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Elastase 1 and immunoreactive trypsin were assessed by a RIA technique in the sera of 29 control subjects, 24 pancreatic cancer patients, 22 patients with chronic pancreatitis and 31 with extra-pancreatic diseases to ascertain and compare their usefulness in chronic pancreatic disease diagnosis. Increased levels of elastase 1 were detected in 60.9% of pancreatic cancer and in 61.1% of chronic pancreatitis patients; low values were found in only two subjects with pancreatic disease. A close correlation between the two enzymes was found in patients suffering from pancreatic cancer and chronic pancreatitis. These data suggest that serum elastase 1, as well as immunoreactive trypsin, is of limited value in chronic pancreatic disease diagnosis; increased levels of the two enzymes always occur simultaneously; low immunoreactive trypsin values together with normal elastase 1 serum levels are detectable in a number of patients with chronic pancreatitis and severe exocrine insufficiency. [ABSTRACT FROM AUTHOR]

The Hodgkin lymphoma International Study for Individual Care (HoLISTIC) Consortium's A-HIPI model, developed in 2022 for advanced-stage classical Hodgkin lymphoma (cHL), predicts survival within 5 years amongst newly diagnosed patients. This study validates its performance in the Brazilian Hodgkin lymphoma registry. By 2022, the Brazilian HL registry included 1357 cHL patients, with a median 5-year follow-up. Probabilities for 5-year progression-free survival (PFS) and overall survival (OS) were calculated using A-HIPI-model equations. Discrimination (Harrell C-statistic/Uno C-statistic) and calibration measures assessed external validation and calibration. Lab values beyond the allowed range were excluded, mirroring the initial A-HIPI analysis. A total of 694 advanced-stage cHL patients met the original inclusion criteria (age 18-65 years, Stage IIB-IV). Median age was 31 years; 46.3% were females. Stage distribution was IIB (33.1%), III (27.4%), IV (39.5%). Bulky disease in 32.6%. Five-year PFS and OS were 68.4% and 86.0%, respectively. Harrell C-statistics were 0.60 for PFS and 0.69 for OS, and Uno C-statistics were 0.63 for PFS and 0.72 for OS. Calibration plots demonstrated well-calibrated predictions with calibration slopes of 0.91 and 1.03 for 5-year OS and PFS, respectively. Despite differing patient, clinical characteristics, and socioeconomic factors, the baseline prediction tool performed well in the Brazilian cohort, demonstrating adequate discrimination and calibration. This supports its reliability in diverse settings., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Competing Interests: The authors declare they have no conflicts of interest.

The treatment of older patients with Hodgkin lymphoma (HL) remains a challenge. We sought to identify the treatment patterns and outcomes in older HL patients included in the Brazilian HL registry (NCT02589548). A total of 136 patients with HIV-negative classic HL, aged ≥ 60 years, diagnosed between 2009 and 2018, were analyzed. The median age was 66 years old (60-90), 72% had advanced disease, 62% had a high IPS, and 49% had a nodular sclerosis subtype. Median follow-up was 64 months for alive patients. ABVD was the front-line treatment in 96% of patients. Twenty-one patients (15%) died during front-line treatment. The 5-year PFS and 5-year OS rates were 55% and 59%, respectively. The 5-year OS rates in localized and advanced disease were 81% and 51% (p=0.013). Lung toxicity developed in 11% of the patients treated with ABVD. Bleomycin was administered for > 2 cycles in 65% of patients. Compared with 2009-2014, there was a decrease in the use of bleomycin for > 2 cycles in 2015-2018 (88% × 45%, p<0.0001). The impact of socioeconomic status (SES) on outcomes was studied in patients treated with ABVD. After adjusting for potential confounders, lower SES remained independently associated with poorer survival (HR 2.22 [1.14-4.31] for OS and HR 2.84 [1.48-5.45] for PFS). Treatment outcomes were inferior to those observed in developed countries. These inferior outcomes were due to an excess of deaths during front-line treatment and the excessive use of bleomycin. SES was an independent factor for shorter survival., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic lymphocytic leukaemia (CLL) has a highly variable clinical course. In addition to biological factors, socioeconomic factors and health system characteristics may influence CLL outcome. Data from the Brazilian Registry of CLL were analyzed to compare clinical and treatment-related characteristics in patients with CLL, from public or private institutions. A total of 3326 patients from 43 centres met the eligibility criteria, of whom 81% were followed up at public hospitals and 19% at private hospitals. The majority were male (57%), with a median age of 65 years. Comparing public and private hospitals, patients in public hospitals were older, had more advanced disease at diagnosis, and more frequently had elevated creatinine levels. All investigated prognostic markers were evaluated more often in private hospitals. First-line treatment was predominantly based on chlorambucil in 41% of the cases and fludarabine in 38%. Anti-CD20 monoclonal antibody was used in only 36% of cases. In public hospitals, significantly fewer patients received fludarabine-based regimens and anti-CD20 monoclonal antibodies. Patients from public hospitals had significantly worse overall survival (71% vs. 90% for private hospitals, p  < 0.0001) and treatment-free survival (32% vs. 40%, for private hospitals, p  < 0.0001) at seven years. Our data indicate striking differences between patients followed in public and private hospitals in Brazil. A worse clinical condition and lack of accessibility to basic laboratory tests and adequate therapies may explain the worse outcomes of patients treated in public institutions., Competing Interests: The authors declare they have no conflicts of interest., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Myeloproliferative neoplasms polycythemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis constitute a group of haematological diseases. The comprehensive assessment of signaling pathway activation in blood cells may aid the understanding of MPN pathophysiology. Thus, levels of post-translational protein modifications and total protein expression were determined in MPN patients and control leukocytes by using reverse-phase protein arrays (RPPA). Compared to control samples, p-SRC, p-CTNNB1, c-MYC, MCL-1, p-MDM2, BAX and CCNB1 showed higher expression in PV samples than controls. P-JAK2/JAK2 and pro-apoptotic BIM showed differential expression between JAK2 V617F-positive and -negative ET patients. Apoptosis, cancer and PI3K/AKT pathways proteins showed differential expression among the studied groups. For most of the proteins analyzed using Western-Blot and RPPA, RPPA showed higher sensitivity to detect subtle differences. Taken together, our data indicate deregulated protein expression in MPN patients compared to controls. Thus, RPPA may be a useful method for broad proteome analysis in MPN patients´ leukocytes.

Objective: Atherosclerosis and restenosis are largely ruled by inflammation. The aim of this study was to test the effects of a short-course, high-dose oral prednisone on the release of interleukin-6 (IL-6) and tumour necrosis factor (TNF)-alpha from circulating monocytes and on the neointimal growth that follows bare metal stent (BMS) implantation. In a sub-group of patients activated NF-kappaB was also evaluated., Methods: Out of 40 patients with coronary artery disease treated with BMS implantation, 20 were randomly assigned to receive oral prednisone during 40 days according to a standardized protocol. In non-stimulated and stimulated (LPS and PMA) monocytes we evaluated the release of IL-6 and TNF-alpha, and NF-kappaB p50 subunit translocation at baseline, at 10 and 30 days. Late luminal loss (LLL) 9 months after angioplasty was calculated by quantitative coronary angiography., Results: Plasma concentrations of prednisone correlated inversely with IL-6 and TNF-alpha release (R2=0.45, p=0.04 and R2=0.69, p=0.005, respectively) and NF-kappaB activation from monocytes (R2=0.58, p=0.01). The reduction of TNF-alpha release and NF-kappaB activation were significantly related (R2=0.56, p=0.01). Prednisone patients showed a significantly larger reduction of cytokine release and NF-kappaB activation compared to non-treated patients, at 10 days and 30 days. LLL was lower in the prednisone group (0.44+/-0.35 mm versus 0.80+/-0.53 mm, p=0.02) and correlated with reduction of TNF-alpha (R2=0.41, p=0.01)., Conclusions: High doses of oral prednisone reduce NF-kappaB pathway activation and pro-inflammatory cytokine release in circulating activated monocytes of patients treated with coronary stenting. TNF-alpha release reduction correlates with decreased LLL., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

To compare efficacy and tolerability of combination treatment with metformin and sulfonylurea with each of these drugs alone in the treatment of type 2 diabetes, 88 type 2 diabetic subjects (hemoglobin A1c [HbA1c] levels, 8.0%+/-1.0%; age, 57.3+/-7.1 years; body mass index [BMI]. 27.0+/-2.6 kg/m2; diabetes duration, 9.8+/-8.2 years; means +/- SD) were randomly assigned to double-blind treatment with metformin (500 to 3,000 mg/d), glibenclamide (5 to 15 mg/d), or their combination (metformin 400 to 2,400 mg/d + glibenclamide 2.5 to 15 mg/d) for 6 months. Thereafter, groups were crossed over for the following 6 months. Thus, each patient received metformin or glibenclamide alone, and the combination treatment. Doses were titrated to obtain HbA1c levels < or = 6.0% and fasting plasma glucose levels less than 140 mg/dL. Eighty patients concluded both treatment periods and were included in the analysis of treatment efficacy. In patients receiving metformin or glibenclamide alone, the maximal dose was reached in 21 and 25 patients, respectively; 8 and 15 of these subjects, respectively, required the maximal dose when they were on the combination treatment. During the study, 4 (10.0%) subjects receiving metformin, 7 (17.1%) receiving glibenclamide, and 31 (39.2%) receiving the combination treatment reached HbA1c levels < or = 6.0%. Moreover, when efficacy of the combination treatment on glycemic control was compared with that of single-drug therapies in each individual patient, the combination was significantly more effective than either metformin or glibenclamide (HbA1c after treatment, 6.1%+/-1.1% v 7.3%+/-1.4%, and 6.5%+/-0.7% v 7.6%+/-1.5%, respectively, both P<.0001). In conclusion, combination treatment with metformin and sulfonylurea is more effective than these drugs alone in improving glycemic control in type 2 diabetes, while also allowing a reduction of the dosage of each drug.

The aim of the present study was to evaluate whether the inhibitory effect on pancreatic A-cell exerted by hyperglycemic hyperinsulinemia and/or by somatostatin administration is impaired in human obesity. For this purpose plasma glucagon concentrations were measured in 8 obese and 8 nonobese nondiabetic subjects during a 4-h hyperglycemic clamp. Synthetic cyclic somatostatin-14 was infused at the rate of 2.5 nmol/min during the third hour of the study. Fasting plasma glucagon was higher in obese than in nonobese subjects (242 +/- 32 vs 163 +/- 15 pg/ml, p less than 0.05) (mean +/- SEM). In the last 20 min of the glucose infusion period preceding somatostatin administration (100-120 min of the study) plasma glucagon averaged 195 +/- 26 pg/ml in obese and 122 +/- 13 pg/ml in nonobese subjects (p less than 0.05), with a reduction of 19 +/- 3% in the former and 28 +/- 4% in the latter (p = n.s.). In both groups somatostatin infusion did not result in a further decrease in plasma glucagon, which averaged 192 +/- 27 pg/ml in obese and 123 +/- 16 pg/ml in nonobese subjects (p less than 0.05) in the 160-180 min period of the study. Also after discontinuing somatostatin infusion plasma glucagon levels did not change. These results suggest that in human obesity hyperglycemic hyperinsulinemia has a normal inhibitory effect on pancreatic A-cell and that somatostatin administration has no additive effect on hyperglycemia and hyperinsulinemia in either obese or nonobese nondiabetic subjects.

A novel monoclonal antibody based enzyme immunoassay (EIA) method for the measurement of the human cationic trypsinogen (NeoScreen, AGEN Biomedical Ltd., Acacia Ridge, Australia) in dried blood spots for the neonatal screening of cystic fibrosis was evaluated. The calibration standards provided as dried blood spots by AGEN are highly unstable and must be replaced with user prepared materials. Reference values from control individuals were obtained by parametric methods. A preliminary comparison with a polyclonal antibody based RIA method (Trypsik, SORIN Biomedica, Saluggia, Italy) was performed. Regression analysis between the RIA and the EIA methods gave a coefficient of correlation of 0.58 for RIA values less than 40 micrograms/L and of 0.77 for RIA values greater than or equal to 40 micrograms/L. Average CV of the within-run imprecision for the EIA method was 19.6% and for the RIA method 28.8%. CVs of the between-run imprecision at low, intermediate and high values for the EIA method were 23.7%, 15.8%, 15.6% and for the RIA method 20.6%, 14.4%, 11.2%. The diagnostic accuracy analyzed by a Receiver Operating Characteristics (ROC) curve of the RIA method gave a maximum accuracy of 190.9 while that of a simulated ROC curve for the EIA method was 193.0. We found that the precision and the diagnostic accuracy of the EIA method (AGEN) are equal to or better than those of one of the RIA methods.

In a group of 167 patients with acute viral hepatitis (AVH), 11 with type A hepatitis, 125 with type B and 31 type non A, non B, the following enzymes were studied: serum amylase (S-AMY) and its isoenzymes (pancreatic and salivary type), urinary amylase (U-AMY), serum lipase (S-TGL) and serum immunoreactive trypsin (i-TRY). In all groups of patients, in the acute phase of illness, a significant increase in S-AMY was observed, in particular in hepatitis type B and non A, non B (p less than 0.001). An increase in U-AMY excretion was recorded in patients with type A hepatitis. S-TGL levels were significantly higher in all groups, especially in patients with type A hepatitis. i-TRY was only slightly higher in patients with hepatitis A and non A, non B. S-AMY isoenzymes showed a peculiar pattern: the pancreatic type (2) of isoamylase was found to be prevalent in 66% of patients with AVH while in controls the salivary type (1) was prevalent in most cases. Pancreatic enzyme alterations correlated neither with laboratory hepatic function tests nor with the clinical syndrome. These results suggest that a pancreatic injury is not uncommon in AVH, although it is seldom severe.

The authors report the behaviour of serum concentration of thyroglobulin (TG) after fine needle aspiration biopsy of the thyroid. Compared with the basal level, serum concentration of thyroglobulin increase of 70% three minutes and of 341% sixty minutes after this maneuver. The authors agree with those who believe an interval of 10-15 days between fine needle aspiration biopsy of the thyroid and determination of serum concentration of thyroglobulin is necessary.

We measured in 193 patients, admitted to our wards for symptoms and signs suggestive of pancreatic or digestive malignancy, the serum levels of five tumor-associated antigens (CA 19-9, CA 50, CA 125, TPA, CEA) and we evaluated their diagnostic accuracy both when used alone and in combination. For CA 19-9 and CA 50 a sensitivity for pancreatic cancer as high as 92 and 88%, respectively, and specificity of 91.8% were found. A lower sensitivity vs. pancreatic cancer was found for the other tumor markers, and vs. the other digestive and nondigestive malignancies for all tumor markers (apart for CA 19-9 and CA 50 vs. biliary carcinomas). As for the combined assays, the best figures were found vs. pancreatic cancer for CA 19-9 plus CA 50, CA 50 plus CEA, CA 50 plus CA 125; a sensitivity by far worse vs. the other gastrointestinal cancers was found for all the possible combinations. We conclude that in selected symptomatic patients some tumor-marker determinations can be useful in identifying those with a high probability of harboring a pancreatic cancer, to be further studied or operated upon. The clinical relevance of this in patients already symptomatic is at present unclear.