Lipohypertrophy in Elderly Insulin-Treated Patients With Type 2 Diabetes.

BACKGROUND: The number of older adults with insulin-treated diabetes mellitus (DM) is steadily increasing worldwide. Errors in the insulin injection technique can lead to skin lipohypertrophy (LH), which is the accumulation of fat cells and fibrin in the subcutaneous tissue. While lipohypertrophic lesions/nodules (LHs) due to incorrect insulin injection techniques are very common, they are often flat and hardly visible and thus require thorough deep palpation examination and ultrasonography (US) for detection. Detection is crucial because such lesions may eventually result in poor diabetes control due to their association with unpredictable insulin release patterns. Skin undergoes fundamental structural changes with aging, possibly increasing the risk for LH. We have therefore investigated the effect of age on the prevalence of LHs and on factors potentially associated with such lesions. METHODS: A total of 1227 insulin-treated outpatients with type 2 DM (T2DM) referred to our diabetes centers were consecutively enrolled in the study. These patients underwent a thorough clinical and US evaluation of the skin at injection sites, as previously described, with up to 95% concordance betweenthe clinical and US screening techniques. Of these 1227 patients, 718 (59%) had LH (LH+) and 509 (41%) were LH-free (LH-). These patients were then assigned to two age class groups (≤ 65 years and > 65 years), and several clinical features, diabetes complication rates, and injection habits were investigated. RESULTS: Comparison of the two age subgroups revealed that 396 (48%) and 322 (79%) patients in the younger and older groups, respectively, had LHs (p < 0.001). Compared to the younger subgroup, the older subgroup displayed a higher LH rate in the abdomen (52.9 vs. 38.3%; p < 0.01) and a lower rate in the arms (25.4 vs. 35.8%; p < 0.05), thighs (26.7 vs. 33.4%; p < 0.05), and buttocks (4.9 vs. 26.2%; p < 0.01). In older subjects, the most relevant parameters were: habit of injecting insulin into LH nodules (56 vs. 47% [younger subjects]; p < 0.01), rate of post-injection leakage of insulin from injection site (drop-leaking rate; 47 vs. 39% [younger subjects]; p < 0.05), and rate of painful injections (5 vs. 16% [younger subjects]; p < 0.001). Multivariate analysis showed a stronger association between LH and poor habits, as well as between several clinical parameters, among which the most relevant were hypoglycemic events and glycemic variability. DISCUSSION: The higher rate of post-injection drop-leaking and pain-free injections might find an explanation in skin changes typically observed in older adults, including lower thickness, vascularity and elasticity, and a more prominent fibrous texture, all of which negatively affect tissue distensibility. Consequently, in addition to the well-known association between aging skin impaired drug absorption rate, aging skin displays a progressively decreasing ability to accommodate large volumes of insulin-containing fluid. CONCLUSIONS: The strong association between LH rate and hypoglycemic events plus glycemic variability suggests the need (1) to take specific actions to prevent and control the high risk of acute cardiovascular events expected to occur in older subjects in the case of hypoglycemic events, and (2) to identify suitable strategies to fulfill the difficult task of performing effective educational programs specifically targeted to the elderly. TRIAL REGISTRATION: Trial registration number 172-11:12.2019, Scientific and Ethical Committee of Campania University "Luigi Vanvitelli", Naples, Italy).

Insulin-Induced Skin Lipohypertrophy in Type 2 Diabetes: a Multicenter Regional Survey in Southern Italy.

INTRODUCTION: Lipohypertrophies (LHs) due to incorrect insulin injection techniques have been described in the literature for decades. Their rate averages 38%, but this is still controversial because of the vast range reported by different publications, most of which fail to describe the selected detection protocol and therefore are not entirely reliable. We still need to identify the real LH rate, and only consistently using a standardized method in a large cohort of insulin-treated (IT) patients make this possible. METHODS: Our group performed thorough clinical skin examinations on patients suffering from type 2 diabetes mellitus (T2DM): 1247 IT T2DM outpatients were examined according to a standardized protocol, previously published elsewhere, as well as an ultrasound scan of the same skin areas to assess the degree of concordance between the two methods and to evaluate the demographic, clinical, and behavioral risk factors (RF) as well as metabolic consequences of identified LHs. RESULTS: The concordance between the two methods was 99%. Identified risk factors for LHs were needle reuse, failure to rotate injection sites, and ice-cold insulin injections. High HbA1c values, wide glycemic variability, and longstanding proneness to hypoglycemia with a high rate of ongoing hypoglycemic events proved to be significantly associated with LHs, too; the same applied to cardiovascular and renal complications as well as to living alone and being retired. CONCLUSIONS: Based on a strict well-structured methodology, our data confirmed what has already been reported in the literature on factors leading to, or associated with, LHs and, for the first time in adults, indicated cryotrauma from ice-cold insulin injections and specific social conditions as factors facilitating LH occurrence. HCPs should therefore plan a yearly clinical examination of all injection sites to improve patient quality of life through better glucose control and a reduced rate of hypoglycemic events. TRIAL REGISTRATION: Trial registration no. 127-11.01.2019, approved by the Scientific and Ethics Committee of Campania University "Luigi Vanvitelli," Naples, Italy.

A randomized, open-label, comparative, crossover trial on preference, efficacy, and safety profiles of lispro insulin u-100 versus concentrated lispro insulin u-200 in patients with type 2 diabetes mellitus: a possible contribution to greater treatment adherence.

BACKGROUND: Several outstanding pharmacological advances making innovative drugs sophisticateddevices available during the last few years. Nevertheless too many patients still disappointingly fail to meetthe metabolic targets suggested by current guidelines. Incorrect insulin administration techniques may greatly affect metabolic control in T2DM people. The aim of our study was to compare glycemic control associated with a concentrated insulin analog preparation (U-200 lispro) in people with T2DM to the one observed with standard U-100 lispro. The secondary endpoint of our study was patients' preference and performance ratings of U-200 lispro. METHODS: 126 patients with T2DM were enrolled. They were also assessed for limited joint mobility syndrome (LJMS),defined as limitation in at least two anatomical areas of the dominant upper extremity. After a 4-weekstructured insulin injection education period. Half of them were randomized to U-100 lispro, half to U-200 and after 12 weeks they were switched to the other preparation for 12 weeks. At the end a questionnaire was also administered to investigate patient preference. RESULTS: No significant variation in fasting blood glucose, HbA1c, severe or mild hypoglycemic rate and daily fast-acting insulin analog dose was observed with U-100 lispro while U-200 lispro treatment was associated with a significant improvement of all the above mentioned parameters and with around 20% decrease in insulin requirement. Moreover patients' answers to the questionnaire pointed out a higher preference for U-200 lispro for continuing treatment due to fewer difficulties completing injection. DISCUSSION: The explanation of better metabolic results with the U-200 device might be the lower inner piston inertia and volume and shorter duration of a complete injection. CONCLUSIONS: Checking for LJIMS before insulin prescription could be adopted as a standard practiceaimed at choosing the most suitable device for patient's specific characteristics and abilities. The use of U-200 lispro might improve treatment adherence and metabolic control. This would also result intocost reduction by saving about half the amount of pens per year and of time spent to both fill prescriptionand dump the pharmacy.

Bronquiolitis aguda / Acute bronchiolitis

En la Provincia de Bs.As. la tasa de mortalidad específca por IRA ha disminuido entre los años 2001 y 2010 de 7,1 a 4,4 casos por 10.000 nacidos; siendo un rasgo distintivo el aumento de la mortalidad domiciliaria en el menor de 1 año, situación que se viene registrando desde 2007. Se presenta una situación clínica junto al Flujograma de decisión terapéutica según puntaje clínico en el menor de distintas edades para el síndrome bronquial obstructivo, como también el tratamiento

Can laparoscopic cholecystectomy be safety performed in the elderly?

AIM: To assess the suitability of laparoscopic cholecystectomy in elderly patients, although early reports have questioned the efficacy of this procedure in that patient group. MATERIAL OF STUDY: Retrospective study evaluating the medical records of the elderly patients who underwent laparoscopic cholecystectomy in our surgical unit. Data included age and gender, American Society of Anesthesiologists (ASA) score, comorbid illness, prior abdominal surgery, presentation, operative time, conversion rate, postoperative morbidity, and mortality rates and length of hospital stay. RESULTS: Fifty consecutive patients age 70 or older who underwent laparoscopic cholecystectomy were studied Postoperative complications occurred in five patients. DISCUSSION: Many Studies have shown that the incidence of complicated gallstone disease in the elderly is higher when compared with that of younger patients and gallbladder disease is particularly virulent in the elderly, with high rate of acute cholecystitis, biliary tract disease, increased morbidity, and prolonged hospital stay. This poor outcome has been attributed to the presence of severe co-morbid factors associated with the aging process. Compared to open cholecystectomy, laparoscopic cholecystectomy may cause less postoperative depression of respiratory function and cell-mediated immunity. In our study perioperative mortality rate was 0%. CONCLUSIONS: Laparoscopic cholecystectomy in elderly patients is a relatively safe procedure that can be accomplished with acceptable low morbidity. In this series of geriatric patients, there was no evidence of any increased risk for conversion to an open cholecystectomy, delayed recovery, or prolonged hospitalization.

Aging exacerbates negative remodeling and impairs endothelial regeneration after balloon injury.

Many older patients, because of their high prevalence of coronary artery disease, are candidates for percutaneous coronary interventions (PCI), but the effects of vascular aging on restenosis after PCI are not yet well understood. Balloon injury to the right carotid artery was performed in adult and old rats. Vascular smooth muscle cell (VSMC) proliferation, apoptotic cell death, together with Akt induction, telomerase activity, p27kip1, and endothelial nitric oxide synthase (eNOS) expression was assessed in isolated arteries. Neointima hyperplasia and vascular remodeling along with endothelial cell regeneration were also measured after balloon injury. Arteries isolated from old rats exhibited a significant reduction of VSMC proliferation and an increase in apoptotic death after balloon injury when compared with adult rats. In the vascular wall of adult rats, balloon dilation induced Akt phosphorylation, and this was barely present in old rats. In arteries from old rats, Akt-modulated cell cycle check points like telomerase activity and p27kip1 expression were decreased and increased, respectively, compared with adults. After balloon injury, old rats showed a significant reduction of neointima formation and an increased vascular negative remodeling compared with adults. These results were coupled by a marked delay in endothelial regeneration in aged rats, partially mediated by a decreased eNOS expression and phosphorylation. Interestingly, chronic administration of L-arginine prevented negative remodeling and improved reendothelialization after balloon injury in aged animals. A decreased neointimal proliferation, an impaired endothelial regeneration, and an increase in vascular remodeling after balloon injury were observed in aged animals. The molecular mechanisms underlying these responses seem to be a reduced Akt and eNOS activity.

Effect of stent coating alone on in vitro vascular smooth muscle cell proliferation and apoptosis.

Synthetic polymers, like methacrylate (MA) compounds, have been clinically introduced as inert coatings to locally deliver drugs that inhibit restenosis after stent. The aim of the present study was to evaluate the effects of MA coating alone on vascular smooth muscle cell (VSMC) growth in vitro. Stainless steel stents were coated with MA at the following doses: 0.3, 1.5, and 3 ml. Uncoated/bare metal stents were used as controls. VSMCs were cultured in dishes, and a MA-coated stent or an uncoated bare metal stent was gently added to each well. VSMC proliferation was assessed by bromodeoxyuridine (BrdU) incorporation. Apoptosis was analyzed by three distinct approaches: 1) annexin V/propidium iodide fluorescence detection; 2) DNA laddering; and 3) caspase-3 activation and PARP cleavage. MA-coated stents induced a significant decrease of BrdU incorporation compared with uncoated stents at both the low and high concentrations. In VSMCs incubated with MA-coated stents, annexin V/propidium iodide fluorescence detection showed a significant increase in apoptotic cells, which was corroborated by the typical DNA laddering. Apoptosis of VSMCs after incubation with MA-coated stents was characterized by caspase-3 activation and PARP cleavage. The MA-coated stent induced VSMC growth arrest by inducing apoptosis in a dose-dependent manner. Thus MA is not an inert platform for eluting drugs because it is biologically active per se. This effect should be taken in account when evaluating an association of this coating with antiproliferative agents for in-stent restenosis prevention.