Does Provider Type Affect Bone Health Surveillance in Chronic Pancreatitis?

BACKGROUND: Bone density screening (DEXA) and vitamin D serum assay (Vit-D) are recommended in chronic pancreatitis, but adherence by providers is unknown. AIMS: Assess DEXA/Vit-D testing according to provider type. METHODS: A retrospective cohort study of chronic pancreatitis patients followed in a tertiary hospital (August 2017-2018) was conducted. Provider type was primary care (PCP), gastroenterologist, and pancreas specialist. Chi-square test and multivariable analysis were conducted to assess the relation between provider type and DEXA/Vit-D testing. Subset analyses were performed among patients with fecal elastase < 200 mcg/g. RESULTS: A total of 478 charts were reviewed, and 256 (53.6%) met diagnosis of chronic pancreatitis; 184 (71.9%) definite, 45 (17.6%) probable, and 27 (10.6%) borderline chronic pancreatitis. DEXA was tested in 112/256 (43%) patients; 16/57(28%) patients followed by PCP, 11/38 (28.9%) by gastroenterologists, and 85/161(52.2%) by pancreas specialists (p = 0.001). Vit-D was tested in 210/256 (82.0%) patients; 42/57(73.7%) followed by PCP, 29/38 (76.3%) by gastroenterologists, and 139/161(86.3%) by pancreas specialists (p = 0.06). Multivariate analysis assessing DEXA/Vit-D testing showed pancreas specialists were more likely to test compared to PCP (DEXA: OR 3.70, CI 1.77-7.74, p = 0.001. Vit-D: OR 3.24, CI 1.43-7.38, p = 0.005), but gastroenterologists were not. In patients with low fecal elastase, pancreas specialists were more likely to test DEXA (pancreas specialists: 62.1%, PCP: 40.0%, Gastroenterologists: 11.1%, p = 0.01) and all patients received Vit-D testing. CONCLUSIONS: Chronic pancreatitis patients often do not receive optimal preventive care. Pancreas specialists were more likely to perform DEXA and Vit-D testing compared to PCP and gastroenterologists. More physician education is needed.

Diagnostic value of combination serum assay of lactate dehydrogenase, D-dimer, and C-reactive protein for uterine leiomyosarcoma.

AIM: Leiomyosarcoma is the most common type of uterine sarcoma. In some leiomyosarcoma cases, preoperative diagnosis might be difficult, and they might be treated as benign lesions. We evaluated diagnostic values of preoperative serum lactate dehydrogenase (LDH), D-dimer and C-reactive protein for differentiating leiomyosarcoma. METHODS: From 2008 to 2013, leiomyosarcoma cases in three university hospitals were enrolled. Preoperative serum LDH, D-dimer and C-reactive protein were analyzed if tested. These markers of pathologically diagnosed leiomyoma cases presumed benign (group B) and presumed malignant (group PM) were compared with those of leiomyosarcoma cases (group S). RESULTS: Groups S, PM and B had 36, 28 and 69 cases, respectively. Positive rates of LDH were 66.7%, 14.3% and 0% in groups S, PM and B, respectively. Positive rates of D-dimer and C-reactive protein were 83.3% and 64.5%, 17.9% and 10.7% and 5% and 2.9% in groups S, PM and B, respectively. Positive rates of all three markers were high in the order of leiomyosarcoma, atypical leiomyoma and typical leiomyoma. In group PM, 12 (63.2%) cases were negative for all three markers, whereas 1 (3.3%) case was negative in group S. No case was positive for all markers in group PM, whereas 41.2% leiomyosarcoma cases were positive for all markers. When all parameters were positive, specificity and positive predictive value were 100% in differentiating leiomyosarcoma from group PM. CONCLUSION: Combination of LDH, D-dimer and C-reactive protein could be useful for distinguishing leiomyosarcoma from especially degenerated or atypical leiomyoma.

2,4-Dinitrobenzenesulfonate-functionalized carbon dots as a turn-on fluorescent probe for imaging of biothiols in living cells.

The authors describe a carbon dot-based fluorescent probe for biothiols. Green emissive carbon dots (g-CDs; with λex/λem maxima of 407/505 nm) were synthesized by a one-step solvothermal method starting from 3-diethylaminophenol. They were then covalently functionalized with 2,4-dinitrobenzenesulfonyl chloride to afford 2,4-Dinitrobenzenesulfonate-functionalized CDs (g-CD-DNBS) as a nanoprobe for biothiols. The fluorescence of the g-CD-DNBS is quite weak. Upon addition of biothiols, the DNBS group of the probe is removed by thiol groups. This results in gradual restoration of the green fluorescence. The nanoprobe exhibits high selectivity for biothiols over other amino acids and biological molecules. The detection limits for cysteine, homocysteine and glutathione are 69, 74 and 69 nM (S/N = 3), respectively. The probe was applied to image biothiols in SMMC-7721 cells. Graphical abstract Schematic presentation of the mechanism of 2,4-dinitrobenzenesulfonate-functionalized carbon dots (g-CD-DNBS) for the detection of biothiols. g-CDs: green emissive carbon dots.

Serum uromodulin-a marker of kidney function and renal parenchymal integrity.

Background: An ELISA to analyse uromodulin in human serum (sUmod) was developed, validated and tested for clinical applications. Methods: We assessed sUmod, a very stable antigen, in controls, patients with chronic kidney disease (CKD) stages 1-5, persons with autoimmune kidney diseases and recipients of a renal allograft by ELISA. Results: Median sUmod in 190 blood donors was 207 ng/mL (women: men, median 230 versus 188 ng/mL, P = 0.006). sUmod levels in 443 children were 193 ng/mL (median). sUmod was correlated with cystatin C (rs = -0.862), creatinine (rs = -0.802), blood urea nitrogen (BUN) (rs = -0.645) and estimated glomerular filtration rate (eGFR)-cystatin C (rs = 0.862). sUmod was lower in systemic lupus erythematosus-nephritis (median 101 ng/mL), phospholipase-A2 receptor- positive glomerulonephritis (median 83 ng/mL) and anti-glomerular basement membrane positive pulmorenal syndromes (median 37 ng/mL). Declining sUmod concentrations paralleled the loss of kidney function in 165 patients with CKD stages 1-5 with prominent changes in sUmod within the 'creatinine blind range' (71-106 µmol/L). Receiver-operating characteristic analysis between non-CKD and CKD-1 was superior for sUmod (AUC 0.90) compared with eGFR (AUC 0.39), cystatin C (AUC 0.39) and creatinine (AUC 0.27). sUmod rapidly recovered from 0 to 62 ng/mL (median) after renal transplantation in cases with immediate graft function and remained low in delayed graft function (21 ng/mL, median; day 5-9: relative risk 1.5-2.9, odds ratio 1.5-6.4). Immunogold labelling disclosed that Umod is transferred within cytoplasmic vesicles to both the apical and basolateral plasma membrane. Umod revealed a disturbed intracellular location in kidney injury. Conclusions: We conclude that sUmod is a novel sensitive kidney-specific biomarker linked to the structural integrity of the distal nephron and to renal function.

Dynamics of Humoral Immunity to Myxoma and Rabbit Hemorrhagic Disease Viruses in Wild European Rabbits Assessed by Longitudinal Semiquantitative Serology.

Myxoma virus (MYXV) and rabbit hemorrhagic disease virus (RHDV) are important drivers of the population decline of the European rabbit, an endangered keystone species. Both viruses elicit strong immune responses, but the long-term dynamics of humoral immunity are imperfectly known. This study aimed to assess the determinants of the long-term dynamics of antibodies to each virus based on a longitudinal capture-mark-recapture of wild European rabbits and semiquantitative serological data of MYXV and RHDV GI.2-specific IgG. The study included 611 indirect enzyme-linked immunosorbent assay (iELISA) normalized absorbance ratios for each MYXV and RHDV GI.2 from 505 rabbits from 2018 to 2022. Normalized absorbance ratios were analyzed using log-linear mixed models, showing a significant positive relationship with the time since the first capture of individual rabbits, with monthly increases of 4.1% for antibodies against MYXV and 2.0% against RHDV GI.2. Individual serological histories showed fluctuations over time, suggesting that reinfections boosted the immune response and likely resulted in lifelong immunity. Normalized absorbance ratios significantly increased with the seroprevalence in the population, probably because of recent outbreaks, and with body weight, highlighting the role of MYXV and RHDV GI.2 in determining survival to adulthood. Juvenile rabbits seropositive for both viruses were found, and the dynamics of RHDV GI.2 normalized absorbance ratios suggest the presence of maternal immunity up to 2 months of age. Semiquantitative longitudinal serological data provide epidemiological information, otherwise lost when considering only qualitative data, and support a lifelong acquired humoral immunity to RHDV GI.2 and MYXV upon natural infection. IMPORTANCE This study addresses the long-term dynamics of humoral immunity to two major viral pathogens of the European rabbit, an endangered keystone species of major ecological relevance. Such studies are particularly challenging in free-ranging species, and a combination of longitudinal capture-mark-recapture and semiquantitative serology was used to address this question. Over 600 normalized absorbance ratios of iELISA, obtained from 505 individual rabbits in 7 populations over 5 years, were analyzed using linear mixed models. The results support a lifelong acquired humoral immunity to myxoma virus and rabbit hemorrhagic disease virus upon natural infection and suggest the presence of maternal immunity to the latter in wild juvenile rabbits. These results contribute to understanding the epidemiology of two viral diseases threatening this keystone species and assist in developing conservation programs.

Dynamics of naturally acquired antibody against Haemophilus influenzae type a capsular polysaccharide in a Canadian Aboriginal population.

Severe infections caused by Haemophilus influenzae type a (Hia) have reached alarming rates in some Canadian Aboriginal communities. We sought to estimate the frequency of exposure to this pathogen and timelines for boosting protective antibodies. We developed a model of secondary antigenic challenge (natural exposure), and used data for anti-Hia antibodies in serum samples of healthy and immunocompromised adults in a population of Northwestern Ontario, Canada. We parameterized the model with available estimates from previous studies for the decay rate of antibody and its protective levels against both Hia carriage and invasive disease. Simulations were initialized using antibody concentrations from data. We investigated both the duration of immunity without secondary antigenic challenge and the average time between subsequent exposures to Hia. When there was no new natural exposure, serum antibody concentrations in healthy Aboriginal individuals decreased below the level (1 µg/ml) assumed for protection against invasive Hia disease 3 years after primary exposure. This period was shorter (about 2 years) for Aboriginal individuals suffering from chronic renal failure. We estimated that a new antigenic challenge occurs once in 5 and 2 years for healthy and immunocompromised Aboriginal individuals, respectively. More frequent natural exposure was required to maintain protective antibody levels for non-Aboriginal individuals compared to Aboriginal individuals. The findings suggest that frequent boosting of natural immunity is required to maintain the anti-Hia antibody levels protecting against invasive Hia disease, particularly in individuals with underlying medical conditions. This information has important implications for immunization when an anti-Hia vaccine becomes available.