Comparison of 2 medium cutoff dialyzers versus on-line hemodiafiltration regarding depurative ability and albumin loss: An uncontrolled clinical research.

BACKGROUND: Hemodialysis (HD) techniques that best remove molecules in the middle to high molecular weight range are on-line hemodiafiltration (OL-HDF) and HD with medium cut-off (MCO) membranes. The aim of this study was to compare efficacy and safety of OL-HDF with FxCordiax HDF 800™, with HD with 2 MCO dialyzers: Theranova 500® and the new Elisio 21HX™ dialyzer. METHODS: Fourteen patients following treatment with OL-HDF using FxCordiax HDF 800™ were randomized to receive a consecutive 1-week HD treatment with Theranova 500® and Elisio 21HX™.The reduction rate (RR) of differently sized molecules was compared, as well as the variation rate in molecules smaller than 1000, detected by nuclear magnetic resonance based chemometrics (metabolomics). Albumin loss in dialysate was quantified. RESULTS: Lower RRs were found for molecules around 20 000 with Elisio 21HX™ compared to OL- HDF (RR prolactin 58.5% versus 66.7%, p = 0.034; RR Kappa light chain 63.1% versus 71.8%, p = 0.010). Albumin loss per session was higher with Theranova 500® than with OL-HDF and with Elisio 21HX™ (2249.9 ± 714.1 mg, 815.2 ± 474.0 mg, 442.9 ± 135.9 mg, p < 0.001, respectively). Metabolomic studies suggested, by semi-quantitative analysis, a greater depurative capacity of OL-HDF, followed by Elisio 21HX™, and then Theranova 500®. CONCLUSIONS: In this study, HD with Theranova 500® has proven to be very similar in efficacy to OL-HDF, although with a significantly higher albumin loss. HD with Elisio 21HX™ resulted in lower removal of molecules around 20 000 compared to OL-HDF, with no significant difference compared to Theranova 500®, and with less albumin loss than Theranova 500®.

Methyl Jasmonate and Nanoparticles Doped with Methyl Jasmonate affect the Cell Wall Composition of Monastrell Grape Skins.

The structural composition of the cell wall of grape skins is related to the cell wall integrity and subsequent extraction of the different compounds that are contained inside vacuoles and also the cell wall breakdown products. Different reports have established that methyl jasmonate (MeJ) produces changes in the composition of the grape skin cell wall. The use of elicitors to promote the production of secondary metabolites in grapes has been studied in several reports; however, its study linked to nanotechnology is less developed. These facts led us to study the effect of methyl jasmonate (MeJ) and nanoparticles doped with MeJ (nano-MeJ) on the cell walls of Monastrell grapes during three seasons. Both treatments tended to increase cell wall material (CWM) and caused changes in different components of the skin cell walls. In 2019 and 2021, proteins were enlarged in both MeJ and nano-MeJ-treated grapes. A general decrease in total phenolic compounds was detected with both treatments, in addition to an increment in uronic acids when the grapes were well ripened. MeJ and nano-MeJ produced a diminution in the amount of cellulose in contrast to an increase in hemicellulose. It should be noted that the effects with nano-MeJ treatment occurred at a dose 10 times lower than with MeJ treatment.

Different response of proanthocyanidins from Vitis vinifera cv. Monastrell depending on time of elicitor application.

BACKGROUND: Proanthocyanidins (PAs) are phenolic compounds present in skins and seeds of wine grapes and have great implications for plant physiology and wine quality. There are several strategies to increase PA concentration, such as application of elicitors methyl jasmonate (MeJ) and benzothiadiazole (BTH), compounds that can stimulate defence responses like phenolic compound biosynthesis in wine grapes, which have been applied mainly at veraison (beginning of ripening). We recently evaluated the application of MeJ and BTH on Vitis vinifera cv. Monastrell grapes during veraison and mid-ripening (3 weeks after veraison). Grapes treated at mid-ripening showed higher anthocyanin concentrations than those at veraison. In this trial, over two seasons, we evaluated whether time of application (veraison or mid-ripening) of MeJ and BTH on 'Monastrell' grapes is a determining factor in the biosynthesis and composition of PAs in grapes and their subsequent release into wines. RESULTS: Application of elicitors at different ripening times produced significant differences in the PAs of 'Monastrell' grapes, since those treated at mid-ripening recorded a higher PAs concentration in skin and seeds, and then in the wines produced, compared to grapes treated at veraison. CONCLUSION: Results suggest that despite different environmental conditions endured in each of the two seasons evaluated, application of elicitors at mid-ripening of Monastrell grapes could be used to harvest grapes with higher PA concentration, increasing the functional value of the wines, without altering their organoleptic quality. © 2022 Society of Chemical Industry.

Proanthocyanidins composition in new varieties descended from Monastrell.

BACKGROUND: The wine sector is constantly evolving, in order to adapt to consumer tastes. The organoleptic characteristics in wines are the main factors to obtain quality wines. Proanthocyanidins (PAs) are responsible in an important way for positive aspects in quality wines, such as body and color stability in red wines, but they are also responsible for sensory characteristics that can be negative for their quality when found in excessive concentrations. One strategy to improve grapevines and wines is to obtain new varieties, so our research institute has been selecting some of them from direct crosses between Monastrell and other considered premium varieties such as Cabernet Sauvignon and Syrah. RESULTS: A quantitative analysis in grapes, seeds and wines was carried out during three consecutive seasons (2018, 2019 and 2020) in order to characterize PAs composition and concentration in the following new varieties: MC80 (Monastrell × Cabernet Sauvignon), MC98, MC4, MC18 and MS10 (Monastrell × Syrah). Other aspect to study was the extraction capacity of the different new varieties of PAs during maceration process into must/wine. CONCLUSION: In general, the results showed higher concentrations in PAs in most crosses for the three seasons studied compared to Monastrell variety. It was remarkable that a higher concentration of epigallocatechin was found in most of the wines elaborated with the crosses, being a positive aspect from an organoleptic point of view, since this compound provides softness to the wines. © 2023 Society of Chemical Industry.

Effects of Methyl Jasmonate and Nano-Methyl Jasmonate Treatments on Monastrell Wine Volatile Composition.

The application of methyl jasmonate (MeJ) as an elicitor to enhance secondary metabolites in grapes and wines has been studied, but there is little information about its use in conjunction with nanotechnology and no information about its effects on wine volatile compounds. This led us to study the impact of nanoparticles doped with MeJ (Nano-MeJ, 1mM MeJ) on the volatile composition of Monastrell wines over three seasons, compared with the application of MeJ in a conventional way (10 mM MeJ). The results showed how both treatments enhanced fruity esters in wines regardless of the vintage year, although the increase was more evident when grapes were less ripe. These treatments also achieved these results in 2019 in the cases of 1-propanol, ß-phenyl-ethanol, and methionol, in 2020 in the cases of hexanol and methionol, and in 2021, but only in the case of hexanol. On the other hand, MeJ treatment also increased the terpene fraction, whereas Nano-MeJ, at the applied concentration, did not increase it in any of the seasons. In summary, although not all families of volatile compounds were increased by Nano-MeJ, the Nano-MeJ treatment generally increased the volatile composition to an extent similar to that obtained with MeJ used in a conventional way, but at a 10 times lower dose. Therefore, the use of nanotechnology could be a good option for improving the quality of wines from an aromatic point of view, while reducing the necessary dosage of agrochemicals, in line with more sustainable agricultural practices.

Application of Elicitors in Two Ripening Periods of Vitis vinifera L. cv Monastrell: Influence on Anthocyanin Concentration of Grapes and Wines.

In recent years, it has been demonstrated that the application of elicitors such as methyl-jasmonate (MeJ) and benzothiadiazole (BTH) to wine grapes can increase their phenolic and aromatic compounds if they are treated at the beginning of ripening (veraison). However, the veraison period is short, and it is not always possible to apply the treatments in a few days. Therefore, it would be of great interest to optimize the moment of elicitor application or extend the treatment period. The aim of this paper was to analyze during two consecutive years (2016-2017) the foliar application of MeJ, BTH, and a combination of both, during two different ripening periods of Monastrell grapes (veraison and mid-ripening), and determine the more appropriate moment to increase the concentration of anthocyanins. To carry out this aim, analysis of anthocyanins by HPLC in grapes and wines was mainly performed. The most suitable period for the application of MeJ, BTH, and MeJ + BTH was at mid-ripening, since the grapes showed a greater accumulation of anthocyanins at harvest. However, the MeJ + BTH treatment applied during veraison also obtained similar results, which would allow extending the application period if necessary. However, the increase in the anthocyanin content of grapes was not reflected in all the wines, which may have been due to reinforcement of the skin cell wall as a result of the application of elicitors. Further analysis is needed to improve the maceration process of the Monastrell grapes and the extraction of the anthocyanins that were increased by the treatments applied in the vineyard.

Aromatic Characterization of New White Wine Varieties Made from Monastrell Grapes Grown in South-Eastern Spain.

The aromatic profile of a wine is one of the main characteristics appreciated by consumers. Due to climate change, vineyards need to adapt to new conditions, and one of the strategies that might be followed is to develop new white varieties from Monastrell and other cultivars by means of intervarietal crosses, since white varieties are a minority in south-eastern Spain. Such crosses have already been obtained and have been seen to provide quality white wines of high acidity and with a good aromatic composition. To confirm this, a quantitative analysis was carried out during two vintages (2018 and 2019) in order to study and compare the volatile composition of Verdejo (V) wine with the aromatic composition of several wines made from different crosses between Cabernet Sauvignon (C), Syrah (S), Tempranillo (T), and Verdejo (V) with Monastrell (M), by means of headspace SPME-GC-MS analysis. Wine volatile compounds (alcohols, volatile acids, ethyl esters, terpenes, norisoprenoids, and two other compounds belonging to a miscellaneous group) were identified and quantified using a HS-SPME-GS-MS methodology. An additional sensory analysis was carried out by a qualified tasting panel in order to characterize the different wines. The results highlighted how the crosses MT103, MC69, and MC180 showed significant differences from and better quality than the Verdejo wine. These crosses produced higher concentrations of several aromatic families analyzed, which was supported by the views of the tasting panel, thus confirming their excellent aromatic potential as cultivars for producing grapes well adapted to this area for making white wines.

Study of aromatic profile of different crosses of Monastrell white wines.

BACKGROUND: Aromatic compounds are responsible for the final quality of wines. A semi-quantitative analysis was carried out during two consecutive seasons aiming to determine the volatile composition of 12 new white crosses obtained between Monastrell (M) and other varieties, such as Cabernet Sauvignon (C), Syrah (S) and Tempranillo (T) (MC10, MC180, MC9, MC69, MS30, MS33, MS82, MT103, MT19, MV11, MV67 and MV7), using a methodology based on gas chromatography-solid phase microextraction-mass spectrometry. RESULTS: On the one hand, 30 aromatic compounds were identified belonging to different chemical groups (alcohols, acids, terpenes, norisoprenoids and esters). The results showed how some crosses presented significant differences with respect to their parental. For example, in 2016, Monastrell and Cabernet Sauvignon showed high concentration of alcohols, acids and some terpenes, whereas the corresponding crosses showed a predominance of aromas belonging to esters. In 2017, as a result of edaphoclimatic conditions, the white crosses had higher concentrations of esters and acids. In addition, Monastrell and Cabernet Sauvignon showed similar concentrations of alcohols compared to 2016. On the other hand, sensorial analyses confirmed these results, so that mint and peppermint aromas and a fresh quality were detected in MC69 wine, especially in 2016, and fruity and acid aromas were detected in MC180 wine, which gave it a wide ranging complexity and aromatic potential. CONCLUSION: The present study reports the first investigation of the volatile composition and sensory characteristics of directed crosses white wines obtained from Monastrell and other varieties, such as Cabernet Sauvignon, Syrah, Tempranillo and Verdejo. The results obtained indicate that the use of some of these white crosses could be a good option for growing them in this Mediterranean area as a result of the contribution of a good quality in the wine aroma. © 2019 Society of Chemical Industry.

Autoimmune sequential overlap syndrome (autoimmune hepatitis/primary sclerosing cholangitis) and inflammatory bowel disease: three clinical cases.

Inflammatory bowel disease (IBD) is related to different liver extraintestinal manifestations and occurs with or without a link to disease activity. Primary sclerosing cholangitis (PSC) is the most common hepatobiliary manifestation. Other autoimmune hepatopathies may develop during the evolution of the latter, which is known as overlap syndrome. Sequential overlap syndrome occurs when these conditions appear in subsequent stages, and it is less frequently associated with IBD. We report three cases of sequential overlap syndrome with autoimmune hepatitis as the first manifestation, followed by PSC after 7-19 years and subsequently IBD. Liver extraintestinal manifestations may precede IBD by several years. Therefore, it is crucial to keep this association in mind, thereby reducing the diagnostic delay.

Effect of the Use of Purified Grape Pomace as a Fining Agent on the Volatile Composition of Monastrell Wines.

(1) Background: The lack of viable alternatives for the industrial exploitation of grape pomace is one of the reasons why it is considered a serious environmental pollutant. However, as a byproduct, it could be used as a fining agent, since previous studies have shown that it is able to eliminate undesirable substances in wine. However, the little information available does not describe its effect on wine aroma. (2) Methods: Purified grape pomace extracts were used for fining a red wine and their effect on the volatile compounds of the wine was assessed, comparing the results with those obtained with different commercial fining agents. (3) Results: The results showed how purified grape pomace decreased the total volatile content of a wine to a similar extent as other fining products, such as yeast extracts or gelatin. Among the different families of volatile compounds analyzed, only total esters and terpenes differed from the levels recorded for a control wine, being slightly lower. No statistical differences were found for the rest of the volatile compounds (alcohols, carbonyl, lactones, and acids) compared with the levels measured in control wine. (4) Conclusions: The results suggest that purified grape pomace could be used as a non-allergenic wine fining agent.

Aminosalicylates, thiopurines and methotrexate in inflammatory bowel disease: Is it possible to discontinue the treatment? / Aminosalicilatos, tiopurínicos y metotrexato en la enfermedad inflamatoria intestinal, ¿es posible suspender el tratamiento?

The current goals of treatment in inflammatory bowel disease, both Crohn's disease and ulcerative colitis, are to achieve clinical, endoscopic and ideally histological remission and improve the quality of life of these patients. Current therapies are effective in achieving remission in most cases, but there is a lack of clear guidelines on their optimal duration. This review aims to evaluate the current evidence on the withdrawal of therapy with 5-aminosalicylates, thiopurines and methotrexate. We also aim to identify which specific group of patients, while in remission and in the absence of risk factors, may be able to discontinue therapy without a significant risk of relapse.

Evaluation of de-escalation of anti-TNF-α therapy in inflammatory bowel disease. / Evaluación del retiro progresivo y/o la suspensión de la terapia anti-TNF-α en la enfermedad inflamatoria intestinal.

Anti-tumour necrosis factor α therapy in inflammatory bowel disease has been shown to be effective in clinical practice. After more than a decade using these therapies the question arises about whether there is an appropriate time to suspend these therapies, and how this should be done. This review aims to evaluate the current evidence on these topics concerning anti-tumour necrosis factor α therapies, and eventually identify conditions and subgroups of patients that could potentially be candidates for withdrawal.

Effect of elicitors on the evolution of grape phenolic compounds during the ripening period.

BACKGROUND: The effect of the application of benzothiadiazole (BTH) and methyl jasmonate (MeJ) at veraison on the phenolic composition of grapes from three varieties (Monastrell, Syrah and Merlot) was studied during the ripening period, using HPLC techniques to measure flavonols, anthocyanins and tannins. RESULTS: The effects of the treatments differed in the three varieties, and the maximum concentration of phenolic compounds was not always reached at the end of the ripening period but some days before harvest. At the end of ripening both treated Syrah grapes only differed from control grapes in the flavonol concentration, whereas MeJ-treated Merlot grapes presented higher anthocyanin and skin tannin contents than the control and BTH-treated grapes. Only the anthocyanin content was significantly higher in treated Monastrell grapes at the moment of harvest. CONCLUSION: The results indicate that the moment of elicitor treatment should be more studied since differences between treated and control grapes were, in general greater several days before harvest in all three varieties. © 2016 Society of Chemical Industry.

Redesigning a neighborhood park to increase physical activity: a community-based participatory approach.

BACKGROUND: Community collaboration and active engagement of neighborhood residents in park redesign are promising strategies for creating public spaces that support physical activity. OBJECTIVE: This research brief describes the process of community engagement and discusses outcomes of a participatory park redesign project. METHODS: A community design charrette was held in collaboration with community organizations. Environmental audits of park features and amenities were completed before and after implementation of park redesign. A guided discussion with stakeholders following the park redesign was conducted to discuss challenges, successes, and next steps. RESULTS: Although level of activity among youth observed in the post implementation observations did not differ, there were a greater variety of activities observed among both children and adolescents. Furthermore, the goals of the project related to capacity building and meeting residents' needs were accomplished. CONCLUSIONS: Active participation of residents in a neighborhood park redesign requires time, commitment, and communication from a variety of stakeholders. However, the creation of a park that supports a variety of activity types, and builds community capacity, supports the need for involving stakeholders in redesigning neighborhood parks.

Human T-cell receptor triggering requires inactivation of Lim kinase-1 by Slingshot-1 phosphatase.

Actin dynamics control early T-cell receptor (TCR) signalling during T-cell activation. However, the precise regulation of initial actin rearrangements is not completely understood. Here, we have investigated the regulatory role of the phosphatase Slingshot-1 (SSH1) in this process. Our data show that SSH1 rapidly polarises to nascent cognate synaptic contacts and later relocalises to peripheral F-actin networks organised at the mature immunological synapse. Knockdown of SSH1 expression by CRISPR/Cas9-mediated genome editing or small interfering RNA reveal a regulatory role for SSH1 in CD3ε conformational change, allowing Nck binding and proper downstream signalling and immunological synapse organisation. TCR triggering induces SSH1-mediated activation of actin dynamics through a mechanism mediated by Limk-1 inactivation. These data suggest that during early TCR activation, SSH1 is required for rapid F-actin rearrangements that mediate initial conformational changes of the TCR, integrin organisation and proximal signalling events for proper synapse organisation. Therefore, the SSH1 and Limk-1 axis is a key regulatory element for full T cell activation.

Sentinel Node Biopsy in Patients With Breast Carcinoma Without Axillary Involvement at Diagnosis Receiving Primary Systemic Therapy.

BACKGROUND: Primary systemic therapy (PST) has acquired great importance in breast cancer (BC) in the last few years. In this scenario, even if it is accepted to perform SLNB before PST, most of the guidelines remark the advantages of this practice after it, such as avoiding another surgery to the patient, a rapid start of the treatment and no need of axillary dissection in cases of pathologic complete response (pCR). Nevertheless, the lack of knowledge of the initial axillary state and the need to practice axillary dissection with any axillary disease are claimed to be some other disadvantages. There are no randomized studies yet that can conclude the optimal timing of SLNB in PST, so for the moment we may settle for our common practice. PATIENTS AND METHODS: We studied all the cases attended in the Breast Unit that joined the inclusion criteria between 2011 and 2019 in our hospital and we compared the group with SLNB before PST with the group with SLNB after PST in terms of unnecessary axillary dissection and description features. RESULTS: We included 223 female patients diagnosed with BC and without clinical nor radiological axillary disease (cN0), who had received NAC and SLNB performed before or after it. We observed a higher proportion of high-grade histological tumors (G3), tumors with aggressive phenotypes (Basal like and Her 2 enriched), and younger women in the group of SLNB before NAC compared with the SLNB after NAC group (P < .01). Despite this, we did not find any difference in the number of positive SLNBs or in the number of ALND performed between the 2 groups. We found a higher proportion of ALND with all the lymph node (LN) negatives in the SLNB before NAC group. CONCLUSION: Taking into account that in the observation period we did not use ACOSOG Z0011 criteria with all the SLNBs, we figure out what would have been the real results nowadays following these criteria. In this scenario we conclude that patients with luminal phenotype seemed to benefit from practicing SLNB before NAC in terms of avoiding axillary dissections. We could not make any conclusion in the rest of the phenotypes. However, prospective studies are needed to confirm if this affirmation could be proved.

Prevalence of transthyretin cardiac amyloidosis in elderly patients diagnosed with heart failure.

OBJECTIVE: There is increased interest in studying ATTR-CA, a pathology that primarily affects patients of geriatric age and is frequently underdiagnosed. We aim to establish the prevalence of ATTR-CA in a cohort of patients with a history of HFpEF and to describe its characteristics. METHODS: We conducted a prospective observational study. Patients ≥75 years, clinical history of HFpEF, atrial dilation ≥34ml/m2 and left ventricular wall thickening >13mm, were included. Demographic and analytical parameters were collected, and a comprehensive geriatric assessment was performed, along with a transthoracic echocardiogram and cardiac scintigraphy. Finally, telephone follow-up was carried out at 6 and 12 months. RESULTS: 50 patients were recruited, mean age 86±6 years, 54% women. Age and functional class (I-II vs. III-IV) were factors associated with presenting with ATTR-CA. Patients with positive scintigraphy had a median time to admission of 5.2 months (confidence interval [CI] 95% 0-10.9), while in those with negative scintigraphy, it was 12.2 months (95% CI 11.7-12.8); log-rank: p=0.064. Patients with positive scintigraphy had a median time to the combined endpoint (death and readmission) of 1.9 months (95% CI 0-6.1), and patients with negative scintigraphy of 11.9 months (95% CI 11.7-12); log-rank: p=0.027. CONCLUSIONS: ATTR-CA appears to be a prevalent etiology in elderly patients within the spectrum of HFpEF. Patients with a diagnosis of ATTR-CA had a shorter time to admission for HF and the combined event of death and admission than patients with a negative result on scintigraphy.

A Critical Gap in Seagrass Protection: Impact of Anthropogenic Off-Shore Nutrient Discharges on Deep Posidonia oceanica Meadows.

In the Mediterranean, anthropogenic pressures (specifically those involving nutrient loads) have been progressively moved to deeper off-shore areas to meet current policies dealing with the protection of marine biodiversity (e.g., European Directives). However, conservation efforts devoted to protecting Posidonia oceanica and other vulnerable marine habitats against anthropogenic pressures have dedicated very little attention to the deepest areas of these habitats. We studied the remote influence of off-shore nutrient discharge on the physiology and structure of deep P. oceanica meadows located nearest to an urban sewage outfall (WW; 1 km) and an aquaculture facility (FF; 2.5 km). Light reduction and elevated external nutrient availability (as indicated by high δ15N, total N and P content and N uptake rates of seagrass tissues) were consistent with physiological responses to light and nutrient stress. This was particularly evident in the sites located up to 2.5 km from the WW source, where carbon budget imbalances and structural alterations were more evident. These results provide evidence that anthropogenic nutrient inputs can surpass critical thresholds for the species, even in off-shore waters at distances within the km scale. Therefore, the critical distances between this priority habitat and nutrient discharge points have been underestimated and should be corrected to achieve a good conservation status.

Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD.

BACKGROUND: NAFLD clinical trials have shown suboptimal results, particularly for liver fibrosis, despite the robust preclinical drug development. We aimed to assess the histological response after the experimental treatment versus placebo by carrying out a meta-analysis of NAFLD clinical trials. METHODS: After a systematic review of NAFLD clinical trials to May 2021, applying strict selection criteria, the following primary outcomes were observed: (a) NASH resolution, with no worsening of fibrosis when available; (b) fibrosis improvement ≥ 1 stage, with no worsening of NAS when available; (c) worsening of NAS; (d) worsening of liver fibrosis ≥ 1 stage, including the progression to cirrhosis on histopathology. Other histological, clinical, and biochemical outcomes were considered secondary endpoints. Heterogeneity was explored by subgroup and sensitivity analyses, and univariable meta-regression. RESULTS: Twenty-seven randomized clinical trials were included. The pooled efficacy for NASH resolution receiving experimental therapy was 19% (95%CI 15-23; I2 96.2%) compared with placebo 10% (95%CI 7-12; I2 85.8%) (OR 1.66 (95%CI 1.24-2.21); I2 57.8%), while it was 26% (95%CI 22-29); I2 90%)) versus 18% (95%CI 15-21; I2 59%)) for fibrosis improvement (OR 1.34 (95%CI 1.13-1.58); I2 25.4%). For these outcomes, the therapy showed higher efficacy in trials longer than 48 weeks, with < 60% of diabetic population, and when it targeted FXR, PPAR, and antidiabetic mechanisms, and with a NAS < 5 for NASH resolution. Also, NASH (OR 0.57 (95%CI 0.39-0.84); I2 67%) and fibrosis worsening (OR 0.65 (95%CI 0.46-0.92); I2 61.9%) were prevented with the therapy. CONCLUSION: This meta-analysis provides information about the efficacy of the therapy versus placebo by comparing different and combined trial outcomes such as NASH resolution, fibrosis improvement, and NAS and fibrosis worsening. Changes in the experimental design and selection criteria of the clinical trials might be suitable to increase the efficacy.

IgA Nephropathy Is the Most Common Underlying Disease in Patients With Anticoagulant-Related Nephropathy.

Introduction: Anticoagulant-related nephropathy (ARN) is a relatively novel recognized entity characterized by hematuria-associated acute kidney injury (AKI) in the context of overanticoagulation. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to evaluate underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed. Methods: Retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. Results: A total of 26 patients were included with a median age of 75 years (62-80) and a follow-up period of 10.1 months. Of the patients, 80% were male, and most cases (92%) were on anticoagulation with vitamin K antagonists (VKAs). At admission, median serum creatinine (SCr) level was 4.2 mg/dl (2.8-8.2), median international normalized ratio (INR) 2.4 (1.5-3.4), and 11 patients (42%) required acute dialysis during hospitalization. Kidney biopsy results revealed that all patients except 1 had an underlying nephropathy: IgA nephropathy (IgAN) in 19, probable IgAN in 1, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1. At 12 weeks after discharge, only 6 subjects (24%) attained complete kidney recovery whereas 7 (28%) remained on chronic dialysis. Conclusion: IgAN was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.