Insulin Glargine U100 Utilization in Patients with Type 2 Diabetes in an Italian Real-World Setting: A Retrospective Study

Background. This study is aimed at estimating the proportion of type 2 diabetes mellitus (T2DM) patients treated with basal insulin (insulin glargine U100) and at evaluating daily insulin dose, treatment pattern, and adherence to treatment of these patients. Methods. Data from administrative and laboratory databases of 3 Italian Local Health Units were retrospectively collected and analyzed. All patients with a diagnosis of T2DM between 01/01/2012 and 31/12/2012 were considered, and those with at least a prescription of insulin glargine between 01/01/2013 and 31/12/2014 were included and followed up for one year. For each patient, we evaluated HbA1c levels both at baseline and during the follow-up period and the daily average dose of insulin. Medication adherence was defined by using medication possession ratio (MPR) and reported as proportion of patients with MPR≥80%. Results. 7,422 T2DM patients were available for the study. According to the antidiabetic medication prescribed, patients were categorized into four groups: insulin glargine only, insulin glargine plus oral glucose-lowering drugs, insulin glargine plus rapid-acting insulin, and insulin glargine plus DPP-4 inhibitors. Median daily dose of insulin among insulin glargine only patients was higher than in other groups (35 IU vs. 20 IU, p<0.05), and a higher percentage of them achieved a target HbA1c value of less than 7.0% (53.8% vs. 30%, p<0.001). Adherence to insulin treatment was lowest (41%) in the insulin glargine only group compared to other groups (ranging from 58.4% to 64.4%), p<0.001. Conclusions. A large proportion of T2DM patients treated with insulin fail in achieving the glycemic target of HbA1c level<7%, irrespective of treatment regimen; however, basal insulin only is associated with lower therapeutic unsuccess. Adherence to antidiabetes medications is also suboptimal in these patients and should be addressed to improve long-term outcomes of reducing and preventing microvascular and macrovascular complications

Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe.

Despite its essential role in the (patho)physiology of several diseases, CB2R tissue expression profiles and signaling mechanisms are not yet fully understood. We report the development of a highly potent, fluorescent CB2R agonist probe employing structure-based reverse design. It commences with a highly potent, preclinically validated ligand, which is conjugated to a silicon-rhodamine fluorophore, enabling cell permeability. The probe is the first to preserve interspecies affinity and selectivity for both mouse and human CB2R. Extensive cross-validation (FACS, TR-FRET and confocal microscopy) set the stage for CB2R detection in endogenously expressing living cells along with zebrafish larvae. Together, these findings will benefit clinical translatability of CB2R based drugs

Partial reversibility of the cytotoxic effect induced by graphene-based materials in skin keratinocytes

In the frame of graphene-based material (GBM) hazard characterization, particular attention should be given to the cutaneous effects. Hence, this study investigates if HaCaT skin keratinocytes exposed to high concentrations of few-layer graphene (FLG) or partially dehydrated graphene oxide (d-GO) for a short time can recover from the cytotoxic insult, measured by means of cell viability, mitochondrial damage and oxidative stress, after GBM removal from the cell medium. When compared to 24 or 72 h continuous exposure, recovery experiments suggest that the cytotoxicity induced by 24 h exposure to GBM is only partially recovered after 48 h culture in GBM-free medium. This partial recovery, higher for FLG as compared to GO, is not mediated by autophagy and could be the consequence of GBM internalization into cells. The ability of GBMs to be internalized inside keratinocytes together with the partial reversibility of the cellular damage is important in assessing the risk associated with skin exposure to GBM-containing devices

Increased prothrombin time and platelet counts in living donor right hepatectomy: Implications for epidural anesthesia

The risks and benefits of adult-to-adult living donor liver transplantation need to be carefully evaluated. Anesthetic management includes postoperative epidural pain relief, however, even patients with a normal preoperative coagulation profile may suffer transient postoperative coagulation derangement. This study explores the possible causes of postoperative coagulation derangement after donor hepatectomy and the possible implications on epidural analgesia. Thirty donors, American Society of Anesthesiology 1, with no history of liver disease were considered suitable for the study. A thoracic epidural catheter was inserted before induction and removed when laboratory values were as follows: prothrombin time (PT) > 60%, activated partial thromboplastin time 100,000 mmfpound (mm'). Standard blood tests were evaluated before surgery, on admission to the recovery room, and daily until postoperative day (POD) 5. The volumes of blood loss and of intraoperative fluids administered were recorded. Coagulation abnormalities observed immediately after surgery may be related mostly to blood loss and to the diluting effect of the intraoperative infused fluids, although the extent of the resection appears to be the most important factor in the extension of the PT observed from POD 1. In conclusion, significant alterations in PT and platelet values were observed in our patients who underwent uncomplicated major liver resection for living donor liver transplantation. Because the potential benefits of epidural analgesia for liver resection are undefined according to available data, additional prospective randomized studies comparing the effectiveness and safety of intravenous versus epidural analgesia in this patient population should be performed

DETRITAL CARBONATE GRAINS AS PROVENANCE INDICATORS IN THE UPPER CRETACEOUS PIETRAFORTE FORMATION (NORTHERN APENNINES)

The Upper Cretaceous Pietraforte Formation, an allochthonous unit of the Ligurian domain in the northern Apennines, provides a case study of the importance of detrital carbonate grains for provenance determination in sandstones. The Pietraforte Formation is composed of turbidite sandstones with subordinate conglomerate, deposited in an external sector of the Ligurian ocean, close to the Adriatic margin. The sandstones have a lithic composition, characterized by abundant sedimentary and metasedimentary rock fragments (35-56% of the terrigenous framework), little feldspar (< 7%) that is almost exclusively plagioclase, and a high ratio of fine-to coarse-grained polycrystalline quartzose grains to total quartzose grains (average Q(p)/Q(t) = 0.37). Carbonate rock fragments dominate the lithic association of both sandstones and conglomerates and provide the most detailed information for provenance determination. They are composed primarily of dolostones and a wide variety of limestones containing identifiable age-diagnostic microfossils. Fossils and rock textures of carbonate clasts document the erosion of Upper Triassic to Lower Cretaceous shelf and pelagic carbonate units which can be matched with Mesozoic rock types present in the Tuscan domain of the northern Apennines. Compositional results constrain the source of the Pietraforte Formation sandstones to the western margin of the Adriatic plate, from uplifted sedimentary and metasedimentary rocks of the Tuscan domain and its low-grade metamorphic basement. Coeval intrabasinal sources provided additional supplies to the depositional basin of the Pietraforte Formation; this intrabasinal supply consists of shelf carbonate allochems, planktonic foraminifera and argillaceous rip-up clasts. The presence of carbonate grains from shallow-water environments may indicate the existence during deposition of marginal shelf areas favourable for carbonate allochem production