Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after ...therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾10
cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.
Aliment Pharmacol Ther 2011; 34: 125–145
Summary
Background Cross‐sectional imaging techniques, including ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI), are ...increasingly used for evaluation of Crohn’s disease (CD).
Aim To perform an assessment of the diagnostic accuracy of cross‐sectional imaging techniques for diagnosis of CD, evaluation of disease extension and activity and diagnosis of complications, and to provide recommendations for their optimal use.
Methods Relevant publications were identified by literature search and selected based on predefined quality parameters, including a prospective design, sample size and reference standard. A total of 68 publications were chosen.
Results Ultrasonography is an accurate technique for diagnosis of suspected CD and for evaluation of disease activity (sensitivity 0.84, specificity 0.92), is widely available and non‐invasive, but its accuracy is lower for disease proximal to the terminal ileum. MRI has a high diagnostic accuracy for the diagnosis of suspected CD and for evaluation of disease extension and activity (sensitivity 0.93, specificity 0.90), and is less dependent on the examiner and disease location compared with US. CT has a similar accuracy to MRI for assessment of disease extension and activity. The three techniques have a high accuracy for identification of fistulas, abscesses and stenosis (sensitivities and specificities >0.80), although US has false positive results for abscesses. As a result of the lack of radiation, US or MRI should be preferred over CT, particularly in young patients.
Conclusions Cross‐sectional imaging techniques have a high accuracy for evaluation of suspected and established CD, reliably measure disease severity and complications; they may offer the possibility to monitor disease progression.
Purpose
The aim of the study was to compare the outcomes of patients with post‐COVID‐19 condition undergoing supervised therapeutic exercise intervention or following the self‐management WHO (World ...Health Organization) rehabilitation leaflet.
Methods
A randomized controlled trial was carried out that included 39 participants with post‐COVID‐19 condition who had a chronic symptomatic phase lasting >12 weeks. Comprehensive medical screening, patient‐reported symptoms, and cardiorespiratory fitness and muscular strength were assessed. Patients were randomly assigned to a tailored multicomponent exercise program based on concurrent training for 8 weeks (two supervised sessions per week comprised resistance training combined with aerobic training moderate intensity variable training, plus a third day of monitored light intensity continuous training), or to a control group which followed the WHO guidelines for rehabilitation after COVID‐19.
Results
After follow‐up, there were changes in physical outcomes in both groups, however, the magnitude of the change pre–post intervention favored the exercise group in cardiovascular and strength markers: VO2max +5.7%, sit‐to‐stand −22.7% and load‐velocity profiles in bench press +6.3%, and half squat +16.9%, (p < 0.05). In addition, exercise intervention resulted in a significantly better quality of life, less fatigue, less depression, and improved functional status, as well as in superior cardiovascular fitness and muscle strength compared to controls (p < 0.05). No adverse events were observed during the training sessions.
Conclusion
Compared to current WHO recommendations, a supervised, tailored concurrent training at low and moderate intensity for both resistance and endurance training is a more effective, safe, and well‐tolerated intervention in post‐COVID‐19 conditions.
The dietary inflammatory index (DII) is a new tool to assess the inflammatory potential of the diet. In the present study, we aimed to determine the association between the DII and BMI, waist ...circumference and waist:height ratio (WHtR). We conducted a cross-sectional study of 7236 participants recruited into the PREvención con DIeta MEDiterránea trial. Information from a validated 137-item FFQ was used to calculate energy, food and nutrient intakes. A fourteen-item dietary screener was used to assess adherence to the Mediterranean diet (MeDiet). Sex-specific multivariable linear regression models were fitted to estimate differences (and 95 % CI) in BMI, waist circumference and WHtR across the quintiles of the DII. All nutrient intakes, healthy foods and adherence to the MeDiet were higher in the quintile with the lowest DII score (more anti-inflammatory values) except for intakes of animal protein, saturated fat and monounsaturated fat. Although an inverse association between the DII and total energy was apparent, the DII was associated with higher average BMI, waist circumference and WHtR after adjusting for known risk factors. The adjusted difference in the WHtR for women and men between the highest and lowest quintiles of the DII was 1·60 % (95 % CI 0·87, 2·33) and 1·04 % (95 % CI 0·35, 1·74), respectively. Pro-inflammatory scores remained associated with obesity after controlling for the effect that adherence to a MeDiet had on inflammation. In conclusion, the present study shows a direct association between the DII and indices of obesity, and supports the hypothesis that diet may have a role in the development of obesity through inflammatory modulation mechanisms.
The ultrafast photoinduced ring-opening of 1,3-cyclohexadiene constitutes a textbook example of electrocyclic reactions in organic chemistry and a model for photobiological reactions in vitamin D ...synthesis. Although the relaxation from the photoexcited electronic state during the ring-opening has been investigated in numerous studies, the accompanying changes in atomic distance have not been resolved. Here we present a direct and unambiguous observation of the ring-opening reaction path on the femtosecond timescale and subångström length scale using megaelectronvolt ultrafast electron diffraction. We followed the carbon-carbon bond dissociation and the structural opening of the 1,3-cyclohexadiene ring by the direct measurement of time-dependent changes in the distribution of interatomic distances. We observed a substantial acceleration of the ring-opening motion after internal conversion to the ground state due to a steepening of the electronic potential gradient towards the product minima. The ring-opening motion transforms into rotation of the terminal ethylene groups in the photoproduct 1,3,5-hexatriene on the subpicosecond timescale.
The Mar Menor (SE Spain), the largest hypersaline coastal lagoon of the Mediterranean basin, suffers a severe eutrophication crisis due to the nutrients that receives from the Campo de Cartagena ...watershed, mainly nitrate from intensive agriculture. This paper updates the state of the art in relation with nutrient discharges to the Mar Menor, and summarizes results from different tested Nature-Based Solution (NBS). Specifically, we show i) results from a pilot plant with woodchip bioreactors for nitrate-enriched brine denitrification, and ii) the first results obtained in a pilot plant with bioreactors and constructed wetlands for treatment of agricultural drainage water and leachates, as well as other effluents. Nutrient discharges to the lagoon are highly variable and occur via drainage network, drains, stormwater pipes, direct groundwater discharges from the Quaternary aquifer, and others. For instance, between January 2017 and January 2018 measured daily superficial discharge (floods excluded) ofN-NO3− amounted from 119 kg d−1 to 1084 kg d−1. Estimations subsurface discharges ranged 815 to 3836 kg N-NO3− d−1 in 2018–2020. Field studies in coastal wetlands (e.g. inflow ≈20–30 mg N-NO3− L−1, removal ≈80–90%) and results from pilot plants with bioreactors (e.g. inflow ≈30–40 mg N-NO3− L−1, removal ≈90–95%) and constructed wetlands (e.g. inflow ≈30–40 mg N-NO3− L−1, removal ≈60–70%), showed the good performance of these systems for nutrient retention. Four strategies are considered for reducing nutrient inputs into the Mar Menor, which include a combination of nature-based solutions and best management practices. (i) Reducing the leaching of nitrate to the aquifer and export of nutrients and sediments following heavy rains by improving fertilization, and irrigation routines, and soil conservation measures in the agricultural fields. (ii) Development of effective and scalable tools for denitrification of nitrate-rich brine produced by on-farm desalination plants. (iii) Capture and treatment of polluted water discharged to the Mar Menor via hydrologic networks, subsurface flow, drainage ditches, and others. (iv) Preservation and restoration of coastal wetlands.
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•Mar Menor receives nutrients, mainly from agricultural discharges.•Coastal wetlands acts as buffers protecting the Mar Menor from nutrient inputs.•Bioreactors and CWs are recommended BMP for treatment of nutrient enriched discharges.•In the Campo de Cartagena BMP should be addressed on a watershed scale.•BMP should address fertilization and irrigation protocols and soil conservation.
Fermented dairy products have been associated with a better diet quality and cardio-metabolic profile. However, in Mediterranean populations, these associations have not been well characterized.
The ...aim of this study was to assess the diet quality and the associations between the consumption of total fermented dairy products and their subtypes and the prevalence of Metabolic Syndrome (MetS) components in a Mediterranean population at high cardiovascular risk.
Baseline cross-sectional analyses were conducted on 6,572 men and women (mean age: 65 years) with overweight or obesity and MetS recruited into the PREDIMED-Plus cohort. A 143-item Food Frequency Questionnaire (FFQ) was used, and anthropometrical, biochemical, and blood pressure measurements were recorded. Multivariate-adjusted Cox regressions were fitted to analyze the association between quartiles of consumption of fermented dairy products and their subtypes and MetS components to estimate the relative risk (RR) and 95% confidence intervals (95% CIs).
Participants who were high consumers of fermented dairy products reported a higher consumption of fruit, vegetables, fish, nuts, and whole bread and a lower consumption of white bread, alcohol, and cookies. Participants in the higher quartile showed a lower prevalence of the low HDL-cholesterol component of the MetS (RR=0.88; 95% CI: 0.78-0.98) than those in the lowest quartile of cheese consumption. Cheese consumption was inversely associated with the prevalence of hypertriglyceridemia. Total fermented dairy products, yogurt, and its types were not associated with any of the MetS components.
Compared to nonconsumers, participants consuming fermented dairy products reported a better diet quality and, particularly, cheese consumers presented a lower prevalence of hypertriglyceridemia and low HDL-cholesterol plasma levels, which are MetS components.
•The consumption of total fermented dairy products is associated with a better quality diet and a higher adherence to the Mediterranean diet pattern.•Cheese consumption was inversely associated with a low risk of low HDL-cholesterol plasma levels and hypertriglyceridemia, which are components of the metabolic syndrome.•Yogurt consumption and its different subtypes was not associated with any of the metabolic syndrome components.
Aims/hypothesis We analysed the factors that determine the outcomes of surgical treatment of osteomyelitis of the foot in diabetic patients given early surgical treatment within 12 h of admission and ...treated with prioritisation of foot-sparing surgery and avoidance of amputation. Methods A consecutive series of 185 diabetic patients with foot osteomyelitis and histopathological confirmation of bone involvement were followed until healing, amputation or death. Results Probing to bone was positive in 175 cases (94.5%) and radiological signs of osteomyelitis were found in 157 cases (84.8%). Staphylococcus aureus was the organism isolated in the majority of cultures (51.3%), and in 35 cases (36.8%) it proved to be methicillin-resistant. The surgical treatment performed included 91 conservative surgical procedures, which were defined as those where no amputation of any part of the foot was undertaken (49.1%). A total of 94 patients received some degree of amputation, consisting of 79 foot-level (minor) amputations (42.4%) and 15 major amputations (8%). Five patients died during the perioperative period (2.7%). Histopathological analysis revealed 94 cases (50.8%) of acute osteomyelitis, 43 cases (23.2%) of chronic osteomyelitis, 45 cases (24.3%) of acute exacerbation of chronic osteomyelitis and three remaining cases (1.6%) designated as 'other'. The risks of failure in the case of conservative surgery were exposed bone, the presence of ischaemia and necrotising soft tissue infection. Conclusions/interpretation Conservative surgery without local or high-level amputation is successful in almost half of the cases of diabetic foot osteomyelitis. Prospective trials should be undertaken to determine the relative roles of conservative surgery versus other approaches.
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