Longitudinal analysis of CSF HIV RNA in untreated people with HIV: Identification of CSF controllers.

Interindividual variation of human immunodeficiency virus (HIV) RNA setpoint in cerebrospinal fluid (CSF) and its determinants are poorly understood, but relevant for HIV neuropathology, brain reservoirs, viral escape, and reseeding after antiretroviral interruptions. Longitudinal multicentric study on demographic, clinical, and laboratory correlates of CSF HIV RNA in 2000 follow-up visits from 597 people with HIV (PWH) off antiretroviral therapy (ART) and with plasma HIV RNA > the lower limit of quantification (LLQ). Factors associated with CSF control (CSFC; CSF HIV RNA < LLQ while plasma HIV RNA > LLQ) and with CSF/plasma discordance (CSF > plasma HIV RNA > LLQ) were also assessed through mixed-effects models. Posthoc and sensitivity analyses were performed for persistent CSFC and ART-naïve participants, respectively. Over a median follow-up of 2.1 years, CSF HIV RNA was associated with CD4+ and CD8+ T cells, CSF leukocytes, blood-brain barrier (BBB) integrity, biomarkers of iron and lipid metabolism, serum globulins, past exposure to lamivudine, and plasma HIV RNA (model p < 0.0001). CSFC (persistent in 7.7% over 3 years) and CSF/plasma discordance (persistent in <0.01% over 1 year) were variably associated with the same parameters (model p < 0.001). Sensitivity analyses confirmed most of the previous associations in participants never exposed to ART. Persistent CSFC was associated with higher CD4+ T-cell count nadir (p < 0.001), lower serum globulins (p = 0.003), and lower CSF leukocytes (p < 0.001). Without ART, one in 13 PWH had persistently undetectable CSF HIV RNA, while persistent CSF/plasma discordance was extremely rare over years. Immune responses, inflammation, BBB permeability, and iron and lipid metabolism were all associated with HIV replication in CSF.

Association of serum globulin with all-cause mortality in incident hemodialysis patients.

BACKGROUND: Serum globulin is a major component of total protein and can be elevated in inflammatory disease states. While inflammation is common in hemodialysis patients and associated with mortality and morbidity, the association between serum globulin and mortality has never been examined in hemodialysis patients. METHODS: In a retrospective cohort of 104 164 incident hemodialysis patients treated by a large dialysis organization from 2007 to 2011, we explored the association between baseline serum globulin, albumin: globulin (A:G) ratio and serum protein levels and all-cause, cardiovascular and infection-related mortality with adjustments for demographic variables and laboratory markers of malnutrition and inflammation using Cox proportional hazards models. RESULTS: Patients with a globulin concentration >3.8 g/dL had a higher all-cause and infection-related mortality risk {hazard ratio [HR] 1.11 [95% confidence interval (CI) 1.06-1.16] and HR 1.28 [95% CI 1.09-1.51], respectively} in the fully adjusted model when compared with the reference group of 3.0- <3.2 g/dL. In addition, patients with an A:G ratio <0.75 had a 45% higher all-cause mortality hazard [HR 1.45 (95% CI 1.38-1.52)] and patients with total serum protein <5.5 g/dL had a 34% higher risk of death [1.34 (95% CI 1.27-1.42)] when compared with the reference (A:G ratio 1.05- <1.15 and total serum protein 6.5- <7 g/dL). CONCLUSIONS: Among incident hemodialysis patients, a higher globulin level was associated with a higher mortality risk independent of other markers of malnutrition and inflammation, including albumin. A lower A:G ratio and serum protein was also associated with a higher mortality hazard. The mechanisms that contribute to elevated serum globulin should be further explored.

Serum Globulin Is Associated with Endoscopic Findings and Mucosal Healing in Japanese Patients with Ulcerative Colitis.

BACKGROUND: Serum globulin is an inflammation marker. To date, no evidence regarding the association between serum globulin and disease activity in patients with ulcerative colitis has been reported. AIMS: We evaluated the association between serum globulin and endoscopic activity in patients with ulcerative colitis. METHODS: Serum globulin was divided into tertiles based on the distribution of study subjects (low globulin, ≤ 2.7 g/dl (reference); moderate globulin, 2.7-3.1 g/dl; and high globulin, > 3.1 g/dl). A single endoscopic specialist evaluated the endoscopic findings, and mucosal healing was based on Mayo endoscopic subscore. RESULTS: A total of 277 patients with ulcerative colitis were included in the study. Serum globulin was independently positively associated with diminished or absent vascular markings [moderate: adjusted odds ratio (OR) 3.70 (95% confidence interval, CI: 1.82-7.88) and high: adjusted OR 2.40 (95%CI: 1.20-4.94), p for trend = 0.005]. A similar positive association between globulin and erosion was found [high: adjusted OR 2.00 (95%CI: 1.05-3.86)]. Serum globulin was independently inversely associated with mucosal healing [moderate: adjusted OR 0.37 (95%CI: 0.18-0.73) and high: adjusted OR 0.31 (95%CI: 0.14-0.64), p for trend = 0.001] and adjusted partial mucosal healing [moderate: OR 0.51 (95%CI: 0.26-0.98), p for trend = 0.048]. The inverse association between globulin and mucosal healing was significant in the low but not the high C-reactive protein group. CONCLUSIONS: In patients with ulcerative colitis, serum globulin was significantly positively associated with endoscopic activity, and was significantly inversely associated with mucosal healing, especially in the low C-reactive protein group.

Albumin-to-globulin ratio (AGR) as a potential marker of predicting lupus nephritis in Chinese patients with systemic lupus erythematosus.

OBJECTIVES: To evaluate a potential role of albumin-to-globulin ratio (AGR) in the development of lupus nephritis (LN) and determine the potential to use AGR as a marker for future LN in systemic lupus erythematosus (SLE) patients. METHODS: 194 newly diagnosed SLE patients without renal impairment were followed. The clinical data were collected and analyzed at the time of initial diagnosis of SLE and the end of follow-up. We compared baseline characteristics between those who did or did not develop LN on follow-up. Univariate and multivariate Cox hazard analysis were used to identify predictors of lupus nephritis. RESULTS: Among the 194 newly diagnosed SLE patients without renal impairment, 26 (13.40%) patients were diagnosed with LN during a median follow-up of 53.87 months. On univariate Cox analysis, patients with the history of alopecia, higher SBP, lower AGR, lower CRP, lower C3, lower C4, higher anti-dsDNA Ab, presence of ANA homogeneous patterns or higher SLEDAI had an increased probability of developing LN. In a multivariate model, the history of alopecia (adjust hazard ratio, aHR = 3.614, 95%CI 1.365-9.571 P = 0.010), lower AGR (aHR = 6.968, 95%CI 1.873-25.919, P = 0.004), lower CRP (aHR = 4.230, 95%CI 1.591-11.247, P = 0.004) and higher level of anti-dsDNA (aHR = 2.675, 95%CI 1.008-7.093, P = 0.048) were independently associated with an increased risk of developing LN after adjusting for covariates. CONCLUSION: Our findings indicated that SLE patients with low AGR, low CRP, high anti-dsDNA and the history of alopecia were more likely to develop LN in the course of SLE. AGR shown the greatest hazard for developing LN among them, it may be a strong predictor.

Prognostic value of albumin to globulin ratio in non-muscle-invasive bladder cancer.

PURPOSE: To investigate the prognostic value of preoperative serum albumin to globulin ratio (AGR) in patients with non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of bladder tumor (TURB) with or without intravesical therapy (IVT). MATERIALS AND METHODS: We retrospectively reviewed 1,096 consecutive patients with NMIBC. Levels of albumin and globulin were obtained before TURB and used to calculate the preoperative AGR level. Multivariable Cox regression analyses were performed to assess the prognostic effect of preoperative AGR on oncologic outcomes. Subgroup analyses were performed in patients based on the European Association of Urology (EAU) risk groups for NMIBC. RESULTS: Low AGR levels were observed in 389 (35.5%) patients. The median follow-up was 63.7 months (IQR 25.3-111). On multivariable Cox regression analysis, low AGR was associated with increased risk of progression to muscle-invasive BCa (MIBC) (HR 1.81, 95% CI 1.22-2.68, P = 0.003). The addition of AGR only minimally improved the discrimination ability of a base model that included established clinicopathologic features (C-index = 0.7354 vs. C-index = 0.7162). Low preoperative AGR was not significantly associated with the risk of disease recurrence (P = 0.31). In subgroup analyses based on patients' EAU risk groups, low preoperative AGR was not associated with recurrence-free survival (RFS) (P = 0.59) or progression-free survival (PFS) (P = 0.22) in any of the risk groups. Additionally, in patients treated with Bacillus Calmette-Guerin (BCG) for intermediate- or high-risk NMIBC, low AGR failed to predict disease recurrence or progression. CONCLUSION: Preoperative serum AGR levels independently predicted the risk of disease progression in patients with NMIBC. However, it was not found to be associated with either RFS or PFS in NMIBC patients based on their EAU risk group. This marker seems to have a limited role in NMIBC at the present time. However, further research is needed to investigate this marker in combination with other systemic inflammatory markers to help improve prediction in this heterogeneous group of patients.

Prognostic value of the preoperative albumin-globulin ratio in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

OBJECTIVE: To assess the value of preoperative albumin to globulin ratio for predicting pathologic and oncological outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy in a large multi-institutional cohort. MATERIALS AND METHODS: Preoperative albumin to globulin ratio was assessed in a multi-institutional cohort of 2492 patients. Logistic regression analyses were performed to assess the association of the albumin to globulin ratio with pathologic features. Cox proportional hazards regression models were performed for survival endpoints. RESULTS: The optimal cut-off value was determined to be 1.4 according to a receiver operating curve analysis. Lower albumin to globulin ratios were observed in 797 patients (33.6%) compared with other patients. In a preoperative model, low preoperative albumin to globulin ratio was independently associated with nonorgan-confined diseases (odds ratio 1.32, P = 0.002). Patients with low albumin to globulin ratios had worse recurrence-free survival (P < 0.001), cancer-specific survival (P = 0.001) and overall survival (P = 0.020) in univariable and multivariable analyses after adjusting for the effect of standard preoperative prognostic factors (recurrence-free survival: hazard ratio (HR) 1.31, P = 0.001; cancer-specific survival: HR 1.31, P = 0.002 and overall survival: HR 1.18, P = 0.024). CONCLUSIONS: Lower preoperative albumin to globulin ratio is associated with locally advanced disease and worse clinical outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. As it is difficult to stage disease entity, low preoperative serum albumin to globulin ratio may help identify those most likely to benefit from intensified care, such as perioperative systemic therapy, and the extent and type of surgery.

Clinical Characteristics, Serological and Radiological Longitudinal Changes of Patients with COVID-19.

BACKGROUND: Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) began in Wuhan and rapidly spread globally. The speed and scope of the spread of COVID-19 makes it urgent to define clinical characteristics, serological and radiological changes of the affected patients. METHODS: Seven patients with laboratory-confirmed COVID-19 who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University Yuedong Hospital from January 2020 to March 2020 were retrospectively enrolled and their clinical features, serological and radiological longitudinal changes were analyzed. RESULTS: Among the 7 patients, all (100%) had a clear epidemiological history. The most common symptoms were respiratory symptoms 6 (85.7%), and only 2 (28.6%) of the patients had fever at their first visit. The cohort included 4 (57.1%) common types and 3 (42.9%) severe types. Two (28.6%) common type patients developed to severe type in a short time. All of the 7 patients (100%) had abnormal liver function, normal renal function, and normal procalcitonin. The detection time of specific antibody in 7 patients was 5 - 13 days after symptoms. Before the specific antibody could be detected, the absolute value of lymphocytes decreased in 2 (28.6%) common type cases transferred to severe type cases accompanied with obvious progress in pulmonary imaging. The phenomenon of decreased albumin and elevated globulin occurred in 6 patients (85.7%). The predominant pattern of lung lesions observed was bilateral (71.4%) and mainly near the pleura at the first diagnosis. Bilateral pulmonary involvement occurred in 6 cases (85.7%) during the course of disease. In 4 cases (57.1%) with obvious pulmonary lesions, the absolute value of lymphocytes decreased, albumin decreased, and globulin increased during the course of the disease. CONCLUSIONS: Serum specific antibodies can be detected within 2 weeks of onset. Close observation of the dynamic changes of absolute value of blood lymphocytes, serum albumin, and globulin which were related to pulmonary imaging changes in patients will contribute to assessment of COVID-19.

Preoperative Albumin-Globulin Ratio and Its Association with Perioperative and Long-Term Outcomes in Patients Undergoing Pancreatoduodenectomy.

BACKGROUND: Systemic inflammatory response is involved in natural progression of cancers by different pathways. Albumin-globulin ratio (AGR) has been reported to have impact on prognosis in various solid tumors. OBJECTIVE: To study the significance of AGR on perioperative and long-term outcomes in patients undergoing PD. METHODS: This is a post hoc analysis of the pancreatic surgery database from January 2012 to March 2017. Cutoff value for AGR was calculated by using the receiver operating curve, and the study cohort was divided into group I (AGR ≥1) and group II (AGR <1). Two groups were compared for perioperative and long-term survival outcomes. RESULTS: Two groups were comparable with respect to clinicodemographic variables. Groups I and II had similar perioperative outcomes (p > 0.05) like median hospital stay (14 vs. 15 days), clinically relevant postoperative pancreatic fistula (16.6 vs. 15.7%), hemorrhage (3.1 vs. 2.6%), bile leak (1.4 vs. 0.65%), overall morbidity (30.1 vs. 28.9%), and postoperative mortality (2.7 vs. 3.9%). With a median follow-up of 3 years, median survival, overall survival, and disease-free survival were similar in both groups. CONCLUSION: AGR at the cutoff value of ≥1 was not associated with adverse perioperative and long-term oncological outcomes after PD.

Preoperative Albumin-to-Globulin Ratio Predicts Prognosis in Hepatocellular Carcinoma: A Cohort Study Including Non-Hepatitis Virus-Infected Patients.

INTRODUCTION: We evaluated the prognostic significance of the preoperative albumin-to-globulin ratio (AGR) in patients with hepatocellular carcinoma (HCC) with various liver etiologies. METHODS: We retrospectively analyzed 157 patients with HCC between July 2010 and February 2021. The relationship between clinicopathological variables was investigated using univariate and multivariate analyses. Statistical significance was set at p < 0.05. RESULTS: The mean overall survival (OS) was 24.5 months. The 1-, 3-, and 5-year OS rates were 90.4%, 81.2%, and 68.7%, respectively. Patients were classified into 2 groups: AGR <1.16 (low-AGR group; n = 43) and AGR ≥1.16 (high-AGR group; n = 114). In univariate analysis, OS was significantly reduced in patients with a low AGR (AGR <1.16), an alpha-fetoprotein level ≥25 ng/mL, a tumor size ≥3.5 cm, microvascular invasion, and poor tumor differentiation. In multivariate analysis, a low AGR (hazard ratio [95% confidence interval]) (2.394 [1.092-5.213]; p = 0.030) and microvascular invasion (2.268 [1.019-5.169]; p = 0.045) were independent predictors of OS. DISCUSSION/CONCLUSION: A low AGR was significantly associated with poor OS in patients with HCC, regardless of liver etiology. This may assist in treatment stratification and better management of patients with HCC.

A renewed understanding of anti-human globulin reagents: interference constraints using an optimization method in pretransfusion compatibility tests.

Anti-human globulin (AHG) reagents are widely applied in pretransfusion compatibility tests. The accuracy of detection with AHG reagents is mainly affected by irregular antibodies or cold agglutinins in blood samples, which are related to the human complement system. Although much has been written about various types and applications of AHG reagents, their characteristics, interference factors and optimal selection in pretransfusion compatibility tests still need to be further clarified. Here, we review clinical practice and basic studies that describe each AHG reagent, summarize the advantages and disadvantages of using different AHG reagents in the presence of cold agglutinins or complement-fixing antibodies, explore the potential mechanisms by which the complement system influences detection with AHG reagents and address the question of how to optimally select AHG reagents for clinically significant antibody detection.

Protein Adsorption onto Modified Porous Silica by Single and Binary Human Serum Protein Solutions.

Typical porous silica (SBA-15) has been modified with pore expander agent (1,3,5-trimethylbenzene) and fluoride-species to diminish the length of the channels to obtain materials with different textural properties, varying the Si/Zr molar ratio between 20 and 5. These porous materials were characterized by X-ray Diffraction (XRD), N2 adsorption/desorption isotherms at -196 °C and X-ray Photoelectron Spectroscopy (XPS), obtaining adsorbent with a surface area between 420-337 m2 g-1 and an average pore diameter with a maximum between 20-25 nm. These materials were studied in the adsorption of human blood serum proteins (human serum albumin-HSA and immunoglobulin G-IgG). Generally, the incorporation of small proportions was favorable for proteins adsorption. The adsorption data revealed that the maximum adsorption capacity was reached close to the pI. The batch purification experiments in binary human serum solutions showed that Si sample has considerable adsorption for IgG while HSA adsorption is relatively low, so it is possible its separation.

Effect of celecoxib combined with glucosamine hydrochloride in promoting the functional recovery and decreasing the inflammatory factor levels in patients with knee osteoarthritis.

To explore the role of celecoxib with glucosamine hydrochloride on functional recovery and reduction of inflammatory factors in patients with knee osteoarthritis. Altogether 128 patients with knee osteoarthritis in the middle and early stage admitted to our hospital from January 2018 to July 2019 were selected and grouped into the control group (CG) (celecoxib tablet therapy) and the combination group (ComG) (celecoxib combined with glucosamine hydrochloride therapy). Blood routine indexes and inflammatory factor levels before and after intervention, Lequesne score, VAS pain and adverse reactions of the two groups of patients before and after intervention were explored. Before intervention, there was no evident difference between the two groups in each index (P>0.05). After intervention, the blood routine index IgM rheumatoid factor, albumin/globulin, erythrocyte sedimentation rate and inflammatory factors TNF-α, IL-6, IL-1ß, hs-CRP levels in the ComG were evidently better than those in the CG, while Lequesne score and VAS pain score were lower than those in the CG (P<0.01). The total incidence of adverse reactions in the ComG was evidently lower than that in the CG. Celecoxib combined with glucosamine hydrochloride is effective in the treatment of knee osteoarthritis and has little adverse reactions.

Atomic-resolution crystal structures of the immune protein conglutinin from cow reveal specific interactions of its binding site with N-acetylglucosamine.

Bovine conglutinin is an immune protein that is involved in host resistance to microbes and parasites and interacts with complement component iC3b, agglutinates erythrocytes, and neutralizes influenza A virus. Here, we determined the high-resolution (0.97-1.46 Å) crystal structures with and without bound ligand of a recombinant fragment of conglutinin's C-terminal carbohydrate-recognition domain (CRD). The structures disclosed that the high-affinity ligand N-acetyl-d-glucosamine (GlcNAc) binds in the collectin CRD calcium site by interacting with the O3' and O4' hydroxyls alongside additional specific interactions of the N-acetyl group oxygen and nitrogen with Lys-343 and Asp-320, respectively. These residues, unique to conglutinin and differing both in sequence and in location from those in other collectins, result in specific, high-affinity binding for GlcNAc. The binding pocket flanking residue Val-339, unlike the equivalent Arg-343 in the homologous human surfactant protein D, is sufficiently small to allow conglutinin Lys-343 access to the bound ligand, whereas Asp-320 lies in an extended loop proximal to the ligand-binding site and bounded at both ends by conserved residues that coordinate to both calcium and ligand. This loop becomes ordered on ligand binding. The electron density revealed both α and ß anomers of GlcNAc, consistent with the added α/ßGlcNAc mixture. Crystals soaked with α1-2 mannobiose, a putative component of iC3b, reported to bind to conglutinin, failed to reveal bound ligand, suggesting a requirement for presentation of mannobiose as part of an extended physiological ligand. These results reveal a highly specific GlcNAc-binding pocket in conglutinin and a novel collectin mode of carbohydrate recognition.

Dynamic changes in clinical and CT characteristics of COVID-19 cases with different exposure histories: a retrospective study.

BACKGROUND: To assess the dynamic changes in clinical and CT characteristics of COVID-19 patients with different epidemiology histories. METHODS: Fifty-three discharged COVID-19 patients were enrolled at Beijing YouAn Hospital, Capital Medical University, between January 21 and March 10, 2020. Spearman correlation analysis was performed between CT scores and laboratory indicators. Patients were divided into the Wuhan group (lived in or with travel to Wuhan, numbering 30 cases) and non-Wuhan group (close contacts or unknown exposure, totaling 23 cases). The CT and laboratory findings were compared between and within groups during the clinical process. RESULTS: Fever (88.7%), cough (64.2%), fatigue (34%), and abnormal laboratory indicators, including lymphopenia, reduced albumin, albumin/globulin (A/G), and elevated C-reactive protein (CRP), were mainly observed. Subpleural ground-glass opacities (86.8%) were usually detected at admission. The CT scores were highly correlated with lymphocytes, CRP, albumin, and A/G at initial and follow-ups (all p < 0.05). Four days after admission, most patients (66.7% Wuhan, 47.8% non-Wuhan) showed progression, and the CT scores of Wuhan significantly increased (p = 0.015). Eight days after admission, the vast majority of patients (69.2% Wuhan, 100% non-Wuhan, p = 0.006) presented improvement, and the CT scores of non-Wuhan were significantly lower than Wuhan (p = 0.006). Pneumonia was completely absorbed in most patients 2-4 weeks after discharge. CONCLUSIONS: CT plays a crucial role in the early diagnosis and monitoring of changes in COVID-19. Lymphocytes, CRP, albumin, and A/G are expected to predict disease severity and prognosis. Viral pathogenicity in non-endemic areas may be weaker than core-infected areas. In most patients, lung lesions can disappear around 4 weeks after discharge.

Prognostic impact of preoperative immunonutritional status in rectal mucinous adenocarcinoma.

Aim: To explore the impact of preoperative the albumin-to-globulin ratio (AGR) and the prognostic nutritional index (PNI) on prognosis in rectal mucinous adenocarcinoma (MAC). Methods: A total of 128 patients were included. Results: According to the X-tile analysis, cutoff values of AGR and PNI were 1.1 and 43.8. Preoperative AGR (p = 0.041), preoperative PNI (p = 0.036) and pTNM stage (p = 0.003) were independently associated with overall survival in rectal MAC patients. Distance from the anal verge (p = 0.005), preoperative AGR (p = 0.021), preoperative PNI (p = 0.007) and pTNM stage (p < 0.001) were significantly associated with disease-free survival in rectal MAC patients. Nomograms for overall survival and disease-free survival were developed (C-index: 0.739 and 0.764). Conclusion: Preoperative AGR and PNI can act as effective predictors for survival for rectal MAC patients.

Concomitant monoclonal immunoglobulin deposition disease and crystalglobulin-induced nephropathy with a membranoproliferative pattern of glomerular injury
.

Monoclonal immunoglobulin paraproteins can deposit in the kidney in variable forms and eliciting differing patterns of injury. Crystalglobulin-induced nephropathy is a rare form of monoclonal immunoglobulin deposition in the kidney, characterized by glomerular capillary endoluminal crystalline material evident by light and electron microscopy that exhibits immunoglobulin restriction via immunofluorescence studies. We present a case of a patient with acute kidney injury, and a subsequent kidney biopsy notably revealed concurrent monoclonal immunoglobulin deposition disease (MIDD) and crystalglobulin-induced nephropathy secondary to an IgM/κ monoclonal protein that resulted in a membranoproliferative pattern of glomerular injury. The two process were distinctly evident by ultrastructural crystalline and non-crystalline (as seen with cases of more conventional MIDD) deposits in the glomeruli. The paraprotein constituency is novel (IgM/κ) for crystalglobulin-induced nephropathy (prior cases exhibited IgG/κ restriction) as was the finding of the two monoclonal immunoglobulin deposition processes contributing to development of an active glomerulitis characterized by a membranoproliferative pattern of glomerular injury (crystalglobulin-induced nephropathy has not been associated with an active glomerulitis before).

Plasma proteins facilitates placental transfer of polystyrene particles.

BACKGROUND: Nanoparticles, which are exposed to biological fluids are rapidly interacting with proteins and other biomolecules forming a corona. In addition to dimension, charge and material the distinct protein corona influences the interplay of nanoparticles with tissue barriers. In this study we were focused on the impact of in situ formed human plasma protein corona on the transfer of 80 nm polystyrene nanoparticles (PS-particles) across the human placenta. To study materno-to fetal PS transfer we used the human ex vivo placental perfusion approach, which represents an intact and physiological tissue barrier. To analyze the protein corona of PS particles we performed shotgun proteomics of isolated nanoparticles before and after tissue exposure. RESULTS: Human plasma incubated with PS-particles of 80 nm and subsequent formed protein corona enhanced the transfer across the human placenta compared to PS-corona formed by bovine serum albumin and dextran which served as a control. Quantitative and qualitative changes of plasma proteins determined the changes in PS transfer across the barrier. Based on the analysis of the PS-proteome two candidate proteins, namely human albumin and immunoglobulin G were tested if these proteins may account for the enhanced PS-transfer across the placenta. Interestingly, the protein corona formed by human albumin significantly induced the transfer of PS-particles across the tissue compared to the formed IgG-corona. CONCLUSION: In total we demonstrate the PS corona dynamically and significantly evolves upon crossing the human placenta. Thus, the initial composition of PS particles in the maternal circulation is not predictive for their transfer characteristics and performance once beyond the barrier of the placenta. The precise mechanism of these effects remains to be elucidated but highlights the importance of using well designed biological models when testing nanoparticles for biomedical applications.

Prognostic significance of the albumin-to-globulin ratio for upper tract urothelial carcinoma.

BACKGROUND: Although the albumin-to-globulin ratio (AGR) is a promising biomarker for various malignancies, few studies have investigated its prognostic significance for upper tract urothelial carcinoma (UTUC). METHODS: This retrospective study conformed to the REporting recommendations for tumour MARKer prognostic studies (REMARK) guideline. We reviewed 179 patients with UTUC who underwent radical nephroureterectomy at our institution between 2008 and 2018. Associations of preoperative clinicopathological factors, including the AGR, with cancer-specific survival (CSS) and overall survival (OS) were assessed. The Cox proportional hazards model was used for univariate and multivariable analyses. AGR was dichotomized as < 1.25 and ≥ 1.25, according to the most discriminatory cutoff determined from the receiver operating characteristic curve analysis. RESULTS: During a median follow-up of 34 months after surgery, 37 patients died from UTUC and 13 died of other causes. The preoperative AGR significantly correlated with pathological T stage, pathological N stage, and adjuvant chemotherapy. Multivariate analyses demonstrated that a decreased (< 1.25) preoperative AGR was an independent poor prognostic factor for both CSS (hazard ratio [HR] = 2.81, P <  0.01) and OS (HR = 2.09, P <  0.05). CONCLUSIONS: Preoperative AGR < 1.25 might serve as a useful prognostic marker for patients with UTUC undergoing radical nephroureterectomy.

Preoperative positive urine nitrite and albumin-globulin ratio are independent risk factors for predicting postoperative fever after retrograde Intrarenal surgery based on a retrospective cohort.

BACKGROUND: To determine risk factors for postoperative fever (POF) after retrograding intrarenal surgery (RIRS) and a nomogram for prediction of POF in patients undertaking RIRS has been developed based on the risk factors found. METHODS: This is a retrospective designed-study. A continuous cohort from a single-center database that consisted of 1095 cases undertaking RIRS with complete preoperative medical records from January 2009 to December 2018 was obtained. Independent risk factors were identified according to the multi-variate logistics regression and a further nomogram was developed. The performance of the nomogram was evaluated through three aspects including net clinical benefit, calibration, and discrimination. RESULTS: A total of 31(2.8%) cases had POF after the RIRS. Risk factors included time in RIRS ≥30mins (only the flexible scope use period) (OR: 2.16, 95%CI; 1.01-4.62, P = 0.047), preoperative positive urine culture (OR: 2.55, 95%CI; 1.01-6.42, P = 0.047), preoperative positive urine nitrite (OR: 9.09, 95%CI; 2.99-27.64, P < 0.001), Albumin/globulin ratio (AGR) (OR: 0.14, 95%CI; 0.03-0.74, P = 0.020) were further included in the nomogram to predict the POF probability for individuals. The Hosmer-Lemeshow test showed a goodness-of-fit. The calibration curve demonstrated good agreement between observation and prediction. Decision curve analysis (DCA) demonstrated it was clinical use in RIRS. CONCLUSIONS: The preoperative urine nitrite, AGR, RIRS time, and preoperative urine culture are found to be independent risk factors associated with POF after RIRS. Then we have developed a nomogram taking these factors into account that accurately predicted POF after RIRS.

The Synergistic Value of Time-Averaged Serum Albumin and Globulin in Predicting the First Peritonitis in Incident Peritoneal Dialysis Patients.

BACKGROUND: The prognostic value of serum time-averaged albumin (TA-Alb) and time-averaged globulin (TA-Glo) combination on the peritonitis in peritoneal dialysis (PD) patients is unknown. METHODS: The patients who started PD treatment between July 2013 and 2018 were included. Serum Alb and globulin (Glo) were tested at baseline and monthly during follow-up. TA-Alb and TA-Glo were calculated until first peritonitis occurred or the end of the study. PD patients were divided into 4 groups based on the medians of TA-Alb and TA-Glo separately. Cox regression was conducted to identify the hazard ratios (HRs) of peritonitis among categorical groups. RESULTS: Three hundred and sixty-three patients were included and among them 109 patients experienced first peritonitis. Peritonitis patients had lower baseline Alb, TA-Alb, and TA-Glo levels and ultrafiltration volume. Multivariate cox regression analysis revealed that TA-Alb, TA-Glo, and baseline Alb were significantly associated with first peritonitis. The highest HR existed in Group 1 with lower Alb and lower Glo (HR 4.57, 95% CI 2.36-8.87, p < 0.001) compared with Group 4 with higher Alb and higher Glo. CONCLUSION: Lower TA-Glo is an independent risk factor for the first peritonitis in PD patients. Combined with lower TA-Alb will increase the predictive effect than separate factor alone.