Effects of Periodic Intensive Insulin Therapy: An Updated Review.

BACKGROUND: Traditional insulin treatment for diabetes mellitus with insulin administered subcutaneously yields nonpulsatile plasma insulin concentrations that represent a fraction of normal portal vein levels. Oral hypoglycemic medications result in the same lack of pulsatile insulin response to blood glucose levels. Intensive treatments of significant complications of diabetes are not recommended due to complicated multidrug regimens, significant weight gain, and the high risk of hypoglycemic complications. Consequently, advanced complications of diabetes do not have an effective treatment option because conventional therapy is not sufficient. Intensive insulin therapy (IIT) simulates normal pancreatic function by closely matching the periodicity and amplitude of insulin secretion in healthy subjects; however, the mechanisms involved with the observed improvement are not clearly understood. OBJECTIVE: The current review aims to analyze the pathophysiology of insulin secretion, discuss current therapies for the management of diabetes, provides an updates on the recent advancements of IIT, and proposes its mechanism of action. METHODS: A literature search on PubMed, MEDLINE, Embase, and CrossRef databases was performed on multiple key words regarding the history and current variations of pulsatile and IIT for diabetes treatment. Articles reporting the physiology of insulin secretion, advantages of pulsatile insulin delivery in patients with diabetes patients, efficacy and adverse effects of current conventional insulin therapies for the management of diabetes, benefits and shortcomings of pancreas and islet transplantation, or clinical trials on patients with diabetes treated with pulsed insulin therapy or advanced IIT were included for a qualitative analysis and categorized into the following topics: mechanism of insulin secretion in normal subjects and patients with diabetes and current therapies for the management of diabetes, including oral hypoglycemic agents, insulin therapy, pancreas and islet transplantation, pulsed insulin therapy, and advances in IIT. RESULTS: Our review of the literature shows that IIT improves the resolution of diabetic ulcers, neuropathy, and nephropathy, and reduces emergency room visits. The likely mechanism responsible for this improvement is increased insulin sensitivity from adipocytes, as well as increased insulin receptor expression. CONCLUSIONS: Recent advancements show that IIT is an effective option for both type 1 diabetes mellitus and type 2 diabetes mellitus patient populations. This treatment resembles normal pancreatic function so closely that it has significantly reduced the effects of relatively common complications of diabetes in comparison to standard treatments. Thus, this new treatment is a promising advancement in the management of diabetes. (Curr Ther Res Clin Exp. 2019; 80:XXX-XXX).

Management of Nephrotic Syndrome in the Pregnant Patient.

Objective: To present a case series of pregnant women with nephrotic syndrome, describe maternal and fetal outcomes, and propose treatment strategies. Study Design: A retrospective cohort case review of 11 pregnant women with nephrotic syndrome was performed over 2 years. Treatment regimens and trends were recorded. Linear regression was used for continuous outcomes, and logistic regression for categorical outcomes (p<0.05). Results: On first admission, 3 of 11 patients had a serum creatinine >1.4 mg/dL; all 11 exhibited an antepartum increase in creatinine. Two required antepartum dialysis, and 3 were dialyzed postpartum. Initial mean 24-hour urine protein was 10,522 mg (2,160-36,603) and increased to 26,220 mg (4,650-49,980). Pregravid weight increased from a mean 95 kg (BMI 33.8) to 112 kg (BMI 39.9) at time of delivery. Mean antepartum and postpartum diuresis was 33.2 L (±25.8) and 5.2 L (±8.2), respectively. Mean serum albumin levels were 2 g/dL. Ten patients received intravenous diuretics and 9 received intravenous albumin. Mean gestational age at delivery was 34w 3d (30.4-38.4). Conclusion: Pregnant women with nephrotic syndrome can be managed successfully by a collaborative team of obstetricians and nephrologists with careful diuresis, repletion of albumin, and administration of anticoagulants, when necessary, to deliver a healthy, probably preterm, neonate.

A critical appraisal of the potential harmful effects of terbutaline sulfate use in pregnancy.

Beta2-adrenergic agonist medications such as albuterol and terbutaline are often prescribed during pregnancy to treat conditions such as asthma, pulmonary disease, preterm labor, or acute non-reassuring fetal heart rate abnormalities during labor. Recently a review article questioned the safety of beta2-adrenergic agonist use in pregnancy, postulating a "biologically plausible" link between the use of these agents and autism spectrum disorder in offspring of mothers exposed to these drugs. While it is imperative to determine any harmful effects of any medication during pregnancy, it is important to weigh the risks and known benefits of treatment versus nontreatment of conditions such as preterm labor with medications such as terbutaline, given the known rates of morbidity and mortality associated with prematurity. The purpose of our review and commentary is to explain how and why beta2-adrenergic agonists are used to treat preterm labor and to discuss the merits of the conclusions drawn by the Witter clinical commentary.

Exceptionally Fast Ion Diffusion in Block Copolymer-Based Porous Carbon Fibers.

Confined ionic liquids in hydrophilic porous media have disrupted lattices and can be divided into two layers: An immobile ion layer adheres to the pore surfaces, and an inner layer exhibits faster mobility than the bulk. In this work, we report the first study of ionic liquids confined in block copolymer-based porous carbon fibers (PCFs) synthesized from polyacrylonitrile-block-polymethyl methacrylate (PAN-b-PMMA). The PCFs contain a network of unimodal mesopores of 13.6 nm in diameter and contain more hydrophilic surface functional groups than previously studied porous carbon. Elastic neutron scattering shows no freezing point for 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]BF4) confined in PCFs down to 20 K. Quasi-elastic neutron scattering (QENS) is used to measure the diffusion of [BMIM]BF4 confined in PCFs, which, surprisingly, is 7-fold faster than in the bulk. The unprecedentedly high ion diffusion remarks that PCFs hold exceptional potential for use in electrochemical catalysis, energy conversion, and storage.

In defense of magnesium sulfate.

Magnesium sulfate has been used by obstetricians for more than 25 years to treat preterm labor. Magnesium sulfate is effective in delaying delivery for at least 48 hours in patients with preterm labor when used in higher dosages. There do not seem to be any harmful effects of the drug on the fetus, and indeed there is a neuroprotective effect in reducing the incidence of cerebral palsy in premature newborns weighing less than 1,500 g.

The impact of acute tocolysis on neonatal outcome in women hospitalized with preterm labor at 32 to 34 weeks' gestation.

We compared neonatal outcomes from singleton pregnancies in women hospitalized with preterm labor (PTL) at 32 0/7 to 34 6/7 weeks managed with and without acute tocolysis. Women enrolled for outpatient surveillance who were hospitalized and diagnosed with PTL between 32 0/7; to 34 6/7 weeks' gestation without conditions necessitating interventional delivery during hospitalization were identified ( N = 2921). Patients with contraindications to pregnancy prolongation were excluded ( N = 168). Data were compared between patients whose clinical management included tocolysis ( N = 2342) and patients in whom tocolysis was not utilized ( N = 411). The incidence of preterm birth (77.9% versus 48.1%), low birth weight (48.9% versus 16.7%), neonatal intensive care unit admission (41.4% versus 16.2%), and nursery length of stay > 7 days (28.0% versus 9.7%) were all higher in women not receiving acute tocolysis compared with the acute tocolysis group (all P < 0.001). Using acute tocolysis to prolong pregnancy in patients hospitalized with PTL at 32 0/7 to 34 6/7 weeks' gestation is associated with improved neonatal outcomes.

Preterm labor in twins and high-order multiples.

Preterm labor (PTL) in a multiple gestation occurs frequently and is a common reason for preterm delivery (PTD). Management strategies for multiple gestations must be directed at early detection of PTL and effective strategies to delay or prevent PTD. Unlike singleton gestation where identification of patients at risk for PTL is often difficult, every multiple gestation is at risk for PTL, so all patients can be managed as being at risk. Although PTL is a significant cause of PTD, one must recognize that there are other reasons for delivery in multiple gestations. Clinicians must treat the whole patient and extend the pregnancy to the most advanced gestational age possible that is consistent with the best outcome.

Risks and Benefits of Magnesium Sulfate Tocolysis in Preterm Labor (PTL).

The U.S. Food and Drug Administration issued a drug safety communication on 05/30/2013 recommending "against prolonged use of magnesium sulfate to stop preterm labor (PTL) due to bone changes in exposed babies." In September of 2013, The American Congress of Obstetrics and Gynecologists issued Committee Opinion No. 573 " Magnesium Sulfate Use in Obstetrics" , which supports the short term use of MgSO4 to prolong pregnancy (up to 48 hrs.) to allow for the administration of antenatal corticosteroids." Are these pronouncements by respected organizations short sighted and will potentially result in more harm than good? The FDA safety communication focuses on bone demineralization (a few cases with fractures) with prolonged administration of MgSO4 (beyond 5-7 days). It cites 18 case reports in the Adverse Event Reporting System with an average duration of magnesium exposure of 9.6 weeks (range 8-12 wks). Other epidemiologic studies showed transient changes in bone density which resolved in the short duration of follow up. Interestingly, the report fails to acknowledge the fact that these 18 fetuses were in danger of PTD and the pregnancy was prolonged by 9.6 weeks (e.g. extending 25 weeks to 34.6 wks), thus significantly reducing mortality and morbidity. Evidence does support the efficacy of MgSO4 as a tocolytic medication. The decision to use magnesium, the dosage to administer, the duration of use, and alternative therapies are physician judgments. These decisions should be made based on a reasonable assessment of the risks of the clinical situation (PTL) and the treatments available versus the benefits of significantly prolonging pregnancy.

Is peripartum hysterectomy more common in multiple gestations?

OBJECTIVE: To compare the occurrence of peripartum hysterectomy between singleton and multiple gestations. METHODS: This was a historical cohort study comparing the occurrence of peripartum hysterectomy between singleton and multiple gestations at Banner Good Samaritan Regional Medical Center, Phoenix, Arizona, from January 1, 1996, to December 31, 2001. RESULTS: During the study years, 42,595 singleton, 1,131 twin, 164 triplet, 35 quadruplet, and 2 quintuplet deliveries occurred. A total of 100 peripartum hysterectomies were performed. Of these hysterectomies, 88 occurred in singletons, 5 in twins, 6 in triplets, and 1 in quadruplets. The overall occurrence of peripartum hysterectomy was 2.28 per 1,000, and the occurrence of emergent peripartum hysterectomy was 1.73 per 1,000. Multiple gestations had a significantly greater risk of emergent peripartum hysterectomy than singletons (odds ratio [OR] 6.04, 95% confidence interval [CI] 3.28-11.11; P < .001). This difference was more pronounced among higher-order multiple gestations: twins (OR 2.95, 95% CI 1.22-7.13, P = .03), triplets (OR 25.22, 95% CI 11.02-57.77, P < .001), and quadruplets (OR 19.53, 95% CI 3.34-114.69, P = .04). When compared with singletons, higher-order multiple gestations had nearly a 24-fold increased risk of emergent peripartum hysterectomy (OR 23.97, 95% CI 11.05-51.99, P < .001). CONCLUSION: Multiple gestations have a significantly higher occurrence of emergent peripartum hysterectomy than singletons. This information should be used in counseling and managing patients with these pregnancies.

High-order multiple gestations.

Infertility treatments have produced an increase in multiple gestations with twins accounting for 3.3% of births in the United States in 2002. Over that same time period, premature deliveries increased from 10.7% in 1992 to 12.1% in 2002. High-order multiple gestations have also increased, and virtually all of those deliver prematurely. Clinicians are facing the challenge of managing these complicated pregnancies. Neonatal outcome will primarily depend on the gestational age at delivery and the birth weight of the babies. Care is directed at aggressively and proactively preventing preterm delivery. Ultrasound assessments are made frequently to assess fetal anatomical abnormalities, nuchal translucency, fetal growth, cervical length, amniotic fluid, and biophysical profile. Stress reduction and activity reduction will decrease uterine activity, and tocolytic drugs are employed to decrease background contractions to reduce preterm labor (PTL). Fetal fibronectin testing helps predict risk of PTL, and magnesium sulfate tocolysis is used in aggressive dosing to arrest PTL if it occurs. Outcomes are presented and discussed. Successful outcomes are not only possible, but probable.

Management of wound complications from cesarean delivery.

UNLABELLED: Multiple factors account for the increasing number of cesarean delivery wound complications in the United States; among them are an increase in cesarean delivery and an increase in the number of overweight and obese patients. This article reviews the pathophysiology of acute wound healing. Risk factors for cesarean delivery wound complications are identified and described. Clinical practices that can reduce the risk of developing wound complications, including Centers for Disease Control and Prevention guidelines, are considered. Treatment guidelines to accelerate wound healing such as secondary closure and negative pressure wound therapy in disrupted wounds are proposed. Older guidelines for management of wounds using secondary intention are critiqued. Historical methods of wound care such as the practice of using certain cleansers and the practice of wet to dry dressings are outdated. Modern wound healing products are described. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader should be able to describe the effects of obesity on cesarean delivery wound healing, to improve methods of wound healing in the obese patient, and to explain why wet to dry dressing changes are not effective wound management.

Preterm labor in twins and high-order multiples.

Preterm labor (PTL) is common in multiple gestations. Management of patients includes attempts at prevention of PTL, acute tocolysis when PTL is diagnosed, and long-term maintenance tocolysis. Clinical therapeutics should be aggressively directed at minimizing the background uterine contractions to reduce the incidence of PTL and to provide a greater chance of suppressing PTL allowing delivery at the ideal gestational age.

Indicated and non-indicated preterm delivery in twin gestations: impact on neonatal outcome and cost.

OBJECTIVE: To identify the etiology and impact of preterm delivery in twin gestations. STUDY DESIGN: Twin gestations delivered at 33.0 to 36.9 weeks were identified in a perinatal database, and categorized by indication for delivery. Deliveries were identified as indicated, or non-indicated (discretionary). Neonatal outcomes were measured by birth weight, length of stay, NICU admission, and ventilator utilization. Data were divided and analyzed by indicated or discretionary delivery, and gestational age at delivery. RESULTS: Analyzed were 3252 twin gestations (6504 infants), with 78% having indicated delivery. Of the 22% with discretionary delivery, nearly 40% required NICU admission. With each advancing week of gestation, there was a significant decrease in incidence of NICU admission and nursery days. CONCLUSION: The majority of preterm deliveries were indicated, though 22% were discretionary. It is vital to consider neonatal morbidity and costs related to gestational age when choosing discretionary delivery.

A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin.

OBJECTIVE: To assess the impact of activity restriction (AR) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin (fFN). STUDY DESIGN: Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management. Included were consenting patients with negative fFN, gestational age 23 0/7-33 6/7 weeks, cervical dilation < or =3 cm, and minimal vaginal bleeding. Patients were randomized to AR or no AR. Primary study outcome was incidence of preterm delivery and interval from randomization to delivery. RESULTS: A total of 73 women with negative fFN were randomized (36 with AR, 37 without AR). The overall preterm birth rate was 40%, with 44.4% of patients with AR and 35.1% of patients without AR delivering preterm, p=0.478. CONCLUSION: Maternal AR did not impact pregnancy outcome. The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported.

Management of high-order multiple gestation.

High-order multiple gestation presents unique challenges to the clinician to obtain the best possible outcome. An aggressive proactive approach works best compared with a wait-and-treat strategy when complications occur. Frequent ultrasound evaluations, fetal fibronectin testing, and contraction monitoring are important diagnostic tools. Aggressive weight gain, bed rest, and relaxation techniques are important interventions. Tocolytic drugs are used to prevent preterm labor, and aggressive dosing of MgSO4, terbutaline pumps, and oral agents are advocated to treat preterm labor. Outcome is generally good with high-order multiple gestation with this management protocol.

Consequences of nonindicated preterm delivery in singleton gestations.

OBJECTIVE: To determine the neonatal and economic consequences of nonindicated preterm delivery in singleton gestations. STUDY DESIGN: From a database of women with high-risk pregnancies enrolled for outpatient nursing services between October 1995 and February 2000, singleton gestations with induced labor or scheduled cesarean delivery and a gestational age at delivery of 34-36 weeks were identified. Excluded were women with preterm premature rupture of the membranes or medically indicated delivery. We compared infant neonatal intensive care unit (NICU) admission rates and ventilator use for consecutive weeks and applied a cost model to determine potential savings of delaying delivery. RESULTS: A total of 1,538 pregnancies were analyzed. Risk of NICU admission declined significantly with each advancing week (by > 50%, P <.05). NICU length of stay and total nursery costs decreased significantly between weeks 35 and 36 and weeks 34 and 35. Need for ventilatory assistance increased significantly for infants admitted to the NICU between weeks 34 and 35. The incidence of respiratory distress syndrome decreased 49% between 35 and 36 weeks. CONCLUSION: Prolonging gestation 1 week beyond weeks 34 and 35 has a significant impact on improving neonatal outcome and decreasing associated costs. These factors should be considered when electing to deliver at 34 and 35 weeks.

The evidence regarding maintenance tocolysis.

Preterm delivery is a public health issue of major proportion. More than 12% of deliveries in the United States that occur at less than 37 weeks gestation preterm labor (PTL) represents the largest single reason for preterm birth (PTB). Attempts to prevent PTB have been unsuccessful. This paper of maintenance tocolytic therapy will examine the efficacy and safety of the drugs, both oral and subcutaneous, which have been utilized for prolongation of pregnancy following successful arrest of a documented episode of acute preterm labor. The evidence for oral tocolytics as maintenance therapy as well as parenteral medications for such patients is offered. Finally, the effects in the United States of the Food and Drug Administration (FDA) action on such medications are reported.

The medical and legal aspects of maternal mortality.

Sudden unexpected changes in the life of a family create many different emotions in various family members. The death of a young woman during or after her pregnancy is especially difficult because of the strain it places on family dynamics. One of the consequences is that there is, commonly, a newborn, and perhaps other children, without a mother and caregiver. In families that relied on both parents working, there are financial hardships imposed by the death. There is the emotional void that is felt by her partner, parents, sisters, brothers, and extended family. This extreme stress leads to questions about the death that need to be addressed by the health care providers. If the anger that is part of the grieving process is not adequately resolved, healing cannot occur. It is then that the family may pursue the legal process to help obtain answers about what happened and, more importantly, why it happened to their loved one.

Umbilical artery aneurysm.

BACKGROUND: Umbilical artery aneurysm is a rare condition associated with increased risk for aneuploidy and fetal demise. CASE: We report a case of umbilical artery aneurysm discovered at 27 weeks of gestation in one fetus of a dichorionic, diamniotic twin pregnancy. The patient was hospitalized to monitor for expansion of the aneurysm. Corticosteroids were administered, and, after genetic amniocentesis revealed a normal karyotype, cesarean delivery was performed at 28 2/7 weeks of gestation. Pathologic examination confirmed an umbilical artery aneurysm in the cord of the affected fetus. CONCLUSION: Given the high incidence of aneuploidy associated with umbilical artery aneurysm, it is important to consider karyotype analysis of the affected fetus. If a normal karyotype is identified, early delivery may be warranted to decrease the risk of fetal demise.