Management of patients with chronic heart failure and type 2 diabetes mellitus: the SCODIAC-II study.

SCODIAC was a pilot study which revealed an increasing use of SGLT2i in 123 outpatients affected with Heart Failure (HF) and Type 2 Diabetes Mellitus. SCODIAC-II study, the second phase of the program, has been carried out to determine diagnostic and therapeutic pathways in a larger group of patients and to verify whether the use of innovative antidiabetic therapies could modify echocardiographic parameters and cardiovascular therapies. 406 HF-diabetic patients, referred to Cardiologists and Diabetologists of pertaining healthcare districts in Campania, were enrolled in this retrospective study and divided in Group A, composed of 136 patients with preserved Ejection Fraction (HF-pEF)(> 45%) and Group B, formed of 270 patients with reduced EF (HF-rEF)(≤ 45%). All patients had performed periodic clinical and echocardiographic evaluations. The antidiabetic therapies resulted modified after 1 year with a greater use of GLP1-AR, gliptins and SGLT2i. Cardiovascular therapies resulted also modified with a greater use of sacubitril/valsartan and a reduction of ACEi and ARBs in HF-rEF patients. Echocardiography E velocity, A velocity and E/e' ratio resulted markedly reduced in 25 HF-pEF and in 60 HF-rEF patients treated with SGLT2i, in respect to both the whole sample of subjects at beginning and the other diabetic patients. LAVi resulted reduced only in HF-pEF patients and EF increased only in HF-rEF patients. The approach to the patients with HF and diabetes must necessarily take place in the healthcare districts, be multidisciplinary and integrated. SGLT2i could improve left ventricular function in HF-rEF patients and modify cardiovascular therapies, almost in this setting of patients.Trial registration The protocol was approved by the University of Naples Federico II Ethics Committee and registered at ClinicalTrial.gov (CT04375943). The principles outlined in the Declaration of Helsinki were followed.

Effect of beta- and alpha-glucans on immune modulating factors expression in enterocyte-like Caco-2 and goblet-like LS 174T cells.

Glucans are complex polysaccharides consisting of repeated units of d-glucose linked by glycosidic bonds. The nutritional contribution in α-glucans is mainly given by starch and glycogen while in ß-glucans by mushrooms, yeasts and whole grains, such as barley and spelt well represented in the Mediterranean Diet. Numerous and extensive studies performed on glucans highlighted their marked anti-tumor, antioxidant and immunomodulatory activity. It has recently been shown that rather than merely being a passive barrier, the intestinal epithelium is an essential modulator of immunity. Indeed, epithelial absorptive enterocytes and mucin secreting goblet cells can produce specific immune modulating factors, driving innate immunity to pathogens as well as preventing autoimmunity. Despite the clear evidence of the effects of glucans on immune system cells, there are only limited data about their effects on immune activity of mucosal intestinal cells strictly related to intestinal barrier integrity. The aim of the study was to evaluate the effects of α and ß glucans, alone or in combination with other substances with antioxidant properties, on reactive oxygen species (ROS) levels, on the expression of ROS-generating enzyme DUOX-2 and of the immune modulating factors Tumor Necrosis Factor (TNF-α), Interleukin 1 ß (IL-1ß) and cyclooxygenase-2 (COX-2) in two intestinal epithelial cells, the enterocyte-like Caco-2 cells and goblet cell-like LS174T. In our research, the experiments were carried out incubating the cells with glucans for 18 h in culture medium containing 0.2% FBS and measuring ROS levels fluorimetrically as dihydrodichlorofluoresce diacetate (DCF-DA) fluorescence, protein levels of DUOX-2 by Western blotting and mRNA levels of, TNF-α, IL-1ß and COX-2 by qRT-PCR. α and ß glucans decreased ROS levels in Caco-2 and LS 174T cells. The expression levels of COX-2, TNF-α, and IL-1ß were also reduced by α- and ß-glucans. Additive effects on the expression of these immune modulating factors were exerted by vitamin C. In Caco-2 cells, the dual oxidase DUOX-2 expression is positively modulated by ROS. Accordingly, in Caco-2 or LS174T cells treated with α and ß-glucans alone or in combination with Vitamin C, the decrease of ROS levels was associated with a reduced expression of DUOX-2. The treatment of cells with the NADPH oxidase (NOX) inhibitor apocynin decrease ROS, DUOX-2, COX-2, TNF-α and IL-1ß levels indicating that NOX dependent ROS regulate the expression of immune modulating factors of intestinal cells. However, the combination of vitamin C, α and ß-glucans with apocynin did not exert an additive effect on COX-2, TNF-α and IL-1ß levels when compared with α-, ß-glucans and Vitamin C alone. The present study showing a modulatory effect of α and ß-glucans on ROS and on the expression of immune modulating factors in intestinal epithelial cells suggests that the assumption of food containing high levels of these substances or dietary supplementation can contribute to normal immunomodulatory function of intestinal barrier.

Changes in the Prescription of Glucose-Lowering Medications in Patients With Type 2 Diabetes Mellitus After a Cardiovascular Event: A Call to Action From the DATAFILE Study.

Background Evidence accumulated that some glucose-lowering medications protect against cardiovascular events ( CVEs ) in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease. The present study evaluated if and how glucose-lowering medication prescription pattern changes in T2DM after a CVE. Methods and Results DATAFILE (Diabetes Therapy After a Cardiovascular Event) was a retrospective multicenter study conducted at 12 diabetes mellitus specialist outpatient clinics in Italy. We identified T2DM patients with an incident CVE for whom a follow-up visit was available after the event. We selected control T2DM patients without an incident CVE , who were matched with cases for age, sex, known diabetes mellitus duration, baseline hemoglobin A1c, kidney function, and follow-up time. We extracted clinical variables and compared prescribed therapies at baseline and follow-up. We included 563 patients with and 497 matched patients without an incident CVE . As expected, patients with a subsequent CVE had a higher baseline prevalence of ischemic heart disease. After a median of 9.5 months, in patients with versus those without a CVE , there was a significant increase in the prescription of beta-blockers, loop diuretics, dual antiplatelet therapy, and, among glucose-lowering medications, a significant decrease in metformin. Hemoglobin A1c marginally declined only in the control group, whereas low-density lipoprotein cholesterol decreased only in patients with CVE . Conclusions This study highlights that occurrence of a CVE in T2DM patients did not prime the prescription of glucose-lowering medications provided with cardiovascular protective effects, even though glucose control remained poor. These data emphasize the need to optimize the therapeutic regimen of T2DM patients with established cardiovascular disease, according to updated guidelines.

Current strategies to minimize toxicity of oxaliplatin: selection of pharmacogenomic panel tests.

Oxaliplatin is an anticancer drug routinely used to treat colorectal, gastroesophageal, ovarian, breast, head/neck, and genitourinary cancers. Discontinuation of oxaliplatin treatment is mostly because of peripheral neuropathy, more often than for tumor progression, potentially compromising patient benefit. Several strategies to prevent neurotoxicity have so far been investigated. To overcome this life-threatening side effect, while taking advantage of the antineoplastic activities of oxaliplatin, we describe in detail recent findings on the underlying mechanisms of genetic variants associated with toxicity and resistance to oxaliplatin-based chemotherapy in colorectal cancer. A comprehensive panel of eight polymorphisms, previously validated as significant markers related to oxaliplatin toxicity, is proposed and discussed. In addition, the most common available strategies or methods to prevent/minimize the toxicity were described in detail. Moreover, an early outline evaluation of the genotyping costs and methods was taken in consideration. With the availability of individual pharmacogenomic profiles, the oncologists will have new means to make treatment decisions for their patients that maximize benefit and minimize toxicity. With this purpose in mind, the clinician and lab manager should cooperate to evaluate the advantages and limitations, in terms of costs and applicability, of the most appropriate pharmacogenomic tests for routine incorporation into clinical practice.

Iodized salt improves the effectiveness of L-thyroxine therapy after surgery for nontoxic goitre: a prospective and randomized study.

OBJECTIVE: To investigate whether the addition of iodized salt to daily diet in thyroidectomized patients for nontoxic goitre could influence the effectiveness of nonsuppressive L-thyroxine (L-T4) therapy on thyroid remnant size, during 12 months' follow-up after thyroid surgery. DESIGN AND PATIENTS: A consecutive series of selected 139 patients (26 males, 113 females; median age 45 years, range 30-69 years) living in a moderate iodine-deficient area, and undergoing thyroid surgery for nontoxic multinodular goitre, was enrolled. Patients were assigned randomly to two different therapeutic regimens: 70 patients received L-T4 therapy alone (Gr. L-T4), while the remaining 69 patients took iodized salt on a daily basis in addition to L-T4 treatment (Gr. L-T4 + I). In both groups, the initial L-T4 dose was 1.5 microg/kg/day, which, in our experience, has been shown to be intermediate between suppressive and replacement doses. To avoid the risks of mild thyrotoxicosis and to limit the excessive TSH stimulation of the thyroid remnant, the L-T4 dose was adjusted in those patients with serum TSH levels outside the lowest two-thirds of the normal range (0.3-2.5 mU/l). An ultrasound evaluation of thyroid remnant size was performed after thyroid surgery and 12 months later. RESULTS: After surgery, the median thyroid remnant volume was 3.5 ml (range 0.4-13.9 ml) in Gr. L-T4 and 4.6 ml (range 0.5-12.7 ml) in Gr. L-T4 + I (P = 0.06). After 1 year of follow-up, the patients treated with L-T4 + I obtained a remnant volume reduction (-39.7%, range -87.0% to +91.2%) significantly (P = 0.006) greater than that observed in patients assuming L-T4 alone (-10.2%, range -89.4% to +85.0%). However, the percentage of patients showing an increase in remnant size in the months following surgery was higher in Gr. L-T4 than in Gr. L-T4 + I (22/60 vs. 9/66; P = 0.01). In Gr. L-T4 patients the thyroid remnant volume variation throughout 12 months of treatment was correlated significantly with the size of the thyroid remnant found at the first ultrasound evaluation (R(2) = 0.3; P < 0.001). No such correlation was found in Gr. L-T4 + I patients, for whom the therapy maintains a similar effectiveness in patients with either a large or a small postsurgery thyroid remnant. In patients treated with L-T4 alone, the remnant volume variation was correlated significantly with the median serum TSH values attained in the course of treatment (R2 = 0.4; P < 0.001). The highest reduction in remnant volume was observed only by lowering the serum TSH concentrations. In patients treated with L-T4 plus iodine, instead, the thyroid remnant volume reduction occurred independently of the plasma TSH levels attained in the course of treatment. CONCLUSIONS: Our short-term prospective and randomized study leads us to conclude that, in patients living in a moderate iodine-deficient area and undergoing thyroid surgery for nontoxic goitre: (1) the iodine prophylaxis improves the effects of postsurgery nonsuppressive L-T4 therapy on thyroid remnant size. (2) In patients treated with L-T4 alone the therapeutic effectiveness decreases in the presence of a large postsurgery thyroid remnant. With the addition of iodine, the L-T4 maintains a similar efficacy in patients with either a large or a small remnant. (3) During treatment with L-T4 alone the highest therapeutic effectiveness is attained by lowering the plasma TSH concentration. With the addition of iodized salt to the daily diet the effects of L-T4 on remnant size are relevant independently of the TSH levels.