The vertical dimension of obesity: adverse pregnancy outcomes in the short obese versus tall obese parturient.

The objective of this study was to examine the effect of maternal height on adverse perinatal outcomes in obese parturients. This retrospective study was conducted from January 2015 to December 2015. Patients with BMI ≥ 35.0 kg/m2 before delivery were included and divided into 2 groups based on height. Patients ≤63 inches were in the short stature group and those > 63 inches were in the tall stature group. One hundred and twenty-five patients were in the short stature cohort and 124 in the tall stature cohort. Patients in short cohort had a significantly higher risk of preterm delivery <37 weeks (RR = 4.21 [1.24, 12.88]), spontaneous rupture of membranes (RR 1.47 [1.01-2.16]), and second stage caesarean delivery (CD) (RR 2.64 [1.1-6.39]). After multiple regression analysis, Hispanic race and short stature were independent predictors of preterm birth for obese patients.IMPACT STATEMENTWhat is already known on this subject? Compared to normal weight individuals, those who are obese have at a higher risk of adverse obstetric and perinatal outcomes including gestational diabetes, hypertension, pre-eclampsia, thromboembolism, macrosomia, higher incidence of caesarean deliveries and perinatal mortality.What do the results of this study add? Our findings show that short stature is an independent predictor for adverse perinatal outcomes in obese women. Specifically, short obese patients had significantly higher risk of preterm delivery before 37 weeks and second stage CD.What are the implications of the findings for clinical practice and/or further research? Our findings highlight the need for formulating a tailored plan for preconception health including pregnancy weight goals in short obese women. Additionally, maternal fat distribution and its effect on pro-inflammatory cytokine profiles is a potential area for future research, as maternal body composition may be a better predictor of perinatal outcome than BMI.

Correction to: Trastuzumab Emtansine: A Review of Its Adjuvant Use in Residual Invasive HER2-Positive Early Breast Cancer.

The author has alerted us to the following error.

Trastuzumab Emtansine: A Review of Its Adjuvant Use in Residual Invasive HER2-Positive Early Breast Cancer.

Trastuzumab emtansine (Kadcyla®), an antibody-drug conjugate of trastuzumab (Herceptin®) connected by a thioether linker to the microtubule inhibitor DM1 (a cytotoxic derivative of maytansine), provides direct intracellular delivery of the potent cytotoxin DM1 to HER2-overexpressing cells, while retaining trastuzumab activity. Its approval in metastatic/advanced breast cancer (BC) has been extended to include single-agent adjuvant treatment of HER2-positive early BC in patients with residual invasive disease in the breast and/or lymph nodes after neoadjuvant taxane-based and HER2-targeted treatment. In the pivotal KATHERINE trial in this population, significantly more trastuzumab emtansine than trastuzumab recipients were estimated to be free of invasive disease recurrence at 3 years, with a 50% reduction in the risk of invasive disease recurrence or death. The tolerability of trastuzumab emtansine in early BC was consistent with its known safety profile; as expected, adverse events were more common with trastuzumab emtansine than with trastuzumab. Recently updated international and national treatment guidelines recommend trastuzumab emtansine as a preferred option in this high-risk BC population.

Correction to: Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Their Use and Differential Features.

Page 806, column 1, line 3: The text, which previously read.

Correction to: Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Their Use and Differential Features.

The article Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Their Use and Differential Features, written by KA Lyseng-Williamson, was originally published Online First without open access. After publication in volume 39, issue 8, pages 805-819, Springer Healthcare IME requested that the article be Open Choice to make the article an open access publication. Post-publication open access was funded by an independent educational grant from Novo Nordisk A/S . The article is forthwith distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/ ), which permits any noncommercial use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

Correction to: Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Their Use and Differential Features.

The original version of this article unfortunately contained some mistakes. The corrected details are provided below.

Glucagon-Like Peptide-1 Receptor Analogues in Type 2 Diabetes: Their Use and Differential Features.

Glucagon-like peptide-1 receptor analogues/agonists (GLP-1RAs) are well established as effective adjuncts to lifestyle modification in the treatment of type 2 diabetes (T2D) as monotherapy or in combination with oral glucose-lowering drugs ± insulin. The six subcutaneous GLP-1RA formulations (i.e. twice-daily exenatide, once-daily liraglutide and lixisenatide, and once-weekly dulaglutide, exenatide and semaglutide) currently available in the EU and USA have many similarities, but also some unique features and properties. By stimulating GLP-1 receptors, GLP-1RAs increase insulin secretion and suppress glucagon release in a glucose-dependent manner, thereby improving clinical and patient-reported outcomes related to glycaemic control and weight. They also have been shown to reduce, or at least not increase, the risk of major cardiovascular outcomes. GLP-1RAs are generally well tolerated, with gastrointestinal and injection-site reactions being the most troublesome drug-related adverse events, and are associated with a very low intrinsic risk of hypoglycaemia. Treatment with GLP-1RAs should be customized to meet the clinical needs and personal preferences of the individual.

Correction to: Anakinra in Still's disease: a profile of its use.

[This corrects the article DOI: 10.1007/s40267-018-0572-5.].

Correction to: Macrogol (polyethylene glycol) 4000 without electrolytes in the symptomatic treatment of chronic constipation: a profile of its use.

[This corrects the article DOI: 10.1007/s40267-018-0532-0.].

Anakinra in Still's disease: a profile of its use.

The EU indication for anakinra has been extended to include Still's disease, a serious rare inflammatory disorder of unknown aetiology that comprises adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA). As activated interleukin-1 pathways are associated with the systemic manifestations of these disorders, targeted treatment with anakinra, an interleukin-1 inhibitor, has been investigated. Across clinical and real-world studies in patients with AOSD and SJIA, treatment with anakinra achieved clinical remission/response, provided rapid and sustained improvements in systemic and laboratory manifestations, and allowed the use of corticosteroid- and disease-modifying anti-rheumatic drugs (DMARD) to be reduced or discontinued. The safety profile of anakinra in the treatment of Still's disease is consistent with that in its other approved indications.

Macrogol (polyethylene glycol) 4000 without electrolytes in the symptomatic treatment of chronic constipation: a profile of its use.

Macrogol 4000, a biologically inert, non-absorbable osmotic laxative, is a highly effective and well-tolerated first-line option for the treatment of the symptoms of chronic idiopathic/functional constipation in children and adults. High-molecular-weight (HMW) macrogols ± electrolytes have generally similar efficacy profiles; however, the taste of macrogol 4000 is generally preferred over that of macrogol 3350 + electrolytes. Macrogol 4000 is more effective than lactulose in improving stool frequency and consistency, and is associated with less vomiting and flatulence. Comparisons with other osmotic and bulk-forming laxatives are limited, with macrogol 4000 being at least as, or more effective than, psyllium hydrocolloid and magnesium hydroxide in treating chronic constipation. Current clinical treatment guidelines recommend the use of HMW macrogols over the use of lactulose and bulk-forming laxative in the symptomatic treatment of constipation in children and adults.

Ginkgo biloba extract EGb 761® in the symptomatic treatment of mild-to-moderate dementia: a profile of its use.

EGb 761® (Tanakan®) is a standardized extract of Ginkgo biloba leaves that has demonstrated protective properties against neuronal and vascular damage. Overall, in randomized, placebo-controlled clinical trials and meta-analyses in adults with mild-to-moderate dementia, EGb 761® displayed positive effects, with changes from baseline in outcomes related to cognition, behaviour and global change that are generally better than those shown with placebo. EGb 761® is generally well tolerated, with no safety issues being identified during its many years of widespread use.

Fostamatinib in chronic immune thrombocytopenia: a profile of its use in the USA.

Oral fostamatinib is an orally administered small molecule spleen tyrosine kinase (SYK) inhibitor approved for the treatment of adults with chronic immune thrombocytopenia (ITP) who have an inadequate response to a previous treatment. Fostamatinib has a unique mechanism of action, whereby its active metabolite targets the SYK-mediated pathway of platelet destruction. In clinical trials, fostamatinib provided durable responses in adults with chronic ITP who had not responded or had relapsed following treatment with one or more prior ITP therapies, including corticosteroids, thrombopoietin receptor agonists, rituximab, and/or splenectomy. Most patients who respond to fostamatinib maintain platelet counts of > 50 × 109/L for periods of ≥ 12 months. The most common adverse events reported with fostamatinib in clinical trials were diarrhea, hypertension, nausea, and increased transaminase levels.

Burosumab in X-linked hypophosphatemia: a profile of its use in the USA.

Burosumab (Crysvita®), a fully human IgG1 monoclonal antibody directed at fibroblast growth factor 23 (FGF23), is indicated for the treatment of X-linked hypophosphatemia (XLH), a condition associated with excessive FGF23 production. It directly addresses the excessive FGF23 activity in patients with XLH by binding to FGF23, and inhibiting its signaling. This leads to increased gastrointestinal phosphate absorption and renal phosphate reabsorption, thereby improving serum phosphate levels, and, ultimately, bone mineralization and the risk of bone disease. In clinical trials, subcutaneous burosumab increased serum phosphorus levels in pediatric and adult patients with XLH, as well as significantly improving the severity of rickets in children, and improving pain, stiffness, physical functioning, and fracture/pseudofracture healing in adults. Burosumab is well tolerated by children and adults with XLH, with most treatment-emergent adverse events being of mild to moderate severity.

An Original Suprapannicular Incision Technique for Cesarean Delivery in the Morbidly Obese Parturient.

BACKGROUND: Obese patients are at an increased risk of cesarean delivery and its associated wound complications. We present an alternative incision technique for obese parturients that avoids making a Pfannenstiel incision under the panniculus while still providing access to the lower uterine segment. TECHNIQUE: For our technique, an assistant uses Allis clamps to exert caudal traction on the patient's panniculus and a transverse skin incision is made under the umbilicus, 3 cm below the line joining the anterosuperior iliac crests. On entry to the abdominal cavity, a wound retractor is placed to optimize access to the lower uterine segment so that a low transverse uterine incision can be made. EXPERIENCE: We have used this incision technique on 17 obese patients with no incidence of intraoperative complications, no requirement to perform a vertical hysterotomy incision, and no postoperative wound infections. CONCLUSION: Our technique is a feasible alternative incision for obese parturients that avoids making a subpannicular Pfannenstiel incision and still allows for good access to the lower uterine segment.

Pirfenidone tablets in idiopathic pulmonary fibrosis: a profile of their use.

Pirfenidone (Esbriet®) is available as capsules containing 267 mg of pirfenidone and, more recently, as bioequivalent tablets containing 267, 534 or 801 mg of pirfenidone. Both formulations are indicated to treat idiopathic pulmonary fibrosis (IPF), with pirfenidone being shown to generally reduce the rate of decline in forced vital capacity in patients with mild to moderate IPF, while prolonging progression-free survival and reducing the risk of IPF-related and all-cause mortality. The availability of the tablet formulation reduces the daily pill burden of pirfenidone, as the recommended daily divided maintenance dose of 2403 mg/day may be administered as one 801 mg tablet three times daily instead of three 267 mg capsules three times daily. Pirfenidone is associated with gastrointestinal and skin-related events, with such events generally being manageable.

Effect of Endurance Conditioning on Insulin-mediated Glucose Clearance in Dogs.

INTRODUCTION: Physical activity has been shown to improve insulin sensitivity in subjects with insulin resistance, but the effect of athletic conditioning on subjects with normal insulin sensitivity has received less scrutiny. Because strenuous exercise can be limited by the availability of substrates, it is reasonable to hypothesize that conditioning would increase the capacity for muscle uptake of substrates like glucose and to the extent that improvement in this process would include upregulation of the portions of the glucose uptake pathway in muscle, this increased capacity would also be reflected in insulin sensitivity. Therefore, we tested the hypothesis that conditioning for endurance exercise would result in increased insulin sensitivity using elite racing sled dogs. METHODS: A frequent-sampled intravenous glucose tolerance test was performed on these dogs before and after a full 7-month season of conditioning in preparation for a 1600-km race. RESULTS: Compared with the results in unconditioned dogs, conditioned dogs rapidly cleared the intravenous glucose bolus through increases in both glucose mediated (7.6%·min ± 3.4%·min vs 3.0%·min ± 2.2%·min, P = 0.008) and insulin-mediated (36.3 ± 18.4 × 10 L·min·mU vs 11.5 ± 8.0 × 10 L·min·mU, P = 0.007) mechanisms. The more modest increase in serum insulin after the intravenous glucose bolus in conditioned dogs failed to suppress lipolysis and serum concentrations of nonesterified fatty acids remained constant in the conditioned dogs throughout the 4-h test. CONCLUSIONS: These results, in particular the increase in insulin-independent peripheral uptake of glucose, describe novel alterations in metabolism induced by athletic conditioning that arguably result in near-continuous provision of oxidizable substrates to peripheral muscle in support of sustained muscular work typical of these dogs.

Telotristat Ethyl: A Review in Carcinoid Syndrome Diarrhoea.

Telotristat ethyl (Xermelo®), a first-in-class peripheral tryptophan hydroxylase (TPH) inhibitor, is approved to treat carcinoid syndrome diarrhoea in combination with somatostatin analogue (SSA) therapy in adults inadequately controlled by SSA therapy alone. Some neuroendocrine tumours secrete serotonin (5-HT) into the blood, resulting in frequent bowel movements (BMs) and other symptoms. Telotristat ethyl inhibits TPH, thereby reducing the production of 5-HT and improving carcinoid syndrome diarrhoea. In the 12-week placebo-controlled phase of randomized trials in patients with carcinoid syndrome diarrhoea (most of whom were receiving SSA therapy), the addition of oral telotristat ethyl 250 three times daily provided significant reductions in the frequency of BMs and levels of urinary 5-hydroxyindolacetic acid (u5-HIAA; a metabolite of 5-HT) relative to placebo. Telotristat ethyl 250 mg three times daily was well tolerated, with the proportion of patients reporting at least one treatment-emergent adverse event being similar to that with placebo. With regard to adverse events of special interest, relative to placebo, telotristat ethyl had a comparable incidence of depression-related symptoms, a somewhat higher incidence of gastrointestinal (GI) disorders and a higher incidence of elevated hepatic enzyme levels.

Correction to: Fostamatinib in chronic immune thrombocytopenia: a profile of its use in the USA.

[This corrects the article DOI: 10.1007/s40267-018-0551-x.].

Correction to: Burosumab in X-linked hypophosphatemia: a profile of its use in the USA.

[This corrects the article DOI: 10.1007/s40267-018-0560-9.].