Electrical dry needling versus a non-invasive multicomponent intervention in the treatment of myofascial trigger points in patients with chronic low back pain: A randomised clinical trial.

OBJECTIVE: To compare the effects of electrical dry needling with a non-invasive multi-component intervention in patients with chronic low back pain. DESIGN: A randomised single-blind clinical trial. SETTING: Outpatient Physiotherapy Clinic; home. PARTICIPANTS: Sixty-four patients with chronic low back pain aged 30-65 years. INTERVENTIONS: Six-week electrical dry needling on myofascial trigger points, and a non-invasive multicomponent intervention (home exercise programme, stretching and ischemic compression). MAIN MEASURES: Pain (Visual Analogue Scale), disability (Roland-Morris Disability Questionnaire and Oswestry Disability Index), kinesiophobia (Tampa Scale of Kinesiophobia), quality of life and sleep (Short Form 36-item Health Survey and Pittsburgh Sleep Quality Index), isometric endurance of trunk flexor muscles (McQuade test), lumbar mobility in flexion (finger-to-floor distance), and pressure pain threshold (algometer) were assessed at baseline, after 6 weeks, and after 2 months. RESULTS: ANOVA showed statistically significant differences in group-by-time interaction for most pain pressure thresholds of myofascial trigger points (P < 0.05), for disability (Roland-Morris Disability Questionnaire: F = 6.14, P = 0.016; and Oswestry Disability Index: F = 7.36, P = 0.009), for trunk anteflexion (F = 10.03, P = 0.002) and for habitual sleep efficacy (F = 6.65, P = 0.012), use of hypnotics (F = 4.77, P = 0.033) and total score of quality of sleep (F = 8.23, P = 0.006). CONCLUSIONS: In comparison to a non-invasive multicomponent intervention, electrical dry needling has more positive effects on disability, pain intensity, kinesiophobia, and reducing patients' sensitivity to myofascial trigger points pressure, at post-treatment and at 2 months. CLINICAL TRIAL REGISTRATION NUMBER: NCT04804228. Registered on May 28th, 2021. Available at https://clinicaltrials.gov/ct2/show/NCT04804228.

Effectiveness of balneotherapy in reducing pain, disability, and depression in patients with Fibromyalgia syndrome: a systematic review with meta-analysis.

Balneotherapy, using heated natural mineral waters at 36-38 °C, presents a comprehensive treatment approach for Fibromyalgia Syndrome (FMS). This study aims to assess the effect of balneotherapy in reducing pain intensity, disability, and depression in patients with FMS. We want to assess this effect at just four time-points: immediately at the end of the therapy, and at 1, 3, and 6 months of follow-up. Following PRISMA guidelines, we conducted an aggregate data meta-analysis, registered in PROSPERO CRD42023478206, searching PubMed Medline, Science Direct, CINAHL Complete, Scopus, and Web of Science until August 2023 for relevant randomized controlled trials (RCTs) that assess the effect of balneotherapy on pain intensity, disability, and depression in FMS patients. Methodological quality was assessed using the Cochrane methodology, and the pooled effect was calculated using Cohen's standardized mean difference (SMD) and its 95% confidence interval (95% CI) in a random-effects model. Sixteen RCTs were included in the meta-analysis. Balneotherapy is effective in reducing pain intensity (SMD - 1.67; 95% CI -2.18 to -1.16), disability (SMD - 1.1; 95% CI -1.46 to -0.7), and depression (SMD - 0.51; 95% CI -0.93 to -0.9) at the end of the intervention. This effect was maintained at 1, 3, and 6 months for pain intensity and disability. Balneotherapy improves both pain intensity and disability in patients with FMS, providing evidence that its positive effects are sustained for up to 6 months of follow-up. Nevertheless, it is important to note that the improvement in depression varies across different temporal phases.

Non-Immersive Virtual Reality-Based Therapy Applied in Cardiac Rehabilitation: A Systematic Review with Meta-Analysis.

BACKGROUND: The aim of this systematic review with meta-analysis was to assess the effectiveness of non-immersive virtual reality (niVR) active videogames in patients who underwent cardiac rehabilitation (CR). METHODS: A systematic review with meta-analysis, according to the PRISMA guidelines and previously registered in PROSPERO (CRD42023485240), was performed through a literature search in PubMed (Medline), SCOPUS, WOS, and PEDro since inception to 21 November 2023. We included randomized controlled trials (RCTs) that assessed the effectiveness of an niVR intervention, in comparison with conventional CR and usual care, on aerobic capacity and cardiovascular endurance (physical function), anxiety, depression, and quality of life (QoL). The risk of bias in individual studies was assessed using the Cochrane risk of bias tool. Effect size was estimated using Cohen's standardized mean difference (SMD) and its 95% confidence interval (95% CI) in a random-effects model. RESULTS: Nine RCT that met the inclusion criteria were included in the meta-analysis. The meta-analysis showed a moderate-to-large effect favoring niVR active videogames included in CR in increasing aerobic capacity and cardiovascular endurance (SMD = 0.74; 95% CI 0.11 to 1.37; p = 0.021) and reducing anxiety (SMD = -0.66; 95% CI -1.13 to -0.2; p = 0.006). Only 4.8% of patients reported adverse events while performing niVR active videogames. CONCLUSIONS: Inclusion of niVR active videogames in CR programs is more effective than conventional CR in improving aerobic capacity and cardiovascular endurance and in reducing anxiety.

Evaluation of road safety policies and their enforcement in Mexico City, 2015-2019: an interrupted time-series study.

BACKGROUND: Mexico City approved new road safety policies in 2015, which included lower speed limits and higher fines for traffic offences. In 2019, economic fines were replaced by a point penalty system among other changes. This study evaluates these policies on road traffic collisions, injuries and deaths. METHODS: Collisions data came from insurance collision claims (January 2015 to December 2019) and road traffic deaths from vital registrations (January 2013 to December 2019). We conducted an interrupted time series analysis for each outcome using negative binomial regression models with an offset of insured vehicles (collisions) or total population (deaths). Then, we classified the 16 municipalities in the city into enforcement and no-enforcement groups based on presence or absence of automated traffic enforcement devices and conducted a controlled interrupted time series analysis. RESULTS: The 2015 road safety policies had no effect on total collisions and collisions resulting in injury but were associated with a 0.2% (95% CI -0.3 to 0.0) decline in the mortality trend. The 2019 policies had no effect on total collisions but were associated with a 1.5% increase in the trend of collisions resulting in injuries and with a 2.7% (95% CI 1.0 to 4.5) increase in the mortality trend. Postpolicy trends in enforcement versus no-enforcement municipalities were not significantly different. CONCLUSION: Policies that included high economic penalties for speeding and dangerous behaviours were effective in decreasing traffic mortality while removing economic penalties and replacing them with a point penalty system were associated with an increase in collisions, resulting in injury and mortality.

Domestic Dogs as Sentinels for West Nile Virus but not Aedes-borne Flaviviruses, Mexico.

We tested 294 domestic pet dogs in Mexico for neutralizing antibodies for mosquito-borne flaviviruses. We found high (42.6%) exposure to West Nile virus in Reynosa (northern Mexico) and low (1.2%) exposure in Tuxtla Gutierrez (southern Mexico) but very limited exposure to Aedes-borne flaviviruses. Domestic dogs may be useful sentinels for West Nile virus.

Nomogram based on baseline clinicopathological characteristics for predicting bladder cancer-specific survival to neoadjuvant chemotherapy in muscle-invasive bladder cancer.

PURPOSE: To develop a risk score based on a prognostic model and a nomogram integrating baseline clinicopathological variables to predict bladder cancer-specific survival (BCSS) to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) patients. METHODS: We retrospectively identified a consecutive sample of 247 MIBC patients treated with cisplatin-based NAC-plus-cystectomy in two Spanish hospitals between 2000 and 2019. Age at MIBC diagnosis, sex, histology, lymphovascular invasion, previous non-MIBC, hydronephrosis, and clinical TNM were included in the initial Cox regression model. A risk score was computed based on the final prognostic model and a nomogram was used to estimate BCSS at 2 and 5 years. RESULTS: Median age was 66 years; 89% were males; 83% had pure urothelial carcinoma; 16.2% had previous non-MIBC. Clinical stage was T2N0, T3-4aN0, and Tx-4N + in 24%, 57%, and 19% of patients, respectively. Complete pathological response was seen in 29.4% and downstaging to non-MIBC (ypT1, ypTa, ypTis) in 12.5% of patients. Overall 5-year BCSS was 59%. Four prognostic factors were identified: variant histology, previous non-MIBC, female sex and hydronephrosis. By adding the points attributed to each of these factors, we categorized patients in three groups: low-risk (0 points); intermediate-risk (1-9 points); high-risk (≥ 10 points). Five-year BCSS was 72%, 53%, and 15%, respectively (p < 0.0001). CONCLUSION: We developed a nomogram and risk score based on four baseline clinicopathological characteristics to predict BCSS to NAC-plus-cystectomy in MIBC patients. If validated in prospective studies, this nomogram can be useful for selecting patients likely to benefit from NAC.

Job strain and burnout in Spanish nurses during the COVID-19: resilience as a protective factor in a cross-sectional study.

BACKGROUND: Nurses are frequently exposed to chronic stress in the workplace generating harmful effects such as job strain and burnout. On the contrary, resilience has been shown to be a beneficial variable. The objective of this study was to analyze the relationship between dimensions of the Job Demand Control-Support model, resilience and burnout in nurses, and examine the mediating role of resilience between job strain and burnout. METHODS: A descriptive, cross-sectional study reported in line with the STROBE guidelines. Active nurses were invited to complete an online questionnaire in September, 2020. With snowball sampling, 1013 nurses, with a mean age of 34.71, filled out the Job Content Questionnaire, the Maslach Burnout Inventory and the Resilience Scale. RESULTS: The results showed the existence of four groups of professionals based on job strain. The nurses in the "High Strain" group (high demands and low control) showed higher scores in emotional exhaustion and cynicism, while those in the "Active Job" group scored higher in personal realization and resilience. The findings showed that job strain affects burnout in nurses, and this effect is mediated by resilience. CONCLUSIONS: The findings of this study showed that a high level of resilience could exert a fundamental role in ensuring well-being and proper job performance by nurses. Nursing managers should see to the personable variables or competencies that provide and favor an opportunity for nurses to widen and improve their practice, in pursuance of satisfying and responding better to people's needs and the systems they work for.

Atherogenic indices in pediatric population in South-Southeast region of Mexico.

BACKGROUND: Atherosclerosis is a cardiovascular disease, highly predictable, and associated with different atherogenic indices (AI) in adults. However, such indexes in the pediatric population are far less explored. The objective of this study was to evaluate the AI and the cardiovascular factors in the pediatric population in the South-Southeast of México. METHODS: A total of 481 children between 2 and 17 years old were recruited. Anthropometric evaluation, blood pressure (BP), lipid profile, apolipoprotein A-I (ApoA-I) and apolipoprotein B (ApoB) were measured, and AI were calculated. The population was grouped by age, binary logistic regression analysis was performed to analysis for associations of AI and cardiovascular risk factors. Sensibility and specificity of AI to detect metabolic alteration were evaluated for curve ROC. RESULTS: The atherogenic risk presented a high prevalence in the pediatric population, such as LDL-c/ApoB (86.9%), AIP (78%) and AC (36.6%). Preschoolers showed a higher risk of ApoB/ApoA-I and ApoB/LDL-c, while adolescents have a high risk of AIP. CRI-I and AC were associated with elements of lipid profile and body mass index (BMI). ROC curves analysis shows that AIP is the best index evaluating metabolic syndrome (MS) (0.87) and dyslipidemia (0.91). CONCLUSION: Such pediatric population showed a high risk of AI, mainly by LDL-c/ApoB and AIP. The BMI was the cardiovascular risk factors most frequently related to AI, AIP is the best index for detecting cases of MS and dyslipidemia. This is the first study carried out in the pediatric population from the South-Southeast of Mexico that evaluated the AI.

Efficacy of Robot-Assisted Gait Therapy Compared to Conventional Therapy or Treadmill Training in Children with Cerebral Palsy: A Systematic Review with Meta-Analysis.

BACKGROUND: Motor, gait and balance disorders reduce functional capabilities for activities of daily living in children with cerebral palsy (CP). Robot-assisted gait therapy (RAGT) is being used to complement conventional therapy (CT) or treadmill therapy (TT) in CP rehabilitation. The aim of this systematic review is to assess the effect of RAGT on gait, balance and functional independence in CP children, in comparison to CT or TT. METHODS: We have conducted a systematic review with meta-analysis. A search in PubMed Medline, Web of Science, Scopus, CINAHL, PEDro and SciELO has been conducted for articles published until October 2022. Controlled clinical trials (CCT), in which RAGT was compared to TT or CT and assessed gait speed, step and stride length, width step, walking distance, cadence, standing ability, walking, running and jumping ability, gross motor function and functional independence in children with CP, have been included. Methodological quality was assessed with the PEDro scale and the pooled effect was calculated with Cohen's Standardized Mean Difference (SMD) and its 95% Confidence Interval (95% CI). RESULTS: A total of 15 CCTs have been included, providing data from 413 participants, with an averaged methodological quality of 5.73 ± 1.1 points in PEDro. The main findings of this review are that RAGT shows better results than CT in the post-intervention assessment for gait speed (SMD 0.56; 95% CI 0.03 to 1.1), walking distance (SMD 2; 95% CI 0.36 to 3.65) and walking, running and jumping ability (SMD 0.63; 95% CI 0.12 to 1.14). CONCLUSIONS: This study shows that the effect of RAGT is superior to CT on gait speed, walking distance and walking, running and jumping ability in post-intervention, although no differences were found between RAGT and TT or CT for the remaining variables.

Efficacy of e-Health Interventions in Patients with Chronic Low-Back Pain: A Systematic Review with Meta-Analysis.

Introduction: Low-back pain (LBP) is the leading cause of disability worldwide. Around 75-84% of the world's population will experience LBP at some point, establishing it as a major global health problem. e-Health is the remote delivery of therapeutic services, clinical information, and medical care, and may prove a very useful approach to tackle this pathology. Objectives: To evaluate the efficacy of e-health-based interventions in improving the symptoms of chronic LBP. Methods: A systematic review with meta-analysis was performed in PubMed, Web of Science, and PEDro until January 2022 through the assessment of methodological quality of systematic reviews (AMSTAR). Studies were included in which e-health interventions were used as experimental treatment compared to physical therapy to determine changes in back-specific functional status and pain in patients with chronic LBP. Two reviewers examined the sources individually, calculated the risk of bias, and extracted the data (PROSPERO number CRD42022306130). The effect size was calculated using the standardized mean difference (SMD) and its confidence interval (95% CI). Results: A total of 9 randomized controlled trials with 3,180 participants were included. The results of the findings showed an effect of e-health compared to other physical therapy on short-term (SMD = -0.59, 95% CI: -1.77 to 0.59) and intermediate short-term (SMD = -0.40, 95% CI: -0.91 to 0.11) pain intensity and back-specific functional status in the short term (SMD = -0.20, 95% CI: -0.81 to 0.41) and intermediate short term (SMD = -0.30, 95% CI: -0.74 to 0.14). The effect of e-health compared to minimal intervention on short-term intermediate pain intensity (SMD = -0.64, 95% CI: -1.72 to 0.45) and short-term intermediate back-specific functional status (SMD = -0.39, 95% CI: -0.87 to 0.09). Conclusions: e-Health interventions based on self-maintenance and education are as effective on pain and back-specific functional status as other face-to-face or home-based interventions in patients with chronic LBP, with moderate scientific evidence.

Characterization of an anatomic safe zone surrounding the lower subscapular nerve during an open deltopectoral approach.

BACKGROUND: Due to anatomic variance in subscapular nerve innervation patterns, it is theorized that the dysfunction of the subscapularis could be the result of iatrogenic denervation during mobilization of the subscapularis while exposing the anterior glenohumeral joint in anterior surgical approaches. The purpose of this study was to describe innervation patterns of the subscapularis and to characterize a safe zone when conducting an anterior surgical approach. METHODS: The study used 6 human cadaveric shoulder specimens (12 shoulders total). A deltopectoral approach was used to expose the axillary nerve back to the posterior cord of the brachial plexus and reveal the origins of the upper and lower subscapularis nerves. An anatomic safe zone was characterized by measuring distances from both the upper and lower subscapularis nerve insertions with respect to that of the lateral border of the conjoint tendon, the bicipital groove, superior border of the subscapularis, and the axillary nerve (for the lower subscapular nerve only) with the arm in 30° abduction. RESULTS: The anatomic safe zone of the subscapular nerves medial to the conjoint tendon is less than 32 mm. In relation to the axillary nerve, the safe zone is less than 10 mm inferiorly and 15 mm medially. CONCLUSIONS: This described safe zone with respect to the lateral border of the conjoint tendon and axillary nerve is aimed to provide guidance to reduce iatrogenic injury of the subscapular nerves during anterior shoulder exposure. Extra care should be undertaken while dissecting past this safe zone to prevent iatrogenic subscapular nerve injury.

The Combined Effects of Exercise, Diet, and a Multi-Ingredient Dietary Supplement on Body Composition and Adipokine Changes in Overweight Adults.

BACKGROUND: Very few weight and fat loss supplements undergo finished-product research to examine efficacy. The purpose of this study was to determine the effects of an 8-week diet and exercise program on body composition, hip and waist girth, and adipokines and evaluate whether a dietary supplement containing raspberry ketone, capsaicin, caffeine, garlic, and Citrus aurantium enhanced outcomes. METHODS: Overweight men and women completed this randomized, placebo-controlled, double-blind study. Participants consumed 4 capsules/d of supplement (EXP; n = 18) or placebo (PLA; n = 18). Participants underwent 8 weeks of daily supplementation, calorie restriction (500 kcal < RMR [resting metabolic rate] × 1.2), and supervised progressive exercise training 3 times a week. Body composition, girth, and adipokines were assessed at baseline and postintervention (T1 and T2). RESULTS: Significant decreases in weight (-2.6 ± 0.57 kg, p < 0.001), fat mass (-1.8 ± 0.20 kg; p < 0.001), and percentage body fat (-3.7% ± 0.29%, p < 0.001) and a significant increase in lean body mass (LBM; 1.5 ± 0.26 kg; p < 0.001) were seen from T1 to T2 in both groups. For men, only those in the EXP group increased LBM from T1 to T2 (1.3 ± 0.38 kg; p < 0.05). Hip girth was also reduced, with the women in the EXP group (-10.7 ± 2.15 cm, p < 0.001) having a greater reduction. There was a time by group interaction, with significant decreases in leptin (p < 0.001) and significant increases in adiponectin (p < 0.05) in the EXP group. CONCLUSIONS: Significant improvements in adipokines and leptin support the utility of exercise, diet, and fat loss for impacting inflammatory biomarkers. The improvement in adiponectin with EXP may suggest a unique health mechanism.

A Recombinant Affinity Reagent Specific for a Phosphoepitope of Akt1.

The serine/threonine-protein kinase, Akt1, plays an important part in mammalian cell growth, proliferation, migration and angiogenesis, and becomes activated through phosphorylation. To monitor phosphorylation of threonine 308 in Akt1, we developed a recombinant phosphothreonine-binding domain (pTBD) that is highly selective for the Akt1 phosphopeptide. A phage-display library of variants of the Forkhead-associated 1 (FHA1) domain of yeast Rad53p was screened by affinity selection to the phosphopeptide, 301-KDGATMKpTFCGTPEY-315, and yielded 12 binding clones. The strongest binders have equilibrium dissociation constants of 160⁻180 nanomolar and are phosphothreonine-specific in binding. The specificity of one Akt1-pTBD was compared to commercially available polyclonal antibodies (pAbs) generated against the same phosphopeptide. The Akt1-pTBD was either equal to or better than three pAbs in detecting the Akt1 pT308 phosphopeptide in ELISAs.

[Construction and validation of an instrument to assess primary care level patient satisfaction]. / Construcción y validación de un instrumento para medir la satisfacción de los pacientes del primer nivel de atención médica en la Ciudad de México.

OBJECTIVE: To develop an instrument to assess the satisfaction of patients using health services at the first care level of the city of Mexico (SSA), adapted to the socio-cultural characteristics of the population, and to examine its reliability and validity. METHODS: The instrument reagents were designed using the natural semantic networks technique. The dimensions used have been determined from the literature. Participants included 230 adults with type 2 diabetes attending eight SSA health centers. Subsequently, intelligibility was determined by conducting a pilot, then the construct validity of the instrument by means of exploratory factor analysis was evaluated and its internal consistency was determined by calculating Cronbach's alpha. RESULTS: The questionnaire is composed of six factors with a Likert-type scale. Its consistency showed a Crombach´s alpha of 0.94. The factor structure included 29 reagents that correlated with the six dimensions with factorial loads>0.581 that explained 66.8% of the total variance. CONCLUSIONS: The patient satisfaction questionnaire incorporates the sociocultural characteristics of the target population and has an adequate level of validity and reliability and is quick and easy in application.

[Family medicine in Mexico: Present and future]. / La medicina familiar en México: presente y futuro.

Analyzing the challenges and the future scenario of Family Medicine is a priority to address challenges such as the reduction of benefits granted by social security; to adapt their practice to the changing health profile; and to curb demand for specialized services and contain the high costs of care in the second and third level. The program is aimed at three professional roles: medical care, research, and education. It is imperative review these in the light of changing demographic conditions, the type of health needs arising from new social determinants, the public expectations for greater participation in their care, and the evolution of the health system itself with the advancement of technology and a variety of organizational options with frequently limited resources. For primary care, as the core of a health system that covers principles of equity, solidarity, universality, participation, decentralization, and intra- and inter-sectorial coordination, it is necessary to put at the center of the primary care team the family doctor and not an administrator, who plays an important role in supporting the care team, but can not take the lead.

Numerical prediction of temperature elevation induced around metallic hip prostheses by traditional, split, and uniplanar gradient coils.

PURPOSE: The paper presents a computational study for the estimation of the temperature elevation occurring in a human subject carrying metallic hip prostheses when exposed to the magnetic field produced by gradient coils. METHODS: The simulations are performed through validated numerical codes, which solve the electromagnetic and thermal equations applied to a high-resolution anatomical human model. Three different sets of gradient coils (traditional, split and uniplanar) are considered to evaluate the maximum steady-state temperature elevation in the human body. This result is then rescaled to take into account the waveform of the signal, the duty-cycle and the duration of the scan. RESULTS: Several exposure situations obtained by changing the patient's position are analyzed, finding temperature elevations on the order of some degrees. CONCLUSION: The results are of possible concern and provide evidence of the need for further specific investigations aimed at assuring the safety of potential patients carrying metallic hip implants. Magn Reson Med 74:272-279, 2015. © 2014 Wiley Periodicals, Inc.

Turning Bacteria Suspensions into Superfluids.

The rheological response under simple shear of an active suspension of Escherichia coli is determined in a large range of shear rates and concentrations. The effective viscosity and the time scales characterizing the bacterial organization under shear are obtained. In the dilute regime, we bring evidence for a low-shear Newtonian plateau characterized by a shear viscosity decreasing with concentration. In the semidilute regime, for particularly active bacteria, the suspension displays a "superfluidlike" transition where the viscous resistance to shear vanishes, thus showing that, macroscopically, the activity of pusher swimmers organized by shear is able to fully overcome the dissipative effects due to viscous loss.

Multilayer integral method for simulation of eddy currents in thin volumes of arbitrary geometry produced by MRI gradient coils.

PURPOSE: This article aims to present a fast, efficient and accurate multi-layer integral method (MIM) for the evaluation of complex spatiotemporal eddy currents in nonmagnetic and thin volumes of irregular geometries induced by arbitrary arrangements of gradient coils. METHODS: The volume of interest is divided into a number of layers, wherein the thickness of each layer is assumed to be smaller than the skin depth and where one of the linear dimensions is much smaller than the remaining two dimensions. The diffusion equation of the current density is solved both in time-harmonic and transient domain. RESULTS: The experimentally measured magnetic fields produced by the coil and the induced eddy currents as well as the corresponding time-decay constants were in close agreement with the results produced by the MIM. Relevant parameters such as power loss and force induced by the eddy currents in a split cryostat were simulated using the MIM. CONCLUSION: The proposed method is capable of accurately simulating the current diffusion process inside thin volumes, such as the magnet cryostat. The method permits the priori-calculation of optimal pre-emphasis parameters. The MIM enables unified designs of gradient coil-magnet structures for an optimal mitigation of deleterious eddy current effects.

Prospective serial evaluation of 2-hydroxyglutarate, during treatment of newly diagnosed acute myeloid leukemia, to assess disease activity and therapeutic response.

Mutations of genes encoding isocitrate dehydrogenase (IDH1 and IDH2) have been recently described in acute myeloid leukemia (AML). Serum and myeloblast samples from patients with IDH-mutant AML contain high levels of the metabolite 2-hydroxyglutarate (2-HG), a product of the altered IDH protein. In this prospective study, we sought to determine whether 2-HG can potentially serve as a noninvasive biomarker of disease burden through serial measurements in patients receiving conventional therapy for newly diagnosed AML. Our data demonstrate that serum, urine, marrow aspirate, and myeloblast 2-HG levels are significantly higher in IDH-mutant patients, with a correlation between baseline serum and urine 2-HG levels. Serum and urine 2-HG, along with IDH1/2-mutant allele burden in marrow, decreased with response to treatment. 2-HG decrease was more rapid with induction chemotherapy compared with DNA-methyltransferase inhibitor therapy. Our data suggest that serum or urine 2-HG may serve as noninvasive biomarkers of disease activity for IDH-mutant AML.

Effects of a pre-workout supplement on lean mass, muscular performance, subjective workout experience and biomarkers of safety.

In this prospective, randomized, double-blind, trial conducted in two parts, we examined the effects of a multi-ingredient pre-exercise workout supplement blend of creatine, betaine and a dendrobium extract (MMP) on safety, performance, and body composition in healthy men and women undergoing a supervised program of resistance exercise. Part 1 was an acute hemodynamic safety study wherein forty young, healthy men and women (26.2 ± 5.3 years, 70.4 ± 3.3 inches, 83.7 ± 14.9 kg, 26.0 ± 3.2 kg●m(-2)) ingest one dose of either the MMP or comparator in a randomized, double-blind, comparator controlled, crossover fashion before having their resting heart rate, blood, ECG and comprehensive blood chemistry and blood counts completed. Systolic (SBP) and diastolic (DBP) blood pressures were generally raised (3.0-5.4 mm Hg, p<0.01) following supplementation with MPP whereas in the comparator group SBP was marginally reduced by 0.3 to 1.2 mm Hg, p>0.05 at all time points) and DBP was increased (3.0 - 3.9 mm Hg, p<0.05 at all time points). No changes in EKG-corrected QT interval were observed, and no serious adverse events were reported. Part 2 was a six-week training study wherein forty-three young, healthy men and women (24.3 ± 2.9 years, 70.5 ± 3.1 inches, 83.8 ± 9.6 kg, 26.1 ± 2.7 kg●m(-2)) supplemented with daily pre-workout doses of either the MPP or a comparator in a randomized, double-blind, comparator-controlled fashion while following a standardized resistance training program for six weeks. MPP and the comparator were isocaloric and delivered the same amount of caffeine. Significant improvements in visual analog scale (VAS) scores for energy (p<0.024) and concentration (p<0.041) were found along with consistently higher levels of focus accompanied by less fatigue when MPP was consumed in comparison to comparator during upper body muscular strength-endurance tests at weeks 3 and 6. MPP supplementation for 6 weeks did not improve dual-energy x-ray absorptiometry (DEXA) measures of body composition or objective assessments of exercise performance. Overall, MPP use and administration was well tolerated. Self-reported scores for energy and concentration were significantly greater. Over a six-week training and supplementation period, MPP use was not associated with improvements in performance or body composition. Future studies should confirm these effects over a more prolonged training period.