Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause?

BACKGROUND: Our aim was to identify the pancreatic cancer diabetogenic peptide. METHODS: Pancreatic tumor samples from patients with (n=15) or without (n=7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE. RESULTS: A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C(2)C(12) myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation. CONCLUSIONS: The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus

Pancreatic cancer-associated diabetes mellitus: an open field for proteomic applications.

Background: Diabetes mellitus is associated with pancreatic cancer in more than 80% of the cases. Clinical, epidemiological, and experimental data indicate that pancreatic cancer causes diabetes mellitus by releasing soluble mediators which interfere with both beta-cell function and liver and muscle glucose metabolism. Methods: We analysed, by matrix-assisted laser desorption ionization time of flight (MALDI-TOF), a series of pancreatic cancer cell lines conditioned media, pancreatic cancer patients' peripheral and portal sera, comparing them with controls and chronic pancreatitis patients' sera. Results: MALDI-TOF analysis of pancreatic cancer cells conditioned media and patients' sera indicated a low molecular weight peptide to be the putative pancreatic cancer-associated diabetogenic factor. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of tumor samples from diabetic and non-diabetic patients revealed the presence of a 1500 Da peptide only in diabetic patients. The amino acid sequence of this peptide corresponded to the N-terminal of an S-100 calcium binding protein, which was therefore suggested to be the pancreatic cancer-associated diabetogenic factor. Conclusions: We identified a tumor-derived peptide of 14 amino acids sharing a 100% homology with an S-100 calcium binding protein, which is probably the pancreatic cancer-associated diabetogenic facto

Clinical evaluation of seven tumour markers in lung cancer diagnosis: can any combination improve the results?

In this study we compared the diagnostic utility of: (1) neuron-specific enolase (NSE); (2) squamous cell carcinoma antigen (SCC); (3) carcinoembryonic antigen (CEA); and (4) cytokeratin markers (CYFRA 21-1, TPA, TPM, TPS) in patients with small-cell lung cancer (SCLC) (21 cases) and non-small-cell lung cancer (94 cases). For comparison we also studied 66 patients with benign lung diseases and nine with pleural mesothelioma. NSE levels in SCLC patients were significantly higher than those in all the other groups studied. No significant variations were found among the SCC levels in all groups. CEA levels in patients with adenocarcinoma were significantly higher than those in all other groups studied. CYFRA 21-1 serum levels significantly increased in patients with squamous cell carcinoma and mesothelioma, while TPA, TPS and TPM increased in patients with lung cancer irrespective of the histological type. In patients with SCLC, high levels of all markers except SCC were found when the disease was extensive. In patients with non-SCLC, the highest levels of all tumour markers were usually found in those with advanced disease, although CYFRA 21-1 gave a sensitivity of 44% when a specificity of 95% was fixed in stage I non-SCLC patients. An analysis of receiver operating characteristic curves revealed that the highest diagnostic accuracies in distinguishing benign from malignant lung diseases were achieved with TPM (81%), CYFRA 21-1 (72%), CEA (78%) or TPA (78%) when using cut-off values of 46 Ul-1, 3.0 micrograms l-1, 2.0 micrograms l-1 and 75 Ul-1 respectively. When all patients were considered, the combined evaluation of more than one marker did not significantly improve the results obtained with TPM alone. However, taking into consideration the fact that CYFRA 21-1 is the most sensitive index of early lung tumours and that its combined determination with TPM did not worsen the overall sensitivity and specificity of the latter, the combined use of these two markers may be suggested as a useful took for the diagnosis of lung tumours

Comparison of presepsin, procalcitonin, interleukin-8 and C-reactive protein in predicting bacteraemia in febrile neutropenic adult patients with haematological malignancies

Bacterial infections represent life-threatening complications in patients with febrile neutropenia (FN). Diagnostic biomarkers of infections may help to differentiate bacteraemia from non-bacteraemia FN. We aimed to evaluate the utility of procalcitonin (PCT), presepsin (PS), C-reactive protein (CRP) and interleukin-8 (IL-8) as biomarkers of bacteraemia in adult FN patients with haematological malignancies. Concentrations of PCT, PS, CRP and IL-8 were prospectively measured in 36 FN episodes experienced by 28 oncohaematological patients. 11 out of 36 episodes were classified as bacteraemia. PCT was the best biomarker to predict bacteraemia with the area under the curve (AUC) ROC of 0,9; specificity 100% and positive predictive value 100%, while the most sensitive was IL-8 (90,9%) with AUC ROC of 0,88 and negative predictive value 95,2%. All patients with PCT concentrations above 1,6 \u3bcg/l had bacteraemia. Patients with IL-8 concentrations superior to 170 pg/ml had a 40 times higher risk for bacteraemia than the ones with lower levels. Patients with PS concentrations superior to 410 pg/ml had 24 times higher risk for bacteraemia than the patients with lower levels. PCT has higher accuracy than CRP, IL-8 and PS in predicting bacteraemia in adult hematologic patients with FN

Non-specific oral and cutaneous manifestations of coronavirus disease 2019 in children

Background: Coronavirus Disease 2019 (COVID-19) seems to affect children only marginally, as a result, there is less knowledge of its manifestations in childhood. The purpose of this retrospective cross-sectional study was to investigate the oral and cutaneous manifestations in children affected by COVID-19. Material and Methods: All the medical records of children with COVID-19 admitted to the Pediatric Clinic-ASST Spedali Civili of Brescia from March to April 2020 were reviewed. The following data were recorded: Age, temperature, clinical presentation, oral mucosa lesions, taste alteration and cutaneous lesions. Results: The medical records of twenty-seven pediatric patients (mean age 4,2 years + 1,7) were analyzed. The clinical presentation of the disease mainly included elevated body temperature and cough. The following oral lesions were recorded: Oral pseudomembranous candidiasis (7.4 %), geographic tongue (3.7%), coated tongue (7.4 %) and hyperaemic pharynx (37 %). Taste alteration was reported by 3 patients. Six patients presented cutaneous flat papular lesions. Conclusions: As for our paediatric sample, COVID-19 resulted to be associated with non-specific oral and cutaneous manifestations

Inherited human gp91phox deficiency is associated with impaired isoprostane formation and platelet dysfunction

Platelet isoprostane 8-ISO-prostaglandin F2α (8-iso-PGF2α), a proaggregating molecule, is believed to derive from nonenzymatic oxidation of arachidonic acid. We hypothesized that NADPH is implicated in isoprostane formation and platelet activation

Procalcitonin-guided antibiotic therapy: An expert consensus

Procalcitonin (PCT) is a useful biomarker of bacterial infection and its use is associated to reduced duration of antibiotic therapy in the setting of intensive care medicine. To address the need of practical guidance for the use of PCT in various clinical settings, a group of experts was invited to participate at a consensus process with the aims of defining the rationale for appropriate use of PCT and for improving the management of critically ill patients with sepsis. A group of 14 experts from anesthesiology and critical care, infectious diseases, internal medicine, pulmonology, clinical microbiology, laboratory medicine, clinical pharmacology and methodology provided expert opinion through a modified Delphi process, after a comprehensive literature review. The appropriateness of use of PCT in terms of diagnosis, prognosis and antimicrobial stewardship was assessed for different scenarios or settings such us management of infection in the emergency department, regular wards, surgical wards or in the intensive care unit. Similarly, appropriateness and timing of PCT measurement were evaluated. All the process consisted in three Delphi rounds. PCT use is appropriate in algorithms for antibiotic de-escalation and discontinuation. In this case, reproducible, high sensitive assays should be used. However, initiation or escalation of antibiotic therapy in specific scenarios, including acute respiratory infections, should not be based solely on PCT serum levels. Clinical and radiological findings, evaluation of severity of illness and of patient's characteristics should be taken into proper account in order to correctly interpret PCT results

Increased risk of bone fractures in hemodialysis patients treated with proton pump inhibitors in real world: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS)

Long-term treatment with Proton Pump Inhibitors (PPIs) is associated with an increased risk of fractures in the general population. PPIs are widely prescribed to dialysis patients but to date no study specifically tested, by state-of-art statistical methods, the relationship between PPIs use and fractures in this patient-population. This study aimed to assess whether PPIs use is associated with bone fractures (i.e. hip fractures and fractures other than hip fractures) in a large international cohort of hemodialysis patients. We considered an observational prospective cohort of 27097 hemodialysis patients from the DOPPS study. Data analysis was performed by the Fine & Gray method, considering the competitive risk of mortality, as well as by a cause-specific hazards Cox model dealing death as a censoring event and matching patients according to the prescription time. Out of 27,097 hemodialysis patients, 13,283 patients (49%) were on PPI treatment. Across the follow-up (median:19\u2009months), 3.8 bone fractures x 100 person-years and 1.2 hip fractures x 100 person-years occurred. In multiple Cox models, considering the competitive risk of mortality, the incidence rate of bone (SHR: 1.22, 95% CI: 1.10-1.36, P\u2009<\u20090.001) and hip fractures (SHR: 1.35, 95% CI: 1.13-1.62, P = 0.001) was significantly higher in PPI treated than in PPI untreated patients. These findings held true also in multiple, cause-specific, hazards Cox models matching patients according to the prescription time (bone fractures, HR: 1.47, 95% CI: 1.23-1.76, P\u2009<\u20090.001, hip fractures (HR: 1.85, 95% CI: 1.37-2.50, P\u2009<\u20090.001). The use of PPIs requires caution and a careful evaluation of risks/benefits ratio in hemodialysis patients

Hereditary Deficiency of gp91(phox) Is Associated With Enhanced Arterial Dilatation Results of a Multicenter Study

Background-NADPH oxidase is believed to modulate arterial tone, but its role in humans is still unclear. The objective of this study was to evaluate whether NADPH oxidase is involved in flow-mediated arterial dilation (FMD). Methods and Results-Twenty-five patients with hereditary deficiency of gp91(phox), the catalytic core of NADPH oxidase, (X-CGD), 25 healthy subjects, and 25 obese patients matched for sex and age were recruited. FMD, platelet gp91(phox), serum levels of nitrite and nitrate as markers of nitric oxide generation, oxidized low-density lipoprotein, and urinary excretion of isoprostanes as markers of oxidative stress were determined. Platelet gp91(phox) expression was downregulated in X-CGD patients (1.0+/-0.8 mean fluorescence; P<0.001) and upregulated in obese patients (4.1+/-2.2 mean fluorescence; P=0.01) compared with healthy subjects (2.9+/-1.7 mean fluorescence). Urinary excretion of isoprostanes was reduced in X-CGD patients (41.7+/-33.3 pg/mg creatinine; P = 0.04) and increased in obese patients (154.4+/-91 pg/mg creatinine; P<0.001) compared with healthy subjects (69.5+/-52.4 pg/mg creatinine). Obese patients had higher serum oxidized low-density lipoprotein than healthy subjects (35.3+/-6.7 versus 24.8+/-9.8 U/L; P<0.001) and X-CGD patients (28.5+/-7.2 U/L; P<0.001). X-CGD patients had significantly higher FMD (14.7+/-5.9%) compared with healthy subjects (7.9+/-2.5%; P<0.001); obese patients had lower FMD (5.3+/-3.0%; P+/-0.028) compared with healthy subjects. Serum nitrite and nitrate levels were significantly higher in patients with X-CGD (36.0+/-10.8+/-mol/L; P<0.016) and lower in obese patients (9.3+/-11.0 mu mol/L; P<0.001) compared with healthy subjects (27.1+/-19.1 mu mol/L). Serum nitrite and nitrate levels significantly correlated with FMD (R-s = 0.403, P<0.001) and platelet gp91(phox) (R-s = -0.515, P<0.001). FMD inversely correlated with platelet gp91(phox) (R-s = -0.502, P<0.001) and isoprostanes (R-s = -0.513, P<0.001). Conclusion-This study provides the first evidence that, in humans, gp91(phox) is implicated in the modulation of arterial ton

Pepsinogen A, pepsinogen C, and gastrin as markers of atrophic chronic gastritis in European dyspeptics

Serum levels of pepsinogen and gastrin are parameters that can be used as biomarkers for gastric mucosa. The aim of this study was to validate these serum biomarkers, that is pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, and gastrin, as screening tests for precancerous lesions: atrophic chronic gastritis (ACG) or Helicobacter pylori-related corpus-predominant or multifocal atrophy. The study population was comprised of a subsample of 284 patients from the 451 included in the Eurohepygast cohort, between 1995 and 1997. The concentrations of PGA, PGC, and gastrin were measured by radioimmunoassays. Histological diagnosis was the gold standard. Cut-off points were calculated using receiving operator characteristics (ROC) curves. Factors linked to variation of biomarkers were identified using multivariate linear regression. The mean of each biomarker in the sample was: PGA, 77.4 μg l−1; PGC, 13.2 μg l−1; PGA/PGC, 6.7; and gastrin, 62.4 ng l−1. For ACG patients, the areas under the PGA, PGC, PGA/PGC, and gastrin ROC curves were 0.55, 0.62, 0.73, and 0.58, respectively. The best cut-off point for PGA/PGC was 5.6, with sensitivity 65% and specificity 77.9%. For H. pylori-related corpus-predominant or multifocal atrophy, the areas under the respective ROC curves were 0.57, 0.67, 0.84, and 0.69. The best cut-off point for PGA/PGC was 4.7, with sensitivity 77.1% and specificity 87.4%. The results suggested that only the PGA/PGC ratio can be considered as a biomarker for precancerous lesions of the stomach, and may be useful as a screening test