Assessment trial of the effect of enteral insulin on the preterm infant intestinal microbiota.

BACKGROUND: Insulin might be associated with changes in infant gastrointestinal microbiota. The objective of this randomized controlled trial was to assess the efficacy of two doses of recombinant human(rh) enteral insulin administration compared to placebo in intestinal microbiota. METHODS: 19 preterm patients were recruited at the NICU of La Paz University Hospital (Madrid, Spain). Subjects received 2000 µIU of rh enteral insulin/ml(n = 8), 400 µIU of rh enteral insulin/ml(n = 6) or placebo(n = 5) for 28 days administered once per day. Extracted DNA from fecal samples collected at the beginning and end of treatment were analyzed. The 16S rRNA V4 region was amplified and sequenced in a Miseq(Illumina®) sequencer using 2 × 250 bp paired end. Resulting reads were filtered and analyzed using Qiime2 software. Metabolic activity was assessed by GC. RESULTS: Gestational age and birth weight did not differ between groups. At the phylum level, both insulin treated groups increased the relative abundance of Bacillota, while Pseudomonadota decreased. No change was observed in infants receiving placebo. At the genus level, insulin at both doses showed enriching effects on Clostridium. We found a significant increase in concentrations of fecal propionate in both rh insulin treated groups. CONCLUSION: Rh insulin may modify neonatal intestinal microbiota and SCFAs in preterm infants. IMPACT STATEMENT: Decrease of Pseudomonadota (former Proteobacteria phylum) and increase of Bacillota (former Firmicutes phylum) obtained in this study are the changes observed previously in low-risk infants for NEC. The administration of recombinant enteral insulin may modify the microbiota of preterm new-borns and SCFAs. Modulation of the microbiota may be a mechanism whereby insulin contributes to neonatal intestinal maturation and/or protection.

Short and mid-term neonatal outcomes in high-risk infants undergoing FICare: a case control study.

BACKGROUND: FICare model has been evaluated mostly on the stable preterm infant.We have scaled the model to two implementation levels(basic/advanced),making it suitable for all high-risk neonates.We report on the short- and mid-term outcomes of infants enrolled in a pilot on FICare implementation at our NICU. METHODS: During 52 months study period,families were invited to join the program if their newborns' admission required neonatal specialized care for at least 3 weeks,and trained according to the program's curricula.Following a rigorous sequential admission order,each case(FICare group:134 < 34 weeks;52 term newborns)was matched by a contemporary control(CC:134 < 34 weeks;52 term newborns)and 2 historical controls born within the 3 years prior to FICare site implementation(HC:268 < 34 weeks;104 term newborns),cared as usual RESULTS: FICare intervention started by the end of first week of postnatal life.Rates of breastfeeding during admission and at discharge,and direct breastfeeding upon discharge were higher in FICare compared to CC and HC.Duration of intermediate care hospitalization(preterm and term cohorts)and total hospital length of stay (term cohorts)were shorter in FICare group.Use of Emergency Services after discharge was also lower in the FICare group CONCLUSIONS: Short and mid-term efficacy of FICare on health outcomes and family empowerment in a broader and highly-vulnerable neonatal population supports its generalization in complex healthcare neonatal services. IMPACT STATEMENT: Scaling the FICare model to the critically ill, unstable premature and term infant is feasible and safe. The early intervention shows similar benefits in the short- and mid-term infants' outcomes in the whole spectrum of neonatal specialized care.

XIII International Conference on Kangaroo Mother Care - Different opinions, experiences and related KMC issues: Good practices, stabilisation concept, nutrition and basic respiratory support.

AIM: This study aimed to summarise the views and experiences of the participants in the workshop of the XIII International Conference on Kangaroo Mother Care (KMC). METHODS: The results of the discussions held during the workshop of the XIII International Conference on KMC were summarised. There were 152 participants from 47 countries. Four main KMC topics were discussed: good practices, immediate implementation, nutrition and basic ventilation. RESULTS: Several agreements were reached, namely that professional societies and governments should develop official recommendations to promote KMC as standard care for preterm and low birth weight infants and that parents should be involved as active caregivers in neonatal care units. Moreover, the criteria for referring community-born infants to KMC require standardisation. Important inequalities in resource availability among high-, middle- and low-income countries were recognised for all topics. Specific needs were identified for parenteral nutrition and fortifiers, nasal continuous positive airway pressure (nCPAP) and oxygen blenders, which are rarely available in low- and middle-income countries. Immediate implementation of KMC was discussed as a new concept. Its benefits were recognised, but its application has some variability. CONCLUSION: Adequate preterm care requires a basic neonatal package, including KMC, nCPAP, immediate management protocols and adequate nutrition and feeding strategies. The differences in resources among high-, middle- and low-income countries highlight the wide disparities in neonatal care according to the place of birth.

SALDI-MS and SERS Multimodal Imaging: One Nanostructured Substrate to Rule Them Both.

Imaging techniques based on mass spectrometry or spectroscopy methods inform in situ about the chemical composition of biological tissues or organisms, but they are sometimes limited by their specificity, sensitivity, or spatial resolution. Multimodal imaging addresses these limitations by combining several imaging modalities; however, measuring the same sample with the same preparation using multiple imaging techniques is still uncommon due to the incompatibility between substrates, sample preparation protocols, and data formats. We present a multimodal imaging approach that employs a gold-coated nanostructured silicon substrate to couple surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) and surface-enhanced Raman spectroscopy (SERS). Our approach integrates both imaging modalities by using the same substrate, sample preparation, and data analysis software on the same sample, allowing the coregistration of both images. We transferred molecules from clean fingertips and fingertips covered with plasticine modeling clay onto our nanostructure and analyzed their chemical composition and distribution by SALDI-MS and SERS. Multimodal analysis located the traces of plasticine on fingermarks and provided chemical information on the composition of the clay. Our multimodal approach effectively combines the advantages of mass spectrometry and vibrational spectroscopy with the signal enhancing abilities of our nanostructured substrate.

A model to differentiate WAD patients and people with abnormal pain behaviour based on biomechanical and self-reported tests.

The prevalence of malingering among individuals presenting whiplash-related symptoms is significant and leads to a huge economic loss due to fraudulent injury claims. Various strategies have been proposed to detect malingering and symptoms exaggeration. However, most of them have been not consistently validated and tested to determine their accuracy in detecting feigned whiplash. This study merges two different approaches to detect whiplash malingering (the mechanical approach and the qualitative analysis of the symptomatology) to obtain a malingering detection model based on a wider range of indices, both biomechanical and self-reported. A sample of 46 malingerers and 59 genuine clinical patients was tested using a kinematic test and a self-report questionnaire asking about the presence of rare and impossible symptoms. The collected measures were used to train and validate a linear discriminant analysis (LDA) classification model. Results showed that malingerers were discriminated from genuine clinical patients based on a greater proportion of rare symptoms vs. possible self-reported symptoms and slower but more repeatable neck motions in the biomechanical test. The fivefold cross-validation of the LDA model yielded an area under the curve (AUC) of 0.84, with a sensitivity of 77.8% and a specificity of 84.7%.

Attomolar SERS detection of organophosphorous pesticides using silver mirror-like micro-pyramids as active substrate.

Surface-enhanced Raman spectroscopy (SERS) is gaining importance as an ultrasensitive analytical tool for routine high-throughput analysis of a variety of molecular compounds. One of the main challenges is the development of robust, reproducible and cost-effective SERS substrates. In this work, we study the SERS activity of 3D silver mirror-like micro-pyramid structures extended in the z-direction up to 3.7 µm (G0 type substrate) or 7.7 µm (G1 type substrate), prepared by Si-based microfabrication technologies, for trace detection of organophosphorous pesticides, using paraoxon-methyl as probe molecule. The average relative standard deviation (RSD) for the SERS intensity of the peak displayed at 1338 cm-1 recorded over a centimetre scale area of the substrate is below 13% for pesticide concentrations in the range 10-6 to 10-15 mol L-1. This data underlies the spatial uniformity of the SERS response provided by the microfabrication approach. According to finite-difference time-domain (FDTD) simulations, such remarkable feature is mainly due to the contribution on electromagnetic field enhancement of edge plasmon polaritons (EPPs), propagating along the pyramid edges where the pesticide molecules are preferentially adsorbed. Graphical abstract.

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma.

On May 20, 2016, a conditional marketing authorization valid through the European Union (EU) was issued for daratumumab as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) and who had demonstrated disease progression on the last therapy. The review of daratumumab was conducted under the EMA's accelerated assessment program for drugs that are of major interest for public health, especially from the point of view of therapeutic innovation.Daratumumab monotherapy achieved an overall response rate of 29.2% (95% confidence interval [CI] 20.8 to 38.9) in patients with multiple myeloma who had received at least three prior lines of therapy (including a PI and IMiD) or were double refractory to a PI and an IMiD (Study MMY2002). In patients with multiple myeloma relapsed from or refractory to two or more different prior therapies, including IMiDs (e.g., thalidomide, lenalidomide) and PI, an overall response was observed in 15 patients (35.7%, 95% CI: 21.6 to 52.0) (Study GEN501).On April 28, 2017, the therapeutic indication was extended to include the use of daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. This was based on two subsequent phase III studies of daratumumab in combination with lenalidomide/low-dose dexamethasone (MMY3003) and bortezomib/low dose dexamethasone (MMY3004).The most common side effects (grade 3-4) associated with daratumumab included neutropenia (37%), thrombocytopenia (23%), anemia (16%), pneumonia (10%), lymphopenia (8%), infusion-related reactions (6%), upper respiratory tract infection (5%), and fatigue (5%).The objective of this study was to summarize the scientific review done by the CHMP of the application leading to regulatory approval in the EU. The full scientific assessment report and product information, including the Summary of Product Characteristics (SmPC), are available on the EMA website (www.ema.europa.eu). IMPLICATIONS FOR PRACTICE: A conditional Marketing authorization was issued in the European Union for daratumamb as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, based on the response rate data from two single-agent studies. Darzalex, a novel monoclonal antibody targeted against CD38, demonstrated a durable response rate in a heavily pre-treated population with limited treatment options based on the response rate data from two single-agent studies. The addition of daratumumab to lenalidomide and dexamethasone (study MMY3003), or bortezomib and dexamethasone (MMY3004), demonstrated a positive effect on progression-free survival in patients with multiple myeloma who had received at least one prior therapy. Following submission of the controlled data of the MMY3003 and MMY3004 studies, the efficacy and safety of daratumumab was confirmed and the approval of daratumumab was converted to standard approval.

A prospective analysis of intake and composition of mother's own milk in preterm newborns less than 32 weeks' gestational age.

Background Mothers of preterm (PT) infants have difficulty providing adequate quantities of human milk (HM) for their babies during their hospital stay. The macronutrient content in HM changes over time, varying across and within individual mothers. The research aim of the strudy was to describe the intake of mothers' own milk (MOM) and its composition according to gestational (GA) and postnatal age (PNA) in infants born <32 weeks' GA and to correlate them with neonatal weight, length and morbidities. Methods A prospective observational study of 176 premature infants in a unit without a donor milk bank was conducted. Daily milk intake was recorded. HM macronutrients were determined by mid-infrared spectrophotometric analysis at 7, 15 and 30 days after delivery and monthly until hospital discharge. Results Intake of MOM increased during the first 2 weeks after birth and decreased steadily thereafter. Protein concentration varied inversely with PNA. Carbohydrate and lipid concentrations increased over the first few days and remained stable thereafter. A fall in weight percentiles from birth to 60 days was found. No correlation was found between total protein and calorie intakes at 3 and 15 days of life and growth velocity (GV) between 15 and 30 days, even when broken down into parenteral nutrition (PN), formula and MOM. Conclusion To improve MOM feeding in PT newborns, intensive support strategies at the prenatal stage along entire hospitalization income should be encouraged. New protocols for fortification of HM should be implemented to optimize postnatal weight gain while preserving the health benefits of HM.

Cell-Free DNA as a Biomarker at Diagnosis and Follow-Up in 256 B and T-Cell Lymphomas.

BACKGROUND: Cell-free DNA (cfDNA) analysis has become a promising tool for the diagnosis, prognosis, and monitoring of lymphoma cases. Until now, research in this area has mainly focused on aggressive lymphomas, with scanty information from other lymphoma subtypes. METHODS: We selected 256 patients diagnosed with lymphomas, including a large variety of B-cell and T-cell non-Hodgkin and Hodgkin lymphomas, and quantified cfDNA from plasma at the time of diagnosis. We further selected 49 large B-cell lymphomas (LBCL) and analyzed cfDNA levels at diagnosis (pre-therapy) and after therapy. In addition, we performed NGS on cfDNA and tissue in this cohort of LBCL. RESULTS: Lymphoma patients showed a statistically significant higher cfDNA concentration than healthy controls (mean 53.0 ng/mL vs. 5.6 ng/mL, p < 0.001). The cfDNA concentration was correlated with lymphoma subtype, lactate dehydrogenase, the International Prognostic Index (IPI) score, Ann Arbor (AA), and B-symptoms. In 49 LBCL cases, the cfDNA concentration decreased after therapy in cases who achieved complete response (CR) and increased in non-responders. The median cfDNA at diagnosis of patients who achieved CR and later relapsed was higher (81.5 ng/mL) compared with levels of those who did not (38.6 ng/mL). A concordance of 84% was observed between NGS results in tumor and cfDNA samples. Higher VAF in cfDNA is correlated with advanced stage and bulky disease. CONCLUSIONS: cfDNA analysis can be easily performed in almost all lymphoma cases. The cfDNA concentration correlated with the characteristics of the aggressiveness of the lymphomas and, in LBCL, with the response achieved after therapy. These results support the utility of cfDNA analysis as a complementary tool in the management of lymphoma patients.

Behavioral Problems and Family Impact in Congenital Cytomegalovirus Infection.

We examined behavior (Child Behavior Checklist) and family functioning (Family Impact Questionnaire) in 65 children with congenital cytomegalovirus. Behavioral problems were present in 30.8%. Parents of children with moderate/severe outcomes reported strain on all areas of family functioning. Behavioral problems were associated with negative impact on parental feelings and marital/partnership relationship. Our findings inform planning support services.

Adjusted versus Targeted Fortification in Extremely Low Birth Weight Preterm Infants: Fortin Study-A Randomized Clinical Trial.

Fortified human milk is the first choice for preterm infants. Although individualized fortification is recommended, the optimal method for this population remains uncertain. We conducted a comparative study assessing the growth effects of adjusted (AF) and targeted fortification (TF) in extremely low birth weight (ELBW) infants. This single-center, randomized, controlled clinical trial was conducted at a tertiary neonatal unit in Spain. Eligible participants were premature infants with a birthweight of <1000 g exclusively fed with human milk. A total of 38 patients were enrolled, 15 of them randomized to AF group and 23 to TF group. AF was based on blood urea nitrogen (BUN) concentration and TF on human milk analysis. The primary outcome was weight gain velocity (g/kg/day). No significant differences were found in weight gain velocity at 28 days, at 36 weeks of postmenstrual age, at discharge, nor during the intervention. Protein intake was significantly higher in the AF group (5.02 g/kg/day vs. 4.48 g/kg/day, p = 0.001). No differences were found in the lipid, carbohydrate, and energy intake; in the weight z score change between the different time points; nor in the length and head circumference growth. Both AF and TF are comparable methods of fortification and provide the appropriate growth rate in ELBW infants.

Clinical Impact of Supplementation with Pasteurized Donor Human Milk by High-Temperature Short-Time Method versus Holder Method in Extremely Low Birth Weight Infants: A Multicentre Randomized Controlled Trial.

Nosocomial infections are a frequent and serious problem in extremely low birth weight (ELBW) infants. Donor human milk (DHM) is the best alternative for feeding these babies when mother's own milk (MOM) is not available. Recently, a patented prototype of a High-Temperature Short-Time (HTST) pasteurizer adapted to a human milk bank setting showed a lesser impact on immunologic components. We designed a multicentre randomized controlled trial that investigates whether, in ELBW infants with an insufficient MOM supply, the administration of HTST pasteurized DHM reduces the incidence of confirmed catheter-associated sepsis compared to DHM pasteurized with the Holder method. From birth until 34 weeks postmenstrual age, patients included in the study received DHM, as a supplement, pasteurized by the Holder or HTST method. A total of 213 patients were randomized; 79 (HTST group) and 81 (Holder group) were included in the analysis. We found no difference in the frequency of nosocomial sepsis between the patients of the two methods-41.8% (33/79) of HTST group patients versus 45.7% (37/81) of Holder group patients, relative risk 0.91 (0.64-1.3), p = 0.62. In conclusion, when MOM is not available, supplementing during admission with DHM pasteurized by the HTST versus Holder method might not have an impact on the incidence of catheter-associated sepsis.

Plasmonic nanoparticle sensors: current progress, challenges, and future prospects.

Plasmonic nanoparticles (NPs) have played a significant role in the evolution of modern nanoscience and nanotechnology in terms of colloidal synthesis, general understanding of nanocrystal growth mechanisms, and their impact in a wide range of applications. They exhibit strong visible colors due to localized surface plasmon resonance (LSPR) that depends on their size, shape, composition, and the surrounding dielectric environment. Under resonant excitation, the LSPR of plasmonic NPs leads to a strong field enhancement near their surfaces and thus enhances various light-matter interactions. These unique optical properties of plasmonic NPs have been used to design chemical and biological sensors. Over the last few decades, colloidal plasmonic NPs have been greatly exploited in sensing applications through LSPR shifts (colorimetry), surface-enhanced Raman scattering, surface-enhanced fluorescence, and chiroptical activity. Although colloidal plasmonic NPs have emerged at the forefront of nanobiosensors, there are still several important challenges to be addressed for the realization of plasmonic NP-based sensor kits for routine use in daily life. In this comprehensive review, researchers of different disciplines (colloidal and analytical chemistry, biology, physics, and medicine) have joined together to summarize the past, present, and future of plasmonic NP-based sensors in terms of different sensing platforms, understanding of the sensing mechanisms, different chemical and biological analytes, and the expected future technologies. This review is expected to guide the researchers currently working in this field and inspire future generations of scientists to join this compelling research field and its branches.

Low-Variance Surface-Enhanced Raman Spectroscopy Using Confined Gold Nanoparticles over Silicon Nanocones.

Surface-enhanced Raman spectroscopy (SERS) substrates are of utmost interest in the analyte detection of biological and chemical diagnostics. This is primarily due to the ability of SERS to sensitively measure analytes present in localized hot spots of the SERS nanostructures. In this work, we present the formation of 67 ± 6 nm diameter gold nanoparticles supported by vertically aligned shell-insulated silicon nanocones for ultralow variance SERS. The nanoparticles are obtained through discrete rotation glancing angle deposition of gold in an e-beam evaporating system. The morphology is assessed through focused ion beam tomography, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. The optical properties are discussed and evaluated through reflectance measurements and finite-difference time-domain simulations. Lastly, the SERS activity is measured by benzenethiol functionalization and subsequent Raman spectroscopy in the surface scanning mode. We report a homogeneous analytical enhancement factor of 2.2 ± 0.1 × 107 (99% confidence interval for N = 400 grid spots) and made a comparison to other lithographically derived assemblies used in SERS. The strikingly low variance (4%) of our substrates facilitates its use for many potential SERS applications.

On-chip monitoring of toxic gases: capture and label-free SERS detection with plasmonic mesoporous sorbents.

The detection of the spread of toxic gas molecules in the air at low concentration in the field requires a robust miniaturized system combined with an analytical technique that is portable and able to detect and identify the molecules, as is the case with surface enhanced Raman scattering (SERS). This work aims to address capability gaps faced by first responders in real-time detection, identification and monitoring of neurotoxic gases by developing robust, reliable and reusable SERS microfluidic chips. Thus, the key performance attributes of a portable SERS detection system that must be addressed in detail are its limit of detection, response time and reusability. To this purpose, we integrate a 3D plasmonic architecture based on closely packed mesoporous silica (MCM48) nanospheres decorated with Au nanoparticle arrays, denoted as MCM48@Au, into a Si microfluidic chip designed and used for preconcentration and label-free detection of gases at a trace concentration level. The SERS performance of the plasmonic platform is thoroughly analyzed using DMMP as a model neurotoxic simulant over a 1 cm2 SERS active area and over a range of concentrations from 100 ppbV to 2.5 ppmV. The preconcentration-based SERS signal amplification by the mesoporous silica moieties is evaluated against dense silica counterparts, denoted as Stöber@Au. To assess the potential for applications in the field, the microfluidic SERS chip has been interrogated with a portable Raman spectrometer, evaluated with temporal and spatial resolution and subjected to several gas detection/regeneration cycles. The reusable SERS chip shows exceptional performance for the label-free monitoring of 2.5 ppmV gaseous DMMP.

Evaluation of 4 prognostic indices in follicular lymphoma treated in first line with immunochemotherapy.

Several clinical risk models have been proposed to predict the outcome of follicular lymphoma (FL). The development of next-generation sequencing technologies has allowed the integration of somatic gene mutations into clinical scores to build genotyped-based risk models, such as the m7-Follicular Lymphoma International Prognostic Index (FLIPI). We explored 4 clinical or clinicogenetic-risk models in patients with symptomatic FL who received frontline immunochemotherapy. Of 191 patients with FL grades 1 to 3a, 109 were successfully genotyped. The treatment consisted of rituximab (R) plus cyclophosphamide, vincristine, and prednisone (R-CVP)/cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (72.5%) or R-bendamustine (R-B) (27.5%). The proportion of cases classified as high risk for FLIPI, FLIPI-2, PRIMA-prognostic index, or m7-FLIPI were 39.3%, 14%, 30.3%, and 22%, respectively. No case with low-intermediate FLIPI was upgraded in the m7-FLIPI, but 18 of the 42 high-risk patients with FLIPI were downgraded to low-risk m7-FLIPI. The sensitivity and specificity for the prediction of POD24 were highest for FLIPI. The discrimination between progression-free survival (PFS) and overall survival (OS) was the best for FLIPI (c-index: 0.644 and 0.727, respectively). When analyzed only in patients treated with R-B, m7-FLIPI showed a higher discrimination between PFS and OS. Thus, the FLIPI remains the clinical risk score with higher discrimination in patients with advanced FL treated with immunochemotherapy; however, the performance of the m7-FLIPI should be further investigated in patients treated with R-B.

Breastfeeding practices in neonatal wards in Spain. Neo-BFHI international survey.

INTRODUCTION: In 2017, a worldwide survey was conducted on compliance with the practices promoted by Neo-BFHI (Baby-friendly Hospital Initiative expansion to neonatal wards). OBJECTIVE: To present the results of the Spanish wards that participated in the global survey and compare them with those obtained internationally. MATERIAL AND METHODS: Cross-sectional study through a survey on compliance with the Neo-BFHI ("Three basic principles", "Ten steps adapted to neonatal wards" and "the compliance with the International Code of Marketing of Breast-milk Substitutes" and subsequent relevant World Health Assembly resolutions). Compliance was calculated as the mean in each indicator and a final mean score for each neonatal unit. For the partial and final scores for each country and at the international level, the median was used. All scores ranged between 0 and 100. RESULTS: The response rate in Spain was 90%. The range of the national mean for neonatal wards were from 37 to 99, with no differences in the final score according to the level of care. The global score for Spain (72) is below the international median (77) and this also occurs in 8 of 14 items. The neonatal wards from BFHI designated hospitals, obtained a significantly higher mean global score, and in 9 of 14 items than the non-accredited ones. CONCLUSIONS: Both international and national results indicate an improvement in breast feeding practices in neonatal units. The benefits of the BFHI accreditation of maternity reach neonatal wards. Spain has several key points below the international score.

Molecular and cytogenetic characterization of myelodysplastic syndromes in cell-free DNA.

Molecular and cytogenetic studies are essential for diagnosis and prognosis in patients with myelodysplastic syndromes (MDSs). Cell-free DNA (cfDNA) analysis has been reported to be a reliable noninvasive approach for detecting molecular abnormalities in MDS; however, there is limited information about cytogenetic alterations and monitoring in cfDNA. We assessed the molecular and cytogenetic profile of a cohort of 70 patients with MDS by next-generation sequencing (NGS) of cfDNA and compared the results to sequencing of paired bone marrow (BM) DNA. Sequencing of BM DNA and cfDNA showed a comparable mutational profile (92.1% concordance), and variant allele frequencies (VAFs) strongly correlated between both sample types. Of note, SF3B1 mutations were detected with significantly higher VAFs in cfDNA than in BM DNA. NGS and microarrays were highly concordant in detecting chromosomal alterations although with lower sensitivity than karyotype and fluorescence in situ hybridization. Nevertheless, all cytogenetic aberrations detected by NGS in BM DNA were also detected in cfDNA. In addition, we monitored molecular and cytogenetic alterations and observed an excellent correlation between the VAFs of mutations in BM DNA and cfDNA across multiple matched time points. A decrease in the cfDNA VAFs was detected in patients responding to therapy, but not in nonresponding patients. Of note, cfDNA analysis also showed cytogenetic evolution in 2 nonresponsive cases. In summary, although further studies with larger cohorts are needed, our results support the analysis of cfDNA as a promising strategy for performing molecular characterization, detection of chromosomal aberrations and monitoring of patients with MDS.

Spinal sagittal alignment, spinal shrinkage and back pain changes in office workers during a workday.

Purpose. Prolonged sitting is a risk factor for the appearance of lower back pain during work. The aim of this study was to observe changes in spinal sagittal alignment, height and the perception of back pain in office workers during a workday. Materials and methods. Forty-one office workers (20 women) were enrolled into a cross-sectional study. Height, sitting height and degrees of thoracic kyphosis and lumbar lordosis as well as perceived neck pain, lower back pain and upper back pain were determined, before and after an 8-h workday. Results. At the end of the day, workers had a significant decrease (p = 0.000) in height and sitting height, and upper back pain increased significantly (p = 0.023). In men, spinal shrinkage correlated with neck pain (r = 0.410, p = 0.027), and lumbar lordosis degrees in women correlated negatively with upper back pain at the end of the day (r = -0.440, p = 0.012). Conclusions. Spinal shrinkage equally affects men and women who perform the same work. There are no changes in spinal sagittal alignment throughout the workday in office workers. Office workers show significantly increased pain in the upper back at the end of the day.