Atypical Mal de Meleda in a Hispanic Patient.

Mal de Meleda (MDM) is a rare autosomal palmoplantar keratoderma (PPK) skin disorder (estimated incidence of 1 per 100,000 people) commonly associated with consanguinity and early childhood onset. MDM is characterized by bilateral diffusion of PPK plaques with delimited yellowish lesions that transgredien to the dorsum of the hands and feet. Additional features include nail dystrophy, lichenoid lesions, hyperhidrotic maceration, involvement of the knees and elbows, malodor, fungal superinfections, and digital constrictions. A male patient aged 42 years presented with asymptomatic, chronic, and diffused PPK lesions that progressed to the dorsal surface of the hands and feet, along with knees and elbows involvement. On clinical examination, asymmetrical lesions were observed on the hands, the left palm with yellowish waxy hyperkeratotic plaques, and the right palm with erythematous scaling and hyperkeratotic interphalangeal rings. The soles of the feet presented with yellow waxy hyperkeratotic plaques. In addition, nail dystrophy and loss of dermatoglyphics were observed. Initially, symptomatic topical treatment was established. However, owing to the lack of clinical response, a biopsy was performed, which revealed thickened corneal layer, acanthosis, spongiosis, and perivascular lymphohistiocytic infiltrate. MDM diagnosis was confirmed based on a personal history of consanguinity, clinical presentation with absence of systemic symptoms, and transgredien pattern of the lesions. Systemic treatment with low doses of isotretinoin (10 mg orally everyday) was initiated, and two months later, slight clinical improvement has been observed until date. The present case report describes MDM in a Hispanic patient, who presented with asymmetric PPK lesions on the hands and received isotretinoin treatment.

Synthesis of New Polyheterocyclic Pyrrolo[3,4-b]pyridin-5-ones via an Ugi-Zhu/Cascade/Click Strategy.

A diversity-oriented synthesis (DOS) of two new polyheterocyclic compounds was performed via an Ugi-Zhu/cascade (N-acylation/aza Diels-Alder cycloaddition/decarboxylation/dehydration)/click strategy, both step-by-step to optimize all involved experimental stages, and in one pot manner to evaluate the scope and sustainability of this polyheterocyclic-focused synthetic strategy. In both ways, the yields were excellent, considering the high number of bonds formed with release of only one carbon dioxide and two molecules of water. The Ugi-Zhu reaction was carried out using the 4-formylbenzonitrile as orthogonal reagent, where the formyl group was first transformed into the pyrrolo[3,4-b]pyridin-5-one core, and then the remaining nitrile group was further converted into two different nitrogen-containing polyheterocycles, both via click-type cycloadditions. The first one used sodium azide to obtain the corresponding 5-substituted-1H-tetrazolyl-pyrrolo[3,4-b]pyridin-5-one, and the second one with dicyandiamide to synthesize the 2,4-diamino-1,3,5-triazine-pyrrolo[3,4-b]pyridin-5-one. Both synthesized compounds may be used for further in vitro and in silico studies because they contain more than two heterocyclic moieties of high interest in medicinal chemistry, as well as in optics due to their high π-conjugation.

Improvement of beauvericin production by Fusarium oxysporum AB2 under solid-state fermentation using an optimised liquid medium and co-cultures.

The production of beauvericin (BEA) by Fusarium oxysporum AB2 in liquid medium (SmF) was compared to that on solid medium (SSF) on inert support (polyurethane foam or PUF), using a previously optimised medium. The analysis included two different concentrations of the medium (1 × and 3 ×). Under SSF, the production of BEA (22.8 mg·L-1) was higher relative to SmF (0.8 mg·L-1). The production increased proportionally in the concentrated medium (3 ×) (65.3 mg·L-1); using the concentrated medium in SmF, the production of BEA was completely inhibited, although more biomass was produced. The peak of BEA production was reached on day 7 and remained stable until day 11; sustained production after several days has not been achieved in similar reports. The presence of BEA was corroborated by high-performance liquid chromatography (HPLC) and mass spectrometry. The BEA production profile is shown performing mixed cultures of Fusarium oxysporum AB2 and Epicoccum nigrum TORT using the same system, increasing the production of BEA up to 84.6 mg·L-1. We propose SSF using polyurethane foam (PUF) as a solid support as a new culture system for obtaining secondary metabolites such as BEA.

Ecology and responses to climate change of biocrust-forming mosses in drylands.

Interest in understanding the role of biocrusts as ecosystem engineers in drylands has substantially increased during the past two decades. Mosses are a major component of biocrusts and dominate their late successional stages. In general, their impacts on most ecosystem functions are greater than those of early-stage biocrust constituents. However, it is common to find contradictory results regarding how moss interactions with different biotic and abiotic factors affect ecosystem processes. This review aims to (i) describe the adaptations and environmental constraints of biocrust-forming mosses in drylands, (ii) identify their primary ecological roles in these ecosystems, and (iii) synthesize their responses to climate change. We emphasize the importance of interactions between specific functional traits of mosses (e.g. height, radiation reflectance, morphology, and shoot densities) and both the environment (e.g. climate, topography, and soil properties) and other organisms to understand their ecological roles and responses to climate change. We also highlight key areas that should be researched in the future to fill essential gaps in our understanding of the ecology and the responses to ongoing climate change of biocrust-forming mosses. These include a better understanding of intra- and interspecific interactions and mechanisms driving mosses' carbon balance during desiccation-rehydration cycles.

UAV RGB, thermal infrared and multispectral imagery used to investigate the control of terrain on the spatial distribution of dryland biocrust.

Biocrusts (topsoil communities formed by mosses, lichens, bacteria, fungi, algae, and cyanobacteria) are a key biotic component of dryland ecosystems. Whilst climate patterns control the distribution of biocrusts in drylands worldwide, terrain and soil attributes can influence biocrust distribution at landscape scale. Multi-source unmanned aerial vehicle (UAV) imagery was used to map and study biocrust ecology in a typical dryland ecosystem in central Spain. Red, green and blue (RGB) imagery was processed using structure-from-motion techniques to map terrain attributes related to microclimate and terrain stability. Multispectral imagery was used to produce accurate maps (accuracy > 80%) of dryland ecosystem components (vegetation, bare soil and biocrust composition). Finally, thermal infrared (TIR) and multispectral imagery was used to calculate the apparent thermal inertia (ATI) of soil and to evaluate how ATI was related to soil moisture (r 2 = 0.83). The relationship between soil properties and UAV-derived variables was first evaluated at the field plot level. Then, the maps obtained were used to explore the relationship between biocrusts and terrain attributes at ecosystem level through a redundancy analysis. The most significant variables that explain biocrust distribution are: ATI (34.4% of variance, F = 130.75; p < 0.001), Elevation (25.8%, F = 97.6; p < 0.001), and potential solar incoming radiation (PSIR) (52.9%, F = 200.1; p < 0.001). Differences were found between areas dominated by lichens and mosses. Lichen-dominated biocrusts were associated with areas with high slopes and low values of ATI, with soil characterized by a higher amount of soluble salts, and lower amount of organic carbon, total phosphorus (Ptot) and total nitrogen (Ntot). Biocrust-forming mosses dominated lower and moister areas, characterized by gentler slopes and higher values of ATI with soils with higher contents of organic carbon, Ptot and Ntot. This study shows the potential to use UAVs to improve our understanding of drylands and to evaluate the control that the terrain has on biocrust distribution.

Wild Italian Hyssopus officinalis subsp. aristatus (Godr.) Nyman: From Morphological and Phytochemical Evidences to Biological Activities.

Three specimens of H. officinalis subsp. aristatus were collected in three areas of the Abruzzo region (Italy) and subjected to macroscopic and microscopic observation to support their botanical identification. The essential oils (EOs) obtained from the aerial parts of the samples were characterized with the object to define their phytochemical and pharmaceutical biology profile. They highlight three different chemotypes, including one never seen in previous literature (CIV17-EO, distilled from sample harvested in 2017 at Civitaretenga), that showed a fingerprinting with the predominance of (-)-limonen-10-yl-acetate (67.9%). In 2017 European Food Safety Authority (EFSA) reported the genotoxicity of similar compounds, therefore, to dismiss any safety concern for the CIV17-EO use as flavouring substance, the Ames test was performed with no evidence of mutagenic activity. Safety of use coupled with chemical characterization of this new chemotype set the stage for a better standardization of H. officinalis EOs. The ethanolic extracts, on the other hand, with qualitatively similar chemical profiles in which caftaric, chlorogenic and rosmarinic acid were the main molecules, showed interesting antioxidant activity and a slight cytotoxicity towards the A549 cell line that could indicate a starting point for the evaluation of an additional preventive tool for maintaining health status.

Ocimum campechianum Mill. from Amazonian Ecuador: Chemical Composition and Biological Activities of Extracts and Their Main Constituents (Eugenol and Rosmarinic Acid).

The essential oil (EO), the methanolic (MeOH), and the 70% ethanolic (70% EtOH) extracts obtained from the aerial parts of Ocimum campechianum Mill. (Ecuador) were chemically characterized through gas-chromatography coupled to mass spectrometry detector (GC-MS), high-performance liquid chromatography coupled to diode array-mass spectrometry detectors (HPLC-DAD-MS) and studied for their in vitro biological activity. The radical scavenger activity, performed by spectrophotometric 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, highlighted significant IC50 values for the EO, extracts and their main constituents (eugenol and rosmarinic acid). EO (and eugenol) showed noteworthy activity against Pseudomonas syringae pv. syringae and a moderate effect against clinical Candida strains, with possible synergism in association to fluconazole against the latter microorganisms. The extracts and pure molecules exhibited weak cytotoxic activity against the HaCat cell line and no mutagenicity against Salmonella typhimurium TA98 and TA100 strains, giving indication of safety. Instead, EO showed a weak activity against adenocarcinomic human alveolar basal epithelial cells (A549). The above-mentioned evidence leads us to suggest a potential use of the crude drug, extracts, and EO in cosmetic formulation and food supplements as antioxidant agents. In addition, EO may also have a possible application in plant protection and anti-Candida formulations.

Bottleneck Effect Explained by Le Bail Refinements: Structure Transformation of Mg-CUK-1 by Confining H2O Molecules.

The structure transformation of Mg-CUK-1 due to the confinement of H2O molecules was investigated. Powder X-ray diffraction (PXRD) patterns were collected at different H2O loadings and the cell parameters of the H2O-loaded Mg-CUK-1 material were determined by the Le Bail strategy refinements. A bottleneck effect was observed when one hydrogen-bonded H2O molecule per unit cell (18% relative humidity (RH)) was confined within Mg-CUK-1, confirming the increase in the CO2 capture for Mg-CUK-1.

Improvement of hyponatremia in cirrhosis is associated with improved complex information processing.

BACKGROUND AND AIM: Hyponatremia, a cause of brain dysfunction and risk factor for hepatic encephalopathy, is frequent in patients with advanced cirrhosis and ascites. The interdependence of liver failure and hyponatremia makes it difficult to separate the effects of each on cognitive function. The objective was to assess whether an increase in plasma sodium in patients with cirrhosis and ascites leads to an improvement in cognitive function. METHODS: This is a post-hoc analysis of 250 cirrhosis patients without overt hepatic encephalopathy randomized to receive either placebo or satavaptan, a vasopressin V2 antagonist. The exposure was plasma sodium, and the outcome was the trail-making test (TMT) parts A and B, which assesses speed of information processing, performed before the study starts and after 14 days. The results were analyzed by initial and change to final sodium concentration. RESULTS: At entry, the patients with normonatremia exhibited better results on both the TMT-A (median 56 vs 77.5 s for patients with sodium ≤ 130 mmol/L [P = 0.0059]) and the TMT-B (median 127 vs 170 s for patients with sodium ≤ 130 mmol/L [P = 0.0066]), unrelated to age. Improvement of hyponatremia was more common in patients who received satavaptan (59.7%) than placebo (18.5%). Correction of hyponatremia did not shorten the simple TMT-A but markedly improved the complex TMT-B by an average of 20 s compared with 6.5 s in those with continuing hyponatremia (P = 0.02). Liver status measures remained stable during the period reported. CONCLUSIONS: These data suggest that improvement of hyponatremia in patients with cirrhosis leads to an increase in the speed of complex information processing.

Soil moisture dynamics under two rainfall frequency treatments drive early spring CO2 gas exchange of lichen-dominated biocrusts in central Spain.

BACKGROUND: Biocrusts, communities dominated by mosses, lichens, cyanobacteria, and other microorganisms, largely affect the carbon cycle of drylands. As poikilohydric organisms, their activity time is often limited to short hydration events. The photosynthetic and respiratory response of biocrusts to hydration events is not only determined by the overall amount of available water, but also by the frequency and size of individual rainfall pulses. METHODS: We experimentally assessed the carbon exchange of a biocrust community dominated by the lichen Diploschistes diacapsis in central Spain. We compared the effect of two simulated precipitation patterns providing the same overall amount of water, but with different pulse sizes and frequency (high frequency: five mm/day vs. low frequency: 15 mm/3 days), on net/gross photosynthesis and dark respiration. RESULTS: Radiation and soil temperature, together with the watering treatment, affected the rates of net and gross photosynthesis, as well as dark respiration. On average, the low frequency treatment showed a 46% ± 3% (mean ± 1 SE) lower rate of net photosynthesis, a 13% ± 7% lower rate of dark respiration, and a 24% ± 8% lower rate of gross photosynthesis. However, on the days when samples of both treatments were watered, no differences between their carbon fluxes were observed. The carbon flux response of D. diacapsis was modulated by the environmental conditions and was particularly dependent on the antecedent soil moisture. DISCUSSION: In line with other studies, we found a synergetic effect of individual pulse size, frequency, environmental conditions, and antecedent moisture on the carbon exchange fluxes of biocrusts. However, most studies on this subject were conducted in summer and they obtained results different from ours, so we conclude that there is a need for long-term experiments of manipulated precipitation impacts on the carbon exchange of biocrusts. This will enable a more complete assessment of the impacts of climate change-induced alterations in precipitation patterns on biocrust communities.

Simulated climate change affects how biocrusts modulate water gains and desiccation dynamics after rainfall events.

Soil surface communities dominated by mosses, lichens and cyanobacteria (biocrusts) are common between vegetation patches in drylands worldwide, and are known to affect soil wetting and drying after rainfall events. While ongoing climate change is already warming and changing rainfall patterns of drylands in many regions, little is known on how these changes may affect the hydrological behaviour of biocrust-covered soils. We used eight years of continuous soil moisture and rainfall data from a climate change experiment in central Spain to explore how biocrusts modify soil water gains and losses after rainfall events under simulated changes in temperature (2.5°C warming) and rainfall (33% reduction). Both rainfall amount and biocrust cover increased soil water gains after rainfall events, whereas experimental warming, rainfall intensity and initial soil moisture decreased them. Initial moisture, maximum temperature and biocrust cover, by means of enhancing potential evapotranspiration or by soil darkening, increased the drying rates and enhanced the exponential behaviour of the drying events. Meanwhile, warming reduced their exponential behaviour. The effects of climate change treatments on soil water gains and losses changed through time, with important differences between the first two years of the experiment and five years after its setup. These effects were mainly driven by the important reductions in biocrust cover and diversity observed under warming. Our results highlight the importance of long-term studies to understand soil moisture responses to ongoing climate change in drylands.

Synthesis of New 5-Aryl-benzo[f][1,7]naphthyridines via a Cascade Process (Ugi-3CR/Intramolecular Aza-Diels-Alder Cycloaddition)/Aromatization.

A series of eight new 5-aryl-benzo[f][1,7]naphthyridines were synthesized in 17 to 64% overall yields via an improved MW-assisted cascade-like one pot process (Ugi⁻three component reaction/intramolecular aza-Diels-Alder cycloaddition) coupled to an aromatization process from tri-functional dienophile-containing ester-anilines, substituted benzaldehydes and the chain-ring tautomerizable 2-isocyano-1-morpholino-3-phenylpropan-1-one as starting reagents, under mild conditions. The doubly activated dienophile and the aza-diene functionalities of the eight new Ugi-adducts were exploited to perform an in situ aza-Diels-Alder cycloaddition/aromatization (dehydration/oxidation) process, toward the complex polysubstituted 5-aryl-polyheterocycles, which could be taken as starting point for further SAR studies because the benzo[f][1,7]naphthyridine is the core of various bioactive products. It is relevant to emphasize that the synthesis or isolation of benzo[f][1,7]naphthyridines containing a substituted aromatic ring in the C-5 position, has not been published before.

Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial.

BACKGROUND & AIMS: Patients with decompensated cirrhosis on the waiting list for liver transplantation (LT) commonly develop complications that may preclude them from reaching LT. Circulatory dysfunction leading to effective arterial hypovolemia and activation of vasoconstrictor systems is a key factor in the pathophysiology of complications of cirrhosis. The aim of this study was to investigate whether treatment with midodrine, an alpha-adrenergic vasoconstrictor, together with intravenous albumin improves circulatory dysfunction and prevents complications of cirrhosis in patients awaiting LT. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial (NCT00839358) was conducted, including 196 consecutive patients with cirrhosis and ascites awaiting LT. Patients were randomly assigned to receive midodrine (15-30 mg/day) and albumin (40 g/15 days) or matching placebos for one year, until LT or drop-off from inclusion on the waiting list. The primary endpoint was incidence of any complication (renal failure, hyponatremia, infections, hepatic encephalopathy or gastrointestinal bleeding). Secondary endpoints were mortality, activity of endogenous vasoconstrictor systems and plasma cytokine levels. RESULTS: There were no significant differences between both groups in the probability of developing complications of cirrhosis during follow-up (p = 0.402) or one-year mortality (p = 0.527). Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo (renin -4.3 vs. 0.1 ng/ml.h, p < 0.001; aldosterone -38 vs. 6 ng/dl, p = 0.02, at week 48 vs. baseline). Plasma norepinephrine only decreased slightly at week 4. Neither arterial pressure nor plasma cytokine levels changed significantly. CONCLUSIONS: In patients with cirrhosis awaiting LT, treatment with midodrine and albumin, at the doses used in this study, slightly suppressed the activity of vasoconstrictor systems, but did not prevent complications of cirrhosis or improve survival. LAY SUMMARY: Patients with cirrhosis who are on the liver transplant waiting list often develop complications which prevent them from receiving a transplant. Circulatory dysfunction is a key factor behind a number of complications. This study was aimed at investigating whether treating patients with midodrine (a vasoconstrictor) and albumin would improve circulatory dysfunction and prevent complications. This combined treatment, at least at the doses administered in this study, did not prevent the complications of cirrhosis or improve the survival of these patients.

Warming reduces the cover, richness and evenness of lichen-dominated biocrusts but promotes moss growth: insights from an 8 yr experiment.

Despite the important role that biocrust communities play in maintaining ecosystem structure and functioning in drylands world-wide, few studies have evaluated how climate change will affect them. Using data from an 8-yr-old manipulative field experiment located in central Spain, we evaluated how warming, rainfall exclusion and their combination affected the dynamics of biocrust communities in areas that initially had low (< 20%, LIBC plots) and high (> 50%, HIBC plots) biocrust cover. Warming reduced the richness (35 ± 6%), diversity (25 ± 8%) and cover (82 ± 5%) of biocrusts in HIBC plots. The presence and abundance of mosses increased with warming through time in these plots, although their growth rate was much lower than the rate of lichen death, resulting in a net loss of biocrust cover. On average, warming caused a decrease in the abundance (64 ± 7%) and presence (38 ± 24%) of species in the HIBC plots. Over time, lichens and mosses colonized the LIBC plots, but this process was hampered by warming in the case of lichens. The observed reductions in the cover and diversity of lichen-dominated biocrusts with warming will lessen the capacity of drylands such as that studied here to sequester atmospheric CO2 and to provide other key ecosystem services associated to these communities.

Effects of alfapump™ system on kidney and circulatory function in patients with cirrhosis and refractory ascites.

The alfapump system has been proposed as a new treatment for the management of refractory ascites. The system removes ascites from the peritoneal cavity to urinary bladder, producing a continuous low-volume paracentesis. The aim of the study is to investigate the effects of treatment with the alfapump™ system on kidney and circulatory function in patients with cirrhosis and refractory ascites. This was a prospective study including 10 patients with cirrhosis and refractory ascites. Primary outcomes were changes in glomerular filtration rate (GFR), as assessed by isotopic techniques, and changes in circulatory function assessed by arterial pressure, cardiac output, and activity of vasoconstrictor systems. Secondary outcomes were the need for large-volume paracentesis and adverse events. Follow-up was 1 year. GFR decreased significantly from 67 mL/minute/1.73 m2 (41-90 mL/minute/1.73 m2 ) at baseline to 45 mL/minute/1.73 m2 (36-74 mL/minute/1.73 m2 ) at month 6 (P = 0.04). Mean arterial pressure and cardiac output did not change significantly; however, there was a marked increase in plasma renin activity and norepinephrine concentration (median percent increase with respect to baseline +191% and 59%, respectively). There were 68 episodes of complications of cirrhosis in 8 patients during follow-up, the most frequent being acute kidney injury. In conclusion, treatment with alfapump™ system was associated with marked activation of endogenous vasoconstrictor systems and impairment of kidney function. The chronological relationship observed between kidney impairment and vasoconstrictor systems activation after device insertion suggests a cause-effect relationship, raising the possibility that treatment with alfapump impairs effective arterial blood volume mimicking a postparacentesis circulatory dysfunction syndrome. In this context, the potential role of albumin in counteracting these effects should be investigated in future studies. Liver Transplantation 23 583-593 2017 AASLD.

An efficient Ugi-3CR/aza Diels-Alder/Pomeranz-Fritsch protocol towards novel aza-analogues of (±)-nuevamine, (±)-lennoxamine and magallanesine: a diversity oriented synthesis approach.

A rapid and efficient synthesis of a series of (±)-nuevamine, (±)-lennoxamine and magallanesine aza analogues is described. The synthetic strategy involves Ugi-3CR and two further condensation processes, aza-Diels-Alder cycloaddition and the Pomeranz-Fritsch reaction. The variation of the chain-size in aldehyde moieties provided structural diversity in only two operational reaction steps.

Limited Efficacy of Tolvaptan in Patients with Cirrhosis and Severe Hyponatremia: Real-Life Experience.

BACKGROUND: Vaptans, vasopressin selective V2-receptor antagonists, represent the first pharmacologic approach to the treatment of hypervolemic hyponatremia in cirrhosis. However, information on the use of vaptans for patients with cirrhosis and hyponatremia in a real-life scenario is limited. Therefore, this study evaluated the effect of tolvaptan on serum sodium in patients with cirrhosis and severe hypervolemic hyponatremia. METHODS: Nine patients with cirrhosis and serum sodium ≤125 mEq/L were included. RESULTS: Only 2 of the 9 patients (22%) gained an increase in serum sodium >130 mEq/L that persisted throughout treatment. In the remaining patients, serum sodium did not change or increased during the first days but decreased thereafter despite continuation of treatment. Only 1 patient developed hyperkalemia as a side effect. CONCLUSIONS: The efficacy of tolvaptan in patients with cirrhosis and severe hypervolemic hyponatremia seems to be limited.

Urinary neutrophil gelatinase-associated lipocalin predicts kidney outcome and death in patients with cirrhosis and bacterial infections.

BACKGROUND & AIMS: Infections in cirrhosis are frequently complicated by kidney dysfunction that entails a poor prognosis. Urinary biomarkers may be of potential clinical usefulness in this setting. We aimed at assessing the value of urinary neutrophil gelatinase-associated lipocalin (uNGAL), a biomarker overexpressed in kidney tubules during kidney injury, in predicting clinical outcomes in cirrhosis with infections. METHODS: One-hundred and thirty-two consecutive patients hospitalized with infections were evaluated prospectively. Acute kidney injury (AKI) was defined according to AKIN criteria. uNGAL was measured at infection diagnosis and at days 3 and 7 (ELISA, Bioporto, DK). RESULTS: Patients with AKI (n=65) had significantly higher levels of uNGAL compared to patients without AKI (203 ± 390 vs. 79 ± 126 µg/g creatinine, p<0.001). Moreover, uNGAL levels were significantly higher in patients who developed persistent AKI (n=40), compared to those with transient AKI (n=25) (281 ± 477 vs. 85 ± 79 µg/g creatinine, p<0.001). Among patients with persistent AKI, uNGAL was able to discriminate type-1 HRS from other causes of AKI (59 ± 46 vs. 429 ± 572 µg/g creatinine, respectively; p<0.001). Moreover, the time course of uNGAL was markedly different between the two groups. Interestingly, baseline uNGAL levels also predicted the development of a second infection during hospitalization. Overall, 3-month mortality was 34%. Independent predictive factors of 3-month mortality were MELD score, serum sodium, and uNGAL levels at diagnosis, but not presence or stage of AKI. CONCLUSIONS: In patients with cirrhosis and infections, measurement of urinary NGAL at infection diagnosis is useful in predicting important clinical outcomes, specifically persistency and type of AKI, development of a second infection, and 3-month mortality.

Terlipressin and albumin for type-1 hepatorenal syndrome associated with sepsis.

BACKGROUND & AIMS: Terlipressin and albumin is the standard of care for classical type-1 hepatorenal syndrome (HRS) not associated with active infections. However, there is no information on efficacy and safety of this treatment in patients with type-1 HRS associated with sepsis. Study aim was to investigate the effects of early treatment with terlipressin and albumin on circulatory and kidney function in patients with type-1 HRS and sepsis and assess factors predictive of response to therapy. METHODS: Prospective study in 18 consecutive patients with type-1 HRS associated with sepsis. RESULTS: Treatment was associated with marked improvement in arterial pressure and suppression of the high levels of plasma renin activity and norepinephrine. Response to therapy (serum creatinine <1.5mg/dl) was achieved in 12/18 patients (67%) and was associated with improved 3-month survival compared to patients without response. Non-responders had significantly lower baseline heart rate, poor liver function tests, slightly higher serum creatinine, and higher Child-Pugh and MELD scores compared to responders. Interestingly, non-responders had higher values of CLIF-SOFA score compared to responders (14±3 vs. 8±1, respectively p<0.001), indicating greater severity of acute-on-chronic liver failure (ACLF). A CLIF-SOFA score ⩾11 had 92% sensitivity and 100% specificity in predicting no response to therapy. No significant differences were observed between responders and non-responders in baseline urinary kidney biomarkers. Treatment was safe and no patient required withdrawal of terlipressin. CONCLUSIONS: Early treatment with terlipressin and albumin in patients with type-1 HRS associated with sepsis is effective and safe. Patients with associated severe ACLF are unlikely to respond to treatment.

Type-1 hepatorenal syndrome associated with infections in cirrhosis: natural history, outcome of kidney function, and survival.

UNLABELLED: Type-1 hepatorenal syndrome (HRS) is a common complication of bacterial infections in cirrhosis, but its natural history remains undefined. To assess the outcome of kidney function and survival of patients with type-1 HRS associated with infections, 70 patients diagnosed during a 6-year period were evaluated prospectively. Main outcomes were no reversibility of type-1 HRS during treatment of the infection and 3-month survival. Forty-seven (67%) of the 70 patients had no reversibility of type-1 HRS during treatment of the infection. [Correction to previous sentence added March 10, 2014, after first online publication: "Twenty-three (33%)" was changed to "Forty-seven (67%)."] The main predictive factor of no reversibility of type-1 HRS was absence of infection resolution (no reversibility: 96% versus 48% in patients without and with resolution of the infection; P < 0.001). Independent predictive factors of no reversibility of type-1 HRS were age, high baseline serum bilirubin, nosocomial infection, and reduction in serum creatinine <0.3 mg/dL at day 3 of antibiotic treatment. No reversibility was also associated with severity of circulatory dysfunction, as indicated by more marked activity of the vasoconstrictor systems. In the whole series, 3-month probability of survival was only 21%. Factors associated with poor prognosis were baseline serum bilirubin, no reversibility of type-1 HRS, lack of resolution of the infection, and development of septic shock after diagnosis of type-1 HRS. CONCLUSION: Type-1 HRS associated with infections is not reversible in two-thirds of patients with treatment of infection only. No reversibility of type-1 HRS is associated with lack of resolution of the infection, age, high bilirubin, and no early improvement of kidney function and implies a poor prognosis. These results may help advance the management of patients with type-1 HRS associated with infections.