A Conversation on an Effective, Straightforward, Quantitative Approach to the Outpatient Use of Insulin

For primary care providers, using insulin can present challenges that can be met by a straightforward approach using the following principles. Depending on when it is injected, each component of the insulin regimen has a maximal effect on a specific period of the 24-hour cycle (e.g., overnight, morning, afternoon, or evening). The glucose pattern in that period determines whether the dose of that component of the insulin regimen requires adjusting. Regarding which insulin types and insulin regimens to use, human insulin (NPH and regular) is as effective as analog insulins, and a two-injection intensified insulin regimen is as effective as a four-injection regimen.

Videocapillaroscopy, Insulin-Induced Skin Lipohypertrophy, and Bruising: A Preliminary Approach

Background: Lipohypertrophy (LH) is a frequent cutaneous complication in people with insulin-treated type-2 DM (IT-T2DM). Its pathogenesis is not fully known, however. Retinal and kidney microangiopathy (MIA) is also frequent in such patients, especially in case of poor metabolic control. Aim: To assess whether specific nailfold video-capillaroscopy (NVC) patterns could be identified in MIA-affected IT-T2DM patients, thus eventually helping explain LH pathogenesis. Methods: 50 IT-T2DM patients with LH and 50 without LH undergoing NVC were enrolled. All followed a multiple daily injection regimen and had established retinal and renal microangiopathic complications. Results: While confirming expected MIA-related skin changes in both groups, our data failed to detect any specific NVC pattern in LH-affected patients yet showed the most severe NVC changes to be significantly associated with HbA1c values over 9%. Conclusion: Severe NVC-assessed MIA lesions reflect longstanding poor metabolic control in IT-T2DM rather than contributing to LH pathogenesis.

Is Inflammation Status in Postbariatric Patients Predictive for Their Response to Vitamin B12 Supplementation Therapy?

Background Several studies indicate that there is a relationship between vitamin B12 levels and inflammatory status. Some studies showed a significantly correlation between vitamin B12 status and inflammation. The aim of this study is to investigate the influence of inflammatory status on the effect of different vitamin B12 supplementation regimes. Methods We selected patients with a vitamin B12 deficiency based on methylmalonic acid (MMA) levels. A moderate vitamin B12 deficiency was defined as an MMA blood level between ≥300 and 430 nmol/L. In included patients, C-reactive protein (CRP), leukocytes, serum vitamin B12, and MMA levels were measured at baseline and after 6 months of follow-up. Results A total of 63 patients were included, treated with 3, 6, or no intramuscular vitamin B12 injections. In the 6 intramuscular injections group, the presupplementation CRP levels significantly predicted the response in terms of vitamin B12 increase (P = 0.015). Also, there was a significant reduction in CRP levels (P = 0.03) after 6 injections. There was a significant correlation between presupplementation MMA and presupplementation CRP (r = 0.127, P = 0.049). Conclusion This study showed that presupplementation CRP levels significantly predicted the response on 6 intramuscular vitamin B12 injections in patients after bariatric surgery. Second, the 6 intramuscular injection regimen showed a significant reduction in CRP levels. Third, there was a significant correlation between MMA and presupplementation CRP. This might indicate that there is interplay between the vitamin B12 supplementation and inflammatory levels in patients after bariatric surgery.

Calcium Phosphate Bions Cause Intimal Hyperplasia in Intact Aortas of Normolipidemic Rats through Endothelial Injury

Calcium phosphate bions (CPBs) are formed under blood supersaturation with calcium and phosphate owing to the mineral chaperone fetuin-A and representing mineralo-organic particles consisting of bioapatite and multiple serum proteins. While protecting the arteries from a rapid medial calcification, CPBs cause endothelial injury and aggravate intimal hyperplasia in balloon-injured rat aortas. Here, we asked whether CPBs induce intimal hyperplasia in intact rat arteries in the absence of cardiovascular risk factors. Normolipidemic Wistar rats were subjected to regular (once/thrice per week over 5 weeks) tail vein injections of either spherical (CPB-S) or needle-shaped CPBs (CPB-N), magnesium phosphate bions (MPBs), or physiological saline (n = 5 per group). Neointima was revealed in 3/10 and 4/10 rats which received CPB-S or CPB-N, respectively, regardless of the injection regimen or blood flow pattern in the aortic segments. In contrast, none of the rats treated with MPBs or physiological saline had intimal hyperplasia. The animals also did not display signs of liver or spleen injury as well as extraskeletal calcium deposits. Serum alanine/aspartate transaminases, interleukin-1β, MCP-1/CCL2, C-reactive protein, and ceruloplasmin levels did not differ among the groups. Hence, CPBs may provoke intimal hyperplasia via direct endothelial injury regardless of their shape or type of blood flow.

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six weeks; tissues were collected four, seven, or 14 days after the second injection. Compared to vehicle, chemotherapy increased pro-inflammatory cytokine IL-1β at day seven in the cortex and hippocampus, and reduced gene expression of synaptic marker Shank 3 at all timepoints in cortex, while EPA + DHA increased expression of Shank 3. In Study 2, high or low sucrose/EPA + DHA or No EPA + DHA diets were fed for five weeks; tissues were collected ten days after the second injection. Among chemotherapy-treated mice, brain DHA was higher with low sucrose feeding. Furthermore, low sucrose increased gene expression of Shank 1, while EPA + DHA increased expression of Shank 3 and reduced protein concentrations of pro-inflammatory markers IL-5, IL-6 and KC/GRO in the cortex, but not the hippocampus. Low sucrose, EPA + DHA diets may attenuate neuroinflammation and synaptic damage induced by doxorubicin-based chemotherapy in specific brain regions.

Adding steroids to lidocaine in a therapeutic injection regimen for patients with abdominal pain due to anterior cutaneous nerve entrapment syndrome (ACNES): a single blinded randomized clinical trial

Background and aims Anterior cutaneous nerve entrapment syndrome (ACNES) may result in chronic abdominal pain. Therapeutic options include local injection therapy. Data on the efficacy of adding corticosteroids to these injections is lacking. Methods Patients ≥18 years with ACNES were randomized to receive an injection of lidocaine with (LC-group) or without (LA-group) the addition of methylprednisolone into the point of maximal abdominal wall pain. Pain was recorded using a numeric rating scale (NRS: 0–10) and a verbal rating scale (VRS: 0=no pain, 5=unbearable pain) at baseline and 6 weeks after the start of a bi-weekly injection regimen consisting of a total of three injections. A minimal 50% reduction on NRS and/or two points on VRS were considered successful responses. Results Between February 2014 and August 2016, 136 patients (median age 46 year, range 18–79, 75% females) were randomized (68 vs. 68). The proportion of patients demonstrating a successful response after 6 weeks did not significantly differ between groups (LA 38%, LC 31%, p=0.61). At 12 weeks, the number of patients still experiencing a minimal 50% pain relief had decreased but no group difference was observed (LA 20%, LC 18%, p=0.80). Minor side effects included temporary increase of pain, tenderness at injection sites or transient malaise (LA23/68, LC 29/68, p=0.46). Conclusions Adding corticosteroids to a lidocaine does not increase the proportion of ACNES patients with a successful response to injection therapy. Lidocaine alone can provide long term pain relief after one or multiple injections, in approximately 1 of 5 patients.

Cost-Utility of a Single-Injection Combined Corticosteroid-Hyaluronic Acid Formulation vs a 2-Injection Regimen of Sequential Corticosteroid and Hyaluronic Acid Injections

Research has shown early and sustained relief with a combination therapy of a corticosteroid (CS) and hyaluronic acid (HA) in knee osteoarthritis (OA) patients. This can be administered via a single injection containing both products or as separate injections. The former may be more expensive when considering only product cost, but the latter incurs the additional costs and time of a second procedure. The purpose of this study was to compare the cost-utility of the single injection with the 2-injection regimen. The results of this analysis revealed that the single-injection formulation of a CS and HA may be cost-effective, assuming a willingness-to-pay of $50 000 per quality-adjusted life year gained, for symptomatic relief of OA symptoms. This treatment may also be more desirable to patients who find injections to be inconvenient or unpleasant.