Metal determination in organic fluids of patients with stainless steel hip arthroplasty.

In 20 stainless steel Charnley hip arthroplasties (with a follow-up of 10-13 years) nickel, chromium and manganese levels were measured in blood, plasma and urine by atomic absorption spectrophotometry. Skin patch tests for these metals, and clinical and roentgenographic results of arthroplasty were also assessed. Metal levels in organic fluids were plotted against a control population homogene- ous for age, residence and anamnestic conditions with the first, but which had never undergone a prosthesis or other metallic implant surgical procedure. Nickel levels in blood, plasma and urine, manganese levels in blood and urine and chromium levels in plasma were significantly higher in the hip prostheses popula- tion. Metal ion release from stainless steel prostheses is discussed with regard to implant failure, metal sensitivity and carcinogenesis

Preliminary assessment of persistent organic pollutants (POPs) in tissues of Risso's dolphin (Grampus griseus) specimens stranded along the Italian coasts

Ecotoxicological and pathological research on Grampus griseus (Cuvier, 1812) (Risso's dolphins) is scarce both globally and in the Mediterranean Sea. This species has been classified as "Vulnerable" by the International Union for Conservation of Nature (IUCN) in the Mediterranean Sea.To evaluate the presence of "persistent organic pollutants" (POPs), especially organochlorine compounds (OCs), in the animals, chemical analyses were performed on tissues and organs of Risso's dolphin stranded along the Italian coasts between 1998 and 2021. Toxic contaminants such as hexachlorobenzene (HCB), poly-chlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs) were examined in the blubber, liver, muscle, and brain of 20 animals, and data was correlated with sex, age, and stranding locations

Management of lymphoma survivor patients in Italy: an evaluation by Fondazione Italiana Linfomi

Several outpatient models for the follow-up of cancer survivors have been developed worldwide. A multidisciplinary approach is often necessary to guarantee the best monitoring of long-term toxicities. Guidelines also indicate a close education on healthy lifestyles. In this context, we have analyzed the Italian follow-up modalities of lymphoma survivors, with the aim to have a starting line to hypothesize and plan the best model for Italian hematology centers

Dietary ω-3 fatty acid supplementation improves murine sickle cell bone disease and reprograms adipogenesis

Sickle cell disease (SCD) is a genetic disorder of hemoglobin, leading to chronic hemolytic anemia and multiple organ damage. Among chronic organ complications, sickle cell bone disease (SBD) has a very high prevalence, resulting in long-term disability, chronic pain and fractures. Here, we evaluated the effects of ω-3 (fish oil-based, FD)-enriched diet vs. ω-6 (soybean oil-based, SD)-supplementation on murine SBD. We exposed SCD mice to recurrent hypoxia/reoxygenation (rec H/R), a consolidated model for SBD. In rec H/R SS mice, FD improves osteoblastogenesis/osteogenic activity by downregulating osteoclast activity via miR205 down-modulation and reduces both systemic and local inflammation. We also evaluated adipogenesis in both AA and SS mice fed with either SD or FD and exposed to rec H/R. FD reduced and reprogramed adipogenesis from white to brown adipocyte tissue (BAT) in bone compartments. This was supported by increased expression of uncoupling protein 1(UCP1), a BAT marker, and up-regulation of miR455, which promotes browning of white adipose tissue. Our findings provide new insights on the mechanism of action of ω-3 fatty acid supplementation on the pathogenesis of SBD and strengthen the rationale for ω-3 fatty acid dietary supplementation in SCD as a complementary therapeutic intervention

Usporedba dinamičke analize para iznad otopine i mikroekstrakcije analita na čvrstoj fazi za plinskokromatografsko određivanje BTEX-a u urinu

The aim of this study was to compare two extraction procedures: dynamic headspace-purge and trap (PT) and headspace solid-phase microextraction (HS-SPME) for gas chromatographic determination of benzene, toluene, ethylbenzene, and isomeric xylenes (BTEX) in urine with photoionization (PID) and mass spectrometric (MS) detection, respectively. Both methods showed linearity in the range of interest [(50-2000) ng L-1], good accuracy (80% to 100 %), and repeatability (RSD≤11 %). Detection limits were in the low ng L-1 level for both methods, although slightly greater sensitivity was found for the PT method. In comparison with PT, HS-SPME was simpler and required less time for analysis. Although the analytical features of both examined methods are appropriate for biomonitoring of environmental exposure to BTEX, only the HS-SPME-GC-MS method is recommended for routine analysis of BTEX in urine. The method was applied for the quantitative analysis of BTEX in urine samples collected from non-smokers (n=10) and smokers (n=10).Cilj ovog rada bio je usporediti dva postupka ekstrakcije za plinskokromatografsko određivanje benzena, toluena, etilbenzena i izomera ksilena u urinu. Uspoređene su dinamička analiza para iznad otopine (tzv. purge and trap) uz fotoionizacijski detektor i mikroekstrakcija analita na čvrstoj fazi uz detektor spektrometar masa. Rezultati upućuju na linearnost odziva detektora u ispitivanome koncentracijskom području [(50- 2000) ng L-1], zadovoljavajuću točnost (80 %-100 %) i ponovljivost (RSD ≤11 %). Postignute su niske granice detekcije za obje metode. Mikroekstrakcija analita na čvrstoj fazi uz detektor spektrometar masa pokazala se jednostavnijom i bržom za izvođenje pa se preporučuje za rutinsko određivanje BTEX-a u urinu. Metoda je primijenjena za analizu tih spojeva u uzorcima urina nepušača (n=10) i pušača (n=10)

Interstitial lung disease in a newborn affected by mevalonic aciduria

Introduction: Mevalonic aciduria (MA) is the most severe phenotype of mevalonate-kinase deficiency (MKD), with a onset in early infancy and poor prognosis. MA diagnosis may be challenging in the neonatal period given its rarity and its unspecific symptoms that frequently recall those of other neonatal diseases. To our knowledge, interstial lung involvement has never been described as onset feature in a newborn with MKD. Objectives: We report the case of a newborn affected by MKD characterized by interstitial lung disease. Methods: The patient underwent laboratory and radiology evaluation as clinically indicated. Direct Sanger sequencing was used to screen the 10 exons of the MVK gene. Results: A female neonate born at term from consanguineous parents was referred to our hospital at 16 days of life (DOL) for mild hypotonia and persistent raised inflammatory markers despite antibiotic therapy. Infectious work-up was negative for both viral and bacterial infections. Chest x-ray revealed bilateral perihilar peribronchial thickening. Electroencephalography (EEG) reported moderate diffuse anomalies of background activity without major abnormalities. On DOL 20 the first episode of fever was recorded. Due to worsening tachypnea and persistent abnormal chest x-ray, a pulmonary CT scan was performed and showed diffuse ground-glass bilateral infiltrates consistent with alveolar-interstitial lung disease. On DOL 22 a palpable maculo-papular skin rash appeared on feet and hands, vanishing spontaneously 24 hours later. Bone marrow examination and levels of perforins, neuron-specific enolase and urinary catabolites of catecholamines were normal. A total body MRI was normal except for a mild cerebellar hypoplasia and the known interstitial lung disease. The patient kept presenting hypotonia, relapsing episodes of fever and skin rashes, developed anemia requiring blood transfusions and failure to thrive became evident. Type-I IFN signature was negative. A genetic test was requested, as well as quantification of urinary levels of mevalonic acid, which were markedly above the normal range. Direct Sanger sequencing allowed to detect a homozygous c.709A>T missense mutation in the exon 8 of the MVK gene, coding for a protein substitution p.T237S already classified as pathogenic in the INFEVERS database (http://fmf.igh.cnrs.fr/ISSAID/infevers/) and therefore consistent with the diagnosis of MKD. Both parents and her sister were found to be heterozygous carriers of the same mutation. On DOL 38 treatment with anakinra was started, with prompt regression of fever and skin rash, decrease in inflammatory markers, increase in reticulocytes count and weight gain. Hypotonia improved but persisted. The patient was discharged from hospital on DOL 56 in good clinical conditions, with acute phase reactants within the normal range and mild hypotonia. She is now 4 months old, still on anakinra treatment without adverse events. Conclusion: Autoinflammatory diseases in the neonatal period are a diagnostic challenge. Clinical suspicion is crucial in order to perform specific laboratory and genetic testing and start appropriate treatment. Interstitial lung involvement may be present in MKD and, together with increased inflammatory markers, could be the first manifestation of the disease

Clinical and pharmacological phase I study with accelerated titration design of a daily times five schedule of BBR3464, a novel cationic triplatinum complex

Objectives To define the maximum tolerated dose (MTD), the toxicity and pharmacokinetic profile of BBR3464, a novel triplatinum complex. Patients and methods Fourteen patients with advanced solid tumors not responsive to previous antitumor treatments received BBR 3464 on a daily × 5 schedule every twenty-eighth day. The drug was given as a one-hour infusion with pre-and post-treatment hydration (500 ml in one hour) and no antiemetic prophylaxis. The starting dose was 0.03 mg/m2/day. A modified accelerated titration escalation design was used. Total and free platinum (Pt) concentrations in plasma and urine were assessed by ICP-MS on days 1 and 5 of the first cycle. Results Dose was escalated four times up to 0.17 mg/m2/ day. Short-lasting neutropenia and diarrhea of late onset were dose-limiting and defined the MTD at 0.12 mg/m2 Nausea and vomiting were rare, neither neuro- nor renal toxic effects were observed. BBR3464 showed a rapid distribution phase of 1 hour and a terminal half-life of several days. At 0.17 mg/m2 plasma Cmax and AUC on day 5 were higher than on day 1, indicating drug accumulation. Approximately 10% of the equivalent dose of BBR3464 (2.2%-13.4%) was recovered in a 24-hour urine collection. Conclusions The higher than expected incidence of neutropenia and GI toxicity might be related to the prolonged half-life and accumulation of total and free Pt after daily administrations. Lack of nephrotoxicity and the low urinary excretion support the use of the drug without hydration. The single intermittent schedule has been selected for clinical developmen

Real-world Outcomes of Relapsed/Refractory Diffuse Large B-cell Lymphoma Treated With Polatuzumab Vedotin-based Therapy.

After FDA and EMA approval of the regimen containing polatuzumab vedotin plus rituximab and bendamustine (PolaBR), eligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients in Italy were granted early access through a Named Patient Program. A multicentric observational retrospective study was conducted focusing on the effectiveness and safety of PolaBR in everyday clinical practice. Fifty-five patients were enrolled. There were 26 females (47.3%), 32 patients were primary refractory and 45 (81.8%) resulted refractory to their last therapy. The decision to add or not bendamustine was at physician's discretion. Thirty-six patients underwent PolaBR, and 19 PolaR. The 2 groups did not differ in most of baseline characteristics. The final overall response rate was 32.7% (18.2% complete response rate), with a best response rate of 49.1%. Median disease-free survival was reached at 12 months, median progression-free survival at 4.9 months and median overall survival at 9 months, respectively. Overall, 88 adverse events (AEs) were registered during treatment in 31 patients, 22 of grade ≥3. Eight cases of neuropathy occurred, all of grades 1-2 and all related to polatuzumab. The two groups of treatment did not differ for effectiveness endpoints but presented statistically significant difference in AEs occurrence, especially in hematological AEs, in AEs of grade equal or greater than 3 and in incidence of neuropathy. Our data add useful information on the effectiveness of Pola(B)R in the setting of heavily pretreated DLBCL and may also suggest a better tolerability in absence of bendamustine without compromise of efficacy

High Salt-Content Plasticized Flame-Retardant Polymer Electrolytes

peer reviewe

SUBTYPES OF MATURE T AND NK CELL LYMPHOMAS ACCORDING TO 2016 WHO CLASSIFICATION. PRELIMINARY REPORT OF THE INTERNATIONAL PROSPECTIVE T‐CELL PROJECT 2.0

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