Sedimentary organic matter, prokaryotes, and meiofauna across a river-lagoon-sea gradient

In benthic ecosystems, organic matter (OM), prokaryotes, and meiofauna represent a functional bottleneck in the energy transfer towards higher trophic levels and all respond to a variety of natural and anthropogenic disturbances. The relationships between OM and the different components of benthic communities are influenced by multiple environmental variables, which can vary across different habitats. However, analyses of these relationships have mostly been conducted by considering the different habitats separately, even though freshwater, transitional, and marine ecosystems, physically linked to each other, are not worlds apart. Here, we investigated the quantity and nutritional quality of sedimentary OM, along with the prokaryotic and meiofauna abundance, biomass, and biodiversity, in two sampling periods, corresponding to high vs. low freshwater inputs to the sea, along a river-to-sea transect. The highest values of sedimentary organic loads and their nutritional quality, prokaryotic and meiofaunal abundance, and biomass were consistently observed in lagoon systems. Differences in the prokaryotic Operational Taxonomic Units (OTUs) and meiofaunal taxonomic composition, rather than changes in the richness of taxa, were observed among the three habitats and, in each habitat, between sampling periods. Such differences were driven by either physical or trophic variables, though with differences between seasons. Overall, our results indicate that the apparent positive relationship between sedimentary OM, prokaryote and meiofaunal abundance, and biomass across the river-lagoon-sea transect under scrutiny is more the result of a pattern of specifically adapted prokaryotic and meiofaunal communities to different habitats, rather than an actually positive 'response' to OM enrichment. We conclude that the synoptic analysis of prokaryotes and meiofauna can provide useful information on the relative effect of organic enrichment and environmental settings across gradients of environmental continuums, including rivers, lagoons, and marine coastal ecosystems

Management of Hypothyroidism in Internal Medicine: Patient Profile and Effects of an Educational Programme in the Cluster-Randomized FADOI TIAMO Study.

Background and aims: There is still limited knowledge regarding the clinical profile and appropriateness of treatment in patients with hypothyroidism hospitalized in Internal Medicine (IM) Departments in Italy. The aim of this study is to evaluate: 1) the characteristics of patients and possible deviations from national and international clinical practice recommendations (CPRs) in evidence-based guidelines (EBGs); 2) the improvement of patient management by means of a standardized educational programme (EP). Methods: A nationwide multicentre study, comprising two replications of a retrospective survey (phases 1 and 3) with an intervening EP (phase 2) in half of the centres and no EP in the other half, was conducted. The EP was based on outreach visits. Centres were assigned to the two arms of the study, labelled the training group (TG) and control group (CG) respectively, by cluster randomization. Four EBGs and 39 CPRs provided the basis on which 22 treatment management indicators were identified (7 referring to the time of hospital admission, 15 to post-admission). Results: The 21 participating centres recruited 587 hospitalized patients with hypothyroidism, 421 of which were females (71.7%, mean age 74.1 + 14.4 yrs): 318 in phase 1 and 269 in phase 3. The cause of hypothyroidism was unknown in 282 patients (48%). Evaluation at the time of admission identified satisfactory adherence to CPRs (>50%) for 63.6% of the indicators. In the phase 3, TG centres showed significant improvement vs CG in 4 of the 15 post-admission indicators, while 1 out of 15 was significantly worse. Conclusions: The EP based on outreach visits significantly improved some indicators in the management of patients with hypothyroidism, with specific reference to appropriateness of TSH dosage and levothyroxine (LT4) treatment modality. Clinical trial registration: ClinicalTrials.gov, identifier NCT05314790

Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma

Background: Trastuzumab has recently shown efficacy in the treatment of HER2-positive advanced gastric adenocarcinoma. Although antibody-based therapies target the metastatic disease, HER2 status is usually evaluated in the primary tumour because metastatic sites are rarely biopsied. The aim of this study was to compare HER2 status in primary and paired metastatic sites of gastric adenocarcinoma. Methods: The HER2 status was assessed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in 72 secondary lesions of gastric adenocarcinoma and in the corresponding primary tumours. Results: Concordance of FISH results, evaluable in 68 primary and matched metastatic sites, was 98.5%. Concordance of IHC results, available in 39 of the 72 paired cases, was 94.9%. Only one case showed discordance between primary tumour and metastasis, being negative by both IHC and FISH in the primary and showing HER2 overexpression and amplification in the corresponding pancreatic lymph node metastasis. Conclusion: The high concordance observed between HER2 results obtained by both IHC and FISH on primary tumours and corresponding metastases suggests that in gastric cancer HER2 status is maintained in most cases unchanged during the metastatic process. Keywords: HER2, gastric cancer, FISH, immunohistochemistr

Impact of immunochemotherapy with R-bendamustine or R-CHOP for treatment naïve advanced-stage follicular lymphoma: A subset analysis of the FOLL12 trial by Fondazione Italiana Linfomi

We conducted a post hoc analysis of the FOLL12 trial to determine the impact of different initial immunochemotherapy (ICT) regimens on patient outcomes. Patients were selected from the FOLL12 trial, which included adults with stage II–IV follicular lymphoma (FL) grade 1–3a and high tumor burden. Patients were randomized 1:1 to receive either standard ICT followed by rituximab maintenance (RM) or the same ICT followed by a response-adapted approach. ICT consisted of rituximab-bendamustine (RB) or rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP), per physician's decision. A total of 786 patients were included in this analysis, 341 of whom received RB and 445 R-CHOP. RB was more frequently prescribed to older subjects, females, patients without bulky disease, and those with grade 1–2 FL. After a median of 56 months of follow-up, R-CHOP and RB had similar progression-free survival (PFS) (Hazard Ratio for RB 1.11, 95% CI 0.87–1.42, p = 0.392). Standard RM was associated with improved PFS compared to response-adapted management both after R-CHOP and RB. Grade 3–4 hematologic adverse events were more frequent with R-CHOP during induction treatment and more frequent with RB during RM. Grade 3–4 infections were more frequent with RB. RB was also associated with a higher incidence of transformed FL. R-CHOP and RB showed similar activity and efficacy, but with different safety profiles and long-term events, suggesting that the treating physician should carefully select the most appropriate chemotherapy regimen for each patient based on patient's individual characteristics, choices, and risk profile

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

Quality of life and treatment satisfaction in adults with Type 1 diabetes: A comparison between continuous subcutaneous insulin infusion and multiple daily injections

Aims: The aim of this case-control study was to compare quality of life (QoL) and treatment satisfaction in adults with Type 1 diabetes (T1DM) treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Methods: Consecutive patients aged between 18 and 55 years, and attending diabetes clinics for a routine visit, completed the Diabetes-Specific Quality-of-Life Scale (DSQOLS), the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the SF-36 Health Survey (SF-36). Case (CSII) and control subjects (MDI) were recruited in a 1 : 2 ratio. Results: Overall, 1341 individuals were enrolled by 62 diabetes clinics; 481 were cases and 860 control subjects. Cases had a longer diabetes duration and were more likely to have eye and renal complications. Age, school education, occupation and HbA1c were similar. Of control subjects, 90% followed glargine-based MDI regimens and 10% used NPH-based MDI regimens. On multivariate analysis, after adjusting for socioeconomic and clinical characteristics, scores in the following areas of the DSQOLS were higher in cases than control subjects: diet restrictions (β = 5.96; P < 0.0001), daily hassles (β = 3.57; P = 0.01) and fears about hypoglycaemia (β = 3.88; P = 0.006). Treatment with CSII was also associated with a markedly higher DTSQ score (β = 4.13; P < 0.0001) compared with MDI. Results were similar when CSII was compared separately with glargine- or NPH-based MDI regimens. Conclusions: This large, non-randomized, case-control study suggests quality of life gains deriving from greater lifestyle flexibility, less fear of hypoglycaemia, and higher treatment satisfaction, when CSII is compared with either glargine-based or NPH-based MDI regimens. © 2008 The Authors

Exchange of nutrients and oxygen across the sediment-water interface below a Sparus aurata marine fish farm in the north-western Mediterranean Sea

Purpose: This study analyzes the effects of aquaculture activities in open seawater in the north-western coastal waters of the Mediterranean Sea. It is the first of its kind to be based on benthic flux data gathered in situ below fish farms for this particular area. Materials and methods: Samples were collected on four sampling campaigns over a 1-year cycle under a Sparus aurata fish farm facility where benthic fluxes were measured in situ using light and dark benthic chambers. Bottom water and sediment samples were also collected. Data were compared to those for a nearby control station. Results and discussion: Significant differences were found (ANOVA, p < 0. 05) between concentrations of organic matter (OM), total phosphorus and redox potentials in sediments located under the cages and those of the control station. The consumption of dissolved oxygen (DO) by sediment and positive ammonium (NH4 +) fluxes was stimulated by OM content, with correlations of r = -0. 60 (p < 0. 01) and r = 0. 70 (p < 0. 01), respectively. The OM content of sediments was found to be consistently higher under the cages than at the control station, with the highest value (1. 8 ± 0. 7 %) under the cages observed during the early summer; values of DO and NH4 + fluxes were -64 ± 17 and 12. 7 ± 1. 0 mmol m-2 day-1, respectively. PO4 3- fluxes were consistently higher in the fish farm sediments (between 0. 58 and 0. 98 mmol m-2 day-1) than those observed at the control station. Nitrate (NO3 -) fluxes were found to be consistently negative due to denitrification occurring in the sediments and were related to the concentration of NO3 - in bottom waters (r = 0. 92, p < 0. 01). Si fluxes were shown to be associated with water temperature (r = 0. 59, p < 0. 05). Conclusions: The results imply that sediments located below cages accumulate organic matter originating from aquaculture activities, especially during summer months when this activity increases. Sediments undergo biogeochemical changes that mainly affect fluxes of DO, NH4 + and soluble reactive phosphorus, although these do not seem to have a significant impact on the quality of the water column due to the hydrodynamic characteristics of the area. © 2012 Springer-Verlag.We would like to thank the Caja del Mediterraneo for a predoctoral fellowship fund for this research and Antonio Asuncion Acuigroup Maremar manager for the facilities and support in conducting the study. The translation of this paper was funded by the Universidad Politecnica de Valencia, Spain. We are grateful for the valuable comments of the anonymous reviewers on previous versions of the manuscript.Morata Higón, T.; Sospedra, J.; Falco Giaccaglia, SL.; Rodilla Alama, M. (2012). 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Nitrate Reduction Functional Genes and Nitrate Reduction Potentials Persist in Deeper Estuarine Sediments. Why?

Denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are processes occurring simultaneously under oxygen-limited or anaerobic conditions, where both compete for nitrate and organic carbon. Despite their ecological importance, there has been little investigation of how denitrification and DNRA potentials and related functional genes vary vertically with sediment depth. Nitrate reduction potentials measured in sediment depth profiles along the Colne estuary were in the upper range of nitrate reduction rates reported from other sediments and showed the existence of strong decreasing trends both with increasing depth and along the estuary. Denitrification potential decreased along the estuary, decreasing more rapidly with depth towards the estuary mouth. In contrast, DNRA potential increased along the estuary. Significant decreases in copy numbers of 16S rRNA and nitrate reducing genes were observed along the estuary and from surface to deeper sediments. Both metabolic potentials and functional genes persisted at sediment depths where porewater nitrate was absent. Transport of nitrate by bioturbation, based on macrofauna distributions, could only account for the upper 10 cm depth of sediment. A several fold higher combined freeze-lysable KCl-extractable nitrate pool compared to porewater nitrate was detected. We hypothesised that his could be attributed to intracellular nitrate pools from nitrate accumulating microorganisms like Thioploca or Beggiatoa. However, pyrosequencing analysis did not detect any such organisms, leaving other bacteria, microbenthic algae, or foraminiferans which have also been shown to accumulate nitrate, as possible candidates. The importance and bioavailability of a KCl-extractable nitrate sediment pool remains to be tested. The significant variation in the vertical pattern and abundance of the various nitrate reducing genes phylotypes reasonably suggests differences in their activity throughout the sediment column. This raises interesting questions as to what the alternative metabolic roles for the various nitrate reductases could be, analogous to the alternative metabolic roles found for nitrite reductases