E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation.

Post-translational modifications by ubiquitin-like proteins (UBLs) are essential for nearly all cellular processes. Ubiquitin-related modifier 1 (Urm1) is a unique UBL, which plays a key role in tRNA anticodon thiolation as a sulfur carrier protein (SCP) and is linked to the noncanonical E1 enzyme Uba4 (ubiquitin-like protein activator 4). While Urm1 has also been observed to conjugate to target proteins like other UBLs, the molecular mechanism of its attachment remains unknown. Here, we reconstitute the covalent attachment of thiocarboxylated Urm1 to various cellular target proteins in vitro, revealing that, unlike other known UBLs, this process is E2/E3-independent and requires oxidative stress. Furthermore, we present the crystal structures of the peroxiredoxin Ahp1 before and after the covalent attachment of Urm1. Surprisingly, we show that urmylation is accompanied by the transfer of sulfur to cysteine residues in the target proteins, also known as cysteine persulfidation. Our results illustrate the role of the Uba4-Urm1 system as a key evolutionary link between prokaryotic SCPs and the UBL modifications observed in modern eukaryotes.

Production of activated carbon from agave residues and its synergistic application in a hybrid adsorption-AOPs system for effective removal of sulfamethazine from aqueous solutions.

Tequila production in Mexico generates large quantities of agave bagasse (AB), a waste that could be used more efficiently. AB has a high cellulose, hemicellulose, and lignin content, which allows its use as a precursor for synthesizing carbonaceous materials. In the present work, the synthesis of activated carbon impregnated with Fe2+ (AG-Fe-II) and Fe3+ (AG-Fe-III) was carried out and evaluated in a hybrid adsorption-AOP (advanced oxidation process) methodology for sulfamethazine removal (SMT). The materials were characterized before and after the process to determine their morphological, textural, and physicochemical properties. Subsequently, the effect of the main operational variables (pH, initial SMT concentration, mass, and activator dosage) on the hybrid adsorption-degradation process was studied. The Fenton-like reaction was selected as the AOP for the degradation step, and potassium persulfate (K2S2O8) was used as an activating agent. The main iron crystallographic phases in AG-Fe-II were FeS, with a uniform distribution of iron particles over the material's surface. The main crystallographic phase for AG-Fe-III was Fe3O4. The hybrid process achieved 61% and 78% removal efficiency using AG-Fe-II and AG-Fe-III samples, respectively. The pH and initial SMT concentration were the most critical factors for removing SMT from an aqueous phase. Finally, the material was successfully tested in repeated adsorption-degradation cycles.

Performance of novel Ca-biocomposites produced from banana peel and eggshell for highly efficient removal and recovery of phosphate from domestic wastewater.

Using biowaste-based adsorbents to remove phosphorus (P) from wastewater offers significant benefits concerning eutrophication mitigation and addressing waste management challenges. In this work, Ca-biocomposites were prepared by pyrolysis (700 °C) of a mixture of banana peel (BP) and eggshell (ES). The mass ratio of BP to ES was varied in 2:1, 1:1, and 1:2 ratios. Among the tested mixtures, the BPES-1:2 sample exhibited excellent P removal performance, reaching a maximum P adsorption capacity (Qmax) of 214 ± 5 mg P/g. The adsorption process fitted well with the Avrami order kinetic model (R2 > 0.996) and the Liu isotherms model (R2 > 0.997). The excellent fit of the experimental data to the Avrami model suggests that chemisorption is the dominant interaction mechanism, leading to precipitation through the formation of calcium phosphates. Additionally, the Liu model anticipates that the energetic characteristics of the adsorbent's active sites cannot be identical. This is in agreement with the presence of Ca(OH)2 and CaCO3 in the adsorbent material, where the Ca(OH)2 active sites are preferred by the adsorbate molecules (PO43-) for occupation. Furthermore, thermodynamic analysis revealed that P adsorption is a spontaneous process of exothermic nature (ΔH° < 0). The calculated activation energy for the process (72.81 kJ/mol) suggests the P adsorption mechanism involves strong chemical bonding between the adsorbent and P species. In addition, precipitation of apatite (Ca5(PO4)3OH), a vital component in fertilizer production, was observed during the adsorption process. In tertiary treated wastewater applications, the BPES-1:2 biocomposite demonstrated a P removal efficiency of 90%. The solubility of P in a 2% formic acid solution was 100%, while the water-soluble P content was measured at 5.6%. These findings highlight the product's sustainable and environmentally beneficial nature by demonstrating its potential as a slow-release fertilizer, contributing to the application of the 3R slogan: Reduce, Reuse, Recycle. This value-added product is promising in supplying nutrients to plants over an extended period while minimizing the risk of nutrients leaching into the environment.

Sargassum macroalgae from Quintana Roo as raw material for the preparation of high-performance phosphate adsorbent from aqueous solutions.

Currently, the large volumes of Sargassum biomass (Sgs) arriving on Caribbean coasts are a problem that must be solved quickly. One alternative is to obtain value-added products from Sgs. In this work, Sgs is demonstrated to be a high-performance Ca - bioadsorbent for phosphate removal by a heat pretreatment at 800 °C that produces biochar. According to XRD analysis, calcined Sgs (CSgs) have a composition of 43.68%, 40.51%, and 8.69% of Ca(OH)2, CaCO3, and CaO, making CSgs a promising material for phosphate removal and recovery. Results demonstrated that CSgs have a high capacity to adsorb P over a wide range of concentrations (25-1000 mg P/L). After P removal, at low P concentration, the adsorbent material is rich in apatite (Ca5(PO4)3OH), and at high P concentration, brushite (CaHPO4•2H2O) was the main P compound. The CSg reached a Qmax of 224.58 mg P/g, which is higher than other high-performance adsorbents reported in the literature. The phosphate adsorption mechanism was dominated by chemisorption, followed by precipitation according to the pseudo-second-order kinetic model. The solubility of P (74.5 wt%) in formic acid solution and the water-soluble P (24.8 wt%) for CSgs after P adsorption indicated that the final product presents the potential to be used as fertilizer for acid soils. This biomass's processability and high phosphate adsorption performance for P removal make CSgs a potential material for wastewater treatment, and subsequent use of these residues as fertilizer offers a circular economy solution to this problem.

The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results.

Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these cellular events provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment. Among other issues-such as incomplete mechanistic knowledge and faulty clinical trial design-a key contributor to prior translational failures may be insufficient scientific rigor during preclinical assessment: nonblinded outcome assessment; missing randomization; inappropriate sample sizes; and preclinical assessments in young male animals that ignore relevant biological variables, such as age, sex, and relevant comorbid diseases. Promising results are rarely replicated in multiple laboratories. We sought to address some of these issues with rigorous assessment of candidate treatments across 6 independent research laboratories. The Stroke Preclinical Assessment Network (SPAN) implements state-of-the-art experimental design to test the hypothesis that rigorous preclinical assessment can successfully reduce or eliminate common sources of bias in choosing treatments for evaluation in clinical studies. SPAN is a randomized, placebo-controlled, blinded, multilaboratory trial using a multi-arm multi-stage protocol to select one or more putative stroke treatments with an implied high likelihood of success in human clinical stroke trials. The first stage of SPAN implemented procedural standardization and experimental rigor. All participating research laboratories performed middle cerebral artery occlusion surgery adhering to a common protocol and rapidly enrolled 913 mice in the first of 4 planned stages with excellent protocol adherence, remarkable data completion and low rates of subject loss. SPAN stage 1 successfully implemented treatment masking, randomization, prerandomization inclusion/exclusion criteria, and blinded assessment to exclude bias. Our data suggest that a large, multilaboratory, preclinical assessment effort to reduce known sources of bias is feasible and practical. Subsequent SPAN stages will evaluate candidate treatments for potential success in future stroke clinical trials using aged animals and animals with comorbid conditions.

Imaging the water snow-line during a protostellar outburst.

A snow-line is the region of a protoplanetary disk at which a major volatile, such as water or carbon monoxide, reaches its condensation temperature. Snow-lines play a crucial role in disk evolution by promoting the rapid growth of ice-covered grains. Signatures of the carbon monoxide snow-line (at temperatures of around 20 kelvin) have recently been imaged in the disks surrounding the pre-main-sequence stars TW Hydra and HD163296 (refs 3, 10), at distances of about 30 astronomical units (au) from the star. But the water snow-line of a protoplanetary disk (at temperatures of more than 100 kelvin) has not hitherto been seen, as it generally lies very close to the star (less than 5 au away for solar-type stars). Water-ice is important because it regulates the efficiency of dust and planetesimal coagulation, and the formation of comets, ice giants and the cores of gas giants. Here we report images at 0.03-arcsec resolution (12 au) of the protoplanetary disk around V883 Ori, a protostar of 1.3 solar masses that is undergoing an outburst in luminosity arising from a temporary increase in the accretion rate. We find an intensity break corresponding to an abrupt change in the optical depth at about 42 au, where the elevated disk temperature approaches the condensation point of water, from which we conclude that the outburst has moved the water snow-line. The spectral behaviour across the snow-line confirms recent model predictions: dust fragmentation and the inhibition of grain growth at higher temperatures results in soaring grain number densities and optical depths. As most planetary systems are expected to experience outbursts caused by accretion during their formation, our results imply that highly dynamical water snow-lines must be considered when developing models of disk evolution and planet formation.

Elderly Patients Benefit From Enhanced Recovery Protocols After Colorectal Surgery.

BACKGROUND: Enhanced recovery protocols (ERAS) aim to decrease physiological stress response to surgery and maintain postoperative physiological function. Proponents of ERAS state these protocols decrease lengths of stay (LOS) and complication rates. Our aim was to assess whether elderly patients receive the same benefit as younger patients using ERAS protocols. METHODS: We queried patients from 2015 to 2017 at our institution with Enhanced Recovery in Surgery (ERIN) variables from the targeted colectomy NSQIP database. The patients were divided into sextiles and analyzed for readmission, LOS, return of bowel function, tolerating diet, mobilization, and multimodal pain management comparing the youngest sextile to the oldest sextile. RESULTS: Two hundred sixty-two patients (73% colectomies) were enrolled in ERAS. When compared with the youngest sextile (age 19-43.8), the oldest sextile (age 71.4-92.5) had similar readmission rates at 9.8% versus 9.5% (P-value = 0.87), quicker return of bowel function, average 1.9 d versus 3.7 d (P-value < 0.01), and tolerated diet quicker, average POD 2.4 d versus 5.1 d (P-value < 0.01). There was a slight decrease in the use of multimodal pain management 88% versus 100% (P-value = 0.07), but mobilization on POD1 was slightly better in the elderly at 80% versus 78% (P-value = 0.76). Elderly patients enrolled in ERAS had an average LOS of 4.9 days versus 7.8 in the younger patients (P-value = 0.08). Among elderly non-ERAS patients average LOS was 14.6 days. CONCLUSION: Overall, elderly patients fared better or the same on the ERIN variables analyzed than the younger cohort. ERAS protocols are beneficial and applicable to elderly patients undergoing colorectal surgery.

Recalibration and External Validation of the Risk Analysis Index: A Surgical Frailty Assessment Tool.

OBJECTIVE AND BACKGROUND: The Risk Analysis Index (RAI) predicts 30-, 180-, and 365-day mortality based on variables constitutive of frailty. Initially validated, in a single-center Veteran hospital, we sought to improve model performance by recalibrating the RAI in a large, veteran surgical registry, and to externally validate it in both a national surgical registry and a cohort of surgical patients for whom RAI was measured prospectively before surgery. METHODS: The RAI was recalibrated among development and confirmation samples within the Veterans Affairs Surgical Quality Improvement Program (VASQIP; 2010-2014; N = 480,731) including major, elective noncardiac surgery patients to create the revised RAI (RAI-rev), comparing discrimination and calibration. The model was tested externally in the American College of Surgeons National Surgical Quality Improvement Program dataset (NSQIP; 2005-2014; N = 1,391,785), and in a prospectively collected cohort from the Nebraska Western Iowa Health Care System VA (NWIHCS; N = 6,856). RESULTS: Recalibrating the RAI significantly improved discrimination for 30-day [c = 0.84-0.86], 180-day [c = 0.81-0.84], and 365-day mortality [c = 0.78-0.82] (P < 0.001 for all) in VASQIP. The RAI-rev also had markedly better calibration (median absolute difference between observed and predicted 180-day mortality: decreased from 8.45% to 1.23%). RAI-rev was highly predictive of 30-day mortality (c = 0.87) in external validation with excellent calibration (median absolute difference between observed and predicted 30-day mortality: 0.6%). The discrimination was highly robust in men (c = 0.85) and women (c = 0.89). Discrimination also improved in the prospectively measured cohort from NWIHCS for 180-day mortality [c = 0.77 to 0.80] (P < 0.001). CONCLUSIONS: The RAI-rev has improved discrimination and calibration as a frailty-screening tool in surgical patients. It has robust external validity in men and women across a wide range of surgical settings and available for immediate implementation for risk assessment and counseling in preoperative patients.

Correlation between female sex, IL28B genotype, and the clinical severity of bronchiolitis in pediatric patients.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) that impact on the differential expression of interleukin 28B (IL28B) are implicated in the progression of viral-induced diseases. In this prospective longitudinal cohort study, we evaluated the association between IL28B SNPs rs12979860 and rs8099917 and the clinical outcome of bronchiolitis in pediatric patients. METHODS: A total of 682 infants suffering from bronchiolitis, categorized based on the final clinical outcome as mild or severe, were genotyped for IL28B SNPs rs12979860 and rs8099917. RESULTS: When infants were categorized exclusively based on the final clinical outcome, no association was established between IL28B SNPs and the severity of bronchiolitis. However, when stratified by sex, the homozygotes for the minor alleles of rs12979860 (T) and rs8099917 (G) were associated with a mild disease in girls but not in boys. CONCLUSION: SNPs rs12979860 and rs8099917 correlate with the severity of bronchiolitis and display a sex bias, where GG rs8099917 and TT rs12979860 genotypes are associated with a mild disease in girls but not in boys. These findings suggest that innate immunity and female sex links with the outcome of the diseases induced by respiratory viruses, such as RSV.

Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains.

H3N2 viruses continuously acquire mutations in the hemagglutinin (HA) glycoprotein that abrogate binding of human antibodies. During the 2014-2015 influenza season, clade 3C.2a H3N2 viruses possessing a new predicted glycosylation site in antigenic site B of HA emerged, and these viruses remain prevalent today. The 2016-2017 seasonal influenza vaccine was updated to include a clade 3C.2a H3N2 strain; however, the egg-adapted version of this viral strain lacks the new putative glycosylation site. Here, we biochemically demonstrate that the HA antigenic site B of circulating clade 3C.2a viruses is glycosylated. We show that antibodies elicited in ferrets and humans exposed to the egg-adapted 2016-2017 H3N2 vaccine strain poorly neutralize a glycosylated clade 3C.2a H3N2 virus. Importantly, antibodies elicited in ferrets infected with the current circulating H3N2 viral strain (that possesses the glycosylation site) and humans vaccinated with baculovirus-expressed H3 antigens (that possess the glycosylation site motif) were able to efficiently recognize a glycosylated clade 3C.2a H3N2 virus. We propose that differences in glycosylation between H3N2 egg-adapted vaccines and circulating strains likely contributed to reduced vaccine effectiveness during the 2016-2017 influenza season. Furthermore, our data suggest that influenza virus antigens prepared via systems not reliant on egg adaptations are more likely to elicit protective antibody responses that are not affected by glycosylation of antigenic site B of H3N2 HA.

Lower Limb Tendinopathy Tissue Changes Assessed through Ultrasound: A Narrative Review.

Tendinopathy is a common disease that affects athletes, causing pain and dysfunction to the afflicted tendon. A clinical diagnose is usually combined with imaging and, among all the existing techniques, ultrasound is widely adopted. The aim of this review is to sum up the existing evidence on ultrasound as an imaging tool and guide for treatments in lower limbs tendinopathy. Using three different databases-PubMed, MEDLINE and CENTRAL-a literature search has been performed in May 2020 combining MeSH terms and free terms with Boolean operators. Authors independently selected studies, conducted quality assessment, and extracted results. Ultrasound imaging has a good reliability in the differentiation between healthy and abnormal tendon tissue, while there are difficulties in the identification of tendinopathy stages. The main parameters considered by ultrasound imaging are tendon thickness, hypoechogenicity of tendon structure and neovascularization of the tendon bound tissue. Ultrasound-guide is also used in many tendinopathy treatments and the available studies gave encouraging results, even if further studies are needed in this field.

Enterovirus A71 Infection and Neurologic Disease, Madrid, Spain, 2016.

We conducted an observational study from January 2016 through January 2017 of patients admitted to a reference pediatric hospital in Madrid, Spain, for neurologic symptoms and enterovirus infection. Among the 30 patients, the most common signs and symptoms were fever, lethargy, myoclonic jerks, and ataxia. Real-time PCR detected enterovirus in the cerebrospinal fluid of 8 patients, nasopharyngeal aspirate in 17, and anal swab samples of 5. The enterovirus was genotyped for 25 of 30 patients; enterovirus A71 was the most common serotype (21/25) and the only serotype detected in patients with brainstem encephalitis or encephalomyelitis. Treatment was intravenous immunoglobulins for 21 patients and corticosteroids for 17. Admission to the pediatric intensive care unit was required for 14 patients. All patients survived. At admission, among patients with the most severe disease, leukocytes were elevated. For children with brainstem encephalitis or encephalomyelitis, clinicians should look for enterovirus and not limit testing to cerebrospinal fluid.

Outcomes and Durability of Endovascular Aneurysm Repair in Octogenarians.

BACKGROUND: Endovascular aneurysm repair (EVAR) accounts for the majority of all abdominal aortic aneurysm (AAA) repairs in the United States. EVAR utilization in the aging population is increasing due to the minimally invasive nature of the procedure, the low associated perioperative morbidity, and early survival benefit over open repair. The objective of this study is to compare the outcomes of octogenarians after elective EVAR to their younger counterparts, a question that can be answered by a long-term, institutional data set. METHODS: This was a retrospective series of 255 patients, who underwent elective EVAR within our institution from 2008 to 2015. A comparative analysis of patients aged 80 years and older and less than 80 years was performed. Outcomes measured included perioperative death and myocardial infarction (MI), length of stay, and readmission within 30 days. Aneurysm reintervention, long-term surveillance imaging, and aneurysm-related deaths were also evaluated. In addition, subset analyses of octogenarians were compared for survival at 24 months. RESULTS: Overall, 255 patients were included in our analysis. Fifty-nine patients were octogenarians, and 196 patients were nonoctogenarians. The mean age difference between the two groups was significant (84.5 years [SD, ±3.44] vs. 69.6 years [SD, ±6.13] in the ≥80 and <80 groups, respectively; P < 0.0001). There was no significant difference in the mean aneurysm size (6.03 cm [SD, ±1.12] vs. 5.535 cm [SD, ±0.9]; P < 0.06) between the ≥80 and < 80 groups. Octogenarians had higher rates of perioperative MI (5% vs. 1%, P < 0.04), thirty-day mortality (7% vs. 0%, P < 0.003), a higher number of perioperative complications (0.64 incidence per patient [SD, ±1.11] vs. 0.31 [SD, ±0.69], P < 0.005), and a longer mean hospital stay (5.34 [SD, ±5.75] days vs. 3.16 [SD, ±3.23] days, P < 0.0003), and they were also less likely to be discharged home after surgery (75% vs. 91%, P < 0.002). In the evaluated long-term outcomes, the two groups were similar with regard to aneurysm reintervention (10% vs. 9%, P < 0.06) and the stability of aneurysm sac size on imaging at last follow-up (71% vs. 80%, P < 0.27). The overall aortic related cause of death was different between the groups (8% vs. 1%, P < 0.003); however, the long-term aortic related mortality was not different between the two groups (2% vs. 1%, P < 0.4). Finally, a subset analysis of the octogenarian group was performed comparing patients based on survival status at 24 months. Higher preoperative creatinine (1.73 mg/dL [SD, ±1.54] vs. 1.15 mg/dL [SD, ±0.46]) and lower preoperative hematocrit (33.9% [SD, ±3.43] vs. 37.2% [SD, ±4.9]) along with number of perioperative complications (1.2 incidence per patient [SD, ±1.74] vs. 0.45 [SD, ±0.73]) were associated with death at 24 months after the index operation. CONCLUSIONS: Elective endovascular repair of AAA in octogenarians carries a higher risk of perioperative mortality but acceptable long-term outcomes. Appropriateness of elective EVAR in octogenarians should be answered based on this potential short-lived survival benefit, taking into account that advanced age should not be the sole basis of exclusion for otherwise suitable candidates for elective EVAR.

Premature T Cell Senescence in Pediatric CKD.

An individual's immune function, susceptibility to infection, and response to immunosuppressive therapy are influenced in part by his/her T cell maturation state. Although childhood is the most dynamic period of immune maturation, scant information regarding the variability of T cell maturation in children with renal disease is available. In this study, we compared the T cell phenotype in children with renal failure (n=80) with that in healthy children (n=20) using multiparameter flow cytometry to detect markers of T cell maturation, exhaustion, and senescence known to influence immune function. We correlated data with the degree of renal failure (dialysis or nondialysis), prior immunosuppression use, and markers of inflammation (C-reactive protein and inflammatory cytokines) to assess the influence of these factors on T cell phenotype. Children with renal disease had highly variable and often markedly skewed maturation phenotypes, including CD4/CD8 ratio reversal, increased terminal effector differentiation in CD8+ T cells, reduction in the proportion of naïve T cells, evidence of T cell exhaustion and senescence, and variable loss of T cell CD28 expression. These findings were most significant in patients who had experienced major immune insults, particularly prior immunosuppressive drug exposure. In conclusion, children with renal disease have exceptional heterogeneity in the T cell repertoire. Cognizance of this heterogeneity might inform risk stratification with regard to the balance between infectious risk and response to immunosuppressive therapy, such as that required for autoimmune disease and transplantation.

Utility of Prostate Cancer Screening in Kidney Transplant Candidates.

Screening recommendations for prostate cancer remain controversial, and no specific guidelines exist for screening in renal transplant candidates. To examine whether the use of prostate-specific antigen (PSA)-based screening in patients with ESRD affects time to transplantation and transplant outcomes, we retrospectively analyzed 3782 male patients ≥18 years of age undergoing primary renal transplant evaluation during a 10-year period. Patients were grouped by age per American Urological Association screening guidelines: group 1, patients <55 years; group 2, patients 55-69 years; and group 3, patients >69 years. A positive screening test result was defined as a PSA level >4 ng/ml. We used univariate analysis and Cox proportional hazards models to identify the independent effect of screening on transplant waiting times, patient survival, and graft survival. Screening was performed in 63.6% of candidates, and 1198 candidates (31.7%) received kidney transplants. PSA screening was not associated with improved patient survival after transplantation (P=0.24). However, it did increase the time to listing and transplantation for candidates in groups 1 and 2 who had a positive screening result (P<0.05). Furthermore, compared with candidates who were not screened, PSA-screened candidates had a reduced likelihood of receiving a transplant regardless of the screening outcome (P<0.001). These data strongly suggest that PSA screening for prostate cancer may be more harmful than protective in renal transplant candidates because it does not appear to confer a survival benefit to these candidates and may delay listing and decrease transplantation rates.

EphB3 signaling propagates synaptic dysfunction in the traumatic injured brain.

Traumatic brain injury (TBI), ranging from mild concussion to severe penetrating wounds, can involve brain regions that contain damaged or lost synapses in the absence of neuronal death. These affected regions significantly contribute to sensory, motor and/or cognitive deficits. Thus, studying the mechanisms responsible for synaptic instability and dysfunction is important for protecting the nervous system from the consequences of progressive TBI. Our controlled cortical impact (CCI) injury produces ~20% loss of synapses and mild changes in synaptic protein levels in the CA3-CA1 hippocampus without neuronal losses. These synaptic changes are associated with functional deficits, indicated by >50% loss in synaptic plasticity and impaired learning behavior. We show that the receptor tyrosine kinase EphB3 participates in CCI injury-induced synaptic damage, where EphB3(-/-) mice show preserved long-term potentiation and hippocampal-dependent learning behavior as compared with wild type (WT) injured mice. Improved synaptic function in the absence of EphB3 results from attenuation in CCI injury-induced synaptic losses and reduced d-serine levels compared with WT injured mice. Together, these findings suggest that EphB3 signaling plays a deleterious role in synaptic stability and plasticity after TBI.

Excising Additional Margins at Initial Breast-Conserving Surgery (BCS) Reduces the Need for Re-excision in a Predominantly African American Population: A Report of a Randomized Prospective Study in a Public Hospital.

BACKGROUND: Margin status is an important prognostic factor for local recurrence after breast conserving surgery (BCS) for breast cancer. We designed a prospective randomized trial to evaluate the effect of shave margins on positive margins and locoregional recurrence (LRR). METHODS: Patients were randomized to BCS or BCS with resection of 5 additional margins (BCS + M). Tumor margins were classified as negative [>2 mm for ductal carcinoma in situ (DCIS); >1 mm for invasive carcinoma] based on guidelines at the time of accrual. RESULTS: A total of 75 patients with stage 0-III breast cancer (76 samples) were randomized, mean age 59.6 years with median follow-up 39.5 months. Overall, 21 patients (27.6 %) had positive margins: 14 had undergone BCS and 7 BCS + M (p = 0.005). Of the 21 patients with positive margins, 19 had DCIS on final pathology (OR 7.56; 95 % CI 1.52-37.51).All patients with positive margins were offered re-excision; 11 had negative final margins after re-excision surgery. Overall, 6 patients (8.3 %) developed LRR with recurrence being more common in the BCS group when compared with the BCS + M group (17.2 vs 2.3 %; p = 0.025). CONCLUSIONS: Taking additional cavity shave margins at the time of initial excision resulted in a reduction in positive margin rate, a decrease in return to operating room for re-excision, and lower LRR.

Prevalence of hospital malnutrition in cancer patients: a sub-analysis of the PREDyCES® study.

PURPOSE: In oncology patients, hospital malnutrition is associated with a greater risk of morbidity and mortality. The objective of this study was to determine the prevalence of nutritional risk and the clinical and economic consequences of hospital malnutrition in oncology patients hospitalised in Spanish centres. METHODS: This was an observational, cross-sectional, multicentre study. The prevalence of nutritional risk was determined using the Nutrition Risk Screening(®)-2002 (NRS(®)-2002). RESULTS: Four hundred one oncology patients were included; 33.9% (136/401) were at nutritional risk (NRS(®)-2002 ≥ 3) at admission and 36.4% (135/371) at discharge. On average, patients at nutritional risk were more elderly and had lower weights, body mass indices and arm and calf circumferences, as well as lower serum albumin levels than patients not at risk. Mean duration of hospitalisation and healthcare costs were greater in patients at nutritional risk at discharge (12.1 days; 95% confidence interval (CI) 10.83-13.39) than in well-nourished patients (8.6 days; 95% CI 7.86-9.40). Only a third of the patients at risk of malnutrition at discharge had received any kind of nutritional support. CONCLUSIONS: This study shows that hospital malnutrition is a prevalent and undertreated condition in oncology patients that is associated with longer hospital stays and increased healthcare costs.

The Association Between Hospital Finances and Complications After Complex Abdominal Surgery: Deficiencies in the Current Health Care Reimbursement System and Implications for the Future.

OBJECTIVE: To determine the relationship between complications after 3 common general surgery procedures and per-episode hospital finances. BACKGROUND: With impending changes in health care reimbursement, maximizing the value of care delivered is paramount. Data on the relative clinical and financial impact of postoperative complications are necessary for directing surgical quality improvement efforts. METHODS: We reviewed the medical records of patients enrolled in the American College of Surgeons' National Surgical Quality Improvement Program who underwent pancreaticoduodenectomy, hepatectomy, and colectomy at a single academic institution between September 2009 and August 2012. Clinical outcomes data were subsequently linked with hospital billing data to determine hospital finances associated with each episode. We describe the association between postoperative complications, hospital length of stay, and different financial metrics. Multivariable linear regression modeling tested linear association between postoperative outcomes and cost data. RESULTS: There was a positive association between the number of surgical complications, payments, length of stay, total charges, total costs, and contribution margin for the three procedures. Multivariable models indicated that complications were independently associated with total cost among the selected procedures. Payments increased with complications, offsetting increased costs. CONCLUSIONS: In the current fee-for-service environment, the financial incentives are misaligned with quality improvement efforts. As we move to a value-driven method of reimbursement, administrators and health care providers alike will need to focus on improving the quality of patient care while remaining conscious of the cost of care delivered. Reducing complications effectively improves value.

Renal safety of intravenous gadolinium-enhanced magnetic resonance imaging in patients awaiting liver transplantation.

Renal dysfunction in cirrhosis carries a high morbidity and mortality. Given the potential risk of contrast-induced nephropathy associated with iodinated intravenous contrast used in computed tomography (CT), alternate contrast modalities for abdominal imaging in liver transplant candidates need to be examined. The purpose of this study was to examine the renal safety of magnetic resonance imaging (MRI) with gadolinium in patients awaiting liver transplantation. The study involved a retrospective analysis of 352 patients of abdominal MRI with low-dose gadobenate dimeglumine (MultiHance) (0.05 mmol/kg) in patients with cirrhosis and without renal replacement therapy at a single center during the period from 2007 to 2013. For each case, serum creatinine before and within a few days after the MRI were compared. In addition, the patients were analyzed for the development of nephrogenic systemic fibrosis (NSF), a reported complication of gadolinium in chronic kidney disease. The pre-MRI serum creatinine values ranged from 0.36 to 4.86 mg/dL, with 70 patients (20%) having values ≥ 1.5 mg/dL. A comparison of the pre- and post-MRI serum creatinine values did not demonstrate a clinically significant difference (mean change = 0.017 mg/dL; P = 0.38), including those patients with a pre-MRI serum creatinine ≥ 1.5 mg/dL. In addition, no cases of NSF were noted. In conclusion, our findings suggest that MRI with low-dose gadobenate dimeglumine (MultiHance) is a nonnephrotoxic imaging modality in liver transplant candidates, and its use can be cautiously expanded to liver transplant candidates with concomitant renal insufficiency.