Preoperative Risk Factors for Predicting Postoperative Human Serum Albumin Infusion after Hip Fracture Surgery: Development and Validation of a Nomogram

Background: As one of the adverse events after hip fracture surgery, hypoalbuminemia is usually treated using human serum albumin infusion. However, the application of human serum albumin may cause complications such as postsurgical infection and increased mortality. Aims: To examine the preoperative risk factors of human serum albumin infusion after hip fracture surgery, establish a nomogram prediction model, and verify its accuracy. Study Design: A retrospective cross-sectional study. Methods: Eligible patients who underwent hip fracture surgery were divided into the infusion and non-infusion groups according to whether human serum albumin was infused or not. All patients were divided randomly into a training set and a testing set in line with the ratio of 7:3. In the training set, independent risk factors of postoperative human serum albumin infusion were determined by univariate logistic regression analysis, LASSO regression, and multivariate logistic regression analysis. Then, a nomogram model was established. Furthermore, the receiver operating characteristic curve and calibration curve were plotted, and decision curve analysis was performed for the training and testing sets to assess the predictability, discriminative ability, and clinical usefulness of the model. Results: This study included a total of 1,339 eligible patients, 141 of whom were injected with human serum albumin postoperatively. Altogether, the training set incorporated 939 patients, and the testing set included 400 patients. Multivariate logistic analysis indicated five independent risk factors, including chronic lung disease (odds ratio, 95% confidence interval, 2.618, 1.413-4.849, p = 0.002), (albumin; odds ratio, 95% confidence interval, 0.842, 0.787-0.900, p < 0.001), prothrombin time (odds ratio, 95% confidence interval, 1.252, 1.071-1.463, p = 0.005), red blood cells (odds ratio, 95% confidence interval, 0.370, 0.228-0.602, p < 0.001), and type of anesthesia (odds ratio, 95% confidence interval, 0.553, 0.327-0.937, p = 0.028). Fracture type, a clinically significant factor, was also considered. Finally, the nomogram model was built based on these seven predictors. The areas under the curve of the nomogram were 0.854 (95% confidence interval, 0.811-0.898) and 0.767 (95% confidence interval, 0.686-0.847) in the training and testing sets separately. As shown in the calibration curve, the predicted result was consistent with the observed one. The decision curve analysis indicated that the nomogram has good clinical value. Conclusion: Low preoperative serum albumin levels, low preoperative red blood cell counts, prolonged preoperative prothrombin time, history of chronic lung disease, and general anesthesia were independent risk factors for postoperative human serum albumin infusion. Besides, the fracture type, clinically significant factor, was also included. The nomogram that combined these six predictors could accurately predict the risk of postoperative human serum albumin infusion.

Development and Validation of a Nomogram for Predicting Albumin Transfusion After Spinal Tuberculosis Surgery: Based on Propensity Score Matching Analysis.

BACKGROUND: There have been few literature reports on the use of perioperative parameters to predict the risk of albumin transfusion after spinal tuberculosis surgery based on the application of nomogram and propensity score matching (PSM) analysis. OBJECTIVE: The purpose was to predict the risk of albumin transfusion after spinal tuberculosis surgery based on a combination of PSM and nomogram. METHODS: The clinical data of the patients were collected in our hospital, including preoperative clinical data, preoperative laboratory tests, and postoperative clinical data. All data were divided into 2 groups, including the albumin transfusion group and the non-albumin transfusion group. The PSM analysis was used to adjust the baseline data of the 2 groups. The nomogram was further constructed. The practicability and predictive ability of the model were evaluated. RESULTS: A total of 494 cases were collected in this article; 102 pairs by PSM analysis were used to construct the nomogram. There were statistical differences in surgical approach, aspartate aminotransferase/alanine aminotransferase levels, drainage, and kyphosis by logistic analysis, and these parameters were included in the construction of the nomogram. The C-index of the prediction model was 0.734. The area under the curve was 0.73 and the net benefit was between 0.13 and 0.99. The calculated C-index was 0.71 by the internal verification method. CONCLUSIONS: The PSM analysis had a good matching effect and the nomogram had a good predictive ability. Surgical approach, aspartate aminotransferase/alanine aminotransferase levels, drainage, and kyphosis might be predictors of albumin transfusion after spinal tuberculosis surgery.

Multiphysics Modeling and Simulation of Subcutaneous Injection and Absorption of Biotherapeutics: Sensitivity Analysis.

PURPOSE: A multiphysics simulation model was recently developed to capture major physical and mechanical processes of local drug transport and absorption kinetics of subcutaneously injected monoclonal antibody (mAb) solutions. To further explore the impact of individual drug attributes and tissue characteristics on the tissue biomechanical response and drug mass transport upon injection, sensitivity analysis was conducted and reported. METHOD: Various configurations of injection conditions, drug-associated attributes, and tissue properties were simulated with the developed multiphysics model. Simulation results were examined with regard to tissue deformation, porosity change, and spatiotemporal distributions of pressure, interstitial fluid flow, and drug concentration in the tissue. RESULTS: Injection conditions and tissue properties were found influential on the mechanical response of tissue and interstitial fluid velocity to various extents, leading to distinct drug concentration profiles. Intrinsic tissue porosity, lymphatic vessel density, and drug permeability through the lymphatic membrane were particularly essential in determining the local absorption rate of an mAb injection. CONCLUSION: The sensitivity analysis study may shed light on the product development of an mAb formulation, as well as on the future development of the simulation method.

Polymerized albumin restores impaired hemodynamics in endotoxemia and polymicrobial sepsis.

Fluid resuscitation following severe inflammation-induced hypoperfusion is critical for the restoration of hemodynamics and the prevention of multiorgan dysfunction syndrome during septic shock. Fluid resuscitation with commercially available crystalloid and colloid solutions only provides transient benefits, followed by fluid extravasation and tissue edema through the inflamed endothelium. The increased molecular weight (M.W.) of polymerized human serum albumin (PolyHSA) can limit fluid extravasation, leading to restoration of hemodynamics. In this prospective study, we evaluated how fluid resuscitation with PolyHSA impacts the hemodynamic and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model. Additionally, we evaluated fluid resuscitation with PolyHSA in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Resuscitation with PolyHSA attenuated the immune response and improved the maintenance of systemic hemodynamics and restoration of microcirculatory hemodynamics. This decrease in inflammatory immune response and maintenance of vascular wall shear stress likely contributes to the maintenance of vascular integrity following fluid resuscitation with PolyHSA. The sustained restoration of perfusion, decrease in pro-inflammatory immune response, and improved vascular integrity that results from the high M.W. of PolyHSA indicates that a PolyHSA based solution is a potential resuscitation fluid for endotoxic and septic shock.

Albumin in Advanced Liver Diseases: The Good and Bad of a Drug!

Human serum albumin is the most abundant plasma protein, and it regulates diverse body functions. In patients with advanced and decompensated cirrhosis, serum albumin levels are low because of a reduction in the hepatocyte mass due to disease per se and multiple therapeutic interventions. Because of their oncotic and nononcotic properties, administration of human albumin solutions (HAS) have been found to be beneficial in patients undergoing large-volume paracentesis or who have hepatorenal syndrome or spontaneous bacterial peritonitis. Albumin also improves the functionality of the immune cells and mitigates the severity and risk of infections in advanced cirrhosis. Its long-term administration can modify the course of decompensated cirrhosis patients by reducing the onset of new complications, improving the quality of life, and probably providing survival benefits. There is, however, a need to rationalize the dose, duration, and frequency of albumin therapy in different liver diseases and stages of cirrhosis. In patients with acute-on-chronic liver failure, potentially toxic oxidized isoforms of albumin increase substantially, especially human nonmercaptalbumin and 2, and nitrosoalbumin. The role of administration of HAS in such patients is unclear. Determining whether removal of the pathological and dysfunctional albumin forms in these patients by "albumin dialysis" is helpful, requires additional studies. Use of albumin is not without adverse events. These mainly include allergic and transfusion reactions, volume overload, antibody formation and coagulation derangements. Considering their cost, limited availability, need for a health care setting for their administration, and potential adverse effects, judicious use of HAS in liver diseases is advocated. There is a need for new albumin molecules and economic alternatives in hepatologic practice.

Entropy-Driven Quick Loading of Functional Proteins in Nanohydrogels for Highly Efficient Tumor Targeting Therapy.

With the gradual deep understanding of the tumorigenesis and development process, nanodrug are thought to have great prospects for individualized treatment of tumors. To deliver adequate concentration of active ingredients to targeted tissues, proteins are usually used as carriers to avoid clearance by the immune system. Herein, a new strategy is developed for preparation of the protein-functionalized targeting nanodrugs; different kinds of proteins (albumin, horseradish, transferrin, and ricin) can be quickly loaded in polyacrylic acid nanohydrogels (PAA-NGs) without discrimination within 1 min under the strong driving force of entropy; and the loading efficiency can reach 99% with about 50% loading content. Meanwhile, the activity of the released protein can be well retained. After oriented binding of the targeting agent on the surface of the nanocarriers by a unique and facile technique, the protein-loaded nanodrug exhibits excellent tumor cell uptake and targeting effect. The excellent targeting ability from the oriented binding is further proved by comparing with the non-oriented targeting system. With quick loading of the anti-tumor protein of ricin and oriented binding of transferrin protein (Tf), the targeting nanodrug (PAA-BB@Ricin/Tf) shows a remarkable anti-tumor effect. This study proves a new universal delivery and targeting strategy for improving the nanodelivery system, which has great potentials for clinical application.

Role of Liver Growth Factor (LGF) in Parkinson's Disease: Molecular Insights and Therapeutic Opportunities.

Parkinson's disease is the most common neurodegenerative movement disorder with unclear etiology and only symptomatic treatment to date. Toward the development of novel disease-modifying agents, neurotrophic factors represent a reasonable and promising therapeutic approach. However, despite the robust preclinical evidence, clinical trials using glial-derived neurotrophic factor (GDNF) and neurturin have been unsuccessful. In this direction, the therapeutic potential of other trophic factors in PD and the elucidation of the underlying molecular mechanisms are of paramount importance. The liver growth factor (LGF) is an albumin-bilirubin complex acting as a hepatic mitogen, which also exerts regenerative effects on several extrahepatic tissues including the brain. Accumulating evidence suggests that intracerebral and peripheral administration of LGF can enhance the outgrowth of nigrostriatal dopaminergic axonal terminals; promote the survival, migration, and differentiation of neuronal stem cells; and partially protect against dopaminergic neuronal loss in the substantia nigra of PD animal models. In most studies, these effects are accompanied by improved motor behavior of the animals. Potential underlying mechanisms involve transient microglial activation, TNF-α upregulation, and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) and of the transcription factor cyclic AMP response-element binding protein (CREB), along with anti-inflammatory and antioxidant pathways. Herein, we summarize recent preclinical evidence on the potential role of LGF in PD pathogenesis, aiming to shed more light on the underlying molecular mechanisms and reveal novel therapeutic opportunities for this debilitating disease.

On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites.

BACKGROUND & AIMS: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. METHODS: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. RESULTS: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5-4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. CONCLUSION: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin - 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. LAY SUMMARY: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.

Co-administration of paclitaxel and 2-methoxyestradiol using folate-conjugated human serum albumin nanoparticles for improving drug resistance and antitumor efficacy.

The use of chemotherapeutic drug paclitaxel (PTX) for the treatment of tumors has several limitations, including multidrug resistance (MDR) and serious adverse reactions. This research aims to co-encapsulate PTX and the chemosensitizer 2-methoxyestradiol (2-ME) into folate-conjugated human serum albumin nanoparticles (FA-HSANPs) to reduce multiple drug resistance and improve antitumor efficiency. The results show PTX/2-ME@FA-HSANPs had uniform particle size (180 ± 12.31 nm) and high encapsulation efficacy. It also exhibited highly potent cytotoxicity and apoptosis-inducing activities in the G2/M phase of PTX-resistant EC109/Taxol cells. Moreover, PTX/2-ME@FA-HSANPs not only displayed better inhibition of tumor growth in S-180 tumor-bearing mice than PTX alone but also reduced pathological damage to normal tissues. In summary, PTX/2-ME@FA-HSANPs could be a promising vehicle for tumor therapy and reducing drug resistance. This research will also provide references for other MDR treatment.

Investigating the Effect of Fresh Frozen Plasma and Albumin on DNA Damage and Oxidative Stress Biomarkers in Poisoning Cases by Organophosphates.

The efficacy of albumin and fresh frozen plasma (FFP) and their effects on biomarkers of oxidative stress has been evaluated. In a randomized clinical control trial, 33 poisoned patients by Organophosphate (OP) were enrolled in the research and divided into three groups. The first group underwent conventional treatments by atropine and pralidoxime (control group); the second and third groups, in addition to traditional treatments, received albumin and FFP. Cholinesterase (ChE) enzyme activity, total antioxidant capacity (TAC), serum thiol groups (TTG), malonyl aldehyde (MDA) and DNA damage were measured in all treatment and control groups. Patients were matched in terms of demographic characteristics at the beginning of the study. ChE activity was increased in all three groups during treatment, which was more noticeable in the FFP group and was statistically significant in both albumin and FFP group compared to the control group (p<0.05). TAC increased, and TTG decreased in FFP and albumin groups compared to the control group; no significant difference was observed. MDA decreased in albumin and FFP and was significantly different in the FFP group compared to the control group (p<0.05). The amount of DNA damage in FFP and albumin groups decreased, and there was a significant difference compared to the control group (p<0.05). According to the results of this study, due to the decrease of oxidative damage parameters and the increase of antioxidant parameters in albumin and specially FFP groups, FFP may be considered as an adjunctive treatment for OP poisoning.

Physiologically inspired culture medium prolongs the lifetime and insulin sensitivity of human hepatocytes in micropatterned co-cultures.

Given significant species-specific differences in liver functions, cultures of primary human hepatocytes (PHHs) are useful for assessing drug metabolism and to mitigate the risk of drug-induced hepatotoxicity in humans. While significant advances have been made to keep PHHs highly functional for 2-4 weeks in vitro, especially upon co-culture with both liver- and non-liver-derived non-parenchymal cells (NPCs), the functional lifespan of PHHs is 200-400 days in vivo. Therefore, it is desirable to determine culture conditions that can further prolong PHHs functions in vitro for modeling chronic drug exposure, disease pathogenesis, and to provide flexibility to the end-user for staggering drug incubations across multiple culture batches. Most PHH culture platforms utilize supraphysiologic levels of glucose and insulin and bovine-derived serum when including NPCs, which can alter PHH functions. Therefore, here we developed a culture medium containing physiologic levels of glucose (5 mM), insulin (500 pM), and human serum (10 % v/v) and tested its effects on micropatterned co-cultures (MPCCs) in which PHHs are organized onto collagen domains of empirically optimized dimensions and surrounded by 3T3-J2 murine fibroblasts that express liver-like molecules and induce higher PHH functions than liver-derived NPCs. Our physiologically-inspired culture medium allowed better retention of PHH morphology, polarity, and functions (albumin and urea, cytochrome-P450 activities, and sensitivity to insulin-mediated inhibition of gluconeogenesis) for up to 10 weeks relative to the traditional medium. Finally, PHHs in the physiologic medium displayed clinically-relevant responses to prototypical drugs for hepatoxicity and cytochrome-P450 induction. Ultimately, our physiologic culture medium could find broader utility for the continued development of PHH-NPC co-cultures for drug development, investigating the effects of patient-derived sera on PHH functions and disease phenotypes, and for use in cell-based therapies.

Congenital nephrotic syndrome: is early aggressive treatment needed? Yes.

Congenital nephrotic syndrome (CNS) was primarily considered one disease entity. Hence, one treatment protocol was proposed in the beginning to all CNS patients. Today, with the help of gene diagnostics, we know that CNS is a heterogeneous group of disorders and therefore, different treatment protocols are needed. The most important gene defects causing CNS are NPHS1, NPHS2, WT1, LAMB2, and PLCE1. Before active treatment, all infants with CNS died. It was stated already in the mid-1980s that intensive medical therapy followed by kidney transplantation (KTx) should be the choice of treatment for infants with severe CNS. In Finland, early aggressive treatment protocol was adopted from the USA and further developed for treatment of children with the Finnish type of CNS. The aim of this review is to state reasons for "early aggressive treatment" including daily albumin infusions, intensified nutrition, and timely bilateral nephrectomy followed by KTx at the age of 1-2 years.

Congenital nephrotic syndrome: is early aggressive treatment needed?-No.

The management of infants with congenital nephrotic syndrome (CNS) is very challenging as they are prone to severe complications such as hemodynamic disturbances, infections, thromboses, and impaired growth, and most will develop end-stage kidney disease (ESKD) within a few years. Since the seventies, an "aggressive" approach, including daily albumin infusions, early nephrectomies, dialysis, and transplantation, has dramatically improved survival and morbidity. More recent case-note reviews have reported successful conservative treatment (using optimized nutrition, complication prophylaxis, and delayed renal replacement therapy), which led to similarly good outcomes and low complication rates. This questions the indications for early preemptive bilateral nephrectomy and dialysis given the mortality and morbidity rates in dialysis in infants and their life-long management with possible repeated transplantations. Two large series provide the most recent evidences supporting the conservative management: firstly, at least 55% children with CNS are not spontaneously in ESKD at the age of 2 years; secondly, albumin tapering/discontinuation and hospital discharge are possible before nephrectomy; and lastly, CNS complication rates are similar in case of preemptive nephrectomies or conservative care. Until now, no clear genotype-phenotype correlation has been identified to guide clinical management. Taken together, these data support the safety of conservative care until ESKD in a subset of patients with CNS.

HSA-curcumin nanoparticles: a promising substitution for Curcumin as a Cancer chemoprevention and therapy.

BACKGROUND: Many solutions have been evaluated to deal with "chemotherapy and radiation-resistant cancer cells' as well as "severe complications of chemotherapy drugs". One of these solutions is the use of herbal compounds with antioxidant properties. Among these antioxidant compounds, curcumin is identified as the strongest one to inhibit cancerous cells proliferation. However, its clinical trials have encountered many constraints, because curcumin is insoluble in water and unstable in physiological conditions. To overcome these limitations, in this study, curcumin was conjugated with human serum albumin (HSA) and its effects on breast cancer cell lines were also measured. METHODS: After making of HSA-curcumin nanoparticles (NPs) by the desolvation technique, they were characterized by the FTIR, DLS, TEM, and SEM method. At the end, its anticancer effects have been examined using MTT test and apoptosis assay. RESULTS: The FTIR graph confirmed that curcumin and HSA have been conjugated along with each other. Particles size was reported to be 220 nm and 180 nm by DLS and SEM, respectively. The zeta potential of HSA-curcumin NPs was -7 mV, while it was -37 mV for curcumin. The MTT and apoptosis assay results indicated that the toxicity of HSA-curcumin NPs on the normal cell are less than curcumin; however, its anti-cancer effects on the cancer cells are much greater, compared to curcumin. CONCLUSION: HSA-curcumin NPs increase curcumin solubility in water as well as its stability in physiological and acidic conditions. These factors have the ability of overwhelming the limitations on using curcumin alone, and they could result in a significant increase in the toxicity of curcumin on the cancer cells without increasing its toxicity on the normal cells. Grapical abstract.

Preparation, radiolabeling with 99mTc and 67Ga and biodistribution studies of albumin nanoparticles covered with polymers. / Preparación, radiomarcaje con 99mTc y 67Ga y estudios de biodistribución de nanopartículas de albúmina con recubrimientos poliméricos.

OBJECTIVE: To optimize radiolabeling with 99mTc and 67Ga of albumin nanoparticles coated with 4 differents synthetic polymers and to evaluate their stability in vivo and in vitro, as well as their biodistribution in vivo after intravenous administration. MATERIAL AND METHODS: The nanoparticles were prepared using albumin and NOTA-modified albumin by the desolvation method and coated with 4 different polymers; HPMC, GMN2, GPM2 and GTM2. They were purified, lyophilized and characterized. Radiolabelling with 99mTc was perfomed with 74 MBq of 99mTc sodium pertechnetate, previously reduced with and acid solution of tin chloride at different concentrations (0.003, 0.005, 0.007, 0.01, 0.05 and 0.1mg/ml) and at different times (5, 10, 15, 30 and 60minutes) and temperatures (room temperature, 40°C and 60°C). Radiolabelling with 67Ga was perfomed by incubation of the nanoparticles with 37 MBq of 67Gallium chloride (obtained from commercial gallium-67 citrate) at different times (10 and 30minutes) and temperatures (room temperature, 30°C and 60°C), and posterior purification with microconcentrators. The radiochemical purity was evaluated by TLC. Stability studies of radiolabeled nanoparticles in physiological serum and blood plasma were perfomed. Biodistribution studies of nanoparticles coated with GPM2 polymer were carried out in Wistar rats after intravenous administration of the nanoparticles. Control animals were carried out with 99mTc sodium pertechnetate and 67Ga chloride. To do so, the animals were killed and activity in organs was measured in a gamma counter. RESULTS: 99mTc labeling was carried out optimally with a tin concentration of 0.007mg/ ml for the GPM2 nanoparticles and 0.005mg / ml for the rest of the formulations, with a radiolabelling time of 10minutes at room temperature. In the case of 67Ga the label was optimized at 30° C temperature and 30minutes of incubation. In both cases the radiochemical purity obtained was greater than 97%. The nanoparticles showed high stability in vitro after 48hours of labeling (70% nanoparticles labeled with 99mTc and 90% those labeled with 67Ga). Biodistribution studies of nanoparticles 99mTc -GPM2 and 67Ga -NOTA-GPM2 showed a high accumulation of activity in the liver at 2 and 24hours after intravenous administration. CONCLUSION: The labeling procedure with 99mTc and 67Ga of albumin and albumin modified with NOTA nanoparticles allows obtaining nanoparticles with high labeling yields and adequate in vitro stability, allowing their use for in vivo studies.

Albumin: Indications in chronic liver disease.

Albumin is currently employed as a plasma expander to prevent and treat specific complications of cirrhosis with ascites, such as the prevention of paracentesis-induced circulatory dysfunction and renal dysfunction induced by spontaneous bacterial peritonitis, as well as the diagnosis and treatment of acute kidney injury and hepatorenal syndrome. Recently, evidence has shown that long-term albumin administration in patients with decompensated cirrhosis reduces mortality and incidence of complications, eases the management of ascites, is cost effective, and has a good safety profile.

Virus-mimicking mesoporous organosilica nanocapsules with soft framework and rough surface for enhanced cellular uptake and tumor penetration.

An enveloped virus with soft and rough shells has strong penetration ability for cells. Inspired by the unique structure of virus, we successfully constructed virus-mimicking mesoporous organosilica nanocapsules (denoted as VMONs) for the first time by decorating small-sized silica nanoparticles on soft mesoporous organosilica hollow spheres. TEM and SEM images reveal that the prepared VMONs display uniform diameters (240 nm), a soft framework, a rough surface, and excellent dispersity. Quantitative nanomechanical mapping further demonstrates that the VMONs possess an extremely low Young's modulus (36 MPa) and a scraggly surface. In view of the successful construction of the virus-mimicking nanocapsules, the VMONs are further modified with human serum albumin (HSA) and Cy5.5-maleimide (Mal-Cy5.5) to investigate their cell penetration ability. Flow cytometry analysis reveals that the internalization of VMONs@HSA-Cy5.5 increases 2.74-fold compared to that of the conventional mesoporous nanosphere. Confocal laser scanning microscopy images show that the VMONs@HSA-Cy5.5 diffuses deeper for multicellular spheroids compared to both hard and soft mesoporous organosilica nanospheres. The penetration ability of the VMONs and SMONs increases 18.49 and 6.13-fold compared to that of MONs at the depth of 60 µm. Thanks to the excellent cellular penetration ability, the virus-mimicking VMONs@HSA-Cy5.5 can effectively deliver the anticancer drug doxorubicin (Dox) into drug-resistant MCF-7/ADR human breast cancer cells and significantly enhance the chemotherapeutic efficacy. Taken together, the constructed virus-mimicking organosilica nanocapsules with a soft framework and a rough surface possess strong cellular internalization and tumor penetration abilities, providing a unique and effective nanoplatform for biomedical applications.

Effect of postoperative hypoalbuminemia and supplement of human serum albumin on the development of surgical site infection following spinal fusion surgery: a retrospective study.

PURPOSE: To determine the association between postoperative hypoalbuminemia and the development of surgical site infection (SSI) and evaluate whether the supplement of exogenous human serum albumin (HSA) in patients following spinal surgery would decrease the rate of postoperative SSI. METHODS: We performed a retrospective review of all patients who underwent lumbar spinal fusion surgery in our institution between January 2014 and December 2018. Patients with postoperative SSI were identified. We reviewed the demographic and clinical records of the patients and performed multiple logistic regression models to clarify the relevance between postoperative hypoalbuminemia, the supplement of HSA and SSI. Statistical adjustment for the potential confounders was also performed to exclude possible variation. RESULTS: Twenty-four of 602 patients developed SSI after lumbar spinal fusion surgery. No statistical significance was found between postoperative hypoalbuminemia and SSI rate (OR 0.74; 95% CI 0.22-2.48; P = 0.6199). However, the supplement of exogenous HSA was significantly associated with increased postoperative SSI rate (OR 1.21; 95% CI 1.05-1.41; P = 0.0094). Interestingly, stratified analyses showed supplement of HSA in patients without postoperative hypoalbuminemia increased the risk of SSI (OR 2.55; 95% CI 1.01-6.45; P = 0.0475), compared with patients with postoperative hypoalbuminemia (OR 1.17; 95% CI 1.00-1.36; P = 0.0434). CONCLUSIONS: The present study suggests that postoperative hypoalbuminemia is not associated with the development of SSI after spinal surgery. However, the supplement of HSA following spinal surgery will increase the rate of SSI. These slides can be retrieved under Electronic Supplementary Material.