High Levels Of Disease Research Articles

Falciparum malaria with haemorrhagic stroke in a 26-year male patient: report of a rare case

BackgroundMalaria continues to cause unacceptably high levels of disease and death despite increased global efforts and is still significant public health problem. African countries are disproportionately affected by malaria. The objective of this study was to describe a rare case of haemorrhagic stroke as a possible complication of malaria in a 26-year-old male patient.Case presentationA 26-year-old male from southwest Ethiopia presented with complaint of loss of consciousness (LOC) of 12 h duration. He had fever, headache, vomiting, chills, rigors and shivering three days prior to the loss of consciousness. On physical examination, pulse rate 116 beats/min, blood pressure of 120/90 mmHg, respiratory rate was 24 breaths/min, a temperature of 38.9◦C and oxygen saturation of 94%. Nervous system examination; stuporous with Glasgow Coma Scale (GCS) 10/15(M5, E3, V2). Blood film and RDT confirmed a Plasmodium falciparum infection and a non-contrast CT scan found a right cerebral parenchymal haemorrhage.Discussion and conclusionThe presented case described a very rare case of a 26-year-old male patient who was diagnosed with left side hemiparesis secondary to a haemorrhagic stroke, associated with P. falciparum malaria. This report highlights the fact that malaria with stroke should be considered a differential diagnosis in a patient presenting with body weakness in a malaria endemic area and in individuals who had travel history to malaria endemic areas.

Molecular characterization of Streptococcus pyogenes (StrepA) non-invasive isolates during the 2022-2023 UK upsurge.

At the end of 2022 into early 2023, the UK Health Security Agency reported unusually high levels of scarlet fever and invasive disease caused by Streptococcus pyogenes (StrepA or group A Streptococcus). During this time, we collected and genome-sequenced 341 non-invasive throat and skin S. pyogenes isolates identified during routine clinical diagnostic testing in Sheffield, a large UK city. We compared the data with that obtained from a similar collection of 165 isolates from 2016 to 2017. Numbers of throat-associated isolates collected peaked in early December 2022, reflecting the national scarlet fever upsurge, while skin infections peaked later in December. The most common emm-types in 2022-2023 were emm1 (28.7 %), emm12 (24.9 %) and emm22 (7.7 %) in throat and emm1 (22 %), emm12 (10 %), emm76 (18 %) and emm49 (7 %) in skin. While all emm1 isolates were the M1UK lineage, the comparison with 2016-2017 revealed diverse lineages in other emm-types, including emm12, and emergent lineages within other types including a new acapsular emm75 lineage, demonstrating that the upsurge was not completely driven by a single genotype. The analysis of the capsule locus predicted that only 51 % of throat isolates would produce capsule compared with 78% of skin isolates. Ninety per cent of throat isolates were also predicted to have high NADase and streptolysin O (SLO) expression, based on the promoter sequence, compared with only 56% of skin isolates. Our study has highlighted the value in analysis of non-invasive isolates to characterize tissue tropisms, as well as changing strain diversity and emerging genomic features which may have implications for spillover into invasive disease and future S. pyogenes upsurges.

Health Status and Healthcare Utilization Patterns of Emergency Department Patients Who Prefer a Language Other Than English.

Immigrants, nearly half of whom prefer a language other than English (LOE), face structural barriers to healthcare. This subgroup is believed to be at increased risk for reduced access to quality healthcare, yet few studies have examined the health needs and utilization patterns of LOE-preferring patients who seek care in the Emergency Department (ED). Given that the ED is often an entry point to the health system, we sought to characterize the health patterns of this population in an urban ED setting. We conducted a retrospective chart review of the electronic medical records of 1,566 patients who utilized interpreter services in the ED or Urgent Care) at an urban safety net hospital. We found that LOE-preferring patients had high levels of chronic disease. We also found that the majority of these patients had not seen a primary care provider (PCP) within the study period. PCP visits were positively associated with ED utilization suggesting that those without a PCP are less likely to receive ED care. These findings point to a need for greater policy and community health solutions addressing the high burden of chronic disease and underutilization of healthcare for those with LOE preferences.

Perspectives from the Local Community on Strategies for Community Transformation in Uganda’s Public Universities

Several Universities in Sub-Saharan Africa (SSA) rarely have a clearly defined strategy for transforming communities. This is partly because some are still built on colonial models, which place a strong focus on theory, rote learning, and memorisation, where learners duplicate the content during examinations with little or no impact on the community. As a result, the surrounding communities continue to grapple with high levels of poverty, illiteracy, poor housing, disease, and poor-quality health and hygiene. This study explores the strategies Gulu University is using to transform the post-conflict community of Gulu City, northern Uganda. A cross-sectional research design was used involving 390 households. Self-administered questionnaires were employed to collect data on community perceptions of the operationalisation of the different strategies employed by Gulu University to transform the community. Descriptive statistics was used to determine the most outstanding strategies and their associated variables, while chi-square test was performed to assess the relationship between community perception of the existence of Gulu University and the strategies of community transformation. Findings revealed that, first, Gulu University’s strategy of knowledge application has been perceived by the surrounding community to have worked well by increasing employment opportunities, providing young people with opportunities for meaningful livelihood activities, reducing crime, and fostering enterprise development in the surrounding community. Second, the strategy of partnerships and community projects has paid off by providing scholarships to help community members further their education. However, there is still more to be done in terms of knowledge generation strategy through skill training, knowledge transmission strategy through technology transfer, primary health care, better farming engagements, and innovative business services, as well as partnerships and community projects strategy via enterprise development. Furthermore, findings indicated that there was a significant association between community perceptions of transformation and the existence of Gulu University. The findings highlight potential areas of focus for Gulu University and other Ugandan universities for formulating policies that higher institutions of learning can employ to transform communities. Besides, future research should explore the dimensions of community transformation that influence the role of higher institutions of learning in transforming communities

Endophytic bacteria nano-formula: A promotor for plant growth and systemic acquired resistance against sheath blight disease on rice

Sheath blight disease significantly affected growing rice crop and caused yield losses. This study identified two endophyte bacterial isolates, Bacillus subtilis, and Pseudomonas brassicacearum subsp. Neoaurantiaca, significantly inhibit Rhizoctonia solani AG1 IA mycelial growth. Further, the analysis of the culture filtrate for the two identified bacteria recorded a set of bioactive components that have antifungal activity and enhance plant growth. We prepared a novel nano-formula using the advantages of nano natural charcoal (NCNPs) as an organic matter and enriched with alginate to improve the nano-formula porosity and keep the viability of the loaded bacteria up to 18 months. Two methods (soil application and root dipping) were used to evaluate the impact of bacteria nano-formula on rice growth and rice sheath blight (ShB) disease under artificial inoculation with R. solani at greenhouse conditions. The root dipping with P. brassicacearum NCNPs alginate (PBNF-R) and B. subtillus NCNPs alginate (BSNF-R) recorded the highest performance in the rice growth traits, and a high control level of the rice ShB disease by decreasing relative lesion height and percent disease index. In addition, PBNF-R and BSNF-R increase the defense-related enzyme production in the plant cell (peroxidase, polyphenol oxidase, and phenylalanine ammonia‐lyase) and, consequently, the plant immunity. Moreover, both upregulate the gene expression levels of OsNPR1, OsWRKY45, OsPR10, and OsAOS2, which are related to the plant defense mechanism. Finally, here we introduce the first application of bacteria nano-formula as a safe environmental approach to control the rice ShB disease, promoting growth and thousand-grain weight in rice.

Developing oral health services for people experiencing severe and multiple disadvantage: a case study from Southwest England.

People experiencing severe and multiple disadvantage (SMD) have disproportionately high levels of dental disease and tooth loss but have limited access to dental care. This paper presents an evidence-based case study of co-designing, implementing, evaluating and refining a community dental clinic for people experiencing SMD in the Southwest of England. It shares challenges, lessons, and solutions. Tailored interventions that coordinate flexible and responsive care are important for facilitating dental access for individuals experiencing SMD. Participatory approaches can deliver a range of impacts both on research and service development. No single fixed model of co-design can be applied in service development, and the choice will vary depending on local context, available resources and joint decision making. Through co-design, vulnerable populations such as those with SMD can shape dental services that are more acceptable, appropriate and responsive to their needs. This approach can also ensure long-term sustainability by bridging treatment pathway development and commissioning.

Multi-Factor Coral Disease Risk: A new product for early warning and management.

Ecological forecasts are becoming increasingly valuable tools for conservation and management. However, there are few examples of near-real-time forecasting systems that account for the wide range of ecological complexities. We developed a new coral disease ecological forecasting system that explores a suite of ecological relationships and their uncertainty and investigates how forecast skill changes with shorter lead times. The Multi-Factor Coral Disease Risk product introduced here uses a combination of ecological and marine environmental conditions to predict the risk of white syndromes and growth anomalies across reefs in the central and western Pacific and along the east coast of Australia and is available through the US National Oceanic and Atmospheric Administration Coral Reef Watch program. This product produces weekly forecasts for a moving window of 6 months at a resolution of ~5 km based on quantile regression forests. The forecasts show superior skill at predicting disease risk on withheld survey data from 2012 to 2020 compared with predecessor forecast systems, with the biggest improvements shown for predicting disease risk at mid- to high-disease levels. Most of the prediction uncertainty arises from model uncertainty, so prediction accuracy and precision do not improve substantially with shorter lead times. This result arises because many predictor variables cannot be accurately forecasted, which is a common challenge across ecosystems. Weekly forecasts and scenarios can be explored through an online decision support tool and data explorer, co-developed with end-user groups to improve use and understanding of ecological forecasts. The models provide near-real-time disease risk assessments and allow users to refine predictions and assess intervention scenarios. This work advances the field of ecological forecasting with real-world complexities and, in doing so, better supports near-term decision making for coral reef ecosystem managers and stakeholders. Secondarily, we identify clear needs and provide recommendations to further enhance our ability to forecast coral disease risk.

A Scoping Review of the Oral Health Status, Oral Health Behaviours and Interventions to Improve the Oral Health of Children and Young People in Care and Care Leavers.

Children and young people (CYP) in care experience poorer physical health and overall wellbeing in comparison to their peers. Despite this, relatively little is known about what their oral health needs and behaviours are. The aim of this scoping review was to provide a global perspective on the oral health status and behaviours of CYP in care and care leavers. It also aimed to synthesise interventions that have been trialled in this population to improve oral health. Five databases were searched, Ovid Embase, Ovid MEDLINE, CINAHL (EBSCOhost), SocINDEX (EBSCOhost) and Dentistry and Oral Sciences Source (EBSCOhost), alongside grey literature sources up to January 2023. Eligibility criteria were studies that (i) reported on children and adolescents aged 25 years or younger who are currently in formal/informal foster or residential care and care leavers, (ii) pertained to oral health profile, behaviours or oral health promotion interventions (iii) and were published in the English language. Thematic analysis was used to develop the domains for oral health behaviours and interventions. Seventy-one papers were included. Most papers were published from very high or medium Human Development Index countries. CYP in care were found to experience high levels of decay, dental trauma, periodontal disease and poorer oral health-related quality of life. Oral health behaviours included limited oral health self-care behaviours and a lack of oral health-based knowledge. The trialled interventions involved oral health education, supervised brushing and treatment or preventative dental care. This scoping review reveals that CYP in care experience poorer oral health in comparison to their peers. They are also less likely to carry out oral health self-care behaviours. This review highlights a scarcity of interventions to improve the oral health of this population and a paucity of evidence surrounding the oral health needs of care leavers.

How does vector diversity influence the transmission efficiency of yellow dwarf virus? Perspectives from a review

AbstractCereals are some of the most important global crops that contribute directly and indirectly to the production of food for human consumption. Cereal aphids can cause significant damage to wheat, barley and oats, particularly via the transmission of plant viruses that cause devastating plant diseases, such as yellow dwarf disease. High levels of yellow dwarf disease can result in yield losses of around 20%, rising to 80% if infection is severe. Yellow dwarf disease is caused by multiple viruses, including viruses within the families Tombusviridae and Solemoviridae. These include yellow dwarf virus species within the genus Luteovirus (Barley yellow dwarf virus) and Polerovirus (Cereal yellow dwarf virus, Wheat yellow dwarf virus, Maize yellow dwarf virus). Some yellow dwarf virus species are primarily vectored by one aphid species whereas others can be transmitted by multiple vectors. Biological diversity within a given vector species (e.g., genotype, biotype) can influence virus transmission efficiency. However, it is unclear what biological factors drive this variation within a given vector species. Understanding how biological variation in vector populations influences virus transmission efficiency can help to identify biological traits that underpin successful transmission in competent vector populations. Here, the available literature on yellow dwarf virus transmission efficiency is synthesized and significant variation in yellow dwarf virus transmission efficiency is detected between different populations for several vector species. Three biological mechanisms that potentially underpin this variation are proposed.

Trigger finger - Poor outcome of surgery associated with younger age, pain, psoriatic arthritis and atopic disease.

Trigger finger, or stenosing tendovaginitis, is one of the most common causes of hand disability, where a finger or thumb painfully snaps and locks due to a tendon-sheath size mismatch at the A1 pulley. The exact aetiology of trigger finger is unknown, though it is associated with factors like diabetes, rheumatic disease and carpal tunnel syndrome. The main purpose of this prospective study was to explore clinical characteristics and comorbidities in a cohort of 139 patients who underwent surgery for trigger finger and find factors of importance for the outcome 1 year postoperatively. Pain, range of motion, hand function evaluated by the Disabilities of the Arm Shoulder and Hand questionnaire as well as Quinnell grade of triggering were examined preoperatively. Symptom duration, working status, medical history and comorbidities at baseline were also noted. Further, range of motion was evaluated 3 months after surgery, pain and hand function were evaluated 3 and 12 months after surgery. An outcome scale with three levels was defined. The development of any new comorbidities was monitored during an extended postoperative observation period, with a mean duration of 70 months (range: 56-88 months). Poor outcome was strongly associated with younger age (P = 0.0009), a high level of preoperative pain in the operated hand (P = 0.0027), psoriatic arthritis (P = 0.021) and atopic disease (P = 0.028; odds ratio [OR]: 3.87, 95% confidence interval [CI]: 1.15-13.04). A low range of motion preoperatively did not affect the outcome. Carpal tunnel syndrome was the most common comorbidity but did not affect the outcome. A good preoperative range of motion, good hand function and less pain were associated with better outcomes. Younger age, a high level of preoperative pain, psoriatic arthritis and atopic disease were factors associated with a worse outcome of trigger finger surgery. Pain and disability decreased 3 months postoperatively and continued to decrease between 3 and 12 months.

Pilot Randomized Controlled Trial of Multi-Disciplinary Community-Based Biofeedback Vs Health Promotion Programs on Mental Health And Drug Use Among People Experiencing Homelessness

Background: PEH are most vulnerable to COVID-19 due to high levels of chronic disease and social isolation. However, in Skid Row Los Angeles, there are limited resources for mental health and drug treatment services. Biofeedback (BF) has been found to decrease depression and substance use among drug users; however, no studies have assessed the impact of BF on PEH during the COVID-19 pandemic.
 Aim: Our multi-disciplinary team designed and pilot tested an 8-week Heart Rate Variability-Biofeedback (HRV-BF) intervention, utilizing a nurse-led, Community Health Worker model of care with 50 people experiencing homelessness (PEH) as compared with a Health Promotion (HP) program. Our goal was to establish feasibility of the program, and to assess effects HRV-BF on measures of HRV, mental health and drug use as compared to HP.
 Methods: Utilizing Community Based Participatory Research (CBPR) principles, a community advisory board was established to refine the HRV-BF intervention and assess acceptability and feasibility. We enrolled 40 PEH and randomized into HRV-BF vs HP program and assessed a) impact on anxiety and depression; b) HRV and cortisol indices; and c) drug and alcohol use among all participants.
 Results: In total, 40 PEH were enrolled with 36 completing the intervention; 17 HRV-BF and 19 HP. Majority were male (80%) and were equally Black (37.5%) or Hispanic (35%). The mean age of PEH was 49 (SD 16.7), median age 53. The HRV measure RMSSD (root mean square of successive differences between normal heart beats, a time-based variable reflecting vagally mediated HRV), assessed during the resting 5-minute period, showed significant increases in 71% of participants (75% among HRV-BF and 68% among HP), using paired t-tests with natural log transformed variables, p=0.004, and by non-parametric tests, p= 0.006 (p values one-sided). Across the sample, PHQ-9 (depressive symptoms) showed marginally significant improvement (p= 0.09). Anxiety and Mental Health Inventory scores showed improvement, though not significant. Between-group analysis showed the HRV-BF group had better GAD-7 and MHI scores at 8 weeks (post-intervention), though not statistically significant. Chronic disease was found to be high in both groups (67% among HRV-BF and 82% among HP). No significant differences were found in terms of substance use.
 Conclusions: As the first known study to date examining the role of a biofeedback self-regulation training on biomarkers of stress/mental health measures among PEH, our study shows feasibility and acceptability among the study population and positive initial results for both arms of the study. We plan to extend the follow-up period beyond the intervention period of 8 weeks to establish the sustainability of the intervention.
 Funding: Susan Samueli Integrative Health Institute Pilot Studies Award

Heart disease and stroke statistics 2023 update from the American Heart Association-implications for nephrology.

The annual American Heart Association (AHA) and National Institutes of Health statistical report details the most up to date statistics related to heart disease, stroke and cardiovascular risk factors, primarily within the USA. Although not a formal systematic review or meta-analysis, this 600 page report provides the most comprehensive and best summary of cardiovascular statistics for the year in question. Although data are collated from USA data registries, it serves as a critical resource for clinicians, policymakers, administrators and researchers in the northern and southern hemispheres. In this special report, we have chosen to highlight aspects of the document that are relevant to nephrologists, given the overlap of cardiovascular and renal disease. These include (i) key and emerging cardiovascular data signals in the general and chronic kidney disease (CKD) populations, (ii) ethnic and socio-economic disparity, (iii) environmental and behavioural factors that drive high levels of cardiovascular disease and which are key components of the AHA's eight components of the Life Essential cardiovascular health score, and (iv) the impact of COVID-19 both directly and indirectly on heart health. We provide some commentary and critical analysis of both the data and of the production of such data sets suggesting that similar data on CKD could also be published and linked to the AHA and other datasets.

Pediatric Patients with High-Risk B-Cell ALL in First Complete Remission May Benefit from Less Toxic Immunotherapy with Blinatumomab - Results from Randomized Controlled Phase 3 Trial AIEOP-BFM ALL 2017

Background: One of the key questions in trial AIEOP-BFM ALL 2017 focused on the reduction of treatment-related complications by replacing parts of the highly intensive consolidation phase by two courses of Blinatumomab (Blina) in a prospective randomized trial. Herein, we report the toxicity profile of B-cell acute lymphoblastic leukemia (B-ALL) patients (pts) with high-risk (HR) characteristics pending final outcome data. Patients and Methods: 728 pts with HR B-ALL were enrolled from July 15, 2018 to October 31, 2022 in this multicenter trial run in 8 different countries. Patients were included in the HR group in view of the presence of at least one of the following criteria: induction failure; high levels of minimal residual disease (MRD) at day 15 of induction, or at the end of induction (EOI), or at the end of consolidation (EOC); presence of KMT2A::AFF1, of IKZF1+ and positive MRD at EOI (Stanulla et al, JCO 2018), TCF3::HLF, or hypodiploidy. B-ALL pts with one or several of these characteristics represented 20.8% of all pts aged 0-18 years of age with B-ALL. After a 4-drug induction phase, and two weeks of consolidation treatment, patients were randomized to receive Bortezomib in addition to standard consolidation (not part of this report). Before treatment continued with intensive consolidation block HR-1', MRD was analyzed in order to identify patients eligible for subsequent hematopoietic stem cell transplantation (HSCT) based on MRD results. After block HR-1', all B-ALL HR pts were randomized to receive either two courses of consolidation (blocks HR-2', and HR-3'), or two 28-day courses of Blina at 15µg/m 2/d administered by continuous IV infusion (with a 2-week treatment-free interval). Two intrathecal injections of methotrexate (MTX) for CNS prophylaxis were given on days 1 and 29 of each Blina course, respectively. Out of 728 HR B-ALL pts, 619 pts were eligible for randomization [reasons for non-eligibility were: Event (death or relapse) before randomization was due (26), Down syndrome (25; scheduled for a non-randomized intervention with Blina), presence of TCF3::HLF (3; could receive any alternative therapy including Blina), discontinuation/substantial change of preceding therapy (23) or other protocol exclusion criteria (32)]. 572 pts were randomized (92.4% of those eligible). One pt assigned to the experimental arm (EA) and 4 pts assigned to the control arm (CA) received the other arms, respectively. Results: Toxicity was evaluated in randomized pts according to treatment administered during the randomized phase, respectively, until next element started: 268 pts were treated in the control and 281 in the EA (see Table). 16 of them switched in/after the first Blina cycle to the HR blocks due to toxicity or poor response to Blina (due to increasing MRD, >=1x10 -4). Medically relevant adverse reactions of special interest (ARSI) according to MedDRA (specified in the protocol) were evaluated in the randomized treatment phases (CA: HR-2‘/HR-3‘ block, EA: 2 Blina cycles). ARSI were recorded in 61 of 268 pts in the CA (22.8%, 71 ARSI) and in 29 of 281 pts in the EA (10.3% [p<0.001], 33 ARSI); 3 of the 33 ARSI in the EA were related to HR blocks and were observed in 3 of the 16 pts that switched to HR blocks. Life-threatening SAR were seen in 14 pts of the control group (5.2%) and in no patient in the EA (p<0.001). Conclusions: Taken together, these results show for the first time in newly diagnosed pts with HR B ALL, the favorable toxicity profile previously reported with Blinatumomab in pediatric relapsed ALL (Locatelli F et al, JAMA 2021; Brown P et al, JAMA 2021). We have demonstrated that the toxicity profile of Blinatumomab is much more favorable as compared to the intensive chemotherapy approach using HR-blocks. If upcoming analyses of outcome data will show no inferiority of the EA, blinatumomab replacement of some of the intensive chemotherapy blocks will become the new standard of care for treatment if newly diagnosed patients with HR B-ALL.

Frontline Consolidation with Nelarabine for Adults with High-Risk T-Cell Acute Lymphoblastic Leukemia. Results of the Graall-2014/T Atriall Phase 2 Study

Rationale. Acute lymphoblastic leukemia (ALL) with unfavorable biology and/or high minimal residual disease (MRD) levels are at high-risk of disease recurrence. Based on the results of the GRAALL-2005/T study (Trinquand A et al, JCO 2013; Beldjord K et al, Blood 2014), T-ALL patients enrolled in the GRAALL-2014/T trial were classified at high-risk (HR) if presenting an unfavorable 4-gene classifier (absence of NOTCH1/FBXW7 mutations or presence of RAS/PTEN alterations) and/or a post-induction IG/TR MRD1 ≥ 10 -4 (including the need of a salvage course to reach a complete remission [CR]). In the phase 2 ATRIALL sub-study, HR patients were offered to receive nelarabine (NELA) during consolidation and maintenance or as bridge to allogeneic hematopoietic stem cell transplantation (HSCT). The aim of the present report is to compare their outcome to that of similar patients treated in the same GRAALL-2014/T trial but without frontline NELA. Method. Between November 2015 and May 2022, the GRAALL-2014/T included 325 patients with T-ALL. Among these patients, 199 presented with HR features. The ATRIALL sub-study was activated in April 2017. ATRIALL eligibility criteria were defined as HR features, no CNS involvement at baseline, and continuous CR before to start consolidation 2 (first NELA course) at week 12. Based on the results of the COG phase 3 study, the protocol was amended in January 2021 to include patients with CNS involvement at baseline. NELA was given at 1,500 mg/sqm/day at day 1,3 and 5 in combination with etoposide and cyclophosphamide for a maximum of 5 courses during consolidation (2 cycles) and maintenance (3 cycles). Patients with MRD1 ≥ 10 -3 and/or with post-consolidation 1 MRD2 ≥ 10 -4 were eligible for HSCT after one NELA course. A total of 121 patients were included. One patient was excluded due to overt relapse before to start NELA. Eight patients had CNS involvement at baseline. A total of 33 patients included in the GRAALL-2014/T met initial ATRIALL criteria but were not included in the sub-study either before ATRIALL activation (N=21), or during accrual (N=10), or after accrual completion (N=2) and received standard of care (SOC) without NELA. The ATRIALL/CNS- cohort (N=112) was compared to the control cohort (N=33) for MRD response, cumulative incidence of relapse (CIR), disease-free survival (DFS) and overall survival (OS). Results. The median follow-up in the ATRIALL study (n=120) was 2.9 years (95%CI, 2.5-3.5). At 3 years, the CIR, DFS, and OS were 28% (95%CI, 20-37), 67% (95%CI, 55-76), and 71% (95%CI, 61-79), respectively. Patients from the ATRIALL/CNS- (N=112) and control (N=33) cohorts exhibited similar characteristics, except for a longer median follow-up in the control cohort (Figure A). Patients included in the ATRIALL study reached lower post-consolidation MRD3 levels (p=0.05). Among patients with MRD1 ≥10 -4, undetectable MRD3 was achieved in 36/55 (65%) after NELA versus 5/16 (31%) after SOC (p=0.02). When censoring at HSCT time, NELA was associated with a significantly reduced CIR (SHR=0.48; 95%CI, 0.23-0.99; p=0.045) and a trend for a prolonged DFS (HR=0.52; 95%CI, 0.26-1.07; p=0.075) (Figure B,C). This difference did not reach significance when patients were not censored at HSCT time. Indeed, high-risk patients not eligible for HSCT benefited from NELA in terms of CIR (SHR=0.43; 95%CI, 0.20-0.98; p=0.045) and DFS (HR=0.46; 95%CI, 0.21-1.03; p=0.06). Patients with non-ETP ALL had a significantly improved CIR (SHR=0.03; 95%CI, 0.17-0.89; p=0.025) and DFS (HR=0.47; 95%CI, 0.22-0.99; p=0.048), whereas ETP-ALL patients did not benefit from NELA over SOC. There was no benefit of prior NELA in patients who received alloHSCT per protocol. Conclusion. While NELA did not yield an overall improved outcome in the study population, benefits were observed in favorable MRD responders and non-ETP patients. Additional prospective studies are needed to further delineate the specific patient subgroups that might benefit from NELA.

Incidence and predictors of elevated postpartum alanine aminotransferase in chronic hepatitis B mothers: a prospective study protocol

BackgroundThe majority of HBeAg-positive mothers with chronic hepatitis B have high levels of viremia and inactive disease with normal alanine aminotransferase (ALT) during pregnancy. In addition, postpartum disease activation and ALT flare have been reported in the range of 15 − 35%. However, the current International Association Guidelines have not provided clear recommendations and a risk-stratified monitoring schedule. Furthermore, data are lacking on the definition of normal ALT in the postpartum period in mothers with chronic hepatitis B. The clinical features and ALT flare patterns in HBeAg-positive mothers versus HBeAg-negative mothers are not fully explored. Thus, we design a cohort study to investigate the aforementioned area and generate data to assist healthcare providers in better managing mothers with hepatitis B. We aim to assess the frequency of postpartum ALT flares and predictors for such events.MethodThis study is a single-center and prospective cohort study (n = 360) that consists of two groups of patients including HBsAg-positive mothers (n = 120) and healthy mothers without HBV infection (n = 240). In HBeAg-positive mothers, antiviral therapy during late pregnancy is permitted to prevent Mother-to-child transmission (MTCT) but discontinued at delivery if there is no further indication for the treatment. Mothers are enrolled at the gestational weeks of 12–24. After delivery, both mothers and their infants will be followed up until postpartum week 24. Clinical and laboratory data are collected every 4 weeks during the study except there are no follow-up visits at the postpartum weeks 16 and 20. The primary objective is the proportion of patients with postpartum ALT flares. The secondary objectives are independent risk factors during pregnancy for predicting postpartum ALT flares and the normal range of postpartum ALT levels in healthy mothers.DiscussionThe current study focuses on the incidence of postpartum ALT flares in mothers with chronic hepatitis B including subgroup analysis based on HBeAg status. The data will have several clinical implications, such as providing evidence for an appropriate monitoring schedule in CHB mothers after delivery. Further analyses on predictors of such events may assist clinicians in identifying mothers who might develop severe postpartum ALT flares. The data generated from healthy mothers have the potential to identify the patterns of ALT changes during pregnancy and postpartum, so we can gain a better understanding of the normal range of ALT in this subpopulation.Trial Registration Number at the Chinese Clinical Trial RegistryChiCTR2200061130.

Disease decreases variation in host community structure in an old-field grassland.

Disease may drive variation in host community structure by modifying the interplay of deterministic and stochastic processes that shape communities. For instance, deterministic processes like ecological selection can benefit species less impacted by disease. When communities have higher levels of disease and disease consistently selects for certain host species, this can reduce variation in host community composition. On the other hand, when host communities are less impacted by disease and selection is weaker, stochastic processes (e.g., drift, dispersal) may play a bigger role in host community structure, which can increase variation among communities. While effects of disease on host community structure have been quantified in field experiments, few have addressed the role of disease in modulating variation in structure among host communities. To address this, we conducted a field experiment spanning three years, using a tractable system: foliar fungal pathogens in an old-field grassland community dominated by the grass Lolium arundinaceum, tall fescue. We reduced foliar fungal disease burden in replicate host communities (experimental plots in intact vegetation) in three fungicide regimens that varied in the seasonal duration of fungicide treatment and included a fungicide-free control. We measured host diversity, biomass, and variation in community structure among replicate communities. Disease reduction generally decreased plant richness and increased aboveground biomass relative to communities experiencing ambient levels of disease. These changes in richness and aboveground biomass were consistent across years despite changes in structure of the plant communities over the experiment's three years. Importantly, disease reduction amplified host community variation, suggesting that disease diminished the degree to which host communities were structured by stochastic processes. These results of experimental disease reduction both highlight the potential importance of stochastic processes in plant communities and reveal the potential for disease to regulate variation in host community structure.

Identification the immune related marker genes and transcription-factor network in ruptured cerebral aneurysms using bioinformatics analysis and machine-learning strategies

BackgroundAs a high level of mortality and morbidity disease, ruptured cerebral aneurysms (RCA) is the most common cause of intracranial hemorrhage. MethodsThe expression profiles of GSE13353, GSE26969 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between RCA and unruptured cerebral aneurysms (URCA). The Least Absolute Shrinkage Selection Operator (LASSO) and the SVM-RFE (SVM-RFE) analysis were used to screen the potential diagnostic genes for RCA, which were further tested in the validation cohort (GSE54083). The TRRUST database was used to predict transcription factors (TF) and the JASPAR database was used to validate the marker genes and STAT1 binding sites. Finally, the CMAP database was used to predict RCA-associated drugs for clinical transformation. ResultsA total of 120 DEGs were identified. The functional enrichment analysis revealed that NF-kappa B signaling pathway, tuberculosis, rheumatoid arthritis were enriched in the RCA group. NANS, NTRK3, OLFML2A were identified as diagnostic biomarkers of RCA. Transcription of all three marker genes is regulated by the predicted transcription factor STAT1, the CMAP database was eventually used to screen 10 most promising drugs for the treatment of RCA. ConclusionNANS, NTRK3, OLFML2A may become new candidate biomarkers of RCA, moreover, STAT1 plays an important role in the development of RCA. The mentioned immune cells may play a key role in the development and progression of RCA. MEK and MAP kinase inhibitors are the most likely drug mechanisms for RCA therapy.

Invitro senitivity profile of <i>Plasmodium falcifarum</i> clinical isolates to choloroquine and artemisin combination theraphy from Kano and Jigawa States, Nigeria

Malaria continues to cause unacceptably high level of disease and death especially in Africa, with Nigeria bearing the largest burden. Accumulated efforts have been put in place to manage transmission but emergence of Plasmodium falcifarum resistant species has been a major obstacle to the control efforts. This study aimed to evaluate the sensitivity of Plasmodium falcifarum isolate to previously used choloroquine and currently in use Artemisinin and Dihydroartemisinin- amodiaquine in Kano and Jigawa States, Nigeria. Sensitivity of parasite to the drugs was carried out using WHO invitro Micro test procedure. The results revealed high resistance to chloroquine in all the study sites, reduced susceptibility to artemisinin in Hadejia and reduced susceptibility to Dihydro-artemisinin- amodiaquine in Kura and Kano Municiapal. The geometric IC50 values for artemisinin and Dihyrodroartemisiniamodiaquine were found to be below the resistant threshold cut off values as 3.66nM and 1.29nM respectively, while that of chloroquine were far above the threshold value (504.66nM). These indicate that, the P. falcifarum is still resistant to choloroquine and Artemisin and its derivatives are still effective for malaria treatment in the states.

TCRαβ/CD19 cell–depleted HLA-haploidentical transplantation to treat pediatric acute leukemia: updated final analysis

AbstractTCRαβ/CD19 cell depletion is a promising graft manipulation technique frequently used in the context of human leukocyte antigen (HLA)–haploidentical hematopoietic stem cell transplantation (HSCT). We previously reported the results of a phase I-II clinical trial (NCT01810120) to assess the safety and the efficacy of this type of exvivo T-cell depletion in 80 children with acute leukemia, showing promising survival outcomes. We now report an updated analysis on a cohort of 213 children with a longer follow-up (median, 47.6 months for surviving patients). With a 5-year cumulative incidence of nonrelapse mortality of 5.2% (95% confidence interval [CI], 2.8%-8.8%) and a cumulative incidence of relapse of 22.7% (95% CI, 16.9%-29.2%), projected 10-year overall and disease-free survival (DFS) were 75.4% (95% CI, 68.6%-80.9%) and 71.6% (95% CI, 64.4%-77.6%), respectively. Cumulative incidence of both grade II-IV acute and chronic graft-versus-host disease were low (14.7% and 8.1%, respectively). In a multivariable analysis for DFS including type of disease, use of total body irradiation in the conditioning regimen (hazard ratio [HR], 0.5; 95% CI, 0.26-0.98; P = .04), disease status at HSCT (complete remission [CR] ≥3 vs CR 1/2; HR, 2.23; 95% CI, 1.20-4.16; P = .01), and high levels of pre-HSCT minimal residual disease (HR, 2.09; 95% CI, 1.01-4.33; P = .04) were independently associated with outcome. In summary, besides confirming the good outcome results already reported (which are almost superimposable on those of transplant from HLA-matched donors), this clinical update allows the identification of patients at higher risk of treatment failure for whom personalized approaches, aimed at reducing the risk of relapse, are warranted.

Province clustering based on the percentage of communicable disease using the BCBimax biclustering algorithm.

Indonesia needs to lower its high infectious disease rate. This requires reliable data and following their temporal changes across provinces. We investigated the benefits of surveying the epidemiological situation with the imax biclustering algorithm using secondary data from a recent national scale survey of main infectious diseases from the National Basic Health Research (Riskesdas) covering 34 provinces in Indonesia. Hierarchical and k-means clustering can only handle one data source, but BCBimax biclustering can cluster rows and columns in a data matrix. Several experiments determined the best row and column threshold values, which is crucial for a useful result. The percentages of Indonesia's seven most common infectious diseases (ARI, pneumonia, diarrhoea, tuberculosis (TB), hepatitis, malaria, and filariasis) were ordered by province to form groups without considering proximity because clusters are usually far apart. ARI, pneumonia, and diarrhoea were divided into toddler and adult infections, making 10 target diseases instead of seven. The set of biclusters formed based on the presence and level of these diseases included 7 diseases with moderate to high disease levels, 5 diseases (formed by 2 clusters), 3 diseases, 2 diseases, and a final order that only included adult diarrhoea. In 6 of 8 clusters, diarrhea was the most prevalent infectious disease in Indonesia, making its eradication a priority. Direct person-to-person infections like ARI, pneumonia, TB, and diarrhoea were found in 4-6 of 8 clusters. These diseases are more common and spread faster than vector-borne diseases like malaria and filariasis, making them more important.