quality of life. Clinical findings show benefit to attention and executive functions following methylphenidate administration. The current project explored barriers associated with use of methylphenidate in paediatric neuro-oncology services in the UK. Method Qualitative data was gathered by semi-structured questionnaire sent to clinical psychologists/neuropsychologists in 19 of the 21 NHS primary treatment oncology centres in the UK in May 2018. Thematic analytic methods were used to explore the data. Results 11 responses were received from primary treatment centres. Knowledge of the evidence base for methylphenidate in paediatric brain injury was limited. This was primarily attributable to the inadequate resource of psychology into many primary treatment centres, limiting provision to service to a restricted proportion of the patient group. Psychologists reported an interest in exploring the utility of methylphenidate in their patient group. Respondents highlighted the need for provision of accessible research summaries and treatment protocols addressing the potential use of psychostimulants, stating that these would support their team to consider expanding the interventions offered. Conclusions The development of shared resources for clinicians will be important in supporting the application of research findings to clinical practice. We anticipate national collaboration will support the advancement of intervention for the growing clinical population of long-term survivors.

Observational Study: Application of Therapy with Equine Serum for Patients Diagnosed with COVID-19 in Tucumán, Argentina

Purpose: The objective of this work is to make an observational study of the usage in moderate or severe state COVID-19 patients of a new therapeutic commercial product obtained after immunization of horses: CoviFab® ELEA F(ab')2 fragmented equine immunoglobulins anti SARS-CoV2.Methods: Participant Centres depend on the Public Health System of Tucumán, Argentina were recruitment. Subjects were assigned to the Moderate Patient Group (MPG) and the Severe Patient Group (SPG), classified according to WHO criteria.In total, n = 84 were enrolled for this study. The subjects were divided into MPG and SPG. All participants were evaluated by physical examination and COVID-19 infection was diagnosed with positive RT-PCR. Each subject received two doses of 0.16 ml / kg, according to the subject's body weight. A generalized linear model with binomial distribution was adjusted for the number of symptoms. Data was analysed using proportion, bivariate and logistic regression. P-value was considered significant at the p< 0.05 threshold.Results: Both groups were similar in age, sex, and comorbidities. A higher proportion of patient with medical discharge was observed in MPG (91.4%) vs. SPG (55.3%) (p= 0.004). MPG showed 9 times more chance of receiving medical discharge than SPG (9.33 CI= [1.65, 52.81]; p= 0.012). Then, the chance to get medical discharge was independent of variables sex, age, and comorbidities. Conclusions: Treatment with Equine Serum in patients with moderate and severe disease of COVID-19 managed to slightly reduce hospitalization time. This treatment improved the clinical state to obtain medical discharge. The bivariate analysis showed 8 times more chance in MGP versus SGP to receive of medical discharge and this chance was independent of the pre-existent comorbidities.

Evaluation of Oxidative Stress Biomarkers in Patients with Henoch-Schönlein Purpura

Introduction: Henoch-Sch&ouml;nlein Purpura (HSP) is a systemic vasculitic syndrome characterized by non-thrombocytopenic purpura, arthritis/arthralgia, abdominal pain, and glomerulonephritis. The pathogenesis of HSP has not been clearly identified. Oxidative damage has a role in the pathogenesis of most cases. Aim: This study aimed to evaluate changes of oxidative stress by studying parameters like superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in an attempt to identify the role of oxidative stress in HSP from another perspective. Materials and methods: This study enrolled 23 pediatric patients (ten girls and thirteen boys) diagnosed with HSP who were under follow-up at Sutcu Imam University School of Medicine Department of Pediatrics between 2014 and 2016 and twenty healthy children as the control group. The parents of all subjects gave informed consent to participate in the study. In the HSP group, the beginning season of the illness and the systemic involvement during follow-up were determined. Blood specimens were obtained at presentation before any treatment was started. SOD, CAT activities, and MDA values in erythrocyte and plasma samples were compared between the patient group and the healthy children. Results: Twenty-three patients with HSP (13 males, 10 females) and 20 healthy children participated in this study. The mean age of the HSP cases was 8.21&plusmn;3.78 years (range 2-16 years) and of the controls was 8.6&plusmn;4.2 (range 3-14 years). The mean MDA value was 2.95&plusmn;0.71 nmol/ml in the patient group and 2.67&plusmn;0.66 nmol/ml in the control group (p=0.787). The mean level of the CAT enzyme was 1.32&plusmn;0.35 U/g Hb in the patient group and 7.8&plusmn;1.74 U/g Hb in the control group (p=0.001). The mean levels of the SOD enzyme were 3.06&plusmn;0.85 U/g Hb in the patient group and 0.97&plusmn;0.36 U/g Hb in the control group (p=0.001). Conclusions: Although high MDA levels support the role of lipid peroxidation in the pathogenesis of HSP, statistical significance was not reached owing to a limited number of our patients. The reduced CAT enzyme activity is consistent with the findings of previous reports. This finding supports the notion that oxidative stress can play a role in the pathogenesis of HSP. Keypoints: Our findings support the notion that oxidative stress can play a role in the pathogenesis of HSP.