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Background and Aims: Thirty percent of inflammatory bowel disease (IBD) patients hospitalized with flare require salvage therapy or surgery. Additionally, 40% experience length of stay (LOS) > 7 days. No emergency department (ED)-based indices exist to predict these adverse outcomes at admission for IBD flare. We examined whether clinical, laboratory, and endoscopic markers at presentation predicted prolonged LOS, inpatient colectomy, or salvage therapy in IBD patients admitted with flare., Methods: Patients with ulcerative colitis (UC) or colonic involvement of Crohn's disease (CD) hospitalized with flare and tested for Clostridioides difficile infection (CDI) between 2010 and 2020 at two urban academic centers were studied. The primary outcome was complex hospitalization, defined as: LOS > 7 days, inpatient colectomy, or inpatient infliximab or cyclosporine. A nested k-fold cross-validation identified predictive factors of complex hospitalization., Results: Of 164 IBD admissions, 34% (56) were complex. Predictive factors included: tachycardia in ED triage (odds ratio [OR] 3.35; confidence interval [CI] 1.79-4.91), hypotension in ED triage (3.45; 1.79-5.11), hypoalbuminemia at presentation (2.54; 1.15-3.93), CDI (2.62; 1.02-4.22), and endoscopic colitis (4.75; 1.75-5.15). An ED presentation score utilizing tachycardia and hypoalbuminemia predicted complex hospitalization (area under curve 0.744; CI 0.671-0.816). Forty-four of 48 (91.7%) patients with a presentation score of 0 (heart rate < 99 and albumin ≥ 3.4 g/dL) had noncomplex hospitalization., Conclusions: Over 90% of IBD patients hospitalized with flare with an ED presentation score of 0 did not require salvage therapy, inpatient colectomy, or experience prolonged LOS. A simple ED-based score may provide prognosis at a juncture of uncertainty in patient care., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Poor nutritional status is common among patients undergoing lower extremity amputation (LEA). In this study, the association between preoperative hypoalbuminemia, a marker for malnutrition, and postoperative mortality in patients undergoing LEA was explored., Methods: Data on patients undergoing LEA between 2005 and 2017 were retrospectively analyzed from the prospectively collected American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into clinically relevant categories based on their serum albumin level (<2.5, 2.5-3.39, ≥3.4 g/dl) and were further stratified according to amputation level. Operative death was compared across groups and multivariable logistic regression was performed to estimate risk-adjusted odds ratio (AOR)., Results: In 35,383 patients, the rate of 30-day postoperative mortality was 7.6% (n = 2693). Mortality rate was highest in patients with very low albumin levels (11%) as compared to low (6.8%) and normal levels (3.9%). On multivariable analysis, lower albumin levels emerged as a risk-adjusted independent predictor of mortality. After risk-adjustment, patients with very low albumin levels (AOR [95% CI]: 2.25 [1.969-2.56], P < 0.001) and low albumin levels (AOR [95% CI]: 1.42 [1.239-1.616], P < 0.001) had higher odds of mortality when compared to patients with normal albumin levels. On sensitivity analysis, a similar trend was seen in patients undergoing above knee amputation but not in patients undergoing minor amputations., Conclusions: In patients undergoing major LEA, hypoalbuminemia is associated with an increased risk of postoperative mortality in a dose response manner, specifically in above knee amputations. Monitoring and optimizing patients' nutritional status before surgery, when possible, may be warranted and should be further explored., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Hypoalbuminemia is associated with vascular endothelial dysfunction and the development of chronic cardiovascular diseases. However, the relationship between serum albumin concentration and blood pressure changes remains controversial. Community-based longitudinal cohort data collected from Korean Genome and Epidemiology Study were used in this study. Hypoalbuminemia was defined as a serum albumin concentration of ≤ 4.0 g/dL. A total of 4325 participants were categorized into control (n = 3157) and hypoalbuminemia (n = 1168) groups. Serum albumin had a non-linear relationship with the risk of hypertension development. A genome-wide association study revealed 71 susceptibility loci associated with hypoalbuminemia. Among susceptibility loci, genetic variations at rs2894536 in LOC107986598 and rs10972486 in ATP8B5P were related to elevated blood pressure. Serum albumin (HR = 0.654, 95% CI 0.521-0.820) and polymorphisms of rs2894536 (HR = 1.176, 95% CI 1.015-1.361) and rs10972486 (HR = 1.152, 95% CI 1.009-1.316) were significant predictors of hypertension development. Increased albumin concentration instrumented by 2 hypoalbuminemia-associated SNPs (rs2894536 and rs10972486) was associated with decreased HRs for hypertension development (HR = 0.762, 95% CI 0.659-0.882 and HR = 0.759, 95% CI 0.656-0.878). Our study demonstrated that genetically determined hypoalbuminemia is a significant predictor of incipient hypertension.

Idiopathic systemic capillary leak syndrome (ISCLS) is a potentially fatal disorder characterised by 'attacks' of varying intensity of hypovolemic shock in association with haemoconcentration and hypoalbuminaemia. It is a disease of exclusion, and the severity of attacks may mimic sepsis at presentation. We report a case of a lady with recurrent attacks of ISCLS with at least two life-threatening episodes, having been treated elsewhere as a case of steroid insufficiency. The diagnosis is often challenging, and treatment of an acute episode involves the judicious use of fluids and vasopressors, as required. Prophylaxis to prevent further attacks is of varied success.

Background: Early-onset chronic diarrhoea often indicates a congenital disorder. Mutation in diacylglycerol o-acyltransferase 1 (DGAT1) has recently been linked to early-onset chronic diarrhoea. To date, only a few cases of DGAT1 deficiency have been reported. Diarrhoea in those cases was severe and developed in the neonatal period or within 2 months after birth., Case Presentation: Here, we report a female patient with DGAT1 mutations with delayed-onset chronic diarrhoea. The patient had vomiting, hypoalbuminemia, hypertriglyceridemia, and failure to thrive at early infancy. Her intractable chronic diarrhoea occurred until she was 8 months of age. A compound heterozygous DGAT1 mutation was found in the patient, which was first found in the Chinese population. Her symptoms and nutrition status improved after nutritional therapy, including a fat restriction diet., Conclusions: This case expanded our knowledge of the clinical features of patients with DGAT1 mutations. Intractable diarrhoea with delayed onset could also be a congenital disorder.

Background: Hemolytic uremic syndrome (HUS), a common subtype of thrombotic microangiopathy (TMA), is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Shiga toxin-producing Escherichia coli infection is the most common cause of post-diarrheal HUS. Kidney and central nervous system are the primary target organs., Case Presentation: A 64-year-old male presented with HUS following bloody diarrhea. Nephrotic-range proteinuria and hypoalbuminemia were present at the acute stage and renal histology revealed common TMA features. Neurological involvement presented as confusion and impaired cognitive function. Cranial magnetic resonance imaging demonstrated bilateral T2 hyperintensities in the brainstem and insula. The patient received plasma exchange and supportive care. Both the renal and neurological impairments were completely recovered 3 months after the onset., Conclusion: We report an adult patient presenting with nephrotic-range proteinuria and central nervous system involvement at the acute phase of post-diarrheal HUS. The reversibility of the organ damages might predict a favorable outcome.

Background: The possible impact of nutritional status on healing and course of disease in patients with chronic wounds is widely suggested, however, most data are based on small groups of patients with no control group and minor afflictions. Clear diagnostic strategies are missing., Objectives: To analyse in detail the nutritional status of chronic wound patients relative to healthy controls based on a large patient population., Material and Methods: We screened a group of 50 patients for their nutritional status based on body mass index (BMI), the Mini-Nutritional Assessment (MNA), and Nutritional Risk Screening (NRS), as well as additional laboratory investigations. Twenty-five patients suffered from chronic venous leg ulcers and were compared with a matching control group of 25 patients with acute surgical wounds., Results: Patients with chronic venous leg ulcers showed significantly higher BMI, hyperhomocysteinaemia, and higher levels of serum copper but significantly lower levels of vitamin B6, B9 and C, as well as a significantly lower level of zinc. Vitamin D deficiency was present in both groups, however, severe vitamin D deficiency was present only in the leg ulcer group. Mobility was significantly reduced in patients with leg ulcers., Conclusion: Ulcer patients are often obese but suffer from qualitative malnutrition, including a lack of vitamin D, which might be explained by reduced mobility and being housebound. Hypoalbuminaemia, as a sign of protein deficiency, was observed significantly more often in patients with chronic leg ulcers, irrespective of wound area or wound duration.

Carfilzomib-lenalidomide-dexamethasone (KRd) therapy has yielded promising results in patients with newly diagnosed multiple myeloma (NDMM). Cereblon (CRBN) is the direct molecular target of lenalidomide and genetic polymorphisms in CRBN have been associated with lenalidomide efficacy. In this study, we assessed the correlation of five single nucleotide variants (SNVs) in the CRBN gene with clinical response and outcomes in patients with NDMM administered KRd therapy with lenalidomide maintenance, achieving favorable trial endpoints in a prospective Phase II study (NCT01402284). Of the observed SNVs, no associations with KRd therapy response were found in this patient cohort, although strong trends in hypoalbuminemia grade and hyperbilirubinemia grade emerged across the CRBN rs1672753 genotype (P = 0.0008) and the rs1714327 genotype (P = 0.0010), respectively. Our results do not provide conclusive support for the predictive utility of CRBN gene polymorphisms as potential biomarkers of clinical response to lenalidomide-based therapy in our patient population. However, these findings remain to be validated in prospective studies using larger patient populations.

Background & Aims: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections., Methods: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study)., Results: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines., Conclusions: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Rotavirus is a common cause of acute gastroenteritis in children. Manifestations of rotavirus gastroenteritis beyond gastrointestinal tract are rare. Rotavirus has been reported to be associated with encephalopathy, myositis and elevated liver enzymes; but simultaneous presentation of all these conditions in the same child is extremely rare. The authors report a case of 17-mo-old girl who presented with acute rotavirus gastroenteritis with G3 + G9P[8] strain associated with hypernatremia, encephalopathy, myositis, transaminitis and hypoalbuminemia. Child had complete recovery with no neurological sequalae on follow-up, and liver enzymes and albumin returned to normal. The authors suggest that rotavirus infection should be considered in the differential diagnosis of a child with encephalopathy or myositis, particularly if associated with acute diarrhea.

Either hypoglycemia or hypoalbuminemia alone is an independent condition associated with increased risk of mortality in critical illness. This study evaluates whether the mortality risk increases in septic patients if these conditions are combined. Patients admitted to our hospital from 2008 to 2015 who satisfied the definition of sepsis were targeted (n = 336). We classified cases into three groups based on blood glucose (BG) level measured at admission: hypoglycemia (Hypo-G; BG < 80 mg/dl), intermediate glycemia (Inter-G; 80-199 mg/dl), and hyperglycemia (Hyper-G; ≥ 200 mg/dl) group, and then estimated mortality. We also compared the clinical data of these glycemic groups in combination with hypoalbuminemia (Hypo-A) or Inter-G with non-hypoalbuminemia (Inter-G + Nonhypo-A), as a secondary analysis. Diagnostic cut-off level of Hypo-A (< 2.8 mg/dl) was determined using the ROC curve between blood albumin and mortality. In Hypo-G group (n = 40), APACHE II/SOFA scores are significantly higher than in the Inter-G (n = 196) and Hyper-G groups (n = 100). Mortality is 52.5% in the Hypo-G and 60.0% in the Hypo-G with Hypo-A (Hypo-G + Hypo-A) groups. Significantly higher APACHE II or SOFA scores and mortality are observed in the Hypo-G + Hypo-A group compared to the Inter-G + Nonhypo-A group. A higher mortality risk is observed in cases with Hypo-G + Hypo-A (OR 5.065) than those with Hypo-G (OR 3.503), Inter-G (OR 1.175), Hyper-G (OR 1.756) or Hypo-A (OR 3.243), calculated by a single logistic-regression analysis. Hypo-G + Hypo-A in patients with sepsis is related to higher ICU mortality. Physicians should be keenly aware of these conditions to provide immediate intensive treatment after admission of septic patients.

Hypoalbuminemia is associated with inflammation. Despite being addressed repeatedly in the literature, there is still confusion regarding its pathogenesis and clinical significance. Inflammation increases capillary permeability and escape of serum albumin, leading to expansion of interstitial space and increasing the distribution volume of albumin. The half-life of albumin has been shown to shorten, decreasing total albumin mass. These 2 factors lead to hypoalbuminemia despite increased fractional synthesis rates in plasma. Hypoalbuminemia, therefore, results from and reflects the inflammatory state, which interferes with adequate responses to events like surgery or chemotherapy, and is associated with poor quality of life and reduced longevity. Increasing or decreasing serum albumin levels are adequate indicators, respectively, of improvement or deterioration of the clinical state. In the interstitium, albumin acts as the main extracellular scavenger, antioxidative agent, and as supplier of amino acids for cell and matrix synthesis. Albumin infusion has not been shown to diminish fluid requirements, infection rates, and mortality in the intensive care unit, which may imply that there is no body deficit or that the quality of albumin "from the shelf" is unsuitable to play scavenging and antioxidative roles. Management of hypoalbuminaemia should be based on correcting the causes of ongoing inflammation rather than infusion of albumin. After the age of 30 years, muscle mass and function slowly decrease, but this loss is accelerated by comorbidity and associated with decreasing serum albumin levels. Nutrition support cannot fully prevent, but slows down, this chain of events, especially when combined with physical exercise., (© 2018 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals, Inc. on behalf of American Society for Parenteral and Enteral Nutrition.)

Introduction: Acute kidney injury (AKI) is a common and serious complication after hip fracture surgery in older adults. Hypoalbuminemia is a known independent risk factor for AKI. However, few studies have investigated the relationship between early postoperative hypoalbuminemia and AKI after hip fracture surgery. Therefore, we sought to determine the incidence of and risk factors for AKI and the effects of early postoperative hypoalbuminemia on AKI incidence after surgery for hip fractures, especially intertrochanteric fractures of the proximal femur., Patients and Methods: In this retrospective cohort study from a single center, we reviewed the medical records of 481 consecutive patients (>60 years) who underwent surgery for intertrochanteric fracture of the proximal femur. Multiple logistic regression was performed to identify independent risk factors for AKI. After determining the cut-off value of the minimal level of postoperative serum albumin during the first two postoperative days, we divided the patients into two groups: group 1 included 251 patients whose minimal early postoperative serum albumin level was <2.9 g/dL during the first two postoperative days; and group 2 included 230 patients whose minimal early postoperative serum albumin level was ≥2.9 g/dL. The incidence of AKI was analyzed using inverse probability of treatment weighting (IPTW), propensity score matching (PSM), and propensity score matching weighting (PSMW) analyses., Results: The incidence of AKI, defined based on the Kidney Disease Improving Global Outcomes criteria, was 11.8% (n = 57). Chronic kidney disease and the minimal early postoperative serum albumin level <2.9 g/dL at any point during the first two postoperative days were independent risk factors for AKI. The IPTW, PSM, and PSMW analyses comparing the incidence of AKI between the two groups revealed that the minimal early postoperative serum albumin level <2.9 g/dL was significantly associated with AKI development (P < 0.001, P = 0.025, and P = 0.011, respectively)., Conclusion: The incidence of postoperative AKI was 11.8%. Our findings demonstrate that early postoperative hypoalbuminemia is an independent risk factor for AKI in patients undergoing surgery for intertrochanteric fracture of the proximal femur., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives Fatty acids (FAs) have various roles in pro-inflammatory and anti-inflammatory functions. Hypoalbuminemia is often observed in sepsis patients. An imbalance among these compounds formed from FAs caused by hypoalbuminemia may be related to increased mortality in sepsis patients. The purpose of this study was to investigate the correlations between serum albumin and FAs in sepsis and the outcome. Methods This study was an observational investigation. The clinical and laboratory data of sepsis patients were recorded and the Sequential Organ Failure Assessment (SOFA) score was calculated at admission. The serum arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and dihomo-gamma-linolenic acid (DHLA) levels were also measured as FAs. The body mass index (BMI) was used to determine the general nutrition status. Results Two hundred sepsis patients were enrolled during the study period. No significant correlations were observed between the BMI and the SOFA score or the serum albumin level at admission. The FA levels of the non-survivors were significantly lower, but there were no significant differences in the EPA/AA levels of the survivors and non-survivors. A low serum albumin level was closely related to low AA (p<0.0001), EPA (p<0.0001), DHA (p=0.0003), and DHLA levels (p<0.0001). A multiple logistic-regression analysis revealed that a high SOFA score [adjusted odds ratio, 1.19; 95% confidence interval (CI), 1.02-1.39, p=0.026] and low AA (adjusted odds ratio, 0.98; 95% CI, 0.978-0.994, p=0.041) were associated with a poor outcome. Conclusion A lower AA level was an important determinant of the outcome of patients with sepsis. These findings are consistent with the findings of previous studies, which reported that hypoalbuminemia might alter the AA metabolism in sepsis patients.

Background: Serum albumin is a strong prognostic indicator for many disease processes, yet limited data exist regarding its prognostic relationship in pulmonary arterial hypertension (PAH). Our study aims to assess the relationship of hypoalbuminemia with disease severity and mortality in this population., Hypothesis: Serum albumin concentrations are a predictor of outcomes in PAH., Methods: A retrospective review of all patients with World Health Organization group 1 PAH evaluated between March 2001 and August 2008 was performed. Patients were stratified into groups based on serum albumin concentration ≤3.3 g/dL (hypoalbuminemia) vs >3.3 g/dL. Clinical, hemodynamic, and survival comparisons were compared between groups using Student t test and χ 2 test, followed by univariate analysis and multivariate logistic regression., Results: A total of 163/273 (59.7%) patients had a documented serum albumin concentration. Hypoalbuminemia was present in 41 (25.2%) patients and serum albumin ≤3.3 g/dL represented the lowest quartile of serum albumin. Patients with hypoalbuminemia had higher rates of renal dysfunction (26.8% vs 9.8%, P =0.0069) and hepatic dysfunction (29.3% vs 6.6%, P <0.001), and lower hemoglobin levels (11.6 vs 13.4 g/dL, P < 0.001). Hemodynamic and functional capacity assessments were comparable between groups. Independent predictors of mortality included low albumin levels (hazard ratio [HR]: 0.485, P = 0.008), high right atrial systolic area (HR: 1.062, P = 0.003), low Fick-derived cardiac index (HR: 1.465, P = 0.016), and high New York Heart Association functional class (HR: 1.767, P = 0.042). Patients with hypoalbuminemia demonstrated a significantly lower survival rate at latest follow-up (P = 0.01)., Conclusions: Lower serum albumin concentrations in patients with PAH are associated with higher mortality and can serve as a marker of disease severity in this patient population., (© 2018 Wiley Periodicals, Inc.)

Purpose: Episodic nocturnal hypercapnia (eNH) caused by rapid eye movement (REM) sleep-related hypoventilation is often noted in patients with advanced COPD. The purpose of this study was to clarify the clinical significance of eNH and the effectiveness of eNH-targeted noninvasive positive pressure ventilation (NPPV)., Patients and Methods: We enrolled patients with stable, severe, or very severe COPD with daytime arterial partial oxygen pressure PaO 2 ≥55 mmHg and daytime arterial partial carbon dioxide pressure PaCO 2 <55 mmHg, who underwent overnight transcutaneous carbon dioxide pressure (PtcCO 2 ) monitoring from April 2013 to April 2016. We retrospectively compared clinical characteristics, daytime blood gas analysis, frequency of exacerbation, serum albumin levels, and ratio of pulmonary artery to aorta diameter (PA:A ratio), between patients with COPD with and without eNH. For those with eNH, we applied NPPV and compared these clinical characteristics before and after NPPV., Results: Twenty-one patients were finally included in this study. Ten patients (47.6%) were evaluated to have eNH. These patients had lower albumin levels ( p =0.027), larger PA:A ratio ( p =0.019), and higher frequency of exacerbations during the last year ( p =0.036). NPPV for the patients with eNH improved daytime PaCO 2 compared with that 12 months after NPPV ( p =0.011). The frequency of exacerbations 1 year before NPPV decreased 1 year after NPPV ( p =0.030). Serum albumin levels improved 1 year after NPPV ( p =0.001)., Conclusion: In patients with stable severe or very severe COPD, eNH may be a risk factor of exacerbations, hypoalbuminemia, and pulmonary hypertension. NPPV may be effective against hypoalbuminemia and acute exacerbations. However, further study is necessary to validate these findings., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background and Aims: Low serum albumin level is reportedly associated with worse clinical outcomes in patients with chronic kidney disease (CKD). However, associations between decreased serum albumin level and outcomes in non-CKD patients with coronary artery disease (CAD) remain unclear. Therefore, we aimed to evaluate the prognostic value of serum albumin concentrations in stable CAD patients with preserved renal function., Methods and Results: We studied 1316 patients with CAD and preserved renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m 2 ) who underwent their first PCI between 2000 and 2011 and had data available for pre-procedural serum albumin. Patients were assigned to quartiles based on pre-procedural albumin concentrations. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated. Mean albumin concentration was 4.1 ± 0.4 g/dL. During the median follow-up of 7.5 years, 181 events occurred (13.8%). Kaplan-Meier curves revealed that patients with decreased serum albumin concentrations showed a higher event rate for MACE (log-rank, p < 0.0001). Using the highest tertiles (>4.3 g/dL) as reference, adjusted hazard ratios were 1.97 (95% CI, 1.12-3.55), 1.77 (95% CI, 0.99-3.25), and 1.19 (95% CI, 0.68-2.15) for serum albumin concentrations of <3.9, 3.9-4.0, and 4.1-4.3 g/dL, respectively. Decreased serum albumin concentration was associated with MACE even after adjusting for other independent variables (HR, 2.21 per 1-g/dL decrease; 95% CI, 1.37-3.56, p = 0.001)., Conclusion: Decreased serum albumin concentration independently predicted worse long-term prognosis in non-CKD patients after PCI. Pre-procedural serum albumin concentration could offer a useful predictor for patients with CAD and preserved renal function., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The Stewart model for analyzing acid-base disturbances emphasizes serum albumin levels, which are ignored in the traditional Boston model. We compared data derived using the Stewart model to those using the Boston model in patients with nephrotic syndrome., Methods: Twenty-nine patients with nephrotic syndrome and six patients without urinary protein or acid-base disturbances provided blood and urine samples for analysis that included routine biochemical and arterial blood gas tests, plasma renin activity, and aldosterone. The total concentration of non-volatile weak acids (A TOT ), apparent strong ion difference (SIDa), effective strong ion difference (SIDe), and strong ion gap (SIG) were calculated according to the formulas of Agrafiotis in the Stewart model., Results: According to the Boston model, 25 of 29 patients (90%) had alkalemia. Eighteen patients had respiratory alkalosis, 11 had metabolic alkalosis, and 4 had both conditions. Only three patients had hyperreninemic hyperaldosteronism. The Stewart model demonstrated respiratory alkalosis based on decreased PaCO 2 , metabolic alkalosis based on decreased A TOT , and metabolic acidosis based on decreased SIDa. We could diagnose metabolic alkalosis or acidosis with a normal anion gap after comparing delta A TOT [(14.09 - measured A TOT ) or (11.77 - 2.64 × Alb (g/dL))] and delta SIDa [(42.7 - measured SIDa) or (42.7 - (Na + K - Cl)]). We could also identify metabolic acidosis with an increased anion gap using SIG > 7.0 (SIG = 0.9463 × corrected anion gap-8.1956)., Conclusions: Patients with nephrotic syndrome had primary respiratory alkalosis, decreased A TOT due to hypoalbuminemia (power to metabolic alkalosis), and decreased levels of SIDa (power to metabolic acidosis). We could detect metabolic acidosis with an increased anion gap by calculating SIG. The Stewart model in combination with the Boston model facilitates the analysis of complex acid-base disturbances in nephrotic syndrome.

Background: The effects of preoperative malnutrition and preoperative correction of hypoalbuminemia (PCH) on the short- and long-term outcomes in patients with gastric cancer are unclear., Objective: This study aimed to examine the effect of preoperative nutritional status on short- and long-term outcomes in patients who underwent radical gastrectomy, and also explored the role of PCH in malnourished patients with gastric cancer., Methods: We prospectively reviewed data from patients with gastric cancer who were treated in our department between January 2009 and December 2014. The effect of preoperative nutritional status on short- and long-term outcomes in patients who underwent radical gastrectomy was investigated, and we explored whether PCH could improve the short- and long-term outcomes of these patients., Results: A total of 1976 patients were analyzed, including 412 patients in the malnourished group and 1564 in the well-nourished group. The overall incidence of complications in the malnourished group was significantly higher than the well-nourished group (21.4 vs. 15.5%, p = 0.005). Except for incision infection (3.2 vs. 1.6%, p = 0.041), there were no significant differences for other complications. In the malnourished group, 98 cases of preoperative hypoproteinemia were corrected (PCH group), whereas 314 cases were not (NPCH group). The incidence of incision infection in the PCH group was significantly lower than in the NPCH group (0 vs. 4.1%, p = 0.041). The median follow-up time was 39 months (1.0-88.0 months), and the 3-year overall survival (OS; 59.1 vs. 75%, p < 0.001) and disease-free survival (DFS; 54.8 vs. 72.5%, p < 0.001) rates were significantly lower in the malnourished group than in the well-nourished group. A multivariate Cox regression analysis showed that malnutrition was an independent prognostic factor for 3-year OS (hazard ratio [HR] 1.211, 95% confidence interval [CI] 1.01-1.452, p = 0.039) and DFS (HR 1.168, 95% CI 1.013-1.398, p = 0.043). For the malnourished group with stage I gastric cancer, the PCH and NPCH groups showed no significant differences in 3-year OS (90.0 vs. 89.0%, p = 0.227) or DFS (90.0 vs. 87.3%, p = 0.363); however, for the malnourished group with stages II-III gastric cancer, the 3-year OS (69.9 vs. 47.6%, p = 0.013) and DFS (55.4 vs. 43.6%, p = 0.046) rates were significantly higher in the PCH group than in the NPCH group., Conclusions: The incidence of incision infection was significantly higher in patients with malnutrition than in well-nourished patients. The 3-year OS and DFS rates were significantly lower in malnourished patients than in well-nourished patients. PCH may both reduce the incidence of incisional infection in patients with malnutrition and improve 3-year OS and DFS rates for malnourished patients with stages II-III gastric cancer; however, to confirm our findings, further studies are warranted.

Background: Corticosteroid (CS) use is an important marker of poor prognosis in ulcerative colitis (UC). Our aim was to develop and validate a model to predict the risk of CS utilization over the course of disease in newly diagnosed patients with UC., Methods: Newly diagnosed patients with UC from a nationwide VA cohort were followed over time to evaluate factors predictive of CS use. Multivariate logistic regression was performed. Model development was performed in a random 2/3 of the total cohort and then validated in the remaining 1/3. The primary outcome was the use of CS for the management of UC. Candidate predictors included routinely available data at the time of UC diagnosis, including demographics, laboratory results, and index colonoscopy findings., Results: Six hundred ninety-nine eligible patients with UC were followed for a median duration of 8 years. Two hundred eighty-eight patients (41.2%) required CS use for the management of UC. Key predictors for CS utilization selected for the model were as follows: age, non-African American ethnicity, presence of hypoalbuminemia, and iron-deficiency anemia at the time of UC diagnosis, endoscopic extent, or severity of disease at index colonoscopy. Model discrimination was good (area under the receiver operator curve 0.71 [95% confidence interval, 0.66-0.76] for the model including baseline UC extent and 0.71 [95% confidence interval, 0.67-0.76]) for the model including baseline UC severity. Model calibration was consistently good in all models (Hosmer-Lemeshow goodness of fit P > 0.05). The models performed similarly in the internal validation cohort., Conclusions: We developed and internally validated a novel prognostic model to predict CS use among patients with newly diagnosed UC.

Introduction: A case of secondary focal segmental glomerulosclerosis (FSGS) in a heifer is presented. A 30-month-old female German Fleckvieh heifer showed deterioration of the general condition, a poor nutritional status, proteinuria, hypoalbuminemia, and renal azotemia. Pathologically, it was diagnosed with unilateral hydronephrosis, and contralateral renal fibrosis with numerous cysts. Histologically, the fibrotic kidney showed FSGS, hyaline reabsorption droplets in proximal tubular epithelial cells, interstitial fibrosis, and tubulointerstitial inflammation. Apart from that, thrombotic microangiopathy (TMA) was seen in few renal arteries and meningeal arterioles. Pathogenesis of FSGS secondary to unilateral renal parenchymal loss (hydronephrosis) and TMA is discussed.

Background: Neck of femur (NOF) fractures are associated with significant morbidity and mortality in elderly people with multiple co-morbidities; making management of this patient subgroup challenging. Predictors of an increase in morbidity and mortality would therefore provide a useful framework for the assessment and management of this demographic. Within the current literature, hypoalbuminaemia (<35g/dl) has been highlighted as being a good biochemical predictor of short-term mortality (<12 months). Our aims were to assess whether there was an association between low albumin levels and mortality and whether the severity adversely affects outcomes., Materials and Methods: Patients admitted to our large district hospital between January 2011 and December 2012 who had sustained a NOF fracture, were over 65 years old and had a pre-operative albumin level were included. This retrospective, longitudinal, observational study concluded in July 2014. Demographic and pre-operative function and albumin data was collated retrospectively. An association with mortality was made., Results: 471 patients had usable data. Mean pre-operative albumin level was 29.5g/dl (SD 6.22g/dl) in patients who died and 32.8g/dl (SD 6.43g/dl) in patients who survived during the study period. Pre-operative albumin level was significantly associated with survival (hazard ratio 0.957: 95% CI (0.937, 0.978); p<0.001). Thus, a reduction of 1g/dl in pre-operative albumin is associated with an increased hazard of death of 4.3%., Conclusions: Early identification of patients with hypoalbuminaemia on admission with a venous blood sample and timely input from orthogeriatrians could optimise these patients pre- and post-operatively. This may enable rates of morbidity and mortality to fall. Hypoalbuminaemia may be a reasonable predictor of shorter-term mortality in this patient subgroup. However, this may reflect existing co-morbidities rather than an isolated cause. This study supports an association between hypoalbuminaemia and poorer outcome for patients with NOF fractures., Competing Interests: The authors declare that they have no conflict of interest

Background: Oxidative stress produces molecular modifications of serum albumin that disturb its biological functions and interfere with its detection by the bromocresol green assay (BCG). Oxidative stress, inflammation, and hypoalbuminemia are common peritoneal dialysis (PD). This study aimed to evaluate the relationship between serum albumin, oxidized serum albumin (OSA), oncotic pressure, and blood pressure in hypoalbuminemic PD patients., Methods: Twenty-four PD patients with serum albumin levels <3.5 g/dl enrolled in the study. Data were compared between participants with the mean arterial pressure (MAP) <105 mmHg (n = 12) and MAP ≥ 105 mmHg (n = 12)., Results: Serum albumin levels were ≤3.0 g/dl and similar in both groups (p = 0.298). The calculated OSA and oncotic pressure were significantly higher in patients with MAP ≥ 105 mmHg than in those with MAP < 105 mmHg. MAP was positively and marginally correlated with serum albumin levels (measured by BCG) (r = 0.34, p = 0.05), and positively and significantly correlated with the calculated OSA and oncotic pressure (r = 0.44, p = 0.015, r = 0.58, p = 0.002; respectively). The oncotic pressure was positively correlated with the calculated OSA (r = 0.47, p = 0.011)., Conclusion: OSA, undetectable by the commonly used BCG, may contribute to higher blood pressure in hypoalbuminemic PD patients.

In Islamic religion, daytime fasting during the month called Ramadan is an annual practice. In this study, we aimed to investigate the effect of Ramadan fasting and maternal hypoalbuminaemia on neonatal growth parameters. A prospective case-control study was conducted in Diyarbakir and Istanbul, Turkey. The sample size of fasting group was 168 and that of non-fasting group was 170. Demographic characteristics, obstetrics ultrasonographic findings and laboratory parameters of the participants were recorded. Neonatal anthropometric parameters and placental weight were noted. The mean placental weight was significantly higher in the fasting group (p = 0.037). Also, in the fasting group, pregnant women with hypoalbuminaemia had significantly higher placental weight (p = 0.009). In conclusion, the mean placental weight in the fasting group was significantly higher. Also a significant correlation between placental weight and maternal serum albumin level was observed in the fasting group.

It remains unclear whether the abnormal circadian blood pressure (BP) rhythm in non-diabetic chronic kidney disease (CKD) is related to hypoalbuminemia. We evaluated relationships between circadian BP rhythm and serum albumin concentration (SAC) and also examined autonomic nervous activities. Non-diabetic CKD patients with proteinuria (n = 197; 105 men, 92 women; aged 47.0 ± 13.3 years; estimated glomerular filtration rate ≥30 ml/min) were divided into nephrotic syndrome (NS: n = 46, SAC ≤ 30 g/l), hypoalbuminemia (n = 65, 30 < SAC < 40 g/l) and normoalbuminemia (n = 86, SAC ≥ 40 g/l) groups. Non-proteinuria subjects (n = 97, urinary protein/creatinine ratio < 30 mg/g creatinine) were enrolled as the non-proteinuria group. Ambulatory 24 h BP monitoring was conducted in all subjects. Simultaneously, power spectral analysis of heart rate was performed to evaluate the sympathovagal balance. Waking BP was lower in the hypoalbuminemia and NS groups than the other groups. Sleeping/waking mean BP ratio was not different between non-proteinuria (0.87 ± 0.07) and normoalbuminemia (0.89 ± 0.08) groups, but increased significantly (p < 0.05) in the hypoalbuminemia (0.92 ± 0.08) and NS groups (0.96 ± 0.08). Significant reverse correlations were observed between SAC and sleeping/waking mean BP ratio (r = -0.274, p < 0.001) in all patients. Multivariate regression analysis identified SAC and sympathovagal balance as predictors of increased sleeping/waking BP ratios as the dependent variable. In non-diabetic CKD patients with proteinuria, disturbed circadian BP rhythms were related to SAC and 24 h sympathovagal imbalance.

Background: Although survival rates have improved for patients receiving implantable continuous flow left ventricular assist devices (I-CF LVAD), postoperative exercise tolerance levels are not necessarily satisfactory., Methods and results: We enrolled 51 patients who had received an I-CF LVAD and underwent follow-up between 2006 and 2014; all patients underwent cardiopulmonary exercise testing 3 months following surgery: 26 (51%) patients achieved peak oxygen consumption (PV̇O2) ≥14 ml·kg(-1)·min(-1)and had significantly lower readmission rates for cardiovascular events than those with PV̇O2<14 ml·kg(-1)·min(-1)during 2 years of LVAD treatment (17 vs. 43%, P=0.033). Uni- and multivariate logistic regression analyses showed that the preoperative serum albumin (S-ALB) level was an independent predictor for PV̇O2≥14 ml·kg(-1)·min(-1)at 3 months (P=0.023, odds ratio 6.132). Patients with persistently normal S-ALB levels during the perioperative period had the lowest preoperative serum C-reactive protein level (S-CRP, 0.7±0.9 mg/dl), and the majority (77%) showed improved exercise tolerance. Conversely, patients with persistently low S-ALB levels during this period had the highest preoperative S-CRP level (2.8±1.2 mg/dl) and did not achieve the test endpoint., Conclusions: Both pre- and postoperative low S-ALB impedes recovery of exercise tolerance after I-CF LVAD surgery, and this may be attributable to inflammatory responses caused by heart failure.

Background: Hospitals and surgeons simultaneously are pressured to decrease readmissions and duration of stay. We hypothesized that readmissions after endocrine surgery could be predicted by using a novel risk-score., Methods: The National Surgical Quality Improvement Program database was queried for cervical endocrine operations performed during 2011 and 2012. The primary end point was unplanned readmission within 30 days. Multivariable logistic regression was used to create and validate a scoring system to predict unplanned readmissions., Results: Overall, 34,046 cases were included with a readmission rate of 2.8% (n = 947). The most frequent reasons for readmission were hypocalcemia (32.4%) surgical-site infection (8.4%), and hematoma (8.0%) (2012 data only). The readmission risk score was created using the following factors: thyroid malignancy, hypoalbuminemia, renal insufficiency, American Society of Anesthesiologists class, and duration of stay >1 day. Predicted readmission rate by number of risk factors was 1.7 % for 0 risk factors, 3.2% for 1 risk factor (5-11 points), 5.8% for 2 risk factors, 10.5% for 3 risk factors, and 18.0% for 4 risk factors. The model had good predictive ability with c = 0.646., Conclusion: Readmissions after cervical endocrine operations can be predicted. This risk score could be used to direct resource use for preoperative, inpatient, and outpatient care delivery to reduce readmissions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Hypoalbuminemia caused by peritoneal dialysate protein loss, frequently occurs in patients on peritoneal dialysis (PD) and is associated with an increased risk of death. We investigate whether PD dialysis exchange volume (PD volume) could be reduced with tolvaptan (TVP) through increased urine volume (UV)., Methods: The study included 11 stable patients with oliguria undergoing PD. The following parameters were examined-diuretic response and the effect of TVP on peritoneal ultrafiltration (UF), body weight, serum albumin, sodium, arm muscle area (AMA), PD volume, dialysis efficiency calculator (K t/V), and urine and serum osmolarity (OSM)., Results: The average UV increased from 428 ± 178 to 906 ± 285 mL (p = 0.018 by paired t test). Average weekly PD volume decreased from 28,836 ± 5,699 to 23,872 ± 3,569 mL (p = 0.04 by paired t test). Average UF increased from 283 ± 147 to 575 ± 135 mL (p = 0.019 by paired t test). On the other hand, there was no significant difference in the average dialysate K t/V before and after TVP treatment. Serum sodium, AMA, and serum albumin levels were not statistically different before and after TVP treatment. The urine and serum OSM ratio of effective cases before TVP treatment was higher than that of ineffective cases (p = 0.024 by unpaired t test)., Conclusion: Our results indicate that TVP is useful for patients on continuous ambulatory PD who have oliguria and high urine osmolarity. Furthermore, we can reduce PD volume to maintain their nutritional status.

Purpose of Review: To raise awareness among healthcare providers about the clinical and laboratory findings in acute and chronic food protein-induced enterocolitis syndrome (FPIES)., Recent Findings: FPIES can be caused by trivial exposure or rare foods., Summary: FPIES is a non-IgE-mediated reaction that usually presents with acute severe repetitive vomiting and diarrhea associated with lethargy, pallor, dehydration, and even hypovolemic shock. Manifestations resolve usually within 24-48 h of elimination of the causative food. In chronic cases, symptoms may include persistent diarrhea, poor weight gain, failure to thrive, and improvement may take several days after the food elimination. In the acute cases, laboratory evaluation may reveal thrombocytosis and neutrophilia, peaking about 6 h postingestion. Depending on the severity, metabolic acidosis and methemoglobinemia may occur. In chronic cases, anemia, hypoalbuminemia and eosinophilia may be seen. Radiologic evaluation or other procedures, such as endoscopy and gastric juice analysis may show nonspecific abnormal findings. The diagnosis is based on clinical manifestations. Further studies looking at the phenotypes of FPIES are needed to identify clinical subtypes, and to understand the predisposing factors for developing FPIES compared with immediate-type, IgE-mediated gastroenteropathies.

Background: Low serum albumin concentration is a predictor of failure of source control for intra-abdominal infection. However, data on dynamics of albumin synthesis in these patients and to what extent these changes contribute to hypoalbuminemia are relatively scarce. We investigated in a group of patients with gastrointestinal fistula the dynamic response of liver albumin synthesis to intra-abdominal abscess and how these related to hypoalbuminemia and circulating endocrine hormone profiles., Methods: Eight gastrointestinal fistula patients scheduled to undergo percutaneous abscess sump drainage were enrolled prospectively to measure albumin synthesis rates at different stages of the inflammatory response (immediately after diagnosis and 7 d following sump drainage when clinical signs of intra-abdominal sepsis had been eradicated). Eight age-, sex-, and body mass index-matched intestinal fistula patients were studied as control patients. Consecutive arterial blood samples were drawn during a primed-constant infusion (priming dose: 4 micromol·kg(-1), infusion rate: 6 micromol·kg(-1)·min(-1)) to determine the incorporation rate of L-[ring-(2)H5]-phenylalanine directly into plasma albumin using gas chromatography/mass spectrometry analysis., Results: Patients suffering from intra-abdominal infection had reduced plasma albumin and total plasma protein concentrations, compared with control patients. Albumin fractional synthesis rates in patients with intra-abdominal abscess were decreased, compared with those in the control group. When the source of infection was removed, albumin synthesis rates returned to control values, whereas albumin concentrations did not differ significantly from the corresponding concentrations in control subjects and patients with intra-abdominal abscess., Conclusion: Despite nutritional intervention, albumin synthesis rate is decreased in intestinal fistula patients with intra-abdominal abscess; albumin synthesis returns to control values during convalescence.

Aims: The incidence of malignant mesothelioma in the UK is increasing. The aim of this study was to determine the prognostic factors and assess the effect of carboplatin/pemetrexed chemotherapy on survival., Materials and Methods: Cases of malignant mesothelioma diagnosed between 1998 and 2011 were stratified by year of diagnosis. Factors affecting survival were assessed by Cox's proportional hazards regression., Results: In total, there were 202 new cases of malignant mesothelioma between 1998 and 2011. The age-standardised rate (95% confidence interval) increased from 2.84 (2.06-3.60) to 4.44 (3.50-5.4); P = 0.025. Chemotherapy use has increased since 2006: 52% versus 34% (P = 0.007). The median survival (interquartile range) by year diagnosed was 9 (4.0-21.9) versus 10 (3.8-20.1) months for 1998-2005 versus 2006-2011. Independent predictors of survival [hazard ratio (95% confidence interval)] were: histology, sarcomatoid 2.22 (1.49-3.31) and unspecified non-epithelioid 1.50 (1.06-2.14); Eastern Cooperative Oncology Group performance status ≥3 2.86 (1.64-5.00); hypoalbuminaemia 2.07 (1.47-2.92), carboplatin/pemetrexed chemotherapy 0.56 (0.38-0.80)., Conclusion: The incidence of mesothelioma is increasing. Adverse prognostic factors include non-epithelioid histology, performance status and hypoalbuminaemia. Overall survival has not improved significantly, but treatment with carboplatin/pemetrexed chemotherapy is associated with a significant survival benefit., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: Diarrhea has great impact on enteral nutrition. The purpose of this review is to identify the factors leading to diarrhea during enteral nutrition and to provide the published updates on diarrhea prevention through nutritional intervention., Recent Findings: Diarrhea in enteral fed patients is attributed to multiple factors, including medications (major contributor), infections, bacterial contamination, underlying disease, and enteral feeding. Diet management can alleviate diarrhea in enteral feeding. High content of fermentable oligosaccharides, disaccharides, and monosaccharides and polyols (FODMAPs) in enteral formula is postulated to induce diarrhea and lower FODMAPs formula may reduce the likelihood of diarrhea in enterally fed patients. Fiber-enriched formula can reduce the incidence of diarrhea and produce short-chain fatty acids for colonocytes. Ingesting prebiotics, nonviable probiotics or probiotic derivatives, and human lactoferrin may provide alternatives for reducing/preventing diarrhea., Summary: Enteral feeding is not generally considered the primary cause of diarrhea, which is frequently linked to prescribed medications. When diarrhea is apparent, healthcare members should evaluate the possible risk factors and systematically attempt to eliminate the underlying causes of diarrhea before reducing or suspending enteral feeding. Lower FODMAPs formula, prebiotics, probiotic derivatives, and lactoferrin may be used to manage enteral feeding-related diarrhea.

Purpose: Hypoalbuminemia is believed to decrease diuretic effectiveness and contribute to diuretic resistance that is observed in patients with nephrotic syndrome. Hypoalbuminemia is also seen in patients with acute decompensated heart failure (ADHF). However, the role of hypoalbuminemia on the effectiveness of continuous infusion diuretics in patients with ADHF is not known., Methods: To evaluate hypoalbuminemia (albumin ≤ 3 g/dL) and diuretic effectiveness, we performed a retrospective study in 162 patients admitted to a tertiary care center for treatment of ADHF over a 3-year period. All patients received continuous infusion diuretic for at least a 2-day time period., Results: A total of 33 patients were determined to have hypoalbuminemia. Average net urine output over a 2-day study period was similar between patients with and without hypoalbuminemia (-1462 ± 1734 vs -1233 ± 1560 mL, P = .46, respectively). In addition, diuretic doses (furosemide equivalent/24 hours) were similar between the 2 groups (788 ± 671 vs 778 ± 713 mg, P = .91, respectively) as was baseline serum creatinine (1.6 ± 0.6 vs 1.6 ± 0.6 mg/dL, P = .5, respectively)., Conclusion: Overall, hypoalbuminemia did not decrease the diuretic effectiveness when measured by the net urine output in patients receiving continuous infusion diuretics for the treatment of ADHF.

Phenytoin, a commonly used antiepileptic, is difficult to dose optimally due to its narrow therapeutic window, nonlinear pharmacokinetics, extensive protein binding, and participation in clinically significant drug interactions. Although clinicians are aware of the interaction with two widely used antituberculosis agents, rifampin and isoniazid, few reports have described the implications for managing phenytoin dosing in this situation. To our knowledge, only two reports of the clinical experience with this interaction have been published, and only one of these reports involved the addition of isoniazid. We present a case of a 60-year-old man treated with triple antiepileptic therapy, including phenytoin, who experienced seizures shortly after hospital admission. Dosing of phenytoin proved difficult in this patient due to an acute kidney injury and severe hypoalbuminemia requiring hemodialysis. A further complexity was the addition of antituberculosis therapy (rifampin, isoniazid, pyrazinamide, and ethambutol [RIPE]) for suspected tuberculosis meningitis after the patient experienced persistent encephalopathy. Phenytoin concentrations decreased steadily after rifampin and isoniazid initiation despite dose increases, and the free concentration of phenytoin reached a low of less than 0.5 µg/ml on day 8 of RIPE therapy. The patient continued on a stable dose of phenytoin and RIPE therapy for unconfirmed tuberculosis meningitis until discharge. This report is the first description of this drug interaction in 20 years and highlights the need for appropriate management of phenytoin in a patient with complicated needs for pharmacotherapy., (© 2013 Pharmacotherapy Publications, Inc.)

Background: Inflammation, hypoalbuminaemia and peritoneal protein clearance are important predictors of survival in patients treated with peritoneal dialysis (PD). We hypothesized that the common link is abnormal endothelial barrier function. To test this, we explored associations between hypoalbuminaemia, systemic albumin leak and soluble markers of systemic inflammation and endothelial injury., Methods: This was a cross-sectional study of 41 prevalent PD patients. Endothelial barrier function was measured as transcapillary escape rate of (125)I albumin [transcapillary escape rate of albumin (TER(alb))]. Seventeen plasma biomarkers including pro-inflammatory cytokines, endothelial biomarkers and metalloproteinases were measured. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) were used to explore the hypothesis., Results: The mean TER(alb) was 13.7 ± 8.9 (%/h), higher than in non-uraemic subjects 8.22 ± 5.8 (%/h). Three patient clusters were defined from HCA according to their biomarker patterns. Cluster 1 was characterized by inflammation, hypoalbuminaemia, overhydration and intermediate TER(alb). Cluster 2 was non-inflamed, preserved muscle mass and more normal TER(alb). Cluster 3 had highest TER(alb), platelet activation, preserved plasma albumin and intermediate high-sensitivity C-reactive protein levels. Two principal components (PCs) were identified from the biomarker matrix, PC1, indicating platelet activation and PC2, pro-inflammatory. TER(alb) was positively related to PC1 but not PC2. Diabetes and ischaemic heart disease were associated with PC1 and PC2, respectively., Conclusions: This exploratory analysis indicates that endothelial barrier function is decreased in PD patients and is associated with diabetic status and markers of platelet activation more than inflammation. In contrast, hypoalbuminaemia is associated more with inflammation and atherosclerotic disease indicating a more complex relationship between systemic endothelial barrier function, inflammation and hypoalbuminaemia which requires further validation.

Background: Hypoalbuminemia commonly observed in cirrhosis is considered to be mainly related to hepatocellular dysfunction. However, the correlation between the decrease in serum albumin and liver function is far from linear and arguments in favor of an additive role of protein-losing enteropathy have been brought by a few studies., Aim: To assess the potential role of protein-losing enteropathy in a group of patients with cirrhosis, portal hypertension, and hypoalbuminemia., Design and Methods: Eleven patients with documented cirrhosis, portal hypertension, and a low serum albumin level compared to liver function underwent an (111)In-transferrin scintigraphy., Results: Using this sensitive method of investigation, nine exhibited features suggestive of exudative enteropathy. Serum albumin level and digestive protein loss were even correlated (Pearson's coefficient = -0.529, one-sided p = 0.047). Protein loss were however not correlated with the degree of portal hypertension or with the extent of liver dysfunction evaluated by the aminopyrine breath test., Conclusions: Our preliminary data obtained in a small group of selected patients with cirrhosis, portal hypertension, and hypoalbuminemia indicate that protein-losing enteropathy may represent an appreciable and underestimated cause of hypoproteinemia.

The mechanism of edema formation in the nephrotic syndrome has long been a source of controversy. In this review, through the construct of Starling's forces, we examine the roles of albumin, intravascular volume, and neurohormones on edema formation and highlight the evolving literature on the role of primary sodium absorption in edema formation. We propose that a unifying mechanism of sodium retention is present in the nephrotic syndrome regardless of intravascular volume status and is due to the activation of epithelial sodium channel by serine proteases in the glomerular filtrate of nephrotic patients. Finally, we assert that mechanisms in addition to sodium retention are likely operant in the formation of nephrotic edema.

Background & Aims: Malnutrition is common in older persons. However, it is unclear whether malnutrition diagnosed with the Mini Nutritional Assessment (MNA) predicts mortality in older hospitalized patients., Methods: We prospectively studied the impact of the MNA-short form (MNA-SF) and co-morbidities on long-term mortality in 444 patients (mean age 85.3 ± 6.7; 74.0% women) receiving geriatric inpatient care. In a cross-sectional study we studied the interplay between the MNA, nutritional markers and co-morbidities (using the Cumulative Illness Rating Scale, CIRS)., Results: The prevalence of malnutrition and "at risk of malnutrition", defined by MNA-SF, was 25.5 and 50.5% respectively in our prospective study. CIRS scores (HR = 1.09, p < 0.001) and a low BMI (HR = 0.96, p < 0.05), but not the MNA-SF (HR = 0.79 and 0.89 for "at risk" and malnutrition respectively, P = NS), were associated with 4-year mortality. CIRS scores, albumin and other nutritional markers were similar between MNA categories. High CIRS scores and hypoalbuminemia were observed even in patients with normal MNA scores. There was good agreement (>80%) between the MNA-SF and the complete MNA., Conclusions: Malnutrition as diagnosed with the MNA at admission failed to predict long-term mortality in older inpatients, likely due to the overriding impact of co-morbidities and acute disease., (Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP-Zn(2+) complex reveals active site and DNA interaction clefts formed by fusing a histidine triad (HIT) nucleotide hydrolase with a DNA minor groove-binding C(2)HE zinc finger (Znf). An Aptx helical 'wedge' interrogates the base stack for sensing DNA ends or DNA nicks. The HIT-Znf, the wedge and an '[F/Y]PK' pivot motif cooperate to distort terminal DNA base-pairing and direct 5'-adenylate into the active site pocket. Structural and mutational data support a wedge-pivot-cut HIT-Znf catalytic mechanism for 5'-adenylate adduct recognition and removal and suggest that mutations affecting protein folding, the active site pocket and the pivot motif underlie Aptx dysfunction in the neurodegenerative disorder ataxia with oculomotor apraxia 1 (AOA1).

Glomerular diseases are among the most common renal pathologies leading frequently to end-stage renal disease. Clinical disease can be divided into five different groups the features of which are determined by the underlying pathophysiology. One of these five clinical syndromes is the nephrotic syndrome, which is characterized by proteinuria > 3.5 g/day accompanied by hypalbuminemia, hyperlipoproteinemia and pronounced edema. The nephrotic syndrome may be the clinical manifestation of a row of underlying diseases. The pathophysiological basics had remained elusive for decades, yet recently significant progress which allows for establishing new therapeutic strategies has been made. A major breakthrough in understanding the function of the glomerular filter unit has been possible in the last years through both genetic and cell biological studies, which have revealed a crucial role for the visceral epithelial cells of the glomerulus - the podocytes. By now various factors have been found causing podocyte damage, such as toxines, immunological phenomena or systemic disease like diabetes mellitus., (© Georg Thieme Verlag KG Stuttgart · New York.)

Oedema is a common clinical manifestation of nephrotic syndrome. However, the pathophysiological mechanism of sodium retention in nephrotic syndrome has been intensely debated for decades. Several clinical and experimental observations argue against the classic or "underfill" hypothesis of oedema formation in nephrotic syndrome. In many patients, oedema formation in nephrotic syndrome is due to the kidney being intrinsically unable to excrete salt and is unrelated to systemic factors (i.e. hypoalbuminaemia, decreased &ldquo;effective&rdquo; arterial blood volume, and secondary hyperaldosteronism). The cortical collecting duct is the nephron site of sodium retention in nephrotic syndrome. Activation of the epithelial sodium channel in the cortical collecting duct is responsible for sodium retention in nephrotic syndrome. In nephrotic syndrome, a defective glomerular filtration barrier allows the passage of proteolytic enzymes or their precursors, which have the ability to activate the epithelial sodium channel, thereby causing the the subsequent sodium retention and oedema.

Background and Objectives: Peritoneal dialysis (PD) patients may be overhydrated especially when inflammation is present. We hypothesized that patients with a plasma albumin below the median value would have measurable overhydration without a proportional increase in plasma volume (PV)., Design, Setting, Participants, & Measurements: We investigated a cross-sectional sample of 46 prevalent PD patients powered to detect a proportional increase in PV associated with whole body overhydration and hypoalbuminemia. PV was determined from (125)I-labeled albumin dilution, absolute total body water from D dilution (TBW(D)), and relative hydration from multifrequency bioimpedance analysis (BIA; Xitron 4200) expressed as the extracellular water (ECW):TBW(BIA) ratio., Results: Whereas patients with plasma albumin below the median (31.4 g/dl) were overhydrated as determined both by BIA alone (ECW:TBW(BIA) 0.49 versus 0.47, P < 0.036) and the difference between estimated TBW(BIA) and measured TBW(D) (3.55 versus 0.94 L, P = 0.012), corrected PV was not different (1463 versus 1482 ml/m(2), NS). Mean PV was not different from predicted, and its variance did not correlate with any other clinical measures. Multivariate analysis showed that the only independent predictor of whole body overhydration was reduced plasma albumin., Conclusions: Hypoalbuminemia is an important determinant of tissue overhydration in PD patients. This overhydration is not associated with an increased plasma volume. Attempts to normalize the ECW:TBW ratio in hypoalbuminemic, inflamed PD patients may lead to hypovolemia and loss of residual renal function.

We report the case of a 70-year-old man presenting with the development of torsade de pointes (TDP) during infusion of propofol in the setting of severe hypoalbuminemia. TDP developed 15 hours after the beginning of a standard infusion of propofol, following the development of a prominent U wave and prolongation of the QTc interval. While the serum concentrations of electrolytes were within normal ranges, serum albumin as low as 1.4 mg/dL was observed. TDP disappeared during the infusion of isoproterenol, and QTc normalized after the discontinuation of propofol. We hypothesize that hypoalbuminemia increased the free fraction of propofol, causing marked QTc prolongation and TDP.

To determine the nutritional status of chronic hemodialysis (HD) patients and the association of changes in serum albumin levels, C-reactive protein (CRP), low density lipoprotein (LDL) cholesterol and body mass index (BMI) as indicators of nutritional status with the urea reduction ratio (URR) during dialysis, we studied 201 chronic HD patients (97 males and the mean age was 51 +/- 15 years). Diabetes was the cause of chronic kidney disease (CKD) in 34% of the patients, hypertension in 57%, chronic glomerulonephritis in 12%, and obstructive uropathy in 10%. BMI less than 18.5 (under weight) was found in 17% of patients, more 18.5 but less than 25 (normal) in 56%, more than 25 but less than 30 (overweight) in 21%, and more than 30 (obese) in 6%. The laboratory investigations revealed hypercalcemia in 62% of the patients (15 patients were found to have tertiary hyperparathyroidism), total cholesterol less than 100 mg/dL in 6% (mean 152 +/- 37.5 mg/dL), and URR of less than 60% in 12% of patients and greater than 60 but less than 65% in 33%. Hypoalbuminemia was associated with poor URR (P < 0.05), whereas no statistically significant correlation was found between URR and iPTH, LDL cholesterol, CRP and body mass index. We conclude that poor nutritional status was detected among a significant number of our patients with poor dietary education. Increased risk of malnutrition was significantly associated with older age and inadequate dialysis dose. Hypoalbuminemia was the single most important factor associated with poor URR.

The number of people who have diabetes is increasing. Many develop significant complications associated with diabetes, such as neuropathy, retinopathy, and manifestations of cardiovascular disease. Overt diabetic nephropathy is diagnosed most often in patients who have longstanding diabetes and who develop hypertension, loss of renal function, peripheral edema, nephrotic range proteinuria, and hypoalbuminemia. This article discusses the changes in extracellular fluid volume in hypoalbuminemic patients who have diabetic nephropathy and changes in extracellular volume that occur in other forms of glomerular disease associated with hypoalbuminemia. This article also reviews the mechanisms responsible for hypoalbuminemia in proteinuric subjects who have chronic kidney disease.