Designer Spin Models in Tunable Two-Dimensional Nanographene Lattices.

Motivated by recent experimental breakthroughs, we propose a strategy for designing two-dimensional spin-lattices with competing interactions that lead to nontrivial emergent quantum states. We consider S = 1/2 nanographenes with C3 symmetry as building blocks, and we leverage the potential to control both the sign and the strength of exchange with first neighbors to build a family of spin models. Specifically, we consider the case of a Heisenberg model in a triangle-decorated honeycomb lattice with competing ferromagnetic and antiferromagnetic interactions whose ratio can be varied in a wide range. On the basis of the exact diagonalization of both Fermionic and spin models, we predict a quantum phase transition between a valence bond crystal of spin singlets with triplon excitations living in a Kagomé lattice and a Néel phase of effective S = 3/2 in the limit of dominant ferromagnetic interactions.

Gamified Neurorehabilitation Strategies for Post-stroke Motor Recovery: Challenges and Advantages.

PURPOSE OF REVIEW: Stroke is the leading cause of permanent motor disability in the United States (US), but there has been little progress in developing novel, effective strategies for treating post-stroke motor deficits. The past decade has seen the rapid development of many promising, gamified neurorehabilitation technologies; however, clinical adoption remains limited. The purpose of this review is to evaluate the recent literature surrounding the adoption and use of gamification in neurorehabilitation after stroke. RECENT FINDINGS: Gamification of neurorehabilitation protocols is both feasible and effective. Deployment strategies and scalability need to be addressed with more rigor. Relationship between engaged time on task and rehabilitation outcomes should be explored further as it may create benefits beyond repetitive movement. As gamification becomes a more common and feasible way of delivering exercise-based therapies, additional benefits of gamification are emerging. In spite of this, questions still exist about scalability and widespread clinical adoption.

Walking improvement in chronic incomplete spinal cord injury with exoskeleton robotic training (WISE): a randomized controlled trial.

STUDY DESIGN: Clinical trial. OBJECTIVE: To demonstrate that a 12-week exoskeleton-based robotic gait training regimen can lead to a clinically meaningful improvement in independent gait speed, in community-dwelling participants with chronic incomplete spinal cord injury (iSCI). SETTING: Outpatient rehabilitation or research institute. METHODS: Multi-site (United States), randomized, controlled trial, comparing exoskeleton gait training (12 weeks, 36 sessions) with standard gait training or no gait training (2:2:1 randomization) in chronic iSCI (>1 year post injury, AIS-C, and D), with residual stepping ability. The primary outcome measure was change in robot-independent gait speed (10-meter walk test, 10MWT) post 12-week intervention. Secondary outcomes included: Timed-Up-and-Go (TUG), 6-min walk test (6MWT), Walking Index for Spinal Cord Injury (WISCI-II) (assistance and devices), and treating therapist NASA-Task Load Index. RESULTS: Twenty-five participants completed the assessments and training as assigned (9 Ekso, 10 Active Control, 6 Passive Control). Mean change in gait speed at the primary endpoint was not statistically significant. The proportion of participants with improvement in clinical ambulation category from home to community speed post-intervention was greatest in the Ekso group (>1/2 Ekso, 1/3 Active Control, 0 Passive Control, p < 0.05). Improvements in secondary outcome measures were not significant. CONCLUSIONS: Twelve weeks of exoskeleton robotic training in chronic SCI participants with independent stepping ability at baseline can improve clinical ambulatory status. Improvements in raw gait speed were not statistically significant at the group level, which may guide future trials for participant inclusion criteria. While generally safe and tolerable, larger gains in ambulation might be associated with higher risk for non-serious adverse events.

New Cases of Hypochromic Microcytic Anemia Due to Mutations in the SLC11A2 Gene and Functional Characterization of the G75R Mutation.

Divalent metal-iron transporter 1 (DMT1) is a mammalian iron transporter encoded by the SLC11A2 gene. DMT1 has a vital role in iron homeostasis by mediating iron uptake in the intestine and kidneys and by recovering iron from recycling endosomes after transferrin endocytosis. Mutations in SLC11A2 cause an ultra-rare hypochromic microcytic anemia with iron overload (AHMIO1), which has been described in eight patients so far. Here, we report two novel cases of this disease. The first proband is homozygous for a new SLC11A2 splicing variant (c.762 + 35A > G), becoming the first ever patient reported with a SLC11A2 splicing mutation in homozygosity. Splicing studies performed in this work confirm its pathogenicity. The second proband harbors the previously reported DMT1 G75R mutation in homozygosis. Functional studies with the G75R mutation in HuTu 80 cells demonstrate that this mutation results in improper DMT1 accumulation in lysosomes, which correlates with a significant decrease in DMT1 levels in patient-derived lymphoblast cell lines (LCLs). We also suggest that recombinant erythropoietin would be an adequate therapeutic approach for AHMIO1 patients as it improves their anemic state and may possibly contribute to mobilizing excessive hepatic iron.

Postintensive Care Syndrome in Survivors of Critical Illness Related to Coronavirus Disease 2019: Cohort Study From a New York City Critical Care Recovery Clinic.

OBJECTIVE: Determine the characteristics of postintensive care syndrome in the cognitive, physical, and psychiatric domains in coronavirus disease 2019 ICU survivors. DESIGN: Single-center descriptive cohort study from April 21, to July 7, 2020. SETTING: Critical care recovery clinic at The Mount Sinai Hospital in New York City. PATIENTS: Adults who had critical illness due to coronavirus disease 2019 requiring an ICU stay of 7 days or more and who agreed to a telehealth follow-up in the critical care recovery clinic 1-month post hospital discharge. INTERVENTIONS: None. MEASURES AND MAIN RESULTS: Patient-reported outcome measures assessing physical and psychiatric domains were collected electronically, a cognitive test was performed by a clinician, and clinical data were obtained through electronic medical records. Outcome measures assessed postintensive care syndrome symptoms in the physical (Modified Rankin Scale, Dalhousie Clinical Frailty Scale, Neuro-Quality of Life Upper Extremity and Lower Extremity Function, Neuro-Quality of Life Fatigue), psychiatric (Insomnia Severity Scale; Patient Health Questionnaire-9; and Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), and cognitive (Telephone Montreal Cognitive Assessment) domains. The 3-Level Version of Euro-QoL-5D was used to assess the physical and psychiatric domains. A diagnosis of postintensive care syndrome was made in cases with evidence of impairment in at least one postintensive care syndrome domain. We included 45 patients with a mean (sd) age of 54 (13) years, and 73% were male. Ninety-one percent of coronavirus disease 2019 ICU survivors fit diagnostic criteria for postintensive care syndrome. 86.7 % had impairments in the physical domain, 22 (48%) reported impairments in the psychiatric domain, and four (8%) had impairments on cognitive screening. We found that 58% had some degree of mobility impairment. In the psychiatric domain, 38% exhibited at least mild depression, and 18 % moderate to severe depression. Eighteen percent presented Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, scores suggestive of posttraumatic stress syndrome diagnosis. In the Telephone Montreal Cognitive Assessment, 9% had impaired cognition. CONCLUSIONS: Survivors of critical illness related to coronavirus disease 2019 are at high risk of developing postintensive care syndrome. These findings highlight the importance of planning for appropriate post-ICU care to diagnose and treat this population.

Intervention Therapies to Reduce Pain-Related Fear in Fibromyalgia Syndrome: A Systematic Review of Randomized Clinical Trials.

OBJECTIVE: This systematic review aimed to evaluate the effectiveness of different interventions at reducing pain-related fear in people with fibromyalgia and to analyze whether the included trials reported their interventions in full detail. DESIGN: Systematic review. SETTING: No restrictions. METHODS: The Cochrane Library, CINAHL, EMBASE, PsycINFO, PubMed, and Scopus were searched from their inception to April 2020, along with manual searches and a gray literature search. Randomized clinical trials were included if they assessed pain-related fear constructs as the primary or secondary outcome in adults with fibromyalgia. Two reviewers independently performed the study selection, data extraction, risk-of-bias assessment, Template for Intervention Description and Replication (TIDieR) checklist assessment, and grading the quality of evidence. RESULTS: Twelve randomized clinical trials satisfied the eligibility criteria, including 11 cohorts with a total sample of 1,441 participants. Exercise, multicomponent, and psychological interventions were more effective than controls were in reducing kinesiophobia. However, there were no differences in decreasing kinesiophobia when self-management and electrotherapy were used. There were also no differences between groups with regard to the rest of the interventions and pain-related constructs (fear-avoidance beliefs, fear of pain, and pain-related anxiety). However, a serious risk of bias and a very serious risk of imprecision were detected across the included trials. This caused the overall certainty of the judged evidence to be low and very low. Additionally, the included trials reported insufficient details to allow the full replication of their interventions. CONCLUSIONS: This systematic review shows that there are promising interventions, such as exercise, multicomponent, and psychological therapies, that may decrease one specific type of fear in people with fibromyalgia, i.e., kinesiophobia. However, because of the low-very low certainty of the evidence found, a call for action is needed to improve the quality of randomized clinical trials, which will lead to more definitive information about the clinical efficacy of interventions in this field.

Remote Patient Monitoring for Home Management of Coronavirus Disease 2019 in New York: A Cross-Sectional Observational Study.

Background: Coronavirus disease 2019 (COVID-19) poses a global public health emergency, overwhelming health systems worldwide and forcing rapid adoption of telemedicine strategies. Introduction: The COVID-19 Precision Recovery Program (PRP) is a remote patient monitoring (RPM) clinical program that was deployed by a New York health system to perform physiologic and symptomatic monitoring for patients with confirmed or suspected COVID-19 diagnoses. Methods: The present cross-sectional descriptive study reports retrospective data collected from the PRP during the COVID-19 crisis in New York. Results: One hundred twelve patients were included; mean (standard deviation) age was 49 (17.6) years and 60.7% were female. Most prevalent reported comorbidities were hypertension (36.3%), hypercholesterolemia (26.5%), and diabetes (17.7%). Less than half (44.6%) had a positive polymerase chain reaction COVID test (PCR-test), 33% had an unknown COVID status, and 17.9% had a negative test result. The most commonly reported symptoms included dyspnea (55.4%) and anxiety (55.4%). Anxiety was ranked as the most severe symptom (9.8%), followed by difficulty concentrating (4.5%). Symptom presentation did not significantly differ based on PCR-test status. Discussion: RPM can be a valuable tool for delivering care to patients with confirmed or suspected COVID-19 diagnoses. Considering similarities in symptom presentation between PCR-test statuses, access to COVID-related clinical care should not be based on PCR-test results. Conclusions: RPM has strong potential to assist in the effective management of suspected COVID-19 patients.

Hereditary Hyperferritinemia Cataract Syndrome: Ferritin L Gene and Physiopathology behind the Disease-Report of New Cases.

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare disease characterized by high serum ferritin levels, congenital bilateral cataracts, and the absence of tissue iron overload. This disorder is produced by mutations in the iron responsive element (IRE) located in the 5' untranslated regions (UTR) of the light ferritin (FTL) gene. A canonical IRE is a mRNA structure that interacts with the iron regulatory proteins (IRP1 and IRP2) to post-transcriptionally regulate the expression of proteins related to iron metabolism. Ferritin L and H are the proteins responsible for iron storage and intracellular distribution. Mutations in the FTL IRE abrogate the interaction of FTL mRNA with the IRPs, and de-repress the expression of FTL protein. Subsequently, there is an overproduction of ferritin that accumulates in serum (hyperferritinemia) and excess ferritin precipitates in the lens, producing cataracts. To illustrate this disease, we report two new families affected with hereditary hyperferritinemia-cataract syndrome with previous known mutations. In the diagnosis of congenital bilateral cataracts, HHCS should be taken into consideration and, therefore, it is important to test serum ferritin levels in patients with cataracts.

Conservative Interventions Reduce Fear in Individuals With Chronic Low Back Pain: A Systematic Review.

OBJECTIVE: To systematically review and critically appraise the effectiveness of conservative and surgical interventions to reduce fear in studies of people with chronic low back pain, based on the analysis of randomized controlled trials for which fear was a primary or secondary outcome. DATA SOURCES: Electronic databases PubMed, CINAHL, PsycINFO, PEDro, and CENTRAL, as well as manual searches and grey literature were searched from inception until May 2019. STUDY SELECTION: Randomized controlled trials analyzing the effectiveness of conservative and surgical interventions to reduce fear were included. DATA EXTRACTION: Two reviewers independently conducted the search strategy, study selection, data extraction, risk of bias assessment, and quality of the evidence judgment. DATA SYNTHESIS: Sixty-one studies (n=7201) were included. A large number of fear-related search terms were used but only 3 fear constructs (kinesiophobia, fear-avoidance beliefs, fear of falling) were measured in the included studies. Multidisciplinary and psychological interventions as well as exercise reduced kinesiophobia. Fear-avoidance beliefs were reduced by the aforementioned interventions, manual therapy, and electrotherapy. A multidisciplinary intervention reduced the fear of falling. There was moderate evidence of multidisciplinary interventions and exercise to reduce kinesiophobia. There was moderate evidence of manual therapy and electrotherapy to reduce fear-avoidance beliefs. CONCLUSIONS: The present systematic review highlights the potential effectiveness of conservative interventions to reduce kinesiophobia and fear-avoidance beliefs in individuals with chronic low back pain. This information can help health professionals to reduce fear when treating patients with this condition.

Effectiveness of anodal transcranial direct current stimulation to improve muscle strength and motor functionality after incomplete spinal cord injury: a systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: We aimed to investigate the effects of anodal transcranial direct current stimulation (tDCS) against sham on muscle strength and motor functionality after incomplete spinal cord injury (iSCI). SETTING: University of São Paulo, Brazil. METHODS: A preplanned protocol was registered (PROSPERO, CRD42016050444). Pubmed, Embase, Web of Science, Cochrane Central Library and BVS databases were searched independently by two authors up to March 2018. Cochrane Collaboration's Tool was used for the risk of bias assessments. Generic inverse variance and random-effects model were used to calculate pooled effect sizes (ES), 95% confidence intervals (CIs) and p-values in meta-analyses. RESULTS: Six randomized clinical trials met inclusion criteria (n = 78 iSCI individuals) and were included in the meta-analysis. Results showed a marginal significant pooled effect of active tDCS in improving motor functionality with a small ES (SMD = 0.26, 95% CI = -0.00 to 0.53, p = 0.05, I2 = 0%). On the other hand, the pooled effect of active tDCS on muscle strength did not reach statistical significance, in parallel with a small ES (SMD = 0.35, 95% CI = -0.21 to 0.92, p = 0.22, I2 = 0%) when compared with sham tDCS. No significant adverse events were reported. CONCLUSIONS: Overall, there was a significant effect of tDCS in improving motor functionality following iSCI. However, a small ES and the marginal p-value suggest that these results should be interpreted with caution. Further high-quality clinical trials are needed to support or refute the use of tDCS in daily clinical practice.

Type III pleuropulmonary blastoma in a dicer1 germline mutation carrier: The management of residual lung cystic lesions.

Pleuropulmonary blastoma (PPB) is a rare malignancy of childhood. It often represents a manifestation of a hereditary tumor predisposition syndrome (DICER1 syndrome). Because of its malignant potential, surgical resection of cystic lung lesions is recommended in germline DICER1 mutation carriers. We present a case of a 3-year-old male child with type III PPB successfully managed with ifosfamide, vincristine, actinomycin-D, and doxorubicin (IVADo) chemotherapy and surgery. A heterozygous germline pR688X mutation of DICER1 gene was demonstrated. Six years after primary diagnosis, several small lung cysts remained stable without further therapy. The management of residual asymptomatic lung cysts represents a clinical challenge in these patients.

Intensity dependent effects of transcranial direct current stimulation on corticospinal excitability in chronic spinal cord injury.

OBJECTIVE: To investigate the effects of anodal transcranial direct current stimulation (a-tDCS) intensity on corticospinal excitability and affected muscle activation in individuals with chronic spinal cord injury (SCI). DESIGN: Single-blind, randomized, sham-controlled, crossover study. SETTING: Medical research institute and rehabilitation hospital. PARTICIPANTS: Volunteers (N = 9) with chronic SCI and motor dysfunction in wrist extensor muscles. INTERVENTIONS: Three single session exposures to 20 minutes of a-tDCS (anode over the extensor carpi radialis [ECR] muscle representation on the left primary motor cortex, cathode over the right supraorbital area) using 1 mA, 2 mA, or sham stimulation, delivered at rest, with at least 1 week between sessions. MAIN OUTCOME MEASURES: Corticospinal excitability was assessed with motor-evoked potentials (MEPs) from the ECR muscle using surface electromyography after transcranial magnetic stimulation. Changes in spinal excitability, sensory threshold, and muscle strength were also investigated. RESULTS: Mean MEP amplitude significantly increased by approximately 40% immediately after 2mA a-tDCS (pre: 0.36 ± 0.1 mV; post: 0.47 ± 0.11 mV; P = .001), but not with 1 mA or sham. Maximal voluntary contraction measures remained unaltered across all conditions. Sensory threshold significantly decreased over time after 1mA (P = .002) and 2mA (P = .039) a-tDCS and did not change with sham. F-wave persistence showed a nonsignificant trend for increase (pre: 32% ± 12%; post: 41% ± 10%; follow-up: 46% ± 12%) after 2 mA stimulation. No adverse effects were reported with any of the experimental conditions. CONCLUSIONS: The a-tDCS can transiently raise corticospinal excitability to affected muscles in patients with chronic SCI after 2 mA stimulation. Sensory perception can improve with both 1 and 2 mA stimulation. This study gives support to the safe and effective use of a-tDCS using small electrodes in patients with SCI and highlights the importance of stimulation intensity.

Measurable residual disease study through three different methods can anticipate relapse and guide early interventions in childhood acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common cancer among children. Measurable residual disease (MRD, previously named minimal residual disease) study can guide therapy adjustments or preemptive interventions that might avoid hematological relapse. METHODS: Clinical decision making and patient outcome were evaluated in 80 real-life childhood ALL patients, according to the results observed in 544 bone marrow samples analyzed with three MRD methods: multiparametric flow cytometry (MFC), fluorescent in-situ hybridization (FISH) on B or T-purified lymphocytes and patient-specific nested reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Estimated 5 year overall survival and event-free survival were 94% and 84.1%, respectively. A total of 12 relapses in 7 patients were associated with positive MRD detection with at least one of the three methods: MFC (p < 0.00001), FISH (p < 0.00001) and RT-PCR (p = 0.013). MRD assessment allowed the anticipation of relapse and adapted early interventions with different approaches including chemotherapy intensification, blinatumomab, HSCT and targeted therapy to halt relapse in five patients, although two of them relapsed afterwards. CONCLUSION: MFC, FISH and RT-PCR are complementary methods for MRD monitoring in pediatric ALL. Although, our data clearly show that MDR positive detection is associated with relapse, continuation of standard treatment, intensification or other early interventions were able to halt relapse in patients with different risks and genetic background. More sensitive and specific methods are warranted to enhance this approach. However, whether early treatment of MRD can improve overall survival in patients with childhood ALL needs to be evaluated in adequately controlled clinical trials.

Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: a basis for high-definition tDCS.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4 × 1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4 × 1 montage (4 × cathode, surrounding a single central anode; montage radius ~3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4 × 1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject. We provide direct evidence in humans that TES with a 4 × 1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4 × 1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4 × 1-Ring montage for cortically targeted neuromodulation.

Retrospective case-control study to compare exoskeleton-assisted walking with standard care in subacute non-traumatic brain injury patients.

BACKGROUND: Advanced technologies are increasingly used to address impaired mobility after neurological insults, with growing evidence of their benefits for various populations. However, certain robotic devices have not been extensively investigated in specific conditions, limiting knowledge about optimal application for healthcare. OBJECTIVE: To compare effectiveness of conventional gait training with exoskeleton-assisted walking for non-traumatic brain injury during early stage rehabilitation. METHODS: Clinical evaluation data at admission and discharge were obtained in a retrospective case-control design. Patients received standard of care physical therapy either using Ekso GT or not. Within- or between-group statistical tests were performed to determine change over time and interventional differences. RESULTS: This study analyzed forty-nine individuals (33% female), 20 controls and 29 Ekso participants who were equivalent at baseline. Both groups improved in Functional Independence Measure scores and ambulation ability (p < .00001 and p < .001, respectively). Control subjects demonstrated significantly different distance walked and assistance level values at discharge from those who were treated with the exoskeleton (p < .01). CONCLUSION: Robotic locomotion is non-inferior for subacute functional recovery after non-traumatic brain injury. Conventional therapy produced larger gait performance gains during hospitalization. Further research is needed to understand specific factors influencing efficacy and the long-term implications after rehabilitation.

Role of Immersive Virtual Reality in Motor Behaviour Decision-Making in Chronic Pain Patients.

Primary chronic pain is a major contributor to disability worldwide, with an estimated prevalence of 20-33% of the world's population. The high socio-economic impact of musculoskeletal pain justifies seeking an appropriate therapeutic strategy. Immersive virtual reality (VR) has been proposed as a first-line intervention for chronic musculoskeletal pain. However, the growing literature has not been accompanied by substantial progress in understanding how VR exerts its impact on the pain experience and what neurophysiological mechanisms might be involved in the clinical effectiveness of virtual reality interventions in chronic pain patients. The aim of this review is: (i) to establish the state of the art on the effects of VR on patients with chronic pain; (ii) to identify neuroplastic changes associated with chronic pain that may be targeted by VR intervention; and (iii) to propose a hypothesis on how immersive virtual reality could modify motor behavioral decision-making through an interactive experience in patients with chronic pain.

Sensorimotor Uncertainty of Immersive Virtual Reality Environments for People in Pain: Scoping Review.

INTRODUCTION: Decision making and action execution both rely on sensory information, and their primary objective is to minimise uncertainty. Virtual reality (VR) introduces uncertainty due to the imprecision of perceptual information. The concept of "sensorimotor uncertainty" is a pivotal element in the interplay between perception and action within the VR environment. The role of immersive VR in the four stages of motor behaviour decision making in people with pain has been previously discussed. These four processing levels are the basis to understand the uncertainty that a patient experiences when using VR: sensory information, current state, transition rules, and the outcome obtained. METHODS: This review examines the different types of uncertainty that a patient may experience when they are immersed in a virtual reality environment in a context of pain. Randomised clinical trials, a secondary analysis of randomised clinical trials, and pilot randomised clinical trials related to the scope of Sensorimotor Uncertainty in Immersive Virtual Reality were included after searching. RESULTS: Fifty studies were included in this review. They were divided into four categories regarding the type of uncertainty the intervention created and the stage of the decision-making model. CONCLUSIONS: Immersive virtual reality makes it possible to alter sensorimotor uncertainty, but studies of higher methodological quality are needed on this topic, as well as an exploration into the patient profile for pain management using immersive VR.

Is it Possible to Reduce Pain-Related Fear in Individuals with Knee Osteoarthritis? a Systematic Review of Randomised Clinical Trials.

OBJECTIVE: To evaluate the effectiveness of different interventions in reducing pain-related fear outcomes in people with knee osteoarthritis who have or have not had previous knee surgery, and to analyze whether included trials reported their interventions in full detail. METHODS: Systematic searches were carried out in the Cochrane CENTRAL, CINAHL, EMBASE, PEDro, PsycINFO, PubMed, and SPORTDiscus from the inception of the database up to November 2019. Searches were manually updated to July 2021. We included randomized clinical trials that evaluated pain-related fear outcomes as a primary or secondary outcome in adults with knee osteoarthritis. The Cochrane Risk of Bias Tool 2 and the GRADE approach evaluated the risk of bias and the certainty of the evidence, respectively. RESULTS: Eighteen trials were included. Four trials evaluated pain-related fear as a primary outcome and all evaluated kinesiophobia in samples that had previously undergone a knee surgical procedure. These trials found that interventions based primarily on cognitive aspects (e.g. cognitive-behavioral principles) can be effective in reducing kinesiophobia. Trials evaluating pain-related fear as the secondary outcome also found that interventions that included cognitive aspects (e.g. pain neuroscience education) decreased the levels of pain-related fear (e.g. fear of falling or kinesiophobia) in patients with or without a previous knee surgery. However, serious to very serious risk of bias and imprecisions were found in included trials. Thus, the certainty of the evidence was judged as low and very low using the GRADE approach. All trials reported insufficient details to allow a complete replication of their interventions. CONCLUSIONS: Interventions that include cognitive aspects may be the best option to reduce pain-related fear in people with knee osteoarthritis. However, we found a general low and very low certainty of the evidence and the findings should be considered with caution.

Measurable residual disease study through three different methods can anticipate relapse and guide pre-emptive therapy in childhood acute myeloid leukemia.

PURPOSE: Although outcomes of children with acute myeloid leukemia (AML) have improved over the last decades, around one-third of patients relapse. Measurable (or minimal) residual disease (MRD) monitoring may guide therapy adjustments or pre-emptive treatments before overt hematological relapse. METHODS: In this study, we review 297 bone marrow samples from 20 real-life pediatric AML patients using three MRD monitoring methods: multiparametric flow cytometry (MFC), fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). RESULTS: Patients showed a 3-year overall survival of 73% and a 3-year event-free survival of 68%. Global relapse rate was of 25%. All relapses were preceded by the reappearance of MRD detection by: (1) MFC (p = 0.001), (2) PCR and/or FISH in patients with an identifiable chromosomal translocation (p = 0.03) and/or (3) one log increase of Wilms tumor gene 1 (WT1) expression in two consecutive samples (p = 0.02). The median times from MRD detection to relapse were 26, 111, and 140 days for MFC, specific PCR and FISH, and a one log increment of WT1, respectively. CONCLUSIONS: MFC, FISH and PCR are complementary methods that can anticipate relapse of childhood AML by weeks to several months. However, in our series, pre-emptive therapies were not able to prevent disease progression. Therefore, more sensitive MRD monitoring methods that further anticipate relapse and more effective pre-emptive therapies are needed.

A Newborn Screening Program for Sickle Cell Disease in Murcia (Spain).

Sickle cell disease (SCD) is an inherited autosomal recessive hemoglobin disorder caused by the presence of hemoglobin S, a mutant abnormal hemoglobin caused by a nucleotide change in codon 6 of the ß-globin chain gene. SCD involves a chronic inflammatory state, exacerbated during vaso-occlusive crises, which leads to end-organ damage that occurs throughout the lifespan. SCD is associated with premature mortality in the first years of life. The process of sickling provokes asplenia in the first years of life with an increased risk of infection by encapsulated germs. These complications can be life-threatening and require early diagnosis and management. The most important interventions recommend an early diagnosis of SCD to ensure that affected newborns receive immediate care to reduce mortality and morbidity. The newborn screening program in the region of Murcia for SCD began in March 2016. We aimed to determine the incidence of sickle cell anemia and other structural hemoglobinopathies in the neonatal population of the region of Murcia, an area of high migratory stress, and to systematically assess the benefit of newborn screening for SCD, leading to earlier treatment, as well as to offer genetic counseling to all carriers. The prevalence of SCD in our region is similar to others in Spain, except for Catalonia and Madrid. The newborns with confirmed diagnoses of SCD received early attention, and all the carriers received genetic counseling.