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Aim: This post hoc analysis explored whether mealtime fast‐acting insulin aspart treatment provided an advantage in postprandial plasma glucose (PPG) control vs. insulin aspart in people with Type 2 diabetes receiving high doses of bolus insulin. Methods: A post hoc, post‐randomization, subgroup analysis of a 26‐week, randomized, double‐blind, treat‐to‐target trial (onset 2) that compared mealtime fast‐acting insulin aspart vs. mealtime insulin aspart, both in a basal–bolus regimen, in people with Type 2 diabetes uncontrolled on basal insulin therapy and metformin. At the end of trial, the impact of fast‐acting insulin aspart and insulin aspart on PPG control was assessed with a standard liquid meal test and participants were grouped into three post‐randomization subgroups: meal test bolus insulin dose ≤ 10 units per dose (n = 171), > 10–20 units per dose (n = 289) and > 20 units per dose (n = 146). Results: A statistically significant treatment difference in favour of fast‐acting insulin aspart vs. insulin aspart was observed for the change in PPG increment at all post‐meal time points (from 1 to 4 h) for those in the > 20 units bolus insulin subgroup. There was no difference in the magnitude of change from baseline in HbA1c level between fast‐acting insulin aspart and insulin aspart in any of the bolus insulin dose subgroups (data herein). Conclusion: Fast‐acting insulin aspart may hold promise as a more effective treatment compared with insulin aspart for controlling PPG in people with insulin‐resistant Type 2 diabetes. What's new?: The results of this post hoc analysis indicate that fast‐acting insulin aspart may provide an advantage over conventional rapid‐acting insulin analogues in controlling postprandial hyperglycaemia in people with insulin‐resistant Type 2 diabetes requiring basal–bolus therapy. [ABSTRACT FROM AUTHOR]

Summary: Objective: Minimal risk weight loss tools are needed. This study's objective was to confirm Food and Drug Administration submissions of the SmartByte™ System's safety and efficacy. Methods: This 16‐week, prospective, single‐arm, four‐centre, observational study assessed the oral device in combination with a video‐delivered lifestyle programme in adults aged 18–49 years with body mass index 27 to <35 kg m−2. Results: Seventy‐six subjects received the device and video lifestyle instruction. The prespecified per protocol (PP) population (N = 40) required sensor‐verified use of the device ≥7 times per week for 14 of 16 weeks, overall device usage rate of ≥33% and study completion. At week 16, 12 (30%) achieved ≥5% weight loss, 16 (40%) achieved ≥4% and 21 (52.5%) achieved ≥3%. Week 16 mean loss for the PP population was 2.93%, and among 36 participants who did not meet PP criteria, it was 1.45%. Among 76 intent‐to‐treat subjects, two subjects reported three mild to moderate device‐related adverse events, resolving spontaneously (one hard palate abrasion and two tongue lacerations). Conclusion: The System, a minimal risk tool, can help individuals achieve meaningful weight loss, when used with a lifestyle video. More frequent device use was associated with more weight loss, on average, and greater chance of achieving ≥4% or ≥5% weight loss. [ABSTRACT FROM AUTHOR]

Objective The primary objective of this study was to describe the cytological findings of bowel and (penile) skin-lined neovaginas in patients with gender dysphoria (GD) and individuals with a congenital or acquired absence of a natural vagina. The secondary objective was to correlate the cytological findings with clinical characteristics such as oestrogen replacement therapy (ERT). Methods A retrospective review of an institutional pathology archive over a 15-year-period was performed to identify cytological samples of neovaginal vaults. The medical and surgical records of the patients identified (n=20) were evaluated. Results Well-preserved nucleated squamous cells were found in 70% (14/20) of patients. Neovaginal samples showing superficial, intermediate and parabasal cells plus Döderlein flora similar to normal cervical cytology were present in only 10% (2/20). Three samples (15%, 3/20) showed atypical squamous cells of undetermined significance (ASC-US) that were all negative for high-risk human papillomavirus (HR-HPV) types, whereas one case was positive for low-risk (LR) HPV. One patient (5%, 1/20) was diagnosed with an HR-HPV-positive high-grade squamous intraepithelial lesion (HSIL), and one patient (5%, 1/20) had an HR- and LR-HPV-positive low-grade squamous intraepithelial lesion (LSIL). The correlation between the presence of nucleated squamous cells and ERT was significant ( P=.032). Conclusion Cytological findings of the neovagina resemble normal cervical cytology with superficial, intermediate and parabasal cells as well as Döderlein bacilli in a minority of cases. Because precancerous lesions and invasive carcinoma may develop in the neovagina, patients with neovaginas should be subject to cancer screening programmes. [ABSTRACT FROM AUTHOR]

Aim To investigate the safety and efficacy of insulin degludec/liraglutide ( IDegLira), a novel combination product, as add-on therapy for people with Type 2 diabetes uncontrolled on sulphonylurea therapy. Methods In this 26-week, double-blind trial, adults with Type 2 diabetes [HbA1c 53-75 mmol/mol (7.0-9.0%)] were randomized to IDegLira ( n = 289) or placebo ( n = 146) as add-on to pre-trial sulphonylurea ± metformin, titrating to a fasting glycaemic target of 4.0-6.0 mmol/l. Treatment initiation was at 10 dose steps, and maximum dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Results The mean HbA1c decreased from 63 mmol/mol (7.9%) to 46 mmol/mol (6.4%) with IDegLira and to 57 mmol/mol (7.4%) with placebo [estimated treatment difference -11 mmol/mol (95% CI -13; -10) or -1.02% (95% CI -1.18; -0.87); P < 0.001]. The HbA1c target of 53 mmol/mol (<7%) was achieved by 79.2% of participants in the IDegLira group vs 28.8% in the placebo group [estimated odds ratio 11.95 (95% CI 7.22; 19.77); P < 0.001]. Mean weight change was +0.5 kg with IDegLira vs -1.0 kg with placebo [estimated treatment difference 1.48 kg (95% CI 0.90; 2.06); P < 0.001]. Confirmed hypoglycaemia occurred in 41.7 and 17.1% of IDegLira- and placebo-treated participants, respectively, with rates of 3.5 vs 1.4 events/patient-years of exposure [estimated rate ratio 3.74 (95% CI 2.28; 6.13); P < 0.001]. IDegLira was generally well tolerated. The rates of serious adverse events were 20.3 and 8.0 per 100 patient-years of exposure with IDegLira and placebo, respectively, without obvious patterns in the type of events. Conclusions IDegLira can be used in people uncontrolled with sulphonylurea ± metformin to improve efficacy with a safety profile in line with previous DUAL trials. [ABSTRACT FROM AUTHOR]

Aims To investigate, in a 26-week, open-label, randomized, treat-to-target trial, the efficacy and safety of insulin degludec/insulin aspart ( IDegAsp) once daily vs insulin glargine ( IGlar) once daily in adults with Type 2 diabetes, inadequately controlled on basal insulin. Methods Participants were randomized (1:1) to IDegAsp once daily or IGlar once daily in combination with existing oral antidiabetic drugs. IDegAsp once daily was administered with the main evening meal or the largest meal of the day (agreed at baseline); dosing time was maintained throughout the trial. Participants titrated their insulin dose weekly to a mean pre-breakfast self-measured plasma glucose target [3.9-4.9 mmol/l (70-89 mg/dl)]. Results IDegAsp once daily was non-inferior to IGlar once daily in reducing HbA1c after 26 weeks [mean estimated treatment difference IDegAsp once daily − IGlar once daily: −0.03% (95% CI −0.20, 0.14)]. The evening meal glucose increment was significantly lower with IDegAsp once daily vs IGlar once daily [estimated treatment difference IDegAsp once daily − IGlar once daily: −1.32 mmol/l (95% CI −1.93, −0.72); P < 0.05]. The overall confirmed hypoglycaemia rate was higher with IDegAsp once daily (estimated rate ratio 1.43; 95% CI 1.07, 1.92; P < 0.05). The rate of nocturnal hypoglycaemia did not significantly differ between the IDegAsp and IGlar groups [estimated rate ratio 0.80 (95% CI 0.49, 1.30); not significant]. Conclusions In participants with Type 2 diabetes inadequately controlled on basal insulin, IDegAsp once daily improved glycaemic control and was non-inferior to IGlar once daily. IDegAsp led to higher rates of overall hypoglycaemia than IGlar, with no significant difference in rates of nocturnal hypoglycaemia. [ABSTRACT FROM AUTHOR]

The relation is studied between crack initiation from micro-notches in a fully lamellar intermetallic γ-TiAl alloy and the local strain field. These micro-notches were introduced using femtosecond-laser ablation and had dimensions below the average colony size. The specimen under investigation was then subjected to fatigue loading. Continuous monitoring using a travelling optical microscope allowed detecting microcracks at an early stage. Prior to fatigue loading, a sustained load was applied and the local strain field was determined using digital image correlation. This was supplemented by a Finite Element analysis of the notches and their neighbourhood. It was found that a crack was initiated from a notch causing high normal strains in lamella direction, whereas no crack was initiated from notches with high shear strains. [ABSTRACT FROM AUTHOR]

Aims To confirm, in a 26-week extension study, the sustained efficacy and safety of a fixed combination of insulin degludec and liraglutide ( IDegLira) compared with either insulin degludec or liraglutide alone, in patients with type 2 diabetes. Methods Insulin-naïve adults with type 2 diabetes randomized to once-daily IDegLira, insulin degludec or liraglutide, in addition to metformin ± pioglitazone, continued their allocated treatment in this preplanned 26-week extension of the DUAL I trial. Results A total of 78.8% of patients (1311/1663) continued into the extension phase. The mean glycated haemoglobin ( HbA1c) concentration at 52 weeks was reduced from baseline by 1.84% (20.2 mmol/mol) for the IDegLira group, 1.40% (15.3 mmol/mol) for the insulin degludec group and 1.21% (13.2 mmol/mol) for the liraglutide group. Of the patients on IDegLira, 78% achieved an HbA1c of <7% (53 mmol/mol) versus 63% of the patients on insulin degludec and 57% of those on liraglutide. The mean fasting plasma glucose concentration at the end of the trial was similar for IDegLira (5.7 mmol/l) and insulin degludec (6.0 mmol/l), but higher for liraglutide (7.3 mmol/l). At 52 weeks, the daily insulin dose was 37% lower with IDegLira (39 units) than with insulin degludec (62 units). IDegLira was associated with a significantly greater decrease in body weight (estimated treatment difference, −2.80 kg, p < 0.0001) and a 37% lower rate of hypoglycaemia compared with insulin degludec. Overall, all treatments were well tolerated and no new adverse events or tolerability issues were observed for IDegLira. Conclusions These 12-month data, derived from a 26-week extension of the DUAL I trial, confirm the initial 26-week main phase results and the sustainability of the benefits of IDegLira compared with its components in glycaemic efficacy, safety and tolerability. [ABSTRACT FROM AUTHOR]

Aims The long-term efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated over 104 weeks in patients aged 55-80 years with type 2 diabetes mellitus ( T2DM) inadequately controlled on a stable antihyperglycaemic agent regimen. Methods In this randomized, double-blind, phase III study, patients received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period (N = 714) and a 78-week extension period (n = 624). Efficacy endpoints at week 104 included change from baseline in glycated haemoglobin ( HbA1c), fasting plasma glucose ( FPG) and systolic blood pressure, and percent change from baseline in body weight and fasting plasma lipids. Safety was assessed by adverse event ( AE) reports. Results At week 104, canagliflozin 100 and 300 mg were associated with reductions in HbA1c versus placebo (−0.32 and −0.43% vs 0.17%, respectively; overall mean baseline, 7.7%) and more patients achieved HbA1c <7.0% with canagliflozin 100 and 300 mg than with placebo (35.8 and 41.9% vs 20.3%, respectively). Reductions in FPG, body weight and systolic blood pressure, and increases in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were seen with canagliflozin compared with placebo. The overall incidence rates of AEs over 104 weeks were 88.0, 89.8 and 86.1% with canagliflozin 100 and 300 mg and placebo, respectively; serious AE rates were low across treatment groups. The incidence rates of urinary tract infections, genital mycotic infections and osmotic diuresis- and volume depletion-related AEs were higher with canagliflozin than with placebo. Conclusion Canagliflozin improved glycaemic control, reduced body weight and systolic blood pressure, and was generally well tolerated in patients aged 55-80 years with T2DM over 104 weeks. [ABSTRACT FROM AUTHOR]

Aims To show that albiglutide, a glucagon-like peptide-1 receptor agonist, is an effective and generally safe treatment to improve glycaemic control in patients with type 2 diabetes mellitus whose hyperglycaemia is inadequately controlled with pioglitazone (with or without metformin). Methods In this 3-year, randomized, double-blind, placebo-controlled study, 310 adult patients on a regimen of pioglitazone (with or without metformin) were randomly assigned to receive additional treatment with albiglutide [30 mg subcutaneous (s.c.) once weekly, n = 155] or matching placebo (n = 155). The primary efficacy endpoint was change from baseline to week 52 (intention-to-treat) in glycated haemoglobin ( HbA1c). Results The model-adjusted change from baseline in HbA1c at week 52 was significantly better with albiglutide than with placebo (−0.8%, 95% confidence interval −1.0, −0.6; p < 0.0001). Change from baseline fasting plasma glucose was −1.3 mmol/l in the albiglutide group and +0.4 mmol/l in the placebo group (p < 0.0001); a significantly higher percentage of patients reached the HbA1c goals with albiglutide (p < 0.0001), and the rate of hyperglycaemia rescue up to week 52 for albiglutide was 24.4 versus 47.7% for placebo (p < 0.0001). Albiglutide plus pioglitazone had no impact on weight, and severe hypoglycaemia was observed rarely (n = 2). With few exceptions, the results of safety assessments were similar between the groups, and most adverse events ( AEs) were mild or moderate. The 52-week incidence rates for gastrointestinal AEs for albiglutide and placebo were: 31.3 and 29.8%, respectively (diarrhoea: 11.3 and 8.6%; nausea: 10.7 and 11.3%; vomiting: 4.0 and 4.0%). Conclusions Albiglutide 30 mg administered once weekly as an add-on to pioglitazone (with or without metformin) provided effective and durable glucose lowering and was generally well tolerated. [ABSTRACT FROM AUTHOR]

Aim Hypoglycaemia and the fear of hypoglycaemia are barriers to achieving normoglycaemia with insulin. Insulin degludec ( IDeg) has an ultra-long and stable glucose-lowering effect, with low day-to-day variability. This pre-planned meta-analysis aimed to demonstrate the superiority of IDeg over insulin glargine ( IGlar) in terms of fewer hypoglycaemic episodes at equivalent HbA1c in type 2 and type 1 diabetes mellitus (T2DM/T1DM). Methods Pooled patient-level data for self-reported hypoglycaemia from all seven (five in T2DM and two in T1DM) randomized, controlled, phase 3a, treat-to-target trials in the IDeg clinical development programme comparing IDeg once-daily ( OD) vs. IGlar OD were analysed. Results Four thousand three hundred and thirty subjects (2899 IDeg OD vs. 1431 IGlar OD) were analysed. Among insulin-naïve T2DM subjects, significantly lower rates of overall confirmed, nocturnal confirmed and severe hypoglycaemic episodes were reported with IDeg vs. IGlar: estimated rate ratio ( RR):0.83[0.70;0.98]95% CI, RR:0.64[0.48;0.86]95% CI and RR:0.14[0.03;0.70]95% CI. In the overall T2DM population, significantly lower rates of overall confirmed and nocturnal confirmed episodes were reported with IDeg vs. IGlar [ RR:0.83[0.74;0.94]95% CI and RR:0.68[0.57;0.82]95% CI). In the T1DM population, the rate of nocturnal confirmed episodes was significantly lower with IDeg vs. IGlar during maintenance treatment ( RR:0.75[0.60;0.94]95% CI). Reduction in hypoglycaemia with IDeg vs. IGlar was more pronounced during maintenance treatment in all populations. Conclusions The limitations of this study include the open-label design and exclusion of subjects with recurrent severe hypoglycaemia. This meta-analysis confirms that similar improvements in HbA1c can be achieved with fewer hypoglycaemic episodes, particularly nocturnal episodes, with IDeg vs. IGlar across a broad spectrum of patients with diabetes. [ABSTRACT FROM AUTHOR]

Aim: To study the clinical and economic benefits associated with adequate and early initiation and intensification of insulin in people with type 2 diabetes mellitus (T2DM). Methods: A systematic review was performed using published articles from January 2000 to August 2010 that linked intervention, disease, study design and outcomes. Studies were further classified as initiation and intensification based on predefined criteria. Individual studies in systematic reviews and meta-analysis were searched and included if relevant. Results: A total of 2690 articles were screened with 76 (40 initiation and 36 intensification) studies included. Most initiation studies had mean baseline HbA1c values of >8.5%. The endpoint HbA1c values were reduced with insulin treatment in these studies, with endpoint values ranging from 6.6 to 9.8%. Similar results were seen with the intensification studies (endpoint HbA1c: 6.4-9.6%). Addition of insulin to oral antidiabetics (OADs) resulted in better glycaemic control in most studies. Blood glucose levels reduced substantially with OADs + insulin compared with OADs alone. Quality of life outcomes and treatment satisfaction were reported in six studies and not significantly different for insulin vs. OADs. Hypoglycaemic events were manageable with insulin initiation. However, all insulin types were associated with weight gain although the comparison with OADs elicited varying results. Conclusions: Proactive management with early insulin initiation and intensification should be considered in people with T2DM in inadequate glycaemic control. The economic benefits with early initiation and intensification have to be fully explored. [ABSTRACT FROM AUTHOR]

S. Schmid, M. Tinguely, P. Cione, H. Moch and B. Bode Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomas Objective: Diagnosis of low grade non-Hodgkin B-cell lymphomas on cytological material may be problematic and in the past frequently required lymph node excision. We analysed our experience of the value of flow cytometry (FC) as an additional tool for the diagnosis of lymphoproliferative processes in the setting of a university cytology division with a busy fine needle cytology service. Methods: Consecutive cytological specimens with FC over a period of 3 years were retrospectively analysed and correlated with histology and follow-up if available. FC was performed with the following antibodies: CD3, CD4, CD8, CD2, CD7, CD19, CD5, CD10, CD23, lambda and kappa chains. Results: Of 299 probes (273 fine needle aspirations and 26 fluids from 285 patients), 179 cases (60%) were diagnosed as reactive, 91 cases (30%) as malignant or suspicious and 29 cases (10%) as inconclusive. The results of histological examination of the lymph nodes were available in 41 of 91 (45%) malignant or suspicious cases and in 13 of 179 (7%) reactive cytological diagnoses. Cytologically diagnosed malignancy was confirmed in all histologically examined cases. In 12 of 13 reactive cytological cases (92%), a benign process was diagnosed histologically. In 34 of 299 cases (11%) additional molecular investigations of B-cell clonality or specific translocations were performed. The lymphomas most frequently diagnosed were follicular lymphoma and lymphocytic lymphoma, followed by mantle cell and marginal zone lymphomas. Correlation with histology showed a sensitivity of 98% and a specificity of 100% for cytology in our series. Conclusions: FC is an important additional tool in the cytological diagnosis of lymphoproliferative disorders. The combined approach has a high diagnostic value that allows a reliable subclassification of low grade B-cell non-Hodgkin lymphomas. [ABSTRACT FROM AUTHOR]

Most treatments for type 2 diabetes fail over time, necessitating combination therapy. We investigated the safety, tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years. Participants were randomized to receive once-daily liraglutide 1.2 mg, liraglutide 1.8 mg or glimepiride 8 mg. Participants completing the 1-year randomized, double-blind, double-dummy period could continue open-label treatment for an additional year. Safety data were evaluated for the full population exposed to treatment, and efficacy data were evaluated for the full intention-to-treat (ITT) and 2-year completer populations. Outcome measures included change in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and frequency of nausea and hypoglycaemia. For patients completing 2 years of therapy, HbA1c reductions were −0.6% with glimepiride versus −0.9% with liraglutide 1.2 mg (difference: −0.37, 95% CI: −0.71 to −0.02; p = 0.0376) and −1.1% with liraglutide 1.8 mg (difference: −0.55, 95% CI: −0.88 to −0.21; p = 0.0016). In the ITT population, HbA1c reductions were −0.3% with glimepiride versus −0.6% with liraglutide 1.2 mg (difference: −0.31, 95% CI: −0.54 to −0.08; p = 0.0076) and −0.9% with liraglutide 1.8 mg (difference: −0.60, 95% CI: −0.83 to −0.38; p < 0.0001). For both ITT and completer populations, liraglutide was more effective in reducing HbA1c, FPG and weight. Over 2 years, rates of minor hypoglycaemia [self-treated plasma glucose <3.1 mmol/l (<56 mg/dl)] were significantly lower with liraglutide 1.2 mg and 1.8 mg compared with glimepiride (p < 0.0001). Liraglutide monotherapy for 2 years provides significant and sustained improvements in glycaemic control and body weight compared with glimepiride monotherapy, at a lower risk of hypoglycaemia. [ABSTRACT FROM AUTHOR]

Aim: As weight gain and hypoglycaemia associated with glimepiride therapy can negatively impact weight perceptions, psychological well-being and overall quality of life in type 2 diabetes, we investigated whether liraglutide treatment could improve these factors. Methods: Seven hundred and thirty-two patients with type 2 diabetes completed a 77-item questionnaire during a randomized, 52-week, double-blind study with liraglutide 1.2 mg ( n = 245) or 1.8 mg ( n = 242) compared with glimepiride 8 mg ( n = 245). Results: Mean (SE) decreases in glycated haemoglobin levels were greater with liraglutide 1.2 mg [−0.84 (0.08)%] and 1.8 mg [−1.14 (0.08)%] than glimepiride [−0.51 (0.08)%; p = 0.0014 and p < 0.0001, respectively]. Patients gained weight on glimepiride [mean (SE), 1.12 (0.27) kg] but lost weight on liraglutide [1.2 mg: −2.05 (0.28) kg; 1.8 mg: −2.45 (0.28) kg; both p < 0.0001]. Patient weight assessment was more favourable with liraglutide 1.8 mg [mean (SE) score: 40.0 (2.0)] than glimepiride [48.7 (2.0); p = 0.002], and liraglutide 1.8 mg patients were 52% less likely to feel overweight [odds ratio (OR) 0.48; 95% confidence interval (CI): 0.331–0.696]. Mean (SE) weight concerns were less with liraglutide [1.2 mg: 30.0 (1.2); 1.8 mg: 32.8 (1.2)] than glimepiride [38.8 (1.2); p < 0.0001 and p < 0.001, respectively], with liraglutide groups 45% less likely to report weight concern (OR 0.55, 95% CI: 0.41–0.73). Mean (SE) mental and emotional health and general perceived health improved more with liraglutide 1.8 mg [476.1 (2.8) and 444.2 (3.2), respectively] than glimepiride [466.3 (2.8) and 434.5 (3.2), respectively; p = 0.012 and p = 0.033, respectively]. Conclusions: Improved glycaemic control and decreased weight with liraglutide 1.8 mg vs. glimepiride can improve psychological and emotional well-being and health perceptions by reducing anxiety and worry associated with weight gain. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 57-year-old with swelling and an 8-centimeter haematoma localized on the right temple. Microscopic examination revealed several parasitic structures with massive accumulation of eosinophils suggestive of a larval tapeworm infection, with small subunit ribosomal RNA (SSU rRNA gene) identified the parasite as Taenia crassiceps (T. crassiceps). The patient underwent oral therapy with praziquantel and albendazole and did not require surgery.

Aim: To evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro (Humalog ® ) in people with type 1 diabetes on continuous subcutaneous insulin infusion (CSII)., Materials and Methods: This was a phase 3, 16-week, treat-to-target study in patients randomized to double-blind URLi (N = 215) or lispro (N = 217). The primary endpoint was change from baseline HbA1c (non-inferiority margin 4.4 mmol/mol [0.4%]), with multiplicity-adjusted objectives for postprandial glucose (PPG) levels during a meal test, and time spent in the target range 70-180 mg/dL (TIR)., Results: URLi was non-inferior to lispro for change in HbA1c, with a least-squares mean (LSM) difference of 0.3 mmol/mol (95% confidence interval [CI] -0.6, 1.2) or 0.02% (95% CI -0.06, 0.11). URLi was superior to lispro in controlling 1- and 2-h PPG levels after the meal test: LSM difference -1.34 mmol/L (95% CI -2.00, -0.68) or -24.1 mg/dL (95% CI -36.0, -12.2) at 1 h and -1.54 mmol/L (95% CI -2.37, -0.72) or -27.8 mg/dL (95% CI -42.6, -13.0) at 2 h; both p < .001. TIR and time in hyperglycaemia were similar between groups but URLi resulted in significantly less time in hypoglycaemia (<3.0 mmol/L [54 mg/dL]) over the daytime, night-time and 24-h period: LSM difference -0.41%, -0.97% and -0.52%, respectively, all p < .05. The incidence of treatment-emergent adverse events was higher with URLi (60.5% vs. 44.7%), driven by infusion-site reaction and infusion-site pain, which was mostly mild or moderate. Rates of severe hypoglycaemia and diabetic ketoacidosis were similar between groups., Conclusions: URLi was efficacious, providing superior PPG control and less time in hypoglycaemia but with more frequent infusion-site reactions compared with lispro when administered by CSII., (© 2021 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Video abstract: View a video abstract for this article., Aims: This multicentre (N = 104), randomized controlled phase 4 study compared the efficacy and safety of insulin glargine 300 units/mL (Gla-300) with insulin glargine 100 units/mL (Gla-100) in patients with type 1 diabetes (T1D)., Materials and Methods: Patients were randomized 1:1 to self-perform morning Gla-300 or Gla-100 injections daily for 16 weeks. The primary endpoint was percentage of time blood glucose remained in the target range (70-180 mg/dL) during Week 15/16, measured by blinded continuous glucose monitoring. Secondary endpoints included incidence and rate of nocturnal symptomatic hypoglycaemia (≤70 mg/dL), glycaemic variability parameters and safety assessments. Exploratory analyses were performed in patients with glycated haemoglobin (HbA1c) <7.5% at Week 16., Results: Overall, 638 patients with T1D were included (Gla-300, n = 320; Gla-100, n = 318). In the modified intent-to-treat (mITT) population, no differences between Gla-300 and Gla-100 were observed in time in range, in glycaemic variability, or in incidence or rates of nocturnal symptomatic hypoglycaemia. In exploratory analyses of patients with HbA1c <7.5% at Week 16, Gla-300 recipients had greater improvement in time in range over 24 hours, during the day and at night compared with Gla-100 recipients (P < 0.05), with small increases in overall hypoglycaemia., Conclusions: Time in range and glycaemic variability were similar for Gla-300 and Gla-100 recipients at the end of study in the mITT population of relatively well-controlled patients with T1D. In patients with end-of-study HbA1c <7.5%, exploratory analyses suggested that Gla-300 provided improvements in time in range compared with Gla-100., (© 2019 John Wiley & Sons Ltd.)

We investigated the pharmacodynamics (PD) and pharmacokinetics (PK) of BioChaperone insulin Lispro (BCLIS), faster insulin aspart (FIA) and insulin aspart (ASP) in patients with type 1 diabetes using an insulin pump. In this randomized, double-blind, three-way crossover glucose clamp study, 43 patients received a bolus dose of each insulin (0.15 U/kg) in addition to a basal rate (0.01 U/kg/h), delivered via an insulin pump. With BCLIS, the AUC-GIR,0-60 minutes (primary endpoint) was improved compared to ASP (least square means ratio, 1.63; 95% CI, 1.44-1.88; P < 0.0001) and was similar compared to FIA (least square means ratio, 1.06; 95% CI, 0.94-1.18; P = 0.4609). BCLIS showed faster-on PD (t early0.5GIRmax ) than ASP and faster-off PD (t late0.5GIRmax ) than both FIA and ASP. BCLIS also demonstrated significantly higher early exposure (AUCins, 0-60 minutes) and lower late exposure (AUCins,120-600 minutes) than both other insulins. In patients with type 1 diabetes using an insulin pump, BCLIS better mimics prandial insulin secretion and action than ASP and shows a faster off-PD than FIA., (© 2018 John Wiley & Sons Ltd.)

Background: Molecular testing of lung adenocarcinomas (ADCs) is crucial for therapy stratification of patients. Because of the often limited diagnostic material, the authors aimed to explore the suitability of cytology smears for next-generation sequencing (NGS) and compared the results with concurrent histological specimens or cell blocks., Methods: A total of 16 formalin-fixed paraffin-embedded (FFPE) ADCs with known genetic alterations were used as the first cohort for targeted DNA and RNA sequencing. In the second cohort of 8 cases, 8 cytological smears were compared with matching histological specimens or cell blocks for the study. For NGS library amplification, commercially available panels for DNA and RNA sequencing were applied. The Ion Torrent Personal Genome Machine and the Ion Reporter workflow (version 5.0) were used for sequencing., Results: All DNA libraries derived from FFPE and non-formalin-fixed cytological smear samples produced acceptable quality metrics, thereby enabling successful targeted DNA sequencing (100% performance). Targeted RNA sequencing failed in 1 FFPE case and 1 cytology probe by not reaching enough mapped fusion reads (92% performance rate). All previously detected mutations and gene rearrangements could be confirmed (sensitivity of 100%), whereas specificity of the DNA-based NGS assay reached 96%., Conclusions: The results of the current study demonstrated the suitability of non-formalin cytology specimens for the simultaneous NGS testing of lung ADCs using amplicon resequencing panels. These assays allowed for the input of cytological smears equal to concurrent histology or cell blocks and proved to be accurate in the detection of therapeutically actionable somatic mutations and gene rearrangements. Cancer Cytopathol 2017;125:30-40. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Three novel G-protein-coupled receptor genes related to the previously described RA1c gene have been isolated from the mouse genome. Expression of these genes has been detected in distinct areas of the brain and also in the olfactory epithelium of the nose. Developmental studies revealed a differential onset of expression: in the brain at embryonic stage 17, in the olfactory system at stage E12. In order to determine which cell type in the olfactory epithelium expresses this unique receptor type, a transgenic approach was employed which allowed a coexpression of histological markers together with the receptor and thus visualization of the appropriate cell population. It was found that the receptor-expressing cells were located very close to the basal membrane of the epithelium; however, the cells extended a dendritic process to the epithelial surface and their axons projected into the main olfactory bulb where they converged onto two or three glomeruli in the dorsal and posterior region of the bulb. Thus, these data provide evidence that this unique type of receptor is expressed in mature olfactory neurons and suggests that it may be involved in the detection of special odour molecules.