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Albumin infusions improve circulatory and renal function in patients with decompensated cirrhosis. However, there is no convincing evidence that hypoalbuminemia contributes to ascites formation in liver cirrhosis. The aim of our study is to determine the exact role of hypoalbuminemia in the formation of ascites caused by liver cirrhosis and its underlying mechanism. Clinical profiles of patients with liver cirrhosis retrospectively analyzed. The details of albumin involved in ascites formation were investigated in rat model and murine model. Statistical analysis demonstrated hypoalbuminemia was an independent risk factor for ascites formation in patients with liver cirrhosis (OR = 0.722, P < 0.001). In carbon tetrachloride (CCl 4 )-induced rat model of liver cirrhosis, a significant reduction in serum albumin was observed in rats with ascites (13.37 g/L) compared with rats without ascites (21.43 g/L, P < 0.001). In thioacetamide (TAA)-treated mice, ascites amount of heterozygous albumin (Alb +/- ) mice (112.0 mg) was larger than that of wild-type (Alb +/+ ) mice (58.46 mg, P < 0.001). In CCl 4 -induced chronic liver injury, ascites amounts of Alb +/- or Alb +/+ mice were 80.00 mg or 48.46 mg (P = 0.001). Further study demonstrated 24-h urinary sodium excretion in Alb +/- mice was lower than that of Alb +/+ mice in TAA/CCl 4 -induce murine models of liver cirrhosis. Additionally, serum sodium concentration of Alb +/- mice was lower than that of Alb +/+ mice. In cirrhotic mice, higher level of antidiuretic hormone was observed in Alb +/- mice compared with the control; and renal aquaporin (AQP2) expression in Alb +/- mice was significantly higher than that of WT mice. These revealed hypoalbuminemia contributed to the occurrence of ascites in liver cirrhosis through sodium and water retention., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH., (© 2024. The Author(s).)

Introduction: Circulating plasma cells (CPCs) are frequently noted in variable frequencies in the entire spectrum of plasma cells neoplasms. With advent of high sensitivity multi-parametric flow cytometry, it is not only possible to detect CPCs present in very low numbers, but also to categorise them into circulating tumor plasma cells (CTPCs) and circulating normal plasma cells (CNPCs), based on their marker-profile. This study used multi-colour flow cytometry to evaluate the load of both CTPCs & CNPCs at the time of diagnosis and at six months' time-point of therapy, and evaluated associations of both with clinical and laboratory parameters., Methods: Twenty one newly diagnosed MM patients were enrolled. Six to nine millilitres of EDTA-anticoagulated peripheral blood sample was used for flow cytometry. A ten colour antibody panel was used for analysis of CPCs, which were categorised further into CTPCs and CNPCs. Approximately 4.8 million events were acquired for the analysis. The percentage &absolute numbers of CTPCs and CNPCs were noted and the proportion of CTPCs out of all CPCs (CTPCs + CNPCs) were also calculated for evaluating their statistical associations., Results: All 21 patients of newly diagnosed MM showed presence of CPCs (CTPCs and/or CNPCs) at the time of diagnosis. The CTPCs were detected in 76 % of the study population. The median percentage and absolute counts of CTPCs were 0.52 % and 54.9 cells /µL, respectively. CNPCs were found in 95 % and the median percentage and absolute counts of CNPCs were 0.025 % and 2.66 cells/µL. After six months of therapy, CPCs (CTPCs and/or CNPCs) were found in all nine patients evaluated for this assay. CTPCs were found 33 %, with a median of 0.075 % and CNPCs were found in 89 % with a median of 0.01 %. Our study showed that the load of CTPCs was found to be higher in patients with presence of lytic bone lesions, plasmacytoma, presence of PCs on peripheral blood film by light microscopy, presence of Chr 1p32 deletion, expression of CD56 and CD81 on CTPCs, and in patients with absence of very good partial response (VGPR). Conversely, the load of CTPCs was significantly lower in patients with concomitant amyloidosis. Also, percentage of bone marrow plasma cells exhibited a significant positive correlation with the absolute count of CTPCs. We observed that the mean percentage of CNPCs was significantly higher in female patients. The load of CNPCs was lower in patients with thrombocytopenia and with hypoalbuminemia., Conclusion: Increased burden of CTPCs was associated with presence of lytic lesions, plasmacytomas, Chr 1p32 deletion, expression of CD56 and CD81 on tumor cells and with failure to achieve very good partial response. The CNPCs were lower in patients with thrombocytopenia and with hypoalbuminemia. To best ot our knowledge, this is the first study from India on the relevance of circulating tumor plasma cells and the first study in the world to analyse the associations of circulating normal plasma cells in newly diagnosed patients of multiple myeloma. The study also highlights the utility of multi-parametric flow cytometry in identification and enumeration of circulating plasma cells., Micro Abstract: Circulating plasma cells indicates poorer outcomes in patients of multiple myeloma. Twenty one newly diagnosed multiple myeloma patients were evaluated by flow cytometry to enumerate and characterise circulating tumor plasma cells (CTPCs) and circulating normal plasma cells (CNPCs). Higher load of CTPCs correlated with known poor prognostic markers and poor response to therapy., Competing Interests: Declaration of Competing Interest Np potential conflict of interest are reported by authors., (Copyright © 2023. Published by Elsevier Inc.)

Here, we present a case of severe glomerular fibrin thrombosis in a dog with lymphoma. A 3-year-old neutered male Chihuahua presented with acute kidney injury, hypoalbuminemia, and transudate ascites. The dog showed symmetric enlargement of the spleen, which was diagnosed as B-cell lymphoma based on cytology and polymerase chain reaction tests. The dog died after intensive care, and the kidneys were removed for histopathological examination. Light microscopy, immunofluorescence, and electron microscopy analyses were performed for renal pathology; however, the findings did not support the evidence of protein-losing nephropathy. Instead, the endocapillary accumulation of fibrin thrombi was prominent in most glomeruli. A diagnosis of severe glomerular fibrin thrombosis was established, and hypoalbuminemia was considered the underlying cause of kidney damage.

Background: Sarcopenia is associated with poor prognosis in metastatic colorectal cancer (mCRC) patients., Purpose: To investigate the prognostic value of body composition measurement changes measured by computed tomography (CT) in mCRC patients., Material and Methods: The abdominal skeletal muscle density (SMD) and skeletal muscle (SMI) indices, as well as the visceral (VATI) and subcutaneous fat tissue (SATI) indices, were calculated by automatic segmentation method on the abdominal CT images obtained before (n = 71) and after chemotherapy (n = 52). Skeletal muscle gauge (SMG = SMD × SMI) was calculated. We calculated the percentage change of body composition measurements with respect to the first measurements. The cutoff value for the change in SMG was calculated by receiver operating characteristic analysis. Kaplan-Meier and Cox regression analyses were performed to calculate the prognostic value of age, gender, tumor location, metastasis site and carcinoembriogenic antigen (CEA) elevation, hypoalbuminemia, body mass index classification, presence of sarcopenia and SMG changes in terms of overall survival., Results: There was a significant association between SMG change and mortality ( P  = 0.037). According to survival analyses, highly decreased SMG, hypoalbuminemia and CEA variables of the patients were the significant factors ( P  < 0.001, P  = 0.015 and P  = 0.019, respectively). According to multivariate regression analysis, hypoalbuminemia ( P  = 0.004, hazard ratio = 3.60) and highly decreased SMG ( P  < 0.001, hazard ratio = 14.98) were found to be significant prognostic factors together., Conclusion: In mCRC patients, hypoalbuminemia and highly decreased SMG are significant prognostic factors for overall survival. Therefore, we suggest that the change in SMG calculated in follow-up images should also be evaluated in the prognosis estimation of this patient group., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Serum albumin (ALB) and hemoglobin (HGB) are important serum biochemical indices of the nutritional status of patients and are associated with cancer development. We investigated the relationship between ALB and HGB levels and clinicopathologic characteristics of early-stage cervical cancer to determine the influence of ALB and HGB on the prognosis of early-stage cervical cancer., Methods: The clinical data of 560 patients with International Federation of Gynaecology and Obstetrics (FIGO, 2009) stage IA1-IIA2 cervical cancer from January 2005 to December 2010 were retrospectively analyzed. The relationship between serum ALB and HGB levels and clinicopathological characteristics of patients were analyzed. The patients were followed-up for 12-138 months. The effects of ALB and HGB levels on the prognosis were analyzed by Cox regression, log-rank test, and the Kaplan-Meier method., Results: The rate of patients with pelvic lymph node metastasis (PLNM), tumor diameter ≥ 4 cm, lymphovascular space invasion (LVSI), and deep stromal invasion was significantly higher in the anemia and hypoalbuminemia group than in the normal group (P < 0.05). The progression-free survival (PFS) and overall survival (OS) of patients in the hypoalbuminemia group and anemia group were significantly lower than that of the normal group (P < 0.05). FIGO stage, tumor diameter, PLNM, depth of stromal invasion, LVSI, the levels of ALB and HGB were risk factors for the prognosis of cervical cancer patients (P < 0.05)., Conclusion: Patients with hypoproteinemia and anemia in early-stage cervical cancer are more likely to have higher tumor stage, larger tumor size, PLNM, LVSI, and deep stromal invasion. In addition, patients with hypoproteinemia and anemia have a poorer prognosis than those without the condition. Therefore, it is of great significance to detect the ALB and HGB levels of patients and improve the nutritional status of patients in a timely manner for better prognosis of cervical cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Myosteatosis and sarcopenia are forms of muscle depletion that impair the normal physiological function of elderly patients, resulting in a worse prognosis. This study aimed to evaluate the prognostic value of sarcopenia and myosteatosis on postoperative outcomes in elderly patients with colorectal cancer., Methods: From February 2015 to March 2021, a total of 921 elderly patients who underwent curative surgeries for colorectal cancer at 2 centers were enrolled and grouped by the presence of either myosteatosis or sarcopenia. Clinicopathological characteristics and postoperative outcomes were compared between the 2 groups. The independent risk factors for complications and overall survival were evaluated., Results: Patients with myosteatosis had higher incidences of total and surgical complications, longer surgical duration, lower numbers of lymph nodes harvested, and longer postoperative hospital stays. Patients with sarcopenia had higher incidences of total complications, medical complications, and shorter surgical durations. Both conditions had adverse effects on overall survival and disease-free survival. Overweight status (P = .004), hypoalbuminemia (P < .001), myosteatosis, (P = .029) and sarcopenia (P = .017) were independent risk factors for total complications. Hypoalbuminemia (P = .035), myosteatosis (P = .003), sarcopenia (P = .027), and tumor-nodes-metastasis stage (≥Ⅲ; P < .001) were independent negative prognostic factors for overall survival., Conclusion: Myosteatosis and sarcopenia have different characteristics and are associated with poor prognoses in elderly patients with colorectal cancer. Myosteatosis occurs more frequently. Early diagnosis and intervention for myosteatosis should be included in preoperative management, which may improve prognosis in elderly patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The human albumin gene, the most abundant serum protein, is located in the long arm of chromosome 4, near the centromere, position 4q11-3. It is divided by 14 intervening introns into 15 exons, the last of which is untranslated. To date, 74 nucleotide substitutions (mainly missense) have been reported, determining the circulating variants of albumin or pre-albumin. In a heterozygous state, this condition is known as alloalbuminaemia or bisalbuminaemia (OMIM # 103600). The genetic variants are not associated with disease, neither in the heterozygous nor in the homozygous form. Only the variants resulting in familial dysalbuminaemic hyperthyroxinaemia and hypertriiodothyroninaemia are of clinical relevance because affected individuals are at risk of inappropriate treatment or may have adverse drug effects. In 28 other cases, the pathogenic variants (mainly affecting splicing, nonsense, and deletions), mostly in the homozygous form, cause a premature stop in the synthesis of the protein and lead to the condition known as congenital analbuminaemia. In this review, we will summarize the current knowledge of genetic and molecular aspects, functional consequences and potential therapeutic uses of the variants. We will also discuss the molecular defects resulting in congenital analbuminaemia, as well as the biochemical and clinical features of this rare condition.

Older age and poor performance status lead to worse outcomes in acute myeloid leukemia (AML) patients. Hypoalbuminemia is a negative predictor of morbidity and mortality in several malignancies. We evaluated the relationship between baseline serum albumin levels on treatment-related complications, as well as short-term mortality and overall survival (OS) in 756 newly diagnosed AML patients. We conducted a retrospective multicenter study to examine treatment-related complications and OS according to pretreatment serum albumin levels: normal albumin ≥3.5 g/dl, marked hypoalbuminemia <2.5 g/dl, and hypoalbuminemia 2.5-3.4 g/dl. In an adjusted multivariate analysis, a lower baseline albumin was independently associated with a higher number of grade ≥3 complications when adjusting for age, secondary AML, sex and intensive treatment. When comparing normal to markedly low albumin levels, the estimated mean number of complications increases by a factor of 1.35. Patients who had a normal baseline albumin had a 30 day-mortality rate of 4.8%, which was significantly lower compared with patients with hypoalbuminemia (16.5%) and marked hypoalbuminemia (33.9%; p < 0.01). Similarly, 60-day mortality rate was significantly higher in the hypoalbuminemia group (24.0%) and marked hypoalbuminemia group (45%) compared with normal albumin group (8.3%; p < 0.01). Patients with lower baseline albumin levels have increased treatment-related morbidity and mortality, suggesting that pre-treatment serum albumin is an important independent prognostic marker., (© 2021 John Wiley & Sons, Ltd.)

Hypoalbuminemia is associated with the acquisition and severity of infectious diseases, and intact innate and adaptive immune responses depend on albumin. Albumin oxidation and breakdown affect interactions with bioactive lipid mediators that play important roles in antimicrobial defense and repair. There is bio-mechanistic plausibility for a causal link between hypoalbuminemia and increased risks of primary and secondary infections. Serum albumin levels have prognostic value for complications in viral, bacterial and fungal infections, and for infectious complications of non-infective chronic conditions. Hypoalbuminemia predicts the development of healthcare-associated infections, particularly with Clostridium difficile . In coronavirus disease 2019, hypoalbuminemia correlates with viral load and degree of acute lung injury and organ dysfunction. Non-oncotic properties of albumin affect the pharmacokinetics and pharmacodynamics of antimicrobials. Low serum albumin is associated with inadequate antimicrobial treatment. Infusion of human albumin solution (HAS) supplements endogenous albumin in patients with cirrhosis of the liver and effectively supported antimicrobial therapy in randomized controlled trials (RCTs). Evidence of the beneficial effects of HAS on infections in hypoalbuminemic patients without cirrhosis is largely observational. Prospective RCTs are underway and, if hypotheses are confirmed, could lead to changes in clinical practice for the management of hypoalbuminemic patients with infections or at risk of infectious complications.

Background/aims: This study aimed to investigate the factors associated with prolonged hospital stay and in-hospital mortality in patients with pyogenic liver abscess., Methods: We retrospectively reviewed data from patients with pyogenic liver abscess who were admitted between 2005 and 2018 at three tertiary hospitals in Jeonbuk province, South Korea. Prolonged hospital stay was defined as a duration of hospital admission of more than 21 days., Results: A total of 648 patients (406 men and 242 women) diagnosed with pyogenic liver abscess were enrolled in the study. The mean maximal diameter of the liver abscess was 5.4 ± 2.6 cm, and 74.9% of the lesions were single. The three groups were divided according to the maximal diameter of the abscess. Laboratory parameters indicated a more severe inflammatory state and higher incidence of complications and extrahepatic manifestations with increasing abscess size. Rates of percutaneous catheter drainage (PCD) insertion, multiple PCD drainage, and salvage procedures as well as duration of drainage were also higher in the large liver abscess group. Of note, the duration of hospitalization and in-hospital mortality were significantly higher in the large hepatic abscess group. A multivariate analysis revealed that underlying diabetes mellitus, hypoalbuminemia, high baseline high-sensitivity C-reactive protein (hs-CRP) and procalcitonin levels, and large maximal abscess diameter were independent factors associated with prolonged hospital stay. Regarding in-hospital mortality, acute kidney injury at admission and maximal diameter of the abscess were independent factors associated with in-hospital mortality., Conclusions: A large maximal diameter of the liver abscess at admission indicated prolonged hospitalization and poor prognosis. More aggressive treatment strategies with careful monitoring are warranted in patients with large liver abscesses.

The risk of acute functional decline increases with age, and concepts including frailty and post-acute care syndrome have been proposed; however, the effects of the nutritional status currently remain unclear. Patients admitted to the emergency department of Hitachi General Hospital for infectious diseases between April 2018 and May 2019 were included. To identify risk factors for functional decline at discharge, defined as Barthel Index <60, we investigated basic characteristics, such as age, sex, disease severity, the pre-morbid care status, and cognitive impairment, as well as laboratory data on admission, including albumin as a nutritional assessment indicator. In total, 460 surviving patients out of 610 hospitalized for infection were analyzed. In a multivariable logistic regression analysis, factors independently associated with Barthel Index <60 at discharge were age (adjusted OR 1.03, 95%CI 1.01-1.06, p = 0.022), serum albumin (adjusted OR: 0.63, 95%CI: 0.41-0.99, p = 0.043), and the need for care prior to admission (adjusted OR: 5.92, 95%CI: 3.15-11.15, p < 0.001). Hypoalbuminemia on admission in addition to age and the need for care prior to admission were identified as risk factors for functional decline in patients hospitalized for infection. Functional decline did not correlate with the severity of illness.

Background Total blood calcium (TCa) is routinely used to diagnose and manage mineral and bone metabolism disorders. Numerous laboratories adjust TCa by albumin, though literature suggests there are some limits to this approach. Here we report a large retrospective study on agreement rate between ionized calcium (iCa) measurement and TCa or albumin-adjusted calcium measurements. Methods We retrospectively selected 5055 samples with simultaneous measurements of iCa, TCa, albumin and pH. We subgrouped our patients according to their estimated glomerular filtration rate (eGFR), albumin levels and pH. We analyzed each patient's calcium state with iCa as reference to determine agreement rate with TCa and albumin-adjusted calcium using Payne, Clase, Jain and Ridefelt formulas. Results The Payne formula performed poorly in patients with abnormal albumin, eGFR or pH levels. In patients with low albumin levels or blood pH disorders, Payne-adjusted calcium may overestimate the calcium state in up to 80% of cases. Similarly, TCa has better agreement with iCa in the case of hypoalbuminemia, but performed similarly to the Payne formula in patients with physiological albumin levels. The global agreement rate for Clase, Jain and Ridefelt formulas suggests significant improvement compared to Payne calcium adjustment but no significant improvement compared to TCa. Conclusions Total and albumin-adjusted calcium measurement leads to a misclassification of calcium status. Moreover, accurate calcium state determination depends on blood pH levels, whose measurement requires the same pre-analytical restrictions as iCa measurement. We propose that iCa should instead become the reference method to determine the real calcium state.

Renal osteodystrophy (ROD) represents bone disorders related to chronic kidney disease (CKD) and several bone biomarkers are used clinically to predict ROD in CKD and hemodialysis (HD) patients. Serum albumin associates with inflammation other than nutritional status in these patients. Chronic inflammation is proved to relate with bone loss, however, the influence of hypoalbuminemia on bone biomarkers is still unclear. In this study, we evaluated the pattern of bone biomarker changes and further studied the influence of hypoalbuminemia on these biomarkers. A total of 300 maintenance HD patients were evaluated and 223 HD patients were included in the study. The patients were grouped according to serum parathyroid hormone (PTH) levels (PTH ≤150 pg/mL, PTH 150-300 pg/mL, PTH 300-600 pg/mL and PTH >600 pg/mL). Bone biomarkers and inflammatory markers were measured and their relation with PTH levels was determined. Significantly increased interleukin-6 (IL-6) and lower albumin levels were noted among PTH>600 pg/mL group. Bone turnover markers were significantly higher in PTH >600 pg/mL group (p< 0.05). Hypoalbuminemia significantly increased the fibroblast growth factor-23 (FGF-23) and procollagen type 1N-terminal propeptide (P1NP) in PTH ≤150 pg/mL, PTH 150-300 pg/mL, PTH 300-600 pg/mL groups, whereas no such relation was noted among PTH> 600 ng/dL group. In conclusion, hypoalbuminemia represents a chronic inflammation which differently relates to bone turnover markers according to serum PTH levels in SHPT patients. Thus, serum albumin measurement should be considered in determining bone disorders among these patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aim: The aim of this study is to determine the prognostic value of blood albumin (BA) in an unselected population of inpatients. Materials & methods: We performed prospective analysis of the medical documentation of 7279 patients hospitalized between July 2014 and September 2017. Results: Individuals with BA ≥3.35 mg/dl had significantly lower risk of in-hospital death (odds ratio [OR]: 0.22; 95% CI: 0.19-0.27; p < 0.001) and 14-day readmission (OR: 0.64; 95% CI: 0.55-0.77; p < 0.0001). BA concentration was the strongest favorable factor predicting inpatient survival in a Cox hazard regression model (OR: 0.43; 95% CI: 0.36-0.50; p < 0.001), did not correlate with body mass index and actual-to-ideal bodyweight ratio and was strongly affected by numerous non-nutrient factors. Conclusion: BA concentration showed similar or better predictive and diagnostic power in relation to all-cause in-hospital mortality and 14-day readmission among inpatients than selected multifactorial scores.

Although wasting marmoset syndrome (WMS) is one of the biggest problems facing captive marmoset colonies, the mechanisms underlying its pathogenesis remain unclear. In our clinical experience, it is difficult to cure WMS-affected marmosets with severe hypoalbuminemia. Thus, the mechanisms underlying hypoalbuminemia in WMS must be understood. In the present study, we investigated whether intestinal protein loss, a known reason for hypoalbuminemia, occurs in this disease. Fecal α1-proteinase inhibitor (α1-PI, also known as α1-antitrypsin) has been used to diagnose intestinal protein loss in other species. To develop an assay system for this protein, marmoset α1-PI was purified from plasma and antibodies against it were developed using the purified protein. Using the antibodies, a sandwich enzyme-linked immunosorbent assay (ELISA) to measure marmoset α1-PI was developed, and its detection sensitivity for fecal samples was ∼20-fold higher than that of a commercial kit for human α1-PI. From this ELISA, the reference intervals for serum and feces of healthy marmosets were 0.87-1.85 mg/ml and 0.53-395.58 μg/g, respectively. The average concentrations of α1-PI in serum and feces of seven WMS-affected marmosets were 1.17 mg/ml and 1357.58 μg/g, respectively. Although there were no significant differences in the serum concentrations between healthy and WMS-affected marmosets, the fecal concentrations were significantly higher in WMS-affected marmosets than in healthy individuals, suggesting that intestinal protein loss occurs in WMS. Intestinal protein loss of WMS-affected marmosets was significantly attenuated with treatment, suggesting that it is one of the mechanisms involved in the hypoalbuminemia observed in WMS., (© 2019 The Author(s).)

BACKGROUND Cerebral hemorrhage has been increasingly reported in patients with nephrotic syndrome (NS). However, the clinical features and pathogenesis of NS patients with cerebral hemorrhage remain unclear. MATERIAL AND METHODS From January 2007 to August 2017, continuous NS patients with cerebral hemorrhage at the First Affiliated Hospital of Guangxi Medical University were selected. The clinical manifestations, laboratory measurements, and neurological images of these patients were collected and analyzed. RESULTS Acute cerebral hemorrhage was recorded in 15 of 10 461 NS patients. The average age of these 15 patients (9 males and 6 females) was 50.87±23.27 years old. Among these 15 patients, conventional vascular risk factors were identified in 8 patients, hypoalbuminemia and proteinuria were recorded in all 15 patients, coagulopathy was observed in 9 patients, increased D-dimer level was recorded in 13 patients, hyperlipidemia was recorded in 11 patients, and impaired renal function was recorded in 9 patients. The hemorrhage developed in the lobe (n=9), basal ganglia (n=3), cerebellum (n=2), and cerebral hemisphere (n=1). Eight patients were in a coma on the day the cerebral hemorrhage occurred, while 12 patients had a poor prognosis after 30 days of hemorrhage onset. CONCLUSIONS Poor prognosis was recorded in NS patients with cerebral hemorrhage. Although conventional vascular risk factors have only been identified in 8 patients, biochemical abnormalities (hypoalbuminemia, proteinuria, elevated D-dimer, and hyperlipidemia) were recorded in the majority of these 15 patients. Furthermore, most of the hemorrhages developed in the lobes. Coagulopathy might be the potential pathogenesis of cerebral hemorrhage in NS patients.

Background: A study was conducted to evaluate the choroidal thickness (CT) and retinal thickness (RT) in paediatric patients with hypoalbuminaemia caused by nephrotic syndrome (NS). We also studied the correlation between the subfoveal choroidal thickness (SFCT) and serum protein concentration., Methods: This was a cross-sectional study. Fifty-one paediatric patients with hypoalbuminaemia caused by NS and 41 normal subjects were included in the study. Enhanced depth imaging optical coherence tomography (EDI-OCT) was performed to measure the RT and CT. The RT and CT were measured manually at intervals of 0.5 mm along a horizontal line through the macular fovea between 2.5 mm nasal and 2.5 mm temporal to the fovea. Clinical data including measurements of serum proteins were obtained., Results: The mean RTs at the T2.5, T2, N1.5, N2, and N2.5 locations and the average macular horizontal RT were slightly greater in the NS group than those in the control group. The mean CTs at all locations were significantly greater in the NS group than those in the control group; the difference was most significant at the fovea (373.8 ± 74.9 μm vs. 280.2 ± 57.1; p < 0.001). The SFCT in patients with NS was correlated with age (r = - 0.307, p = 0.003), body height (r = - 0.320, p = 0.022), body weight (r = - 0.343, p = 0.014), axial length (AL, r = - 0.237, p = 0.023), total protein (TP, r = - 0.302, p = 0.031), albumin (ALB, r = - 0.285, p = 0.042), prealbumin (PA, r = - 0.303, p = 0.033) and 24-h urine volume (UV, r = - 0.298, p = 0.034). Multiple linear regression analysis showed that the TP concentration and body weight had the highest correlation with the SFCT (R 2  = 0.220, p < 0.05)., Conclusions: The macular RT is slightly increased and the macular CT is significantly increased in paediatric patients with hypoalbuminaemia caused by NS, indicating fluid accumulation in the retina and choroid. There is a negative correlation between the SFCT and serum TP concentration. Thus, the serum TP concentration is an important indicator of CT in patients with hypoalbuminaemia.

Entamoeba histolytica is a protozoan parasite that affects a large proportion of the world's population and causes amoebic dysentery and extra-intestinal disease. Many individuals remain asymptomatic during colonisation; in 10% of individuals, the parasite breaks through the mucosal barrier and leads to invasive disease. An eight-month-old girl who was evaluated for hypo-albuminaemia and was diagnosed with amoebic colitis is reported. To the best of our knowledge, this is the first report of hypo-albuminaemia owing to amoebic colitis in any age group.

Congenital analbuminemia (OMIM # 616000) is an extremely rare autosomal recessive disorder, caused by variations in the albumin gene (ALB), which is generally thought to be a relatively benign condition in adulthood, but seems to be potentially life threatening in the pre- and peri-natal period. The subject of our study was a consanguineous family, in which we identified two analbuminemic individuals. Mutation analysis of ALB revealed that both are homozygous for a previously unreported insertion in exon 9 (c.1098dupT), causing a subsequent frame-shift with the generation of a premature stop codon, and an aberrant truncated putative protein product, p.Val367fsTer12. This variation is present in heterozygous condition in several other members of the family. The phenotype and the molecular genetics of CAA are discussed., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Envenomings by some populations of the Russell's viper (Daboia russelii) are characterized by a systemic capillary leak syndrome (CLS) which causes hemoconcentration, and is associated with the severity of envenoming. We adapted a model of CLS in mice by assessing hemoconcentration. The venom of D. russelii from Pakistan, but not that of another viperid, Bothrops asper, induced hemoconcentration and an increment in vascular permeability, being devoid of hemorrhagic activity at the doses tested. These findings reveal a dichotomous pattern of vasculotoxicity in viperid snake venoms. This difference might depend on variations in venom composition, especially regarding metalloproteinases (SVMPs), which are low in Pakistani D. russelii and high in B. asper. Inhibition of SVMPs and phospholipases A 2 in D. russelii venom did not abrogate hemoconcentration. An hemoconcentration-inducing fraction was obtained by chromatography, which contains vascular endothelial growth factor (VEGF), a known potent inducer of increment in vascular permeability. Exudates collected from tissue injected with venom also induced hemoconcentration, and the effect was inhibited by antivenom. However, the amount of venom in exudate required to induce the effect is low, as compared with venom dissolved in saline solution, hence suggesting that endogenous proteins present in the exudate, probably inflammatory mediators, potentiate the effect.

This article reports a pharmacokinetic case study of intravenous posaconazole in a 49-year-old male patient with intra-abdominal sepsis and hypoalbuminaemia receiving continuous venovenous haemodiafiltration. Concentration-time data following 300 mg intravenous posaconazole was analysed using a population pharmacokinetics approach. The 300-mg intravenous dose appears to be adequate for the treatment of yeast infections; however, for the treatment of invasive aspergillosis in isolated cases of critically ill patients with hypoalbuminaemia, the current dosing may not achieve desired exposure, although steady state exposure data are needed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hypoalbuminaemia has been previously described to predict worse non-relapse mortality (NRM) and inferior overall survival (OS) in allogeneic haematopoietic cell transplant (allo-HCT) recipients. Here, we evaluate the role of hypoalbuminaemia (<35 g/l) at time of onset of acute graft-versus-host disease (aGVHD) when incorporated into the refined aGVHD score. The study population consisted of 522 patients, median age 53 (18-75) years, who underwent an allo-HCT mostly for haematological malignancies. Standard risk (SR) aGVHD comprised 467 patients (89%) and the number of high risk (HR) cases was 55 (11%). Median follow-up for all surviving patients was 26 (3-55) months. Two-year OS was significantly better in patients with SR aGVHD with a serum albumin ≥35 g/l compared to SR with albumin <35 g/l [70% (95% CI = 64-76%) vs. 49% (95% CI = 42-56%), P < 0·0001]. Also, patients with SR aGVHD and a serum albumin level of ≥35 g/l had a significantly lower NRM at 1-year post-transplantation [6% (95% CI = 3-10%) vs. 25% (95% CI = 20-32%), P < 0·0001]. After our findings are validated in a large cohort of patients, we propose that hypoalbuminaemia should be incorporated into the refined aGVHD risk score to further its ability to predict outcomes within this group., (© 2018 John Wiley & Sons Ltd.)

Background: Hypoalbuminemia adversely affects the clinical outcomes of various cancers. The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3-5 weeks after treatment in patients with metastatic renal cell carcinoma (mRCC) who received sorafenib or sunitinib as first-line treatment., Methods: In this single-center, retrospective study, we assessed the progression-free survival (PFS) and overall survival (OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment. PFS and OS were compared between patients with post-treatment hypoalbuminemia (post-treatment albumin level <36.4 g/L) and those with normal post-treatment albumin level (albumin level ≥36.4 g/L). The Memorial Sloan Kettering Cancer Center (MSKCC) risk model stratified mRCC patients into three risk categories. Prognostic values of all patient characteristics including MSKCC risk category were determined by using univariate and multivariate Cox regression models. Prognostic value was further determined using the Harrell concordance index and receiver operating characteristic curve analysis., Results: The median PFS and OS of the 184 patients were 11 months (95% confidence interval [CI] 9-12 months) and 23 months (95% CI 19-33 months), respectively. Patients with post-treatment hypoalbuminemia had significantly shorter median PFS (6 months [95% CI 5-7 months]) and OS (11 months [95% CI 9-15 months]) than patients who had normal post-treatment albumin levels (PFS: 12 months [95% CI 11-16 months], P < 0.001; OS: 31 months [95% CI 24-42 months], P < 0.001), respectively. Multivariate analysis showed that post-treatment hypoalbuminemia was an independent predictor of PFS (hazard ratio [HR], 2.113; 95% CI 1.390-3.212; P < 0.001) and OS (HR, 2.388; 95% CI 1.591-3.585; P < 0.001). Post-treatment hypoalbuminemia could also be combined with the MSKCC risk category for better prediction about OS. The model that included post-treatment hypoalbuminemia and MSKCC risk category improved the predictive accuracy for PFS and OS (c-index: 0.68 and 0.73, respectively) compared with the basic MSKCC risk model (c-index: 0.67 and 0.70, respectively). The prognostic values for PFS and OS of the integrated MSKCC risk model involving post-treatment hypoalbuminemia were significantly more accurate than the basic MSKCC risk model using likelihood ratio analysis (both P < 0.001)., Conclusions: Post-treatment hypoalbuminemia can be considered an independent prognostic factor for patients with mRCC who undergo first-line treatment with tyrosine kinase inhibitors. Additionally, integrating post-treatment serum albumin level into the basic MSKCC risk model can improve the accuracy of this model in predicting patient overall survival and progression-free survival.

Background: Decision-making models for elderly patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) are in great demand., Patients and Methods: The Society of Lymphoma Treatment in Japan (SoLT-J), in collaboration with the West-Japan Hematology and Oncology Group (West-JHOG), collected and retrospectively analyzed the clinical records of ≥65-year-old patients with DLBCL treated with R-CHOP from 19 sites across Japan to build an algorithm that can stratify adherence to R-CHOP., Results: A total of 836 patients with a median age of 74 years (range, 65-96 years) were analyzed. In the SoLT-J cohort ( n  = 555), age >75 years, serum albumin level <3.7 g/dL, and Charlson Comorbidity Index score ≥3 were independent adverse risk factors and were defined as the Age, Comorbidities, and Albumin (ACA) index. Based on their ACA index score, patients were categorized into "excellent" (0 points), "good" (1 point), "moderate" (2 points), and "poor" (3 points) groups. This grouping effectively discriminated the 3-year overall survival rates, mean relative total doses (or relative dose intensity) of anthracycline and cyclophosphamide, unanticipated R-CHOP discontinuance rates, febrile neutropenia rates, and treatment-related death rates. Additionally, the ACA index showed comparable results for these clinical parameters when it was applied to the West-JHOG cohort ( n  = 281)., Conclusion: The ACA index has the ability to stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of elderly patients with DLBCL treated with R-CHOP. The Oncologist 2017;22:554-560 IMPLICATIONS FOR PRACTICE: Currently, little is known regarding how to identify elderly patients with diffuse large B-cell lymphoma who may tolerate a full dose of chemotherapy or to what extent cytotoxic drugs should be reduced in some specific conditions. The Society of Lymphoma Treatment in Japan developed a host-dependent prognostic model consisting of higher age (>75 years), hypoalbuminemia (<3.7 g/dL), and higher Charlson Comorbidity Index score (≥3) for such elderly patients. This model can stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of these patients and thus help clinicians in formulating personalized treatment strategies for this growing patient population., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2017.)

Background: Previous studies have identified hypoalbuminemia as a risk factor for negative outcome in dogs with chronic enteropathy (CE), but it has not been determined whether histopathology differs between CE dogs with and without hypoalbuminemia., Objective: To compare histopathologic findings in dogs with biopsy-diagnosed inflammatory CE with and without hypoalbuminemia., Animals: 83 dogs that had intestinal biopsy performed between January 2010-July 2015. Dogs had signs compatible with CE of at least 3-weeks' duration and no evidence of clinically relevant extra-gastrointestinal (GI) disease or potential non-GI causes of hypoalbuminemia. Dogs had primary diagnosis of inflammatory enteritis based on histopathology., Methods: Dogs were grouped into CE with normoalbuminemia (CEN; serum albumin concentration ≥3.0 g/dL, N = 46) or chronic enteropathy with hypoalbuminemia (CEH; serum albumin concentration <3.0 g/dL, N = 37). A pathologist (SLP) blinded to the groups reviewed biopsy samples and applied the World Small Animal Veterinary Association scoring system to all samples., Results: Intestinal biopsy samples from dogs in the CEH group were significantly more likely to display villous stunting, epithelial injury, crypt distension, and lacteal dilatation, and were more likely to have intraepithelial lymphocytes and lamina propria neutrophils than biopsy samples from dogs in the CEN group. Additionally, higher scores for each of the above listed histopathologic criteria were associated with a lower serum albumin concentration., Conclusions and Clinical Importance: Histopathologic features of chronic inflammatory enteropathy differ between dogs that are hypo- versus normoalbuminemic. Additional work is needed to elucidate the clinical relevance of these differences., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objective: To determine if preoperative hypoalbuminemia is associated with postoperative wound complications among patients with vulvar cancer., Methods: The National Surgical Quality Improvement Program database was queried for cases of vulvar cancer undergoing vulvectomy with or without lymphadenectomy (LND) from 2008 to 2013. Primary outcome was major wound complication. Secondary outcome was minor wound complication. Hypoalbuminemia was defined as albumin<3.5g/dL. Descriptive statistics and multivariable logistic regression were used for analysis., Results: Of 777 vulvar cancer patients, 514 (66.2%) had vulvar surgery alone and 263 (30.3%) had a LND. Median age was 66 (range 20-90) and median BMI was 28.9kg/m(2) (range 14.3-65.5). The incidence of wound complication was 10.4% (81/777) with 48 minor and 39 major complications. There was no difference in major wound complications when a LND was performed (p=1.0). Preoperative albumin was recorded in 429 patients (55.2%). Patients with hypoalbuminemia were more likely to have a major wound complication (OR 2.9 95% CI 1.1-7.3, p=0.02), even after adjusting for BMI, age, preoperative hematocrit, and diabetes (aOR 2.7 95% CI 1.1-7.1, p=0.04). In bivariable analysis, age, diabetes, and BMI were not associated with wound complication. Patients with a wound infection had 10 times the odds of being readmitted within 30days (OR 9.5, 95% CI 4.9-18.4, p<0.01)., Conclusions: Low preoperative albumin is associated with major postoperative wound complications in women undergoing surgery for vulvar cancer. When obtaining informed consent, patients with low albumin should be counseled regarding higher risks of postoperative wound complication., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Although several cases of severe hypoalbuminemia resulting from rice milk have been described in the past, today the use of rice milk without nutritional counseling to treat eczema is still a continuing, poor practice. We describe a kwashiorkor case in an infant with severe eczema exclusively fed with rice milk. It is well documented that rice milk is not a sufficient protein source. Moreover, only a small portion of eczema is triggered by food allergy. In conclusion this case raises the importance of managing dietary changes facing food allergies with responsibility for specialized consensus among pediatricians, nutritionists, endocrinologists and allergists all of them specialist professionals.

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.

We present the results of a study on the influence of albumin and prolactin concentrations and intravascular fluid pH on vein permeability for albumin. Permeability conditions were simulated depending on albumin concentration, pH value and prolactin concentration. In research model an in vitro method was applied using natural membrane - porcine vena cava inferior. Vein permeability was in the 0.63% to 5.69% range. In control variant permeability was ~2.54% and increased ~2 fold at decreased albumin and PRL concentrations. At increased albumin concentration permeability was decreased 4-fold. Albumin concentration significantly influences albumin permeability.

Objective: Serum albumin level is considered to be a marker reflecting the nutritional status in both healthy subjects and patients with malignancies. In this study we sought to investigate the association between pretransplantation serum albumin levels and prognosis among patients with leukemia who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT)., Methods: We retrospectively analyzed the data of 102 patients who underwent alloHSCT from 2004 to 2010. Pretransplant serum albumin, D-dimer, creatinine, and fibrinogen levels drawn within 10 days before transplantation were obtained from patient files. All parameters were divided into 2 groups: normal levels (group 1) versus abnormal levels (group 2). Our normal range of serum albumin is 3.2-5.2 g/dL; patients with pretransplantation albumin level ≥3.2 g/dL were included in group 1 versus group 2 with <3.2 g/dL., Results: The patients included 42 (41.1%) female and 60 (58.9%) male patients. The diagnoses were acute myeloblastic leukemia in 65 (63.7%) and acute lymphoblastic leukemia in 37 (36.3%). The median age was 26.0 years (range, 13-57). Univariate and multivariate analysis showed that patients with serum albumin levels <3.2 g/dL experienced significantly lower overall survival (OS) compared with ≥3.2 g/dL (hazard ratio [HR] 2.32 [range, 1.23-4.54] and HR 2.70 [range 1.38-5.26], respectively; P = .009). The median (range) OS in group 2 was 230.0 (184.0-544.0) days versus 570.5 (249.5-1,101.0) days in group 1 (P = .007). For disease free survival (DFS) evaluation, univariate and multivariate analysis showed that patients with serum albumin levels <3.2 g/dL had significantly lower values compared with patients with serum albumin ≥3.2 g/dL. (HR 2.17 [range 0.98-4.76] and HR 2.85 [range, 1.25-6.66], respectively; P = .046). The median (range) DFS in group 2 was 184.0 (61.0-524.0) days versus 445.0 (199.0-917.5) days in group 1 (P = .045). Among the patient characteristics the presence of infection was a significant independent variable for worse OS (HR 2.12 [range, 0.98-4.36], P = .036). The other parameters-age, sex, donor status, time to transplant interval, conditioning regimens, HLA status, and number of total infused CD34(+) cells-showed no significant effect on OS and DFS (P = .05)., Conclusions: Pretransplantation decreased serum albumin levels were associated with poor survival in patients with leukemia who underwent alloHSCT., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To quantify the impact of preoperative hypoalbuminemia on 30-day mortality and morbidity after gynecologic cancer surgery., Methods: Patients included in the National Surgical Quality Improvement Program (NSQIP) dataset who underwent any non-emergent surgery for gynecologic malignancy between 1/1/2008 and 12/31/2010 were identified. Analysis was conducted with albumin both as a dichotomous variable (<3.5 g/dl was defined as low albumin) and as a continuous variable to determine a clinically relevant cut-off value., Results: Of the total 3171 patients identified, 2110 had preoperative albumin levels available for analysis. In addition, 279 (13.3%) of these patients had low albumin levels. According to multivariate analysis, the low albumin group had significantly higher odds of developing one or more post-operative complications (OR-2,CI: 1.47-2.73, p<0.0001), three or more complications (OR-4.1,CI: 2.31-7.1, p<0.0001), surgical complications (OR-2.39,CI: 1.59-3.58, p<0.0001), thromboembolic complications (OR-2.59,CI: 1.33-5.06, p<0.0001), pulmonary complications (OR-4.06,CI: 2.05-8.03, p<0.0001), or infectious complications (OR-1.84,CI: 1.26-2.69, p<0.0001) and a higher 30-day mortality (OR-6.52,CI: 2.51-16.95, p<0.0001). Upon subgroup analysis, this difference was not found in patients undergoing laparoscopic surgery. In patients undergoing open surgery, the probability of experiencing one or more post-operative complications increased linearly with the decrease in albumin level; however, the probability of patients experiencing three or more complications and 30-day mortality increased sharply as soon as the albumin level decreased below 3g/dl., Conclusion: Preoperative albumin levels <3g/dL identify a population of patients at a very high-risk of experiencing perioperative morbidity and 30-day mortality after open surgery., (© 2013.)

Data on prognostic factors in pelvic PNET are minimal. We analyzed patients with pelvic PNET treated between June 2003 and November 2011 for prognostic factors. Forty-eight (13%) of 374 patients with PNET were pelvic PNET with median age 14.5 years (range: 5-33); 31 (65%) had metastases. After median follow-up of 20.4 months (range: 1.3-64.9), 3-year EFS, OS, and local-control-rate were 13.5 ± 5.5%, 15.4 ± 9%, and 41.3 ± 14.9%, respectively. Hypoalbuminemia (≤3.4 g/dl) predicted inferior EFS and OS for both entire cohort and metastatic group. All patients with hypoalbuminemia (n = 10) had low BMI as compared to 23/38 without hypoalbuminemia (P = 0.02)., (Copyright © 2013 Wiley Periodicals, Inc.)

Objectives/background: Ataxia with oculomotor apraxia defines a group of genetically distinct recessive ataxias including ataxia-telangectasia (A-T, ATM gene), ataxia with oculomotor apraxia type 1 (AOA1, APTX gene) and type 2 (AOA2, SETX gene). Although, a few unique clinical features differentiate each of these forms, the patients also share common clinical signs, such as the presence of cerebellar atrophy, sensorimotor axonal neuropathy, and elevated alpha-fetoprotein (AFP) serum level., Materials and Methods: We selected 22 Italian patients from 21 families, presenting progressive cerebellar ataxia, axonal neuropathy, and elevated serum AFP. We screened the coding regions of ATM, APTX and SETX genes for point mutations by direct sequencing or DHPLC, and searched genomic rearrangements in SETX by MLPA analysis. In selected cases, quantification of ATM and senataxin proteins was performed by Western blot. Clinical, neurophysiological, and neuroimaging data were collected., Results: Thirteen patients (12 families) carried SETX mutations (AOA2, 57%), two were mutated in ATM (A-T), and three in APTX (AOA1). In three remaining patients, we could not find pathogenic mutations, and in one case we found, in homozygosis, the SETX p.K992R polymorphism (population frequency 1-2%). In AOA2 cases, we identified 14 novel and three reported SETX mutations. Signs at onset were gait ataxia and facial dyskinesia, and the age ranged between 11 and 18 years. None had obvious oculomotor apraxia at the latest examination (age 14-45 years). The patient carrying the p.K992R SETX polymorphism had a phenotype similar to that of the diagnosed AOA2 patients, while the other three undiagnosed subjects had a very late onset and a few distinguishing clinical features., Discussion and Conclusions: We describe a large series of 13 AOA2 Italian patients. The phenotype was consistent with previous descriptions of AOA2, except for a higher frequency of strabism, and for the absence of oculomotor apraxia. In our survey ~60% of juvenile-to-adult cases with cerebellar ataxia, sensorimotor neuropathy and increased AFP are due to mutations in the SETX gene, and a smaller percentage to APTX and ATM gene mutations.

Presented correlation relationship between the functional state of the liver and arterial blood flow in children with chronic cholecystocholangitis. Found increases in the number of pigment and enzyme metabolism of liver, which directly depends on the slowing of blood flow in the basin of the hepatic artery. Is proved the inverse relationship growth of angular indices of internal blood flow in the hepatic artery on the lowering proteins.

Background and Objectives: FSGS histologic variants have correlated with outcomes in retrospective studies. The FSGS Clinical Trial provided a unique opportunity to study the clinical impact of histologic variants in a well defined prospective cohort with steroid-resistant primary FSGS., Design, Setting, Participants, & Measurements: Renal biopsies of 138 FSGS Clinical Trial participants aged 2-38 years enrolled from 2004 to 2008 were analyzed using the Columbia classification by core pathologists. This study assessed the distribution of histologic variants and examined their clinical and biopsy characteristics and relationships to patient outcomes., Results: The distribution of histologic variants was 68% (n=94) FSGS not otherwise specified, 12% (n=16) collapsing, 10% (n=14) tip, 7% (n=10) perihilar, and 3% (n=4) cellular. Individuals with not otherwise specified FSGS were more likely to have subnephrotic proteinuria (P=0.01); 33% of teenagers and adults had tip or collapsing variants compared with 10% of children, and subjects with these variants had greater proteinuria and hypoalbuminemia than not otherwise specified patients. Tip variant had the strongest association with white race (86%) and the lowest pathologic injury scores, baseline creatinine, and rate of progression. Collapsing variant had the strongest association with black race (63%, P=0.03) and the highest pathologic injury scores (P=0.003), baseline serum creatinine (P=0.003), and rate of progression. At 3 years, 47% of collapsing, 20% of not otherwise specified, and 7% of tip variant patients reached ESRD (P=0.005)., Conclusions: This is the first prospective study with protocol-defined immunomodulating therapies confirming poor renal survival in collapsing variant and showing better renal survival in tip variant among steroid-resistant patients.

Purpose: To investigate the association between preoperative low serum albumin level and acute kidney injury (AKI) after off-pump coronary artery bypass surgery (OPCAB) METHOD: We assessed preoperative and perioperative risk factors, and preoperative serum albumin concentration in 1,182 consecutive adult patients with preoperative normal renal function who underwent OPCAB surgery. Each patient was categorized by maximal Acute Kidney Injury Network (AKIN) criteria based on creatinine changes within the first 48 h after OPCAB. Logistic regression and propensity analyses were performed to evaluate the association between preoperative low serum albumin level and postoperative AKI., Results: Of the 1,182 patients, 334 (28.3%) developed AKI. Risk factors for AKI were old age, diabetes mellitus, maximal cardiovascular component of the sequential organ failure assessment score, perioperative transfusion, and postoperative C-reactive protein concentration. The risk of AKI was negatively correlated with the volume of crystalloid infused during surgery. A preoperative serum albumin level of <4.0 g/dl was independently associated Ith postoperative AKI [multivariable logistic analysis: odds ratio (OR) 1.83, 95 % confidence interval (CI) 1.27-2.64; P = 0.001; propensity analysis: OR 1.62, 95 % CI 1.12-2.35; P = 0.011). AKI was associated with prolonged stay in the intensive care unit and hospital and a high mortality rate., Conclusions: Preoperative low serum albumin level is an independent risk factor for AKI, and postoperative AKI is associated with poor outcomes after OPCAB in patients with preoperative normal renal function.

Background: Renal amyloidosis (RA) is a progressive and fatal renal disease., Hypothesis: Clinical and pathologic manifestations of RA differ between Chinese Shar-Pei (CSPs) and non-Shar-Pei (NSPs) dogs., Animals: 91 client-owned dogs., Methods: Retrospective review of medical records of dogs with a histological diagnosis of RA. Clinical and clinicopathologic data, hospitalization, complications, and outcome were compared between CSPs and NSPs., Results: Comorbid diseases were present in 64% of all dogs. CSPs were significantly younger compared to NSPs (median, 4.8 years; range: 3.6-17 versus median: 9.0 years; range: 2.4-11.1; P < .0001). The frequency of hypoalbuminemia, the most common biochemical abnormality, was higher in NSPs compared to CSPs (100% versus 64.7%, respectively; P < .001). Median serum creatinine concentration at presentation was 5.5 mg/dL, and was 3-fold higher in CSPs compared to NSPs (P = .005). Increased urine protein : creatinine ratio was present in 96% of all dogs. Nephrotic syndrome was present in 10% of NSPs but not in CSPs. Glomerular amyloid deposition, present in both CSPs (78.6%) and NSPs (95.6%) was most commonly diffuse, global, and severe. Renal medullar amyloidosis was more common in CSPs (100%) compared to NSPs (49.0%, P = .002), as was extrarenal amyloid deposition. The median survival time of all dogs was 5 days (range: 0-443 days). Serum creatinine concentration was significantly and negatively associated with survival (P = .025)., Conclusions and Clinical Relevance: The clinical and pathologic manifestations of amyloidosis differ between CSPs and NSPs. The survival time observed herein was unexpectedly low, and argues for early surveillance and management of the underlying predisposing conditions., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Objectives: The Glasgow Prognostic Score (GPS) is known to reflect the degree of tumor-associated cachexia and inflammation and is associated with survival in various malignancies. We investigated the value of the GPS in patients with cervical cancer., Methods: We included 244 consecutive patients with cervical cancer in our study. The pretherapeutic GPS was calculated as follows: patients with elevated C-reactive protein serum levels (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2, and patients with 1 or no abnormal value were allocated a score of 1 or 0, respectively. The association between GPS and survival was evaluated by univariate log-rank tests and multivariate Cox regression models. The GPS was correlated with clinicopathologic parameters as shown by performing chi2 tests., Results: In univariate analyses, GPS (P < 0.001, P < 0.001), International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001, P < 0.001), and lymph node involvement (P < 0.001, P < 0.001), but not patients' age (P = 0.2, P = 0.07), histological grade (P = 0.08, P = 0.1), and histological type (P = 0.8, P = 0.9), were associated with disease-free and overall survival, respectively. In a multivariate analysis GPS (P = 0.03, P = 0.04), FIGO stage (P = 0.006, P = 0.006), and lymph node involvement (P = 0.003, P = 0.002), but not patients' age (P = 0.5, P = 0.5), histological grade (P = 0.7, P = 0.6), and histological type (P = 0.4, P = 0.6) were associated with disease-free and overall survival, respectively. The GPS was associated with FIGO stage (P < 0.001) and histological grade (P = 0.02)., Conclusions: The GPS can be used as an inflammation-based predictor for survival in patients with cervical cancer.

Aim: To perform a risk factor analysis in patients with "risk organ" multi-system Langerhans cell histiocytosis at diagnosis., Methods: From 1987 to 2007, 77 patients were analyzed. A univariate analysis of the variables, age <2 years, lungs, spleen and hepatic involvement, presence of >or=2 risk involved organs, hypoalbuminemia and the presence of isolated anemia, anemia with thrombocytopenia with or without leukopenia at diagnosis was performed. Statistically significant variables were combined and entered into a multivariate analysis., Results: Fifty-six and 66 evaluable patients had hematologic and hepatic involvement at diagnosis, respectively. Among the hematologic patients, the subgroup of anemia with thrombocytopenia with or without leukopenia showed a significantly lower 5-year survival than the subgroup of isolated anemia (0.19 vs. 0.87, respectively; P=0.0001). Of all the patients, those with hypoalbuminemia had a 5-year survival of 0.16 compared with those with normal albumin levels, who had a 5-year survival of 0.65 (P<0.0001). In multivariate analysis, only anemia with thrombocytopenia with or without leukopenia and hypoalbuminemia were the independent risk factors (relative risk 3.77; confidence interval, 1.7-8.4; P<0.0011 and relative risk 2.59; confidence interval, 1.24-5.4; P<0.0112)., Conclusions: Anemia with thrombocytopenia with or without leukopenia and hypoalbuminemia, were associated with worse prognosis in multi-system Langerhans cell histiocytosis. Other therapeutic strategies should be considered at diagnosis or early during the initial treatment for this high risk subgroup of patients.

DNA single-strand breaks (SSBs) are non-overlapping discontinuities in strands ofa DNA duplex. Significant attention has been given on the DNA SSB repair (SSBR) system in neurons, because the impairment of the SSBR causes human neurodegenerative disorders, including early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), also known as ataxia-oculomotor apraxia Type 1 (AOA1). EAOH/AOA1 is characterized by early-onset slowly progressive ataxia, ocular motor apraxia, peripheral neuropathy and hypoalbuminemia. Neuropathological examination reveals severe loss of Purkinje cells and moderate neuronal loss in the anterior horn and dorsal root ganglia. EAOH/AOA1 is caused by the mutation in the APTX gene encoding the aprataxin (APTX) protein. APTX interacts with X-ray repair cross-complementing group 1 protein, which is a scaffold protein in SSBR. In addition, APTX-defective cells show increased sensitivity to genotoxic agents, which result in SSBs. These results indicate an important role ofAPTX in SSBR. SSBs are usually accompanied by modified or damaged 5'- and 3'-ends at the break site. Because these modified or damaged ends are not suitable for DNA ligation, they need to be restored to conventional ends prior to subsequent repair processes. APTX restores the 5'-adenylate monophosphate, 3'-phosphates and 3'-phosphoglycolate ends. The loss of function of APTX results in the accumulation of SSBs, consequently leading to neuronal cell dysfunction and death.

Goal: Recent studies suggest an increasing prevalence of atypical initial symptoms in patients with celiac disease (CD). The aim of this study was to compare the presenting symptoms of CD at 2 comparable referral institutions in South Florida, and in Ankara, Turkey. We retrospectively reviewed the records of patients with an initial diagnosis of CD by small bowel biopsy during the same (1991 to 2001) 10-year period at Cleveland Clinic Florida and University of Ankara, Turkey. A numerical score was assigned to presenting symptom and signs., Results: There were 28 patients in the South Florida group (51% men) and 40 patients in the Turkish group (35% men) (P=NS). The Turkish patients were significantly younger at diagnosis (36+/-2 y vs. US patients 66+/-3 y) (P<0.0001). Typical celiac symptom scores were similar (Turkey 1.1+/-0.2 vs. South Florida 1.3+/-0.3) (P=NS). Atypical symptom scores were significantly higher in the US patients (1.9+/-0.2) versus those from Turkey (1.2+/-0.1) (P<0.01). The Turkish patients were significantly more likely (P<0.01) to present with chronic diarrhea, hypoalbuminemia, and mactocytosis at the time of diagnosis., Conclusions: Although retrospective, this study points to striking differences in the clinical presentation of CD in individuals in South Florida, United States, and Ankara, Turkey, diagnosed during the same time period at both institutions. Turkish patients were younger, and more likely to present with chronic diarrhea, hypoalbuminemia, and microcytosis-as was more commonly seen in the United States in the 1960s and 70s. These findings raise the question of an interplay of demographics with diet and genetics in the presenting symptoms of CD in these 2 distant geographic areas.

We genetically screened patients with ataxia with ocular motor apraxia type 1 (AOA1)/early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), with a Japanese variant form of Friedreich's ataxia. Three patients were found to have a homozygous insertion mutation of the aprataxin gene (689insT). An elder sister of a patient in this series died of cerebral hemorrhage at the age of 45, and underwent autopsy. In her cerebellar cortex, the mean density of Purkinje cells in the flocculus had predominantly decreased to 6.7% of normal controls, whereas the Purkinje cells in the other areas of the cerebellar hemisphere had decreased to 78.2%. This suggests that the cerebellar flocculus is the primary affected lesion in AOA1/EAOH, which should be associated with ocular motor apraxia., ((c) 2007 S. Karger AG, Basel)

Objective: Hypoalbuminemia in acute stroke patients is associated with increased mortality and morbidity. The aim of our study was to determine the frequency and correlates of hypoalbuminemia in unselected cohort of patients with acute cerebral infarction., Design: Prospective study., Setting: University hospital., Subjects: Seven hundred and five consecutive ischemic stroke patients., Methods: Albumin and other serum protein fractions were measured within 36 h after stroke using electrophoresis., Results: Hypoalbuminemia defined as serum albumin level <35 g/l was found in 45.5% of patients. Serum albumin level correlates significantly with age (r=-0.13, P<0.01), Scandinavian Stroke Scale score (r=0.14, P<0.01), body temperature on admission (r=0.14, P<0.01), leukocyte count (r=-0.17, P<0.01), fasting glucose (r=-0.16, P<0.01), total cholesterol (r=0.14, P<0.01), alpha1-globulin (r=-0.48, P<0.01), alpha2-globulin (r=-0.49, P<0.01), beta-globulin (r=-0.26, P<0.01) and gamma-globulin (r=-0.35, P<0.01)., Conclusions: Hypoalbuminemia is a frequent finding in acute stroke patients and it is associated with more severe stroke and pro-inflammatory pattern of serum protein electrophoresis.

At least four disorders, ataxia telangiectasia (AT), an ataxia-telangiectasia-like disorder, early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH)/ ataxia with oculomotor apraxia type 1 (AOA1), and ataxia with oculomotor apraxia type 2, are accompanied by ocular motor apraxia (OMA), which is an impairment of saccadic eye movement initiation. The characteristic pathological findings of EAOH/AOA1 and AT are a severe loss of Purkinje cells, severe myelin pallor of the posterior columns, and moderate neuronal loss in the dorsal root ganglia and anterior horn. Purkinje cells stimulate the fastigial nucleus and suppress omnipause neurons to initiate saccadic eye movement. The selective loss of Purkinje cells might cause OMA and disturb the cancellation of the vestibulo-ocular reflex. These disorders have the following common clinical features: ataxia, involuntary movements, and peripheral neuronopathy. In addition, the causative genes for these disorders are associated with the DNA/RNA quality control system. The impairment of DNA/ RNA integrity results in selective neuronal loss in these recessive-inherited ataxias.

Hepatic tissue samples were obtained from 26 dogs humanely destroyed because of naturally occurring leishmaniosis (Leishmania infantum). None of the animals had palpable hepatomegaly or any other physical finding or historical evidence indicative of liver failure. However, serum biochemistry revealed hypoalbuminaemia (6/26), increased alkaline phosphatase (ALP) activity (15/26), and increased concentrations of total bilirubin (2/26) and post-prandial bile acids (4/26). Three main histological patterns were identified. In pattern 1 (3/26), the liver microarchitecture remained unchanged apart from the presence of individual or clustered macrophages in the sinusoids. In pattern 2 (20/26), there was multifocal, mild to moderate, granulomatous to pyogranulomatous infiltration of the hepatic parenchyma, particularly in the portal areas. Pattern 3 (3/26), which was the most severe form, was characterized by marked portal lymphoplasmacytic infiltration with occasional broaching of the limiting plate and extension into the adjacent parenchyma. In this pattern there was also mild portal fibrosis, together with lymphoplasmacytic aggregates within the parenchyma and small clusters of lymphocytes and plasma cells within the sinusoids. All three patterns were associated with hepatocyte vacuolation (15/26 dogs), and haemosiderin accumulation within the hepatocyte cytoplasm. Congestion was present in the liver of five dogs. No correlation was found between histopathological pattern and breed, sex, age, clinical manifestations, serum biochemical profile or parasite load in the hepatic tissue; patterns 1-3 may, however, represent sequential stages of hepatic leishmania infection during the chronic course of the disease.

The aim of this study was to identify the main factor affecting compliance and intima-media thickness of the elastic common carotid artery in continuous ambulatory peritoneal dialysis patients. Increased intima-media thickness and decreased arterial compliance are associated with elevated risk of cardiovascular disease. This study included 20 patients and 20 age- and sex- matched healthy control subjects. The compliance and intima-media thickness of the right common carotid artery within 1 cm to the bifurcation were measured three times using high-resolution B-mode echocardiography. Blood samples were obtained to measure levels of hemoglobin, phosphorus, total calcium, total CO2, serum albumin, C-reactive protein, serum total cholesterol, LDL- and HDL-cholesterol and triglycerides. We found that the compliance of common carotid artery was lower in the patient group than in the control group. In the patient group, the compliance of common carotid artery was positively correlated with serum albumin concentration, and intima-media thickness of common carotid artery was negatively correlated with serum albumin levels. Stepwise regression analysis showed that serum albumin concentration was independently related to the compliance of common carotid artery, suggesting hypoalbuminemia can independently give deleterious effects on the arterial wall in continuous ambulatory peritoneal dialysis patients.

Objective: To investigate the fate of the mesangial IgA deposits in the donor kidney after allograft transplantation., Methodology: Routine pre-transplant cadaveric donor kidney biopsy and repeated renal biopsies were performed at months 1, 3, and 6 after renal transplantation. The patients, 342 in number, were divided into IgA positive deposition kidney group (group A, n = 83) and non-IgA deposition kidney group (group B, n = 259). There were no significant differences between the two groups' sex, age, time of hemodialysis, warm ischemia time, cold ischemia time, complement-dependent cytotoxicity, level of panel-reactive assay, and the distribution of original disease., Results: Recipients in group A received donor kidney with glomerular mesangial proliferation and marked diffuse granular IgA deposition. All of them showed edema, nephrotic range protienuria, microhematuria, hypoalbuminemia, hypertension, and delayed graft function. Borderline change was higher in group A than in group B, 37.3 and 16.2% (p < 0.001), respectively. Acute allograft rejection was higher in group A than in group B, 31.3 and 19.3% (p < 0.001), respectively. The glomerular mesangial IgA deposits gradually disappeared from the mesangial regions in grafts of acute rejection. Graft survival in both groups was not significant, being 93.8 and 95.6% in 1 yr, and 86.7 and 88.3% in 3 yr., Conclusion: Clinical features of the recipients which received from donor kidney with glomerular mesangial proliferation and marked diffuse granular IgA deposition: edema, proteinuria, microhematuria, hypoalbuminemia, hypertension, and delayed graft function. The presence of IgA deposits on donated kidney, by a possible increase of the immunogenicity of these kidneys, might be a cause of increased rejection. There were no significant differences between the two groups on long-term allograft survival.