Salivary markers of hepato-metabolic comorbidities in pediatric obesity

Background

The pediatric obesity epidemic calls for the noninvasive detection of individuals at higher risk of complications.

Effect of fibrinogen concentration on the velocity of platelet aggregation

The relationship between fibrinogen binding to its receptor and platelet aggregation has been investigated by comparing 125I-fibrinogen binding and aggregation velocities of gel-filtered platelets in the presence of adenosine diphosphate (ADP). Aggregometric responses at various fibrinogen concentrations are found to be bell-shaped and show a maximum at fibrinogen concentrations (Fmax) similar to the 125I-fibrinogen hemisaturating doses. At higher and lower fibrinogen concentrations, platelet aggregation velocities decrease in a parallel manner. Lowering ADP concentration increases Fmax, in agreement with the modulatory effect of ADP on fibrinogen binding to platelets. Variations of fibrinogen in the range of physiopathologic plasma concentrations affect platelet aggregation induced by any ADP dose. These results clarify the relationship between the fibrinogen binding process and aggregation and demonstrate that plasma fibrinogen concentration has a major influence on the velocity of platelet aggregation.     

Prevalence of abnormal electrocardiograms in a large, unselected population undergoing pre-participation cardiovascular screening.

AIMS: The implementation of 12-lead ECG in the pre-participation screening of young athletes is still controversial and number of issues are largely debated, including the prevalence and spectrum of ECG abnormalities found in individuals undergoing pre-participation screening. METHODS AND RESULTS: We assessed a large, unselected population of 32,652 subjects [26 050 (80%) males], prospectively examined in 19 clinics associated to Italian Sports Medicine Federation. Most were young amateur athletes, aged 8-78 years (median 17), predominantly students (68%), engaged predominantly in soccer (39%), volleyball or basketball (8% each), athletics (6%), cycling (5%), swimming (4%). The ECG patterns were evaluated according to commonly used clinical criteria. The 12-lead ECG patterns were considered normal in 28 799 of the 32 652 athletes (88.2%) and abnormal in 3853 (11.8%). The most frequent abnormalities included prolonged PR interval, incomplete right bundle branch block (RBBB) and early repolarization pattern (total 2280, 7.0%). Distinct ECG abnormalities included deeply inverted T-waves in > 2 precordial and/or standard leads (751, 2.3%), increased R/S wave voltages suggestive of LV hypertrophy (247, 0.8%), conduction disorders, i.e. RBBB (351, 1.0%), left anterior fascicular block (162, 0.5%), and left bundle branch block (19, 0.1%). Rarely, cardiac pre-excitation pattern (42, 0.1%) and prolonged QTc interval (1, 0.03%) were found. CONCLUSION: In a large, unselected population of young athletes undergoing pre-participation screening, the prevalence of markedly abnormal ECG patterns, suggestive for structural cardiac disease, is low (<5% of the overall population) and should not represent obstacle for implementation of 12-lead ECG in the pre-participation screening program.     

Acquired hepatocerebral degeneration in a metastatic neuroendocrine tumor long-term survivor — an update on neuroendocrine neoplasm’s treatment: A case report

BACKGROUNDMetastatic small bowel low-grade neuroendocrine tumors (NETs) have a good prognosis. Surgery is the only curative treatment; however, this may induce advanced liver disease, particularly in long-term survivor patients. Acquired hepatocerebral degeneration or Parkinsonism in cirrhosis is characterized by rapidly progressive extrapyramidal symptoms in patients with advanced liver disease.CASE SUMMARYA 70-year-old man presented to the emergency department with diminished consciousness and disorientation, and was diagnosed with hepatic encephalopathy. The patient was diagnosed in 1993 with a metastatic small bowel NET, for which he twice underwent hepatic surgery, with metastatic resection in 1993 and a right hepatectomy in 2002 to remove two hepatic metastases. In 2003, the patient started first-line chemotherapy and in 2004 started the first of three consecutive biological treatments, followed by radio-molecular therapy, achieving stable disease for 14 years. Disease progression was identified and he underwent an endoscopic retrograde cholangiopancreatography. However, in 2019 advanced liver disease was identified. We diagnosed the development of acquired hepatocerebral degeneration, an unusual long-term side effect after multiple hepatic procedures.CONCLUSIONThe importance of regular and ongoing surveillance in long-term NET survivors who undergo hepatic procedures should be integrated into the therapeutic management plan, as some of these negative outcomes could be prevented.     

Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera

In polycythemia vera, vascular risk assessment is based on age and thrombotic history, while the role of other potential predictors of this risk is still uncertain. Thus, we exploited the large database collected by the observational study of the European Collaboration on Low-Dose Aspirin in Polycythemia Vera (ECLAP) to investigate the association of hematologic variables and cardiovascular risk factors with the thrombotic risk. Among 1638 polycythemic patients followed for 2.7 +/- 1.3 years, there were 205 thromboses. Subjects with hypertension had a mild nonsignificant increase in the risk of arterial thrombosis, while this risk was significantly increased by smoking (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.15-3.14; P = .012). The time-dependent analysis adjusted for potential confounders showed that patients with a white blood cell count above 15 x 10(9)/L, compared with those with a white blood cell count below 10 x 10(9)/L, had a significant increase in the risk of thrombosis (HR, 1.71; 95% CI, 1.10-2.65; P = .017), mainly deriving from an increased risk of myocardial infarction (HR, 2.84; 95% CI, 1.25-6.46; P = .013). Thus, leukocyte count may help in defining the vascular risk of polycythemic subjects.     

The haematocrit and platelet target in polycythemia vera

Polycythemia vera (PV) is a chronic myeloproliferative disorder whose major morbidity and mortality are thrombohaemorragic events and progression to acute leukaemia or myelofibrosis. Whether the haematocrit and platelet count predict such complications remains unclear. The European Collaboration on Low-dose Aspirin in Polycythemia Vera prospective study included 1638 PV patients. A total of 164 deaths (10%), 145 (8.85%) major thrombosis and 226 (13.8%) total thrombosis were encountered during 4393 person-years follow-up (median 2.8 years). In time-dependent multivariable analysis, a haematocrit in the evaluable range of 40-55% was neither associated with the occurrence of thrombotic events, mortality nor with haematological progression in the studied population. The haematocrit of patients in the highest and lowest deciles at baseline was maintained within a narrow interval of haematocrit values ranging from 40% to 47% throughout follow-up. High platelet count was associated with a lower progression rate to acute leukaemia/myelofibrosis, whereas it had no significant relationship with thrombotic events or mortality. Our findings do not suggest that the range of haematocrit (<55%) and platelet counts (<600 x 10(9)/l) we encountered in our population had an impact on the outcome of PV patients treated by current therapeutic strategies.     

A potent neutralizing monoclonal antibody can discriminate amongst IFNgamma from various primates with greater specificity than can the human IFNgamma receptor complex

A monoclonal antibody (AF2) generated against recombinant human interferongamma (IFNgamma) exhibited potent IFNgamma neutralizing activity and prevented human IFNgamma from binding to the cell surface IFNgamma receptor complex. The AF2 antibody also neutralized IFNgamma from higher primates (superfamily Hominoidea) but did not react with IFNgamma from rhesus or other primates in the suborder Anthropoidea IFNgamma from all primates tested, however, could signal via the human IFNgamma receptor complex, as indicated by the ability to upregulate the level of MHC class II molecule expression on the surface of a responsive human cell line. We cloned and sequenced the IFNgamma gene from chimpanzee, gorilla, orangutan, and gibbon, and compared those with the previously reported IFNgamma sequences of human, rhesus, baboon and marmoset. This comparison revealed that, of the primate IFNgammas that were not reactive with AF2, rhesus IFNgamma was most homologous to human IFNgamma, differing at only nine amino acids and containing a one amino acid deletion. Comparing the sequence of human IFNgamma with that of rhesus IFNgamma suggested residues of the human IFNgamma molecule that were involved in the formation of the epitope recognized by the AF2 antibody. Constructing human/rhesus chimeric IFNgamma molecules, combined with site-directed mutagenesis of both human and rhesus IFNgamma revealed that this epitope was dependent upon two non-contiguous amino acids that are juxtaposed in the tertiary structure of IFNgamma. The determinant recognized by AF2 antibody resides in a portion of IFNgamma that is proximal to, but distinct from the surface that interacts with the IFNgamma receptor. Therefore, this neutralizing monoclonal antibody reacts with a conformational determinant that distinguishes primate IFNgammas serologically, but not functionally.     

Resultados del tratamiento a largo plazo de 209 niños con leucemia linfoblástica aguda: experiencia de un grupo multicéntrico en Venezuela

Introduction

We present the results of the treatment of 209 children suffering from acute lymphoblastic leukaemia (ALL) using th 87-01 treatment protocol from the Dana Farber Cancer Institute (DFCI), modified by the Instituto Venezolano de los Seguros Sociales Cooperative Group (IVSS-CG). Protocol 87-01 IVSS-CG is a prospective multi-centred trial for the treatment of children with newly-diagnosed ALL. Our goals were to compare event-free survival (EVS) in a group treated with doxorubicin (dox) at 30 mg/m² versus a group treated with epirubicin (epi) at 40 mg/m² and to evaluate the use of radiotherapy (XRT) of 18 Gy + met-hotrexate (mtx) intrathecal (IT) administered and IT cytarabine (IT-Ara-C). The original protocol recommended using 24 Gy + IT mtx.

Materials and methods

Between 1989 and 1998, 209 patients were treated. They were classified into three groups of standard risk (SR), high risk (HR) and very high risk (VHR) according to the DFCI ALL protocol. Induction treatment phase: all groups received asparaginase (asp), vincristine (vcr), prednisone (pred), epirubicin (epi) or doxorubicin (dox) and IT Ara-C. The SR patients received mtx 40 mg/m² and the HR and the VHR groups received high dose mtx of 4 g/m². The CNS prophy-laxis in SR was mtx IT and 18 Gy irradiation of the cranium, while the HR and VHR groups received mtx + Ara-c IT + 18 Gy. Intensification treatment phase: SR group received vcr; pred, 6-mercatopurine (6-MP) every 3 weeks plus mtx and asp weekly for 20 weeks. The HR and VHR groups received asp weekly up to the cumulative toxic doses of dox or epi. The VHR group received an initial phase of intensification with high dose mtx and Ara-C. The maintenance in all groups was with POMP until 24 months of continuous complete remission.

Results

There were 80 patients (38%) classified as SR, 102 (49%) as HR and 27 (13%) as VHR. With a median follow-up of 8 years, the 8-year disease-free survival (DFS) was 68% ± 4% (DFS ± SE) for all patients, 72% ± 4% of the 80 SR patients, 62% ± 4% for the 102 HR patients and 63% ± 11% for the 27 VHR patients. Comparison of DFS between groups (SR vs. HR vs. VHR) indicated a Chi² of 3.35 which was not statistically significant (p=0.18). The DFS was 62% for the 72 patients who received dox and which was similar to that of the 57 patients who received epi.

Conclusions

There were no statistically significant differences in results between the patients receiving dox and those receiving epi (p=0.79). Radiation at 18 Gy was as effective as 24 Gy in preventing CNS involvement.