Considerations for liver transplantation in deoxyguanosine kinase deficiency: A case series and review of the literature.

BACKGROUND: Deoxyguanosine kinase (DGUOK) deficiency is a rare mitochondrial disorder characterized by early onset liver failure and varying degrees of neurologic dysfunction. Patients typically present during infancy with progressive hepatic dysfunction leading to liver failure, which can precede neurologic deterioration. Outcomes posttransplantation are historically worse than average and the role of liver transplantation remains controversial. These factors, in combination with the increasing number of patients being diagnosed via molecular genetic testing, may impede waitlist access. METHODS: We report our single-center experience with three patients with DGUOK deficiency, all of whom were considered for transplant. We review the current literature regarding management and discuss the role of liver transplantation in DGUOK deficiency-associated liver failure. RESULTS: Two patients presented with hypoglycemia, conjugated hyperbilirubinemia, and lactic acidosis within the first week of life, were diagnosed with DGUOK deficiency prior to 2 months of age and had severe neurologic involvement. The third patient presented in later infancy was diagnosed with DGUOK deficiency at 18 months of age and had minimal neurologic involvement. All three patients were considered for transplant, though only two patients were listed. All three died from complications of end-stage liver failure prior to liver transplantation between the ages of 5-20 months. CONCLUSION: Selection for liver transplantation in DGUOK deficiency is complex, requiring a multidisciplinary team approach. Recent data suggest that liver transplantation can be successful in select patients with absent or mild neurologic manifestations. National databases reporting long-term outcomes posttransplantation are needed.

Sirolimus for management of GI bleeding in blue rubber bleb nevus syndrome: A case series.

Blue rubber bleb nevus syndrome (BRBNS) commonly presents with anemia from bleeding gastrointestinal (GI) vascular malformations. Management is highly variable, as no consensus guidelines for medical treatment currently exist. Sirolimus has been used in BRBNS to decrease GI bleeding and seems well tolerated, though questions remain regarding dosing, duration of therapy, and adverse effects. Here, we report our single-center experience of four pediatric patients with BRBNS who were successfully treated with sirolimus and review the existing literature regarding sirolimus for treatment of GI bleeding in BRBNS. Further prospective studies are needed to establish optimal dosage, drug monitoring, and duration.

Potent and Broad Inhibition of HIV-1 by a Peptide from the gp41 Heptad Repeat-2 Domain Conjugated to the CXCR4 Amino Terminus.

HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4. C34-conjugated coreceptors were expressed on the surface of T cell lines and primary CD4 T cells, retained the ability to mediate chemotaxis in response to cognate chemokines, and were highly resistant to HIV-1 utilization for entry. Notably, C34-conjugated CCR5 and CXCR4 each exhibited potent and broad inhibition of HIV-1 isolates from diverse clades irrespective of tropism (i.e., each could inhibit R5, X4 and dual-tropic isolates). This inhibition was highly specific and dependent on positioning of the peptide, as HIV-1 infection was poorly inhibited when C34 was conjugated to the amino terminus of CD4. C34-conjugated coreceptors could also inhibit HIV-1 isolates that were resistant to the soluble HR2 peptide inhibitor, enfuvirtide. When introduced into primary cells, CD4 T cells expressing C34-conjugated coreceptors exhibited physiologic responses to T cell activation while inhibiting diverse HIV-1 isolates, and cells containing C34-conjugated CXCR4 expanded during HIV-1 infection in vitro and in a humanized mouse model. Notably, the C34-conjugated peptide exerted greater HIV-1 inhibition when conjugated to CXCR4 than to CCR5. Thus, antiviral effects of HR2 peptides can be specifically directed to the site of viral entry where they provide potent and broad inhibition of HIV-1. This approach to engineer HIV-1 resistance in functional CD4 T cells may provide a novel cell-based therapeutic for controlling HIV infection in humans.

Randomized controlled trial of belladonna and opiate suppository during intravesical onabotulinum toxin A injection.

BACKGROUND: Intravesical injection with onabotulinum toxin A injection can be performed in-office under local anesthesia. Rectally administered pain medication presents a potentially feasible and previously uninvestigated adjunct to office-based anesthesia protocols. OBJECTIVE: The primary aim of this study was to determine whether adding a belladonna and opiate suppository to standard lidocaine instillation resulted in reduction of bladder injection pain during onabotulinum toxin A injection procedure. STUDY DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study of patients undergoing onabotulinum toxin A bladder injection at a single clinic. Patients age ≥18 years, who met clinical criteria for invasive treatment of refractory urinary symptoms, had previously documented postvoid residual volumes <150 mL, and elected for in-office intravesical onabotulinum toxin A injection were eligible to participate. Participants were randomized by computer-generated block randomization to receive a belladonna and opiate (belladonna alkaloid with morphine 16.2/7.5 mg) or placebo suppository. Suppositories were placed immediately prior to lidocaine-based anesthesia, which all participants received. All participants underwent a standardized injection procedure using the same rigid cystoscope, needle type, and injection pattern (20 injections total). A 0-10 numeric rating scale was used to assess pain intensity before anesthesia and suppository, 40 minutes after administration of anesthesia and suppository, after first 10 bladder injections, and immediately after completion of 20 injections. Pain increase during procedure was calculated using the difference between score 40 minutes after administration of anesthesia and suppository and score after first 10 bladder injections. Postvoid residual were measured immediately postprocedure and 2 weeks later. Patient satisfaction with pain control was measured using a Likert scale. Our primary outcome was change in pain level from anesthetic baseline to midprocedure (score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository). A final sample size of 26 patients was needed to have 80% power (alpha = 0.05) to detect a 50% reduction in bladder injection pain during the procedure as defined by our primary outcome. An intent-to-treat approach was used for all analyses. RESULTS: In all, 26 participants were enrolled and randomized with 13 in each study arm. Participants in the treatment group were slightly older than in the placebo group (P = .05); there were no statistically significant differences in medical comorbidities. Median score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository for the placebo group and treatment group was 4 (range 1-10) and 5 (range 0,9), respectively (P = .94). Median scores immediately after completion of 20 injections for the placebo group and treatment group were 3 (range 0-10) and 2 (range 0,8), respectively (P = .29). There were no significant differences in preinjection pain scores reported before anesthesia and suppository and at 40 minutes after administration of anesthesia and suppository. Postprocedure postvoid residual >200 mL was noted in 5 (38%) of the placebo group and 3 (23%) of the treatment group (P = .67). Two-week postprocedure postvoid residual >200 mL was noted in 3 (25%) of the placebo group and 2 (15%) of the treatment group (P = .64) for an overall rate of 20%. Eleven (84%) participants in each group reported being "mostly satisfied" or "very much satisfied" with pain control. CONCLUSION: Belladonna and opiate suppository use did not significantly reduce bladder injection pain, or increase risk of urinary retention immediately postprocedure or 2 weeks later. Satisfaction with pain control among onabotulinum toxin A injection patients is high.

Pioneer baby: suggestions for pre- and postnatal health promotion programs from rural English and Spanish-speaking pregnant and postpartum women.

In the United States, more than 9 million rural women (15-44 years old) experience limited access and delivery of reproductive healthcare services. Rurality coupled with lower socio-economic status are associated with increased maternal and neonatal morbidity and mortality. The purpose of this qualitative study was to gain in-depth information from underserved English- and Spanish-speaking pregnant and postpartum rural women on what they would value in a health promotion program. Three focus group sessions were conducted exploring four domains: (1) physical activity, (2) dietary habits, (3) fetal movement/kick counts, and (4) breastfeeding and other support resources. Five overarching themes were observed across domains, with the following health promotion needs: (1) information on safe exercises, (2) advice on healthy food and drink, (3) breastfeeding support, (4) guidance on counting fetal movement, and (5) self- and peer-education. Study findings will inform intervention programming that aims to improve pregnancy and birth outcomes.

Long- but not short-term estradiol treatment induces renal damage in midlife ovariectomized Long-Evans rats.

Clinical recommendations limit menopausal hormone therapy to a few years, yet the impact of a shorter treatment duration on cardiovascular health is unknown. We hypothesized that both short- and long-term estradiol (E2) treatment exerts positive and lasting effects on blood pressure, vascular reactivity, and renal health. This study was designed to mimic midlife menopause, followed by E2 treatment, that either followed or exceeded the current clinical recommendations. Female Long-Evans retired breeders were ovariectomized (OVX) at 11 mo of age and randomized into three groups: 80-day (80d) vehicle (Veh>Veh), 40-day (40d) E2 + 40d vehicle (E2>Veh), and 80d E2 (E2>E2). In comparison to Veh>Veh, both the E2>Veh and E2>E2 groups had lower systolic blood pressure and enhanced mesenteric relaxation in response to estrogen receptor-α stimulation. Despite the reduced blood pressure, E2>E2 induced renal and cardiac hypertrophy, reduced glomerular filtration, and increased proteinuria. Interestingly, kidneys from E2>Veh rats had significantly fewer tubular casts than both of the other groups. In conclusion, long-term E2 lowered blood pressure but exerted detrimental effects on kidney health in midlife OVX Long-Evans rats, whereas short-term E2 lowered blood pressure and reduced renal damage. These findings highlight that the duration of hormone therapy may be an important factor for renal health in aging postmenopausal women.

Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection.

HIV-1 entry into CD4(+) T cells requires binding of the virus to CD4 followed by engagement of either the C-C chemokine receptor 5 (CCR5) or C-X-C chemokine receptor 4 (CXCR4) coreceptor. Pharmacologic blockade or genetic inactivation of either coreceptor protects cells from infection by viruses that exclusively use the targeted coreceptor. We have used zinc-finger nucleases to drive the simultaneous genetic modification of both ccr5 and cxcr4 in primary human CD4(+) T cells. These gene-modified cells proliferated normally and were resistant to both CCR5- and CXCR4-using HIV-1 in vitro. When introduced into a humanized mouse model of HIV-1 infection, these coreceptor negative cells engraft and traffic normally, and are protected from infection with CCR5- and CXCR4-using HIV-1 strains. These data suggest that simultaneous disruption of the HIV coreceptors may provide a useful approach for the long-term, drug-free treatment of established HIV-1 infections.

Alterations in the fecal microbiota in patients with advanced cystic fibrosis liver disease after 6 months of elexacaftor/tezacaftor/ivacaftor.

BACKGROUND: Cystic fibrosis associated liver disease (CFLD) carries a significant disease burden with no effective preventive therapies. According to the gut-liver axis hypothesis for CFLD pathogenesis, dysbiosis and increased intestinal inflammation and permeability permit pathogenic bacterial translocation into the portal circulation, leading to hepatic inflammation and fibrosis. Evaluating the effect of CFTR (cystic fibrosis transmembrane conductance regulator) modulation with elexacaftor/tezacaftor/ivacaftor (ETI) may help determine the role of CFTR in CFLD and increase understanding of CFLD pathogenesis, which is critical for developing therapies. We aimed to characterize the fecal microbiota in participants with CF with and without advanced CFLD (aCFLD) before and after ETI. METHODS: This is an ancillary analysis of stool samples from participants ages ≥12 y/o enrolled in PROMISE (NCT04038047). Included participants had aCFLD (cirrhosis with or without portal hypertension, or non-cirrhotic portal hypertension) or CF without liver disease (CFnoLD). Fecal microbiota were defined by shotgun metagenomic sequencing at baseline and 1 and 6 months post-ETI. RESULTS: We analyzed 93 samples from 34 participants (11 aCFLD and 23 CFnoLD). Compared to CFnoLD, aCFLD had significantly higher baseline relative abundances of potential pathogens Streptococcus salivarius and Veillonella parvula. Four of 11 aCFLD participants had an initially abnormal fecal calprotectin that normalized 6 months post-ETI, correlating with a significant decrease in S. salivarius and a trend towards decreasing V. parvula. CONCLUSIONS: These results support an association between dysbiosis and intestinal inflammation in CFLD with improvements in both post-ETI, lending further support to the gut-liver axis in aCFLD.

The role of hair follicle nestin-expressing stem cells during whisker sensory-nerve growth in long-term 3D culture.

We have previously reported that nestin-expressing hair follicle stem cells can differentiate into neurons, Schwann cells, and other cell types. In the present study, vibrissa hair follicles, including their sensory nerve stump, were excised from transgenic mice in which the nestin promoter drives green fluorescent protein (ND-GFP mice), and were placed in 3D histoculture supported by Gelfoam®. ß-III tubulin-positive fibers, consisting of ND-GFP-expressing cells, extended up to 500 µm from the whisker nerve stump in histoculture. The growing fibers had growth cones on their tips expressing F-actin. These findings indicate that ß-III tubulin-positive fibers elongating from the whisker follicle sensory nerve stump were growing axons. The growing whisker sensory nerve was highly enriched in ND-GFP cells which appeared to play a major role in its elongation and interaction with other nerves in 3D culture, including the sciatic nerve, the trigeminal nerve, and the trigeminal nerve ganglion. The results of the present report suggest a major function of the nestin-expressing stem cells in the hair follicle is for growth of the follicle sensory nerve.

Cystic Fibrosis-Associated Gastrointestinal Disease in Neonates.

See Bonus NeoBriefs videos and downloadable teaching slides Gastrointestinal complications of cystic fibrosis (CF) are often the earliest manifestations of disease and contribute to significant morbidity and mortality. Early diagnosis of CF is paramount, as early intervention has been associated with improved long-term pulmonary and nutritional outcomes. In this review, we describe common gastrointestinal, pancreatic, hepatic, and nutritional manifestations of CF in neonates to aid clinicians in diagnosing and managing the earliest gastrointestinal manifestations of CF. Furthermore, we discuss how the use of CFTR-targeted therapies by pregnant and/or breastfeeding persons may affect CF diagnosis in newborns and their potential impact on halting or reversing CF disease progression.

In vitro recombinants of antibiotic-resistant Chlamydia trachomatis strains have statistically more breakpoints than clinical recombinants for the same sequenced loci and exhibit selection at unexpected loci.

Lateral gene transfer (LGT) is essential for generating between-strain genomic recombinants of Chlamydia trachomatis to facilitate the organism's evolution. Because there is no reliable laboratory-based gene transfer system for C. trachomatis, in vitro generation of recombinants from antibiotic-resistant strains is being used to study LGT. However, selection pressures imposed on in vitro recombinants likely affect statistical properties of recombination relative to naturally occurring clinical recombinants, including prevalence at particular loci. We examined multiple loci for 16 in vitro-derived recombinants of ofloxacin- and rifampin-resistant L(1) and D strains, respectively, grown with both antibiotics, and compared these with the same sequenced loci among 11 clinical recombinants. Breakpoints and recombination frequency were examined using phylogenetics, bioinformatics, and statistics. In vitro and clinical isolates clustered perfectly into two groups, without misclassification, using Ward's minimum variance based on breakpoint data. As expected, gyrA (confers ofloxacin resistance) and rpoB (confers rifampin resistance) had significantly more breakpoints among in vitro recombinants than among clinical recombinants (P < 0.0001 and P = 0.02, respectively, using the Wilcoxon rank sum test). Unexpectedly, trpA also had significantly more breakpoints for in vitro recombinants (P < 0.0001). There was also significant selection at other loci. The strongest bias was for ompA in strain D (P = 3.3 × 10(-8)). Our results indicate that the in vitro model differs statistically from natural recombination events. Additional genomic studies are needed to determine the factors responsible for the observed selection biases at unexpected loci and whether these are important for LGT to inform approaches for genetically manipulating C. trachomatis.

The bulge area is the origin of nestin-expressing pluripotent stem cells of the hair follicle.

Nestin-expressing pluripotent stem cells have been found both in the bulge area (BA) as well as the dermal papilla (DP). Nestin-expressing stem cells of both the BA and DP have been previously shown to be able to form neurons and other non-follicle cell types. The nestin-expressing stem cells from the DP have been termed skin precursor or SKP cells. Both nestin-expressing DP and BA cells have been previously shown to effect repair of the injured spinal cord and peripheral nerve, with the BA being the greater and more constant source of the stem cells. The BA contains nestin-expressing stem cells throughout the hair cycle, whereas nestin-expressing dermal papillae stem cells were found in early and mid-anagen only. Our previous studies have shown that the nestin-expressing stem cells in the BA and DP have similar morphological features. The cells from both regions have a small body diameter of approximately 7 µm with long extrusions, as shown by 2-photon imaging. In the present study, using 2-photon imaging of whisker follicles from transgenic mice expressing nestin-driven green fluorescent protein (ND-GFP), we demonstrate that the BA is the source of the nestin-expressing stem cells of the hair follicle. The nestin-expressing stem cells migrate from the BA to the DP as well as into the surrounding skin tissues including the epidermis, and during wound healing, suggesting that the BA may be the source of the stem cells of the skin itself.

G Protein-Coupled Estrogen Receptor Protects From Angiotensin II-Induced Increases in Pulse Pressure and Oxidative Stress.

Our previous work showed that the G protein-coupled estrogen receptor (GPER) is protective in the vasculature and kidneys during angiotensin (Ang) II-dependent hypertension by inhibiting oxidative stress. The goal of the current study was to assess the impact of GPER deletion on sex differences in Ang II-induced hypertension and oxidative stress. Male and female wildtype and GPER knockout mice were implanted with radiotelemetry probes for measurement of baseline blood pressure before infusion of Ang II (700 ng/kg/min) for 2 weeks. Mean arterial pressure was increased to the same extent in all groups, but female wildtype mice were protected from Ang II-induced increases in pulse pressure, aortic wall thickness, and Nox4 mRNA. In vitro studies using vascular smooth muscle cells found that pre-treatment with the GPER agonist G-1 inhibited Ang II-induced ROS and NADP/NADPH. Ang II increased while G-1 decreased Nox4 mRNA and protein. The effects of Ang II were blocked by losartan and Nox4 siRNA, while the effects of G-1 were inhibited by adenylyl cyclase inhibition and mimicked by phosphodiesterase inhibition. We conclude that during conditions of elevated Ang II, GPER via the cAMP pathway suppresses Nox4 transcription to limit ROS production and prevent arterial stiffening. Taken together with our previous work, this study provides insight into how acute estrogen signaling via GPER provides cardiovascular protection during Ang II hypertension and potentially other diseases characterized by increased oxidative stress.

Nerve Growth and Interaction in Gelfoam® Histoculture: A Nervous System Organoid.

Nestin-expressing hair follicle-associated pluripotent (HAP) stem cells reside mainly in the bulge area (BA) of the hair follicle but also in the dermal papilla (DP). The BA appears to be origin of HAP stem cells. Long-term Gelfoam® histoculture was established of whiskers isolated from transgenic mice, in which there is nestin-driven green fluorescent protein (ND-GFP). HAP stem cells trafficked from the BA toward the DP area and extensively grew out onto Gelfoam® forming nerve-like structures. These fibers express the neuron marker ß-III tubulin-positive fibers and consisted of ND-GFP-expressing cells and extended up to 500 mm from the whisker nerve stump in Gelfoam® histoculture. The growing fibers had growth cones on their tips expressing F-actin indicating that the fibers were growing axons. HAP stem cell proliferation resulted in elongation of the follicle nerve and interaction with other nerves in 3D Gelfoam® histoculture, including the sciatic nerve, trigeminal nerve, and trigeminal nerve ganglion.

Management of Hypertension on the Labor and Delivery Unit: Delivering Care in the Era of Protocols and Algorithms.

INTRODUCTION: Preeclampsia with severe hypertension, which occurs in 5% to 8% of pregnancies, is a leading cause of maternal and perinatal morbidity and mortality in the US. Early recognition and treatment of hypertensive crises can significantly reduce poor outcomes. A protocol to ensure prompt treatment with antihypertensive medication (intravenous labetalol) was implemented at our institution. OBJECTIVE: To determine adherence to this protocol on the Labor and Delivery Unit. DESIGN: Retrospective chart review was performed for patients admitted to the Labor and Delivery Unit between April 2015 and June 2015. Charts were reviewed if the patient had a diagnosis of chronic hypertension, gestational hypertension, superimposed preeclampsia, preeclampsia with severe features, eclampsia, or stroke in pregnancy. Only patients with confirmed severe blood pressures, in which the protocol would be initiated, were included in the final analysis. MAIN OUTCOME MEASURE: Overall compliance with the entire protocol. RESULTS: Of 178 cases reviewed, 58 (32.6%) had confirmed severe blood pressures. Most patients (n = 46, 79.3%) received a diagnosis of preeclampsia with severe features, and most delivered via cesarean delivery (n = 38, 65.5%). No cases were compliant with the entire labetalol protocol. Of 58 patients, 2 (3.5) adequately repeated a confirmation blood pressure within 5 minutes, and 34 (58.6%) were adequately treated with intravenous labetalol according to protocol requirements. CONCLUSION: Labetalol treatment was appropriately initiated in many cases; however, protocol adherence could greatly improve. Potential factors affecting protocol compliance include shift changes, communication issues, and conflicting protocols. Institutions should review protocol compliance to improve care.

Implementing a Protocol to Optimize Detection of Chromosome Abnormalities in Cases of Miscarriage or Stillbirth at a Midwestern Teaching Hospital.

CONTEXT: Results from chromosome testing after spontaneous abortion (SAB) or intrauterine fetal demise (IUFD) are useful in patient counseling; however, results can be inconclusive when cell cultures for chromosomes are unable to grow from products of conception. Chromosomal microarray analysis (CMA) can analyze DNA from nonviable fetal tissue. OBJECTIVE: To examine whether establishing a genetic testing protocol for karyotype and CMA on SAB and IUFD tissues increases diagnostic yield. DESIGN: A retrospective chart review was conducted in cases of SAB or IUFD when karyotyping and/or CMA was requested, comparing two periods: Preprotocol and postprotocol implementation. MAIN OUTCOME MEASURES: Diagnostic yield was compared by using the number of determinate test results in the preprotocol and postprotocol study periods. A case was considered to have indeterminate results when the final genetic test results reported no fetal tissue or no cell culture growth. RESULTS: A total of 55 preprotocol and 52 postprotocol patients were analyzed. Diagnostic yield increased from 72.7% to 94.2% after implementation of the genetic testing protocol (p = 0.0004). Indeterminate results occurred more frequently before compared with after implementation of the protocol. CONCLUSION: A protocol of reflexing to CMA or proceeding directly with CMA gives a higher diagnostic yield in the genetic evaluation of SAB or IUFD. Institutions should consider implementing a genetic testing protocol to improve diagnostic yield. Our study results emphasize the importance of proceeding directly to microarray analysis and give support for current clinical recommendations for genetic testing after fetal demise.

Elastic Abdominal Binders Reduce Cesarean Pain Postoperatively: A Randomized Controlled Pilot Trial.

BACKGROUND: A potential non-pharmacologic way to reduce postoperative pain and bleeding is using an abdominal binder during postoperative recovery. This study aims to determine the effect an elastic abdominal binder has on postoperative pain and hemorrhage after cesarean delivery. METHODS: A randomized, single-site, pilot trial was conducted at two prenatal care clinics and an academic hospital in Kansas. Beginning in April 2013, 60 patients were enrolled if delivering via cesarean. Participants were randomized to receive an abdominal binder or to a control group (did not use binder). Pain levels were reported by questionnaire one day after surgery using a 0 to 10 scale, with 10 being the worst pain. Patient characteristics and blood loss were assessed by medical record review. RESULTS: Of the 56 patients completing the study, 29 (51.8%) were randomized to the binder group and 27 (48.2%) were randomized to the control group. The binder group reported significantly lower pain score (p = 0.019) and average pain score (p = 0.024). There was no difference in body mass index, age, previous surgery, infant birth weight, estimated blood loss, and average dose of pain medication during the first 24 hours after the cesarean delivery between the two groups. There was no difference in pre- and post-operative hemoglobin levels by treatment group (p = 0.406). CONCLUSIONS: Abdominal binders may be associated with improved postoperative pain scores but did not affect postoperative hemorrhage.

Appropriate Use of Prophylactic Antibiotic Agents in Gynecologic Surgeries at a Midwestern Teaching Hospital.

BACKGROUND: The purpose of this study was to establish compliance with guidelines published by the American College of Obstetricians and Gynecologists (ACOG) regarding prophylactic antibiotic use in gynecologic surgery at our institution, and define areas of improvement to promote antibiotic stewardship. PATIENTS AND METHODS: This was a retrospective cohort study at a single, large tertiary care and teaching hospital in Kansas. Patients who underwent inpatient or outpatient gynecologic surgery during 2013 were included. Based on published guidelines for prophylactic antibiotic agents for gynecologic surgery by ACOG, procedures were classified as antibiotic-indicated or antibiotic-not-indicated. Chi-square and Fisher exact test analysis were used to identify factors associated with antibiotic use. RESULTS: Of the 1,735 cases eligible for inclusion, 1,045 (60.2%) had antibiotic agents recommended per guidelines, and appropriate antibiotic agents were given in 1,031 (98.7%) of those cases. In 690 (39.8%) cases, prophylactic antibiotics were either not recommended or the guidelines are not well defined. Of the 690 cases without indication for antibiotic agents, 394 (57.1%) received prophylactic antibiotic agents. Agreement with guidelines varied substantially based on patient age, race, insurance status, area of residence, and if the procedure was a resident case (p < 0.05). Myomectomy, laparoscopy, and ectopic pregnancy procedures received antibiotic agents against recommendations 96.3%, 75.6%, and 45.5% of the time, respectively. CONCLUSIONS: Peri-operative antibiotics are often administered inappropriately to women undergoing gynecologic surgeries for which published guidelines are not well defined. Future studies need to identify strategies to reduce antibiotic use in surgical procedures unlikely to benefit from prophylaxis.

Prescribing Bioidentical Menopausal Hormone Therapy: A Survey of Physician Views and Practices.

BACKGROUND: It is estimated that 1-2.5 million U.S. women use compounded bioidentical menopausal hormone therapy (MHT). However, the proportion of American physicians prescribing compounded bioidentical hormones remains unknown. This study aims to evaluate obstetrician-gynecologists' (OB/GYNs) and family medicine physicians' decisions reflected in prescribing practices of MHT in Kansas, and level of agreement with the American College of Obstetricians and Gynecologists (ACOG) recommendations. METHODS: An Internet-based 38-item survey was electronically disseminated to OB/GYNs and family medicine physicians identified through the Kansas State Board of Healing Arts licensure list. RESULTS: Out of 1349 physicians contacted, 164 (12.2%) responded to the survey. There were 128 (9.5%) responses included in the final analysis. In the past year, 96.1% (123/128) of respondents prescribed conventional MHT, 93.0% (119/128) prescribed Food and Drug Administration (FDA)-approved bioidentical MHT, and 66.1% (84/127) prescribed compounded bioidentical MHT. Of factors influencing MHT-prescribing practices, FDA regulation was not important to 16.7% (21/126) of physicians, whereas customization was important to 68.5% (87/127). There was a significant difference between specialties, 37.7% of OB/GYNs compared with 56.9% of family medicine physicians, regarding the ACOG statement that "patients should be counseled that conventional MHT is more appropriate than compounded preparations" (p = 0.031). Respondents disagreed with ACOG regarding the statements that "the practice of compounding makes it difficult to identify the active agent responsible for various effects" (41.0% of OB/GYNs and 34.8% of family medicine physicians) and "the practice of custom blending commercially available drug products lacks both a strong biological rationale and medical evidence for effectiveness" (36.1% of OB/GYNs and 37.9% of family medicine physicians). CONCLUSIONS: Prescribing practices for MHT vary between specialties. This study identifies a meaningful level of disagreement with ACOG recommendations regarding prescription of compounded rather than FDA-approved MHT. Further research is needed to better understand this level of discordance.

Nestin-Expressing Hair-Follicle-Associated Pluripotent (HAP) Stem Cells Promote Whisker Sensory-Nerve Growth in Long-Term 3D-Gelfoam® Histoculture.

Mouse whiskers containing hair-follicle-associated pluripotent (HAP) stem cells, from nestin-driven green fluorescent protein (ND-GFP) transgenic mice, were placed in 3D histoculture supported by Gelfoam(®). ß-III tubulin-positive fibers, consisting of ND-GFP-expressing HAP stem cells, extended up to 500 mm from the whisker nerve stump in histoculture. The growing fibers had growth cones on their tips expressing F-actin indicating they were growing axons. The growing whisker sensory nerve was highly enriched in ND-GFP HAP stem cells which appeared to play a major role in its elongation and interaction with other nerves placed in 3D culture, including the sciatic nerve, the trigeminal nerve, and the trigeminal nerve ganglion. The results suggested that a major function of HAP stem cells in the hair follicle is for growth of the hair follicle sensory nerve.