Mean Basal Levels Research Articles

7381 Overexpression of Makorin Ring Finger Protein 3 in the Arcuate Nucleus of Postpubertal Female Mice Impacts Neurokinin B and Kisspeptin Co-Expressing Neurons

Abstract Disclosure: S.A. Roberts: None. A. Fontes: None. S. Blau: None. M. Magnuson: None. K.M. McKnight: None. M. Sena-Esteves: None. R.S. Carroll: None. U.B. Kaiser: None. Background: Makorin ring finger protein 3 (MKRN3), an upstream inhibitor of GnRH release, is an important regulator of the age of menarche. Loss-of-function mutations in MKRN3 are the most common genetic etiology of central precocious puberty. However, its potential role in delayed puberty or hypogonadism is not well defined. In mice, expression of Mkrn3 in the hypothalamic arcuate nucleus (ARC), where kisspeptin, neurokinin B and dynorphin (KNDy) co-expressing neurons are located, is high early in life and declines before pubertal onset. Neonatal hypothalamic overexpression of Mkrn3 leads to delayed puberty in female mice and decreased neurokinin B (NKB) and kisspeptin protein levels in the ARC peripubertally. Conversely, Mkrn3-deficient peripubertal mice exhibit increased NKB protein levels in the ARC. We hypothesized that Mkrn3 overexpression in the ARC of postpubertal female mice would result in suppression of the HPG axis, manifested as hypogonadotropic hypogonadism. Methods and Results: Twelve week old adult wild type female mice were injected stereotaxically into the ARC with a novel adeno-associated virus overexpressing Mkrn3 (AAV-Mkrn3-IRES-EGFP; denoted AAV-Mkrn3) or a control virus (AAV-EGFP). Mean body weight did not differ between groups post-injection. AAV-Mkrn3 injected mice spent significantly more time (62.7%) in diestrus three to six weeks post-injection compared to controls (41.3%; P<0.01). Eight weeks post-injection, gonad-intact females were injected with an NKB receptor (NK3R) agonist, senktide (5 nmol or 10 nmol ip). AAV-Mkrn3 mice had a decreased peak LH response twenty minutes post-injection, compared to controls (P<0.001) at both doses. Peak LH levels were also reduced in response to senktide (5 nmol ip) in ovariectomized and estradiol capsule replaced (OVX+E2) AAV-Mkrn3 injected females, compared to controls (P< 0.001). In contrast, in both gonad-intact and OVX+E2 female mice, kisspeptin-10 (1 nmol ip) resulted in similar peak serum LH levels in AAV-Mkrn3 injected mice compared to controls. Immunohistochemistry in the ARC of intact and OVX+E2 AAV-Mkrn3 injected females showed significantly decreased NKB protein expression in AAV-Mkrn3 mice compared to controls. In response to OVX, serum LH levels increased similarly between AAV-Mkrn3 and control-injected mice. LH pulsatility in OVX females, assessed over 3 hours, showed that mean basal LH levels, number of pulses, pulse amplitude and area under the curve did not differ significantly between groups. Conclusions: These findings indicate that MKRN3 can exert inhibitory effects on the reproductive axis in female mice beyond the juvenile period, which has implications as a potential therapeutic target. The blunted response to senktide, and decreased NKB protein levels in the setting of Mkrn3 overexpression, further supports the impact of Mkrn3 on the neuropeptides and/or receptors of KNDy neurons. Presentation: 6/2/2024

Sarscov-2 Antibody Response to COVID-19 MRNA Vaccine in 2024 among Health Care Workers Working in one Selected Public Hospital from Myanmar

Background: The health care workers have been handling with patients who may have symptomatic or asymptomatic coronavirus disease (COVID-19) since 2019. SARS-CoV-2 virus has been producing several variants. (Comirnaty) COVID-19 mRNA Vaccine (nucleoside modified) tozinameran was available in Myanmar in January 2024. This study aimed to assess changes in SARSCoV-2 antibody level in health care workers (HCW) following COVID-19 mRNA Vaccine and to determine the factors influencing antibody response. Methods: An analytic study was conducted in Defense Services General Hospital (1,000 Bedded) in Myanmar in 2024. SARSCoV-2 antibody level was measured twice; prior to COVID-19 mRNA Vaccine and 70 days after vaccination. Data were collected by using standardized forms and analysis was done. Results: A total of 99 HCW were included. All HCW had anti-Spike antibody prior to COVID-19 mRNA Vaccine (basal level); and the minimum level was 904 U/mL. Minimum antibody level as well as mean antibody level became double on Day ‘70’ after vaccination. Mean basal anti-Spike antibody level was 4,195.04 ± 2898.20 U/mL; it rose to 9,115.31± 3518.89 U/mL on Day ‘70’. Female had higher basal anti-Spike antibody level as well as the antibody level on Day ‘70’ than male; the basal level was 7,365 ± 5,460.97 U/mL and 3,878.04 ± 2,334.64 U/mL; and, ‘Day 70’ level was 10,404.67±4,725.860 U/mL and 8,894.85±3,487.904 U/mL respectively. HCW aged over 40 years had higher basal anti-Spike antibody level than that of under 40 years; 5,634.42 ± 3,801.08 U/mL and 3,538.85 ± 2,102.61 U/mL respectively. However, on Day ‘70’, younger age group had better response; 9,564.37±3,265.608 U/mL in younger age group and 7,864.55±4,098.874 U/mL in older age group. Antibody level on ‘Day 70’ was higher in HCW without comorbid disease and HCW with COVID symptoms at the time of vaccination. History of COVID-19 in past 6 months to 1 year prior to COVID-19 mRNA Vaccine did not influence the antibody response. The basal antibody level was lowest in underweight group (2,327.00±668.00 U/mL) and highest in overweight group 5,019.26±3,485.20 U/mL. On ‘Day 70’, the highest level 9,225.03±3,416.99 U/mL was recorded in normal weight group; it was followed by overweight group. Conclusions: All HCW had had acquired immunity to SARSCoV-2 virus in January 2024. Their SARSCoV-2 antibody level became double on Day ‘70’ after one dose of (Comirnaty) COVID-19 mRNA Vaccine (nucleoside modified) tozinameran. Younger age group, female, HCW without comorbid disease, those with normal weight and overweight group, and presence of COVID symptoms at the time of vaccination had better antibody response. Antibody response was not related with history of COVID-19 in past 6 months to 1 year. One dose of COVID-19 mRNA Vaccine was 100% effective in promoting anti-Spike antibody.

Serum androgen dynamics in young women aged 18-40 treated with chemotherapy for breast cancer: an observational, multicentric, prospective study in France

Although the deleterious impact of chemotherapy regimen used to treat women of reproductive age with breast cancer on ovarian reserve has been extensively studied, hardly anything has been reported on the effect of these protocols on theca cell function and ovarian androgen secretion. The aim of this prospective multicentric cohort study was to describe serum levels of total testosterone and androstenedione during chemotherapy and 24-month follow-up in 250 patients <40 years treated for breast cancer. Mean basal levels of androstenedione and total testosterone at diagnosis were 1.68 ng/mL and 0.20 ng/mL respectively. No correlation with age was found. Serum levels of androstenedione and total testosterone rapidly decreased after chemotherapy completion, before slowly increasing and almost returning to basal levels in all patients during 2-year follow-up. In conclusion our study demonstrates a chemotherapy-induced alteration of ovarian thecal function, resulting in a significant decrease in serum androgen levels. This alteration of theca cell function adds to the well-known alteration of granulosa cell function, resulting in a global, but partly transient, ovarian failure in young women treated for breast cancer. These data bring new insight into ovarian physiology and emphasize the need for pre and post-treatment ovarian follow-up. Trial registration: ClinicalTrial.gov identifier NCT01114464

ASSOCIATION BETWEEN MATERNAL BASAL GLUCOSE LEVEL AND INTRAUTERINE GROWTH RESTRICTION: A COMPARATIVE CROSS-SECTIONAL STUDY

Background: Intrauterine life is the most pivotal period of development that determines vital outcomes in postnatal life. Diabetes Mellitus may lead to disturbed fetal growth and maternal vasculopathy resulting in placental insufficiency with subsequent development of intrauterine growth restriction (IUGR). This study aims to find an association between hyperglycemia and the risk of IUGR, comparing pregnancies with IUGR with those with adequate for gestational age pregnancies.&#x0D; Methods: This cross sectional study was conducted in Federal Post Graduate Medical Institute (FPGMI) from January 2015 to January 2016, including 106 pregnant women using non-probability convenient sampling technique. Participants were divided into two groups: Group A comprises of pregnant women with adequate for gestational age pregnancies (n=53) and groups B includes pregnant women with intrauterine growth restricted pregnancies (n=53). Random blood sugar level was estimated by glucose/oxidase test and IUGR was confirmed by ultrasonography at 28-35 weeks of gestation. Shapiro-Wilk test was used to examine data normality and independent t-test was used to compare statistically significant difference. A p- value of &lt;0.05 was considered significant.&#x0D; Results: Mean basal sugar level of group A was 98.9 ± 7.1 mg/dL and that of group B was 97.9 ± 6.0mg/dL. This mean difference was not statistically significant (p-value= 0.566).&#x0D; Conclusion: We found no statistically significant association between raised maternal basal glucose level and the occurrence of intrauterine growth restriction at 28-35 weeks of pregnancy.

Is this the end of intensified insulin therapy and obesity in light of updates with novel medicines?

Introduction: Modern times witness an increased prevalence of obesity and diabetes mellitus. While patients are offered a plan for blood glucose regulation, possible obesity issues, unfortunately, remain ignored. Blood glucose regulation inevitably deteriorates over time in diabetic patients that gradually gain weight.&#x0D; Material and Method: We recruited 42 diabetic patients who applied to our internal medicine outpatient clinic to investigate the impacts of two new generation therapies, sodium-glucose co-transporter-2 inhibitor (SGLT-2i) and glucagon-like peptide-1 receptor agonist (GLP1-RA), on weight. Six patients were excluded from follow-up for various reasons, and the study was finalized with 36 patients. The patients were followed up regarding body mass index (BMI), HbA1c levels, and insulin cessation or dose reduction.&#x0D; Results: We stopped insulin in 20 of 36 patients who started to receive SGLT-2i and GLP1-RA, while the insulin dose was reduced in the remaining patients. While the mean basal HbA1c level of the first group with insulin cessation was 9.13% (min-max: 6.4-14), it was recorded as 7.63% (min-max: 5, 2-10,8) in the sixth month of treatment modification (p &lt; 0.001). Despite a slight HbA1c increase in two patients, we concluded a significant decrease in HbA1c levels in 18 patients. Altogether, these 20 patients experienced an average of 1.5% HbA1c reduction.&#x0D; The findings also revealed that the mean basal BMI value (38.99 kg/m2; min-max: 33.2-43.4) among these 20 patients significantly decreased to 38.13 kg/m2 (0.86 kg/m2) in the sixth month of treatment modification. Among eight patients with reduced insulin and HbA1c level, the mean BMI value changed from 43.05 kg/m2 (min-max: 38.3-52.5) to 40.91 (min-max: 38.1-50) at the sixth-month follow-up. In this case, we may assert that losing weight has a positive impact on blood glucose regulation. However, it changed from 34.87 kg/m2 (min-max: 30.6-38.2) to 35.77 kg/m2 (min-max: 31. 8-39.1) among the other eight patients with reduced insulin but unreduced HbA1c.&#x0D; Conclusion: Overall, we believe that SGLT-2i and GLP1-RA, with significant benefits in both cardiovascular protection and weight control, would be more advantageous when used more frequently in obese patients without obvious contraindications since they rarely cause hypoglycemia and are easily tolerated

Pediatric Groin Surgeries: A Comparison of Analgesic Effects of Caudal Block and Inguinal Field Block Using Plain Bupivacaine.

There is a paucity of studies in the West African sub-region which have compared both the intraoperative and postoperative analgesic effects of caudal block and inguinal field block using plain bupivacaine in groin surgeries in children. The study aimed to compare the duration of analgesia and complications of caudal block and inguinal field block in pediatric groin surgeries. This was a prospective, double-blind randomized study conducted at a tertiary health institution in North Central, Nigeria, over a period of 6 months. A total of 74 children scheduled for day case groin surgeries for inguinal hernia, hydrocoele and palpable undescended testis were recruited into the study. The effectiveness of the analgesic effect was assessed by measuring serum cortisol levels before surgery (i.e. baseline at 8am), 5minutes after caudal block or inguinal field block, and 1-hour after surgery. Post-operative pain was determined using FLACC score (Face, Legs, Activity, Crying and Consolability) every 15 minutes till 6 hours after surgery when the patients were discharged home and the caregivers measured the patients' pain scores using the FLACC score every 1 hour to a maximum duration of 10 hours after surgery. Data obtained from the study was entered into the study proforma and analysed using IBM SPSS version 21.0. The P value was considered statistically significant at <0.05. A total of 74 patients were recruited for this study, with 68 males (91.9%) and 6 females (8.1%). The children's age range was 6 months to 7 years, with a mean age of 3.35 ± 1.90 years. The mean basal serum cortisol levels of the caudal block group and inguinal block group were 11.15 ± 5.38 µg/dL and 10.79 ± 4.92µg/d respectively (p-value = 0.767). Five minutes after caudal block, the mean serum cortisol level was 10.50 ± 5.39µg/dL while inguinal field block was 10.63 ± 4.68µg/dL (p-value = 0.288). The mean serum cortisol level obtained one hour after each procedure was 9.34 ± 4.05 µg/dL for the caudal block group and 10.00 ± 3.56 µg/dL in the inguinal field block group with p-value = 0.275.Using the FLACC score, the mean duration of analgesia in caudal block group was 372.00 ± 71.55 minutes and was inguinal field block group was 387.43 ± 62.65 minutes with a p-value = 0.116. There was no anaesthetic technique related complications that was recorded in both caudal block group and inguinal group during the study period. This study demonstrated that caudal block and inguinal field block using plain bupivacaine provided comparable duration of analgesia in paediatric groin surgeries. Therefore, caudal block or inguinal field block using plain bupivacaine should be recommended for both intraoperative and postoperative analgesia in elective paediatric groin surgeries.

P-664 The effect of LH levels on the day of trigger on the oocyte retrieval and maturation rates in GnRH-antagonist cycles with an agonist trigger

Abstract Study question Are LH levels on day of trigger correlated with the number of oocytes retrieved and oocyte maturation rate in GnRH-antagonist cycles with an agonist trigger? Summary answer Low LH levels on the day of trigger were associated with a lower oocyte retrieval rate yet no correlation with oocyte maturation rates was found. What is known already The concept that a bolus of gonadotrophin-releasing hormone agonist (GnRHa) can replace human chorionic gonadotrophin (HCG) as a trigger of final oocyte maturation was introduced several years ago. GnRHa trigger offers important advantages including the prevention of ovarian hyperstimulation syndrome (OHSS) with the elicitation of an endogenous LH and FSH surge. Therefore, we sought to evaluate whether LH levels on the day of the trigger are associated with the efficacy of the trigger in eliciting endogenous LH surge and thereby influencing oocyte retrieval and oocyte maturation rates. Study design, size, duration This retrospective single center study included all GnRH antagonist cycles triggered with GnRHa trigger (Decapeptyl 0.2mg) performed at our IVF unit between July 2013 and December 2020. We studied the association between LH levels on the day of trigger and the number of oocytes retrieved. Additionally, we studied the effect of LH levels on oocyte maturation rates. Participants/materials, setting, methods All GnRH antagonist cycles triggered with GnRHa trigger were included. Data was acquired through individual review of medical records. Linear regression was used to study the correlation between LH levels and oocyte retrieval and maturation rates. Moreover, LH levels on day of trigger were divided ≤1 IU/L and &amp;gt; 1 IU/L to further investigate this correlation. The ratio between Basal LH and LH on day of trigger was investigated as well. Main results and the role of chance There were 211 GnRH antagonist cycles triggered with GnRH agonist trigger during the study period. The mean age of patients in the study group was 30.1±4.8 y/o, mean basal LH levels were - 6.8±3.4 IU/L, mean Basal FSH levels were - 6.7±1.9IU/L and the mean total dose of gonadotropin administered was 1633.4±680.6 Units. The mean E2 levels were 11,444±7018.5 pmol/L and the mean number of oocytes retrieved was 19.8±10.2. A correlation was found between lower LH levels on the day of trigger and the number of oocytes retrieved (p &amp;lt; 0.001). No correlation was found between LH levels on the day of trigger and oocyte maturation rates (p = 0.82). The ratio between Basal LH and LH on day of trigger was not found to be a significant factor influencing either the number of oocytes retrieved or oocyte maturation rate. When dividing the group by LH on day of trigger to below and above 1, a borderline difference was found relating to oocyte retrieval rate between the two groups (p = 0.06). Limitations, reasons for caution The retrospective nature of the study is the main limitation. Patients receiving GnRHa trigger are mainly a selective population of either high responders or patients for fertility preservation stimulated to retrieve many oocytes, therefore findings may not be applicable to normal or poor responders. Wider implications of the findings Low LH levels on day of trigger were found associated with lower oocyte retrieval rates. GnRHa has become an alternative to standard hCG triggering in certain situations. These are preliminary findings of an ongoing study designed to investigate the efficacy of GnRHa trigger according to cycle parameters including LH levels. Trial registration number not applicable

Assessment of Ovarian Reserve in Patients with Migraine

Objective The aim of our study is to investigate the relationship between migraine and ovarian reserve. Methods The study group consists of women between the ages of 25-51, including 44 patients diagnosed with migraine and 43 controls. Ovarian reserves were performed by antral follicle count and measured anti-Müllerian hormone level. The cohort was divided into four subgroups according to age as follows: 30 years and below, 31-35 years, 36-40 years, and 41 years of age and above. Results Of the 87 individuals included in this study, 44 were migraine patients, and 43 were healthy controls. The mean ages of the study and control groups were 34.3 (minimum: 25, maximum: 51) and 36.5 (minimum: 27, maximum: 51) years, respectively. There was no statistically significant difference between the two groups regarding age (p=0.48). In the study and control groups, respectively; mean AMH levels were 2.67 ± 2.46 ng/mL and 2.55 ± 2.38 ng/mL (p=0.819), mean basal FSH levels were 7.92 ± 2.52 U/L and 9.11 ± 3.19 U/L (p=0.066), mean basal LH levels were 6.35 ± 3.59 U/L and 6.06 ± 2.86U/L (p=0.681), mean basal estradiol levels were 65.02 ± 69.54 ng/L and 49.47 ± 27.08 ng/L (p=0.244), and mean AFC were 10.9 ± 3.9 and 10.2 ± 3.7 (p=0.435). Between subgroups aged ≤30 years, serum anti-Müllerian hormone levels were found to be significantly different (p=0.036). There was no statistically significant difference between any age subgroups in terms of antral follicle count. Conclusion In conclusion, detecting possible reduction of ovarian reserves in reproductive-age (especially younger than 30 years) migraine patients by utilizing anti-Müllerian hormone and ultrasonographic markers would allow these women to make cognizant decisions regarding marriage and family planning, as well as inform them whether they are in early menopause risk

Effectiveness, Safety, and Adherence to Treatment of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Real Practice

PurposeTo evaluate the effectiveness, adverse reactions, and adherence to treatment of hypolipidemic inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9is) in a context of real clinical practice. MethodsWe present an observational, retrospective, descriptive, multicenter study of patients with hypercholesterolemia who began treatment with PCSK9is between January 2017 and December 2019, with a minimum treatment period of 3 months. The main variable we recorded was the frequency of cardiovascular events (cardiovascular death, myocardial infarction, stroke, coronary revascularization, and hospitalization for unstable angina) in patients treated with PCSK9is. We recorded patient demographic characteristics and cardiovascular risk factors at onset of treatment as well as LDL-C levels and their reductions at 3, 6, 12, and 24 months. We calculated adherence to treatment and recorded the adverse reactions during treatment. FindingsA total of 154 patients were studied, 64 (41.6%) of whom were treated with alirocumab and 90 (58.4%) with evolocumab. The initial dose of alirocumab was 75 mg every 14 days in 48 patients (75%) and 150 mg eery 14 days in 16 (25%). All patients who in the evolocumab group received a dose of 140 mg every 14 days. The mean (SD) basal LDL-C level was 159.6 (50.1) mg/dL, the level at 3 months was 87.9 (49.9) mg/dL (mean [SD] decrease, 44.5% [28.2%]), the level at 6 months was 86.7 (49.2) mg/dL (mean [SD] decrease, 46.3% [25.6%]), and the level at 12 months was 80.5 (41.4) (mean [SD] decrease, 48.9% [23.0%]). These values were maintained at 24 months (mean [SD], 80.3 [41.8] mg/dL; mean [SD] decrease, 47.9% [27.8%]). The percentage decrease of LDL-C for both drugs was approximately 50%, which was maintained until 24 months after treatment. Six patients (3.9%) presented with some cardiovascular event: acute myocardial infarction (2 [1.3%]), stroke (1 [0.65%]), coronary revascularization (1 [0.65%]), and hospitalization for unstable angina (2 [1.3%]). We did not see any adverse reactions related to PCSK9i treatment in 76.5% of patients. In the first 6 months, adherence to treatment with PCSK9is, measured as the possession ratio, was a mean (SD) of 99.4% (3.9%). In the rest of the study period (6–24 months), the mean (SD) adherence to treatment was 99.2% (4.7%). ImplicationsThe frequency of cardiovascular events in patients treated with PCSK9is was low and occurred despite adequate adherence to treatment (100% possession ratio) with PCSK9is and concomitant treatment with other hypolipidemics. The effectiveness of PCSK9is is similar to that referred to in other published studies with PCSK9is, and this was maintained in the long term (24 months) with few adverse events, all of which were mild.

Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine.

BackgroundThere is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine.MethodsSegments of small intestine, 1.5–3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer’s solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5–3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury.ResultsAfter a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP.ConclusionsThis novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions.

Dexmedetomidine versus fentanyl as adjunct to ropivacaine-dexamethasone for labor analgesia: a randomized control study

Background and aims Although intrathecal analgesia is an effective option during labor, there is a need to establish sustainable and assured analgesia during the entire labor process. We aimed to compare the effect of dexmedetomidine versus fentanyl as an adjuvant to low-dose ropivacaine-dexamethasone for intrathecal labor analgesia in primigravida women.Patients and methods The study was conducted after approval of ethical committee of Al Azhar University Hospital. A total of 60 primiparous women classified in American Society of Anesthesiologists classes II with a singleton pregnancy in active labor were given combined spinal epidural analgesia. This was a double-blind randomized controlled trial that allocated them in two groups of 30 patients each. Group I received intrathecal 2.5 mg of 0.1% ropivacaine (diluted to 2.5 ml with normal saline)+5 μg dexmedetomidine+4 mg dexamethasone. Occurrence of any adverse reaction was observed for ten min. Group II received 25 μg of fentanyl instead of 5 μg dexmedetomidine. For both groups, epidural top-ups of 10 ml of 1% ropivacaine were given when parturients complained of two painful contractions (visual analog scale ≥4), after epidural test dose of 3 ml of 0.5% ropivacaine was slowly injected via epidural catheter and no occurrence of adverse reaction was observed 10 min later. Data collected were demographic profile of the patients, intrathecal block characteristics, needs for epidural activation before delivery, and maternal and fetal adverse effects. The primary study goal was to prove the analgesic efficacy and safety of intrathecal selective sensory block on both mother and fetus, whereas the study secondary goal was to prove that intrathecal single dose injection could be used as an effective alternative option in labor analgesia as well as epidural analgesia. Catecholamine level (epinephrine and norepinephrine) was measured using enzyme-linked immunosorbent assay technique.Results The mean age (years), weight (kg), height (cm), and BMI (kg/m2) in group I were 24.3±3.30, 65.4±16.2, 161.3±4.6, and 22.3±3.4, respectively, whereas in group II were 25.23±4.44, 66.3±15.6, 160.4±4.3, and 22.2±3.1, respectively, with insignificant difference (P>0.05). Mean visual analog scale score before onset of analgesia in group I and group II was 8.59±1.22 and 8.7±1.14, respectively. The time to full cervical dilatation was 120.14±10.2 in group I and 120.0±10.6 in group II, and the mean duration of second stage of labor was 12.02±1.37 min in group I and 11.83±0.93 min in group II. The mean duration of analgesia was statistically significant (lower) in group II (221.83±22.26) as compared with group I (296.33±44.83) (P<0.001). The mean analgesia in group I (12.3±1.8) and group II (12.1±1.7) was statistically insignificant (P>0.05). The mean highest sensory levels in group I and group II were statistically insignificant, that is, T5 (T4–T8) versus T6 (T4–T7) (P>0.05). The sensory region time in group II was greater (241.83±22.26 min) as compared with group I (329.83±44.10), with P value less than 0.001. Neither maternal nor fetal adverse events were statistically significant different between both groups (P>0.05). The mean basal norepinephrine level in pg/ml in group I was 130.30±27.6 and in group II was 103.50±20.6, with P value more than 0.05. At 2 h, norepinephrine level in pg/ml was 119.90±24.1 in group I and 90.50±13.6 in group II, with P value more than 0.05. At baseline, the epinephrine level in pg/ml in group I and group II was 59.20±11.3 and 53.20±10.3, respectively, whereas at 2 h, the epinephrine level in pg/ml was 57.90±9.1 in group I and 49.20±8.6 in group II, with P value more than 0.05.Conclusion Ropivacaine-dexamethasone combined with dexmedetomidine for intrathecal block achieved a potent selective sensory block with prolonged duration of analgesia, delayed S1 regression time, and limited maternal and fetal adverse effects than intrathecal ropivacaine-dexamethasone combined with fentanyl. However, dexmedetomidine or fentanyl provides a safe and efficacious adjuvant to intrathecal ropivacaine-dexamethasone in primigravida women with rapid onset, profound analgesia, and hemodynamic stability throughout the labor.

Perceptions and Barriers on the Use of PCSK9 Inhibitors in Heterozygous Familial Hypercholesterolemia

To evaluate the effectiveness, adverse reactions, and adherence to treatment of hypolipidemic inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9is) in a context of real clinical practice.We present an observational, retrospective, descriptive, multicenter study of patients with hypercholesterolemia who began treatment with PCSK9is between January 2017 and December 2019, with a minimum treatment period of 3 months. The main variable we recorded was the frequency of cardiovascular events (cardiovascular death, myocardial infarction, stroke, coronary revascularization, and hospitalization for unstable angina) in patients treated with PCSK9is. We recorded patient demographic characteristics and cardiovascular risk factors at onset of treatment as well as LDL-C levels and their reductions at 3, 6, 12, and 24 months. We calculated adherence to treatment and recorded the adverse reactions during treatment.A total of 154 patients were studied, 64 (41.6%) of whom were treated with alirocumab and 90 (58.4%) with evolocumab. The initial dose of alirocumab was 75 mg every 14 days in 48 patients (75%) and 150 mg eery 14 days in 16 (25%). All patients who in the evolocumab group received a dose of 140 mg every 14 days. The mean (SD) basal LDL-C level was 159.6 (50.1) mg/dL, the level at 3 months was 87.9 (49.9) mg/dL (mean [SD] decrease, 44.5% [28.2%]), the level at 6 months was 86.7 (49.2) mg/dL (mean [SD] decrease, 46.3% [25.6%]), and the level at 12 months was 80.5 (41.4) (mean [SD] decrease, 48.9% [23.0%]). These values were maintained at 24 months (mean [SD], 80.3 [41.8] mg/dL; mean [SD] decrease, 47.9% [27.8%]). The percentage decrease of LDL-C for both drugs was approximately 50%, which was maintained until 24 months after treatment. Six patients (3.9%) presented with some cardiovascular event: acute myocardial infarction (2 [1.3%]), stroke (1 [0.65%]), coronary revascularization (1 [0.65%]), and hospitalization for unstable angina (2 [1.3%]). We did not see any adverse reactions related to PCSK9i treatment in 76.5% of patients. In the first 6 months, adherence to treatment with PCSK9is, measured as the possession ratio, was a mean (SD) of 99.4% (3.9%). In the rest of the study period (6–24 months), the mean (SD) adherence to treatment was 99.2% (4.7%).The frequency of cardiovascular events in patients treated with PCSK9is was low and occurred despite adequate adherence to treatment (100% possession ratio) with PCSK9is and concomitant treatment with other hypolipidemics. The effectiveness of PCSK9is is similar to that referred to in other published studies with PCSK9is, and this was maintained in the long term (24 months) with few adverse events, all of which were mild.

Systemic estradiol levels with low-dose vaginal estrogens.

Objectives:To critically evaluate published systemic estradiol levels during use of low-dose vaginal estrogens considering detection method and estrogen dose; describe challenges with accurately measuring estradiol; and determine the normal estradiol level range in postmenopausal women.Methods:PubMed was searched for studies reporting systemic estradiol levels with lower-dose vaginal estrogens (≤25 μg estradiol or 0.3 mg conjugated equine estrogens). Estradiol levels at baseline and during treatment, area under the curve, and maximum estradiol concentrations were summarized by dose within assay type. A proposed range of systemic estradiol in normal, untreated, postmenopausal women was estimated by conservatively pooling means and standard deviations from published studies.Results:Mean basal estradiol levels were 3.1 to 4.9 pg/mL using liquid or gas chromatography/mass spectroscopy (LC or GC/MS/MS) with a range of undetectable to 10.5 pg/mL using radioimmunoassay. Systemic estradiol levels with vaginal estrogens reflected their doses as measured with LC or GC/MS/MS in different studies: 7.1 to 9.1 pg/mL and 16.7 to 22.7 pg/mL with a 25-μg softgel capsule insert and a tablet insert, respectively; 4.6 to 7.4 pg/mL and 6.6 to 14.8 pg/mL with a 10-μg softgel capsule and a tablet insert, respectively; and 3.6 to 3.9 pg/mL with a 4-μg softgel capsule insert. A mean systemic estradiol concentration ranging from undetectable to 10.7 pg/mL is proposed as an estimate for basal estradiol levels in normal, untreated, postmenopausal women. Systemic estradiol absorption may be influenced by the placement of estradiol higher (as with an applicator) versus lower (as without an applicator) in the vagina, as estradiol transport to the uterus would be more likely further away than closer to the introitus.Conclusion:Serum estradiol concentrations were generally lower when measured with more specific and sensitive assays. Estradiol absorption was dose-dependent, and may be influenced by dose, formulation, and positioning in the vagina. Very low systemic estradiol absorption with low/ultralow-dose vaginal estrogens may potentially decrease any adverse events that may be associated with higher doses of vaginal estrogens used for treating moderate to severe VVA due to less estradiol exposure.

Is gonadotropin-releasing hormone agonist usage really leading to thyroid dysfunction?

ObjectivesGonadotropin-releasing hormone agonist (GnRHa) could influence the levels of sex hormones and thyroid hormones. The aim of this study was to investigate the effect of GnRHa on thyroid function.Materials and methodsThe data of the patients were collected from the registrations of July 2014–October 2014. A total of 41 women who underwent one-time IVF cyclus were evaluated in this cross-sectional study. The patients were categorized into two groups according to the serum T3, T4, and TSH levels before and 2 weeks’ after the administration of GnRHa.ResultsMean basal TSH and mean TSH levels on hCG day were 1.98 ± 0.77 and 1.75 ± 0.70, respectively. The difference between the two groups was statistically significant (p < 0.05). GnRHa did not lead to statistically significant difference on serum-free T3 and T4 levels.ConclusionsIn conclusion, our results demonstrate that GnRHa led to a decrease on serum TSH level. Serum-free T3 and T4 levels were remained unchanged and this might be due to early measurement of the hormone levels (just 2 weeks later from GnRHa administration).

Stress-related behavior of horses in adapted therapeutic riding lessons and hippotherapy sessions

In order to determine whether therapeutic riding could result in higher levels of stress than recreational riding, hypothalamic-pituitary-adrenal (HPA) axis response was evaluated in six horses by monitoring circulating β-endorphin, ACTH and cortisol concentrations. Horses were already accustomed to be trained both for therapy and riding school activity since 2004. Intervention consisted of 60-minute therapeutic sessions, two times per week for 6 weeks with different riders: disabled and recreational riders (session A and B respectively). The therapeutic riders' group (A) consisted of six children with psychomotor disabilities; the recreational riders' group (B) consisted of six healthy children without any previous horse riding experience. Horses were asked to perform the same gaits and exercises at all sessions, both with disabled and healthy users.The statistical analysis showed that during both sessions the mean basal β-endorphin and ACTH levels of horses did not show any significant changes, while the one way RM-ANOVA showed significant effects of sessions A on the cortisol (F = 11.50; P < 0.01) levels. Horses submitted to sessions A showed lower cortisol levels both at 5 min (P < 0.001) and at 30 min (P < 0.005) after therapeutic sessions than those after session B.Results suggest that in tested horses and for the variables settled, HPA axis was less responsive to disabled than healthy, recreational riders. Among the endocrine responses, cortisol was one of the indicators of HPA axis stress response.

MON-LB049 Central Precocious Puberty as a Presenting Sign of Non-Classical Congenital Adrenal Hyperplasia: Prevalence and Clinical Characteristics

Context: Central precocious puberty (CPP) may be the first presentation of non-classical congenital adrenal hyperplasia (NCCAH) in girls. Data on the prevalence and the clinical phenotype of CPP associated with NCCAH are sparse. Objectives: To study the clinical and laboratory characteristics that could differentiate idiopathic CPP from CPP associated with NCCAH and to determine the prevalence of NCCAH among girls with CPP. Design: Case-control study. Setting: Tertiary pediatric endocrinology institute. Participants and Methods: From 2008 to 2017, 147 girls who had undergone stimulation tests with gonadotropin-releasing hormone and Synacthen were diagnosed with CPP, of whom 7 (4.8%) were eventually diagnosed with NCCAH. These 7 patients together with 30 girls who presented with CPP in1984-2008 and were later diagnosed with NCCAH comprised the NCCAH group. Demographic, anthropometric, clinical, and laboratory data were compared between the NCCAH group and the 140 girls with idiopathic CPP (ICPP group). Results: No between-group differences were found in height, weight, body mass index, bone age, and Tanner stage. Mean basal levels of androstenedione, DHEAS, and 17-OHP were significantly higher in the NCCAH group, although ranges overlapped between the groups, and stimulated cortisol level was higher in the ICPP group. Conclusions: NCCAH was found in 4.8% of girls presenting with true CPP over a 10-year period, and no one parameter could differentiate between the diagnoses. Thus, in girls with true CPP from populations in which NCCAH is prevalent, assessment of adrenal androgens is required and ACTH test should be considered. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Pretreatment with somatostatin analogs does not affect the anesthesiologic management of patients with acromegaly.

Acromegaly may be associated with an increased risk of complex intraoperative management and anesthetic complications. No study addressed whether pretreatment with somatostatin receptor ligands (SRLs) affects anesthesiologic management. We studied 211 consecutive acromegalic patients who had a recorded intraoperative computerized anesthetic record (ICAR) available for analysis. Ninety-six (45.5%) patients were SRL-pretreated while 115 patients were treatment naïve. Treatment with SRLs reduced mean basal growth hormone level from 23.8 ± 4.2 to 5.9 ± 1.3µg/L. Normalization of insulin-like growth factor-1 was achieved in 26 patients (27.1%). The frequency of comorbidities at surgery was similar in the two groups. Five patients with difficult intubation were naïve (4.3%) as compared with 5 SRL-pretreated patients (5.2%; P = 1.0). ICAR registration did not show any significant change of intraoperative vital parameters in the two groups of patients as well as in the intraoperative utilization of drugs. Total duration of anesthesia and surgery were similar in the two groups. Four patients with an intraoperative adverse event were naïve (3.5%) as compared with 4 SRL-pretreated patients (4.2%; P = 1.00). Remission of disease occurred in 83 of 114 naïve patients (72.8%) and in 57 of 93 SRL-pretreated patients (61.3%; P = 0.11). SRL-pretreatment of patients with acromegaly had no significant impact on intraoperative anesthesiologic management. Despite a better Cormack-Lehane score in SRL-pretreated than in naïve patients, the rate of difficult intubation was similar in both groups. SRL-pretreatment did not affect the rate of surgical remission or complications as well.

Central Precocious Puberty as a Presenting Sign of Nonclassical Congenital Adrenal Hyperplasia: Clinical Characteristics.

Central precocious puberty (CPP) may be the first presentation of nonclassical congenital adrenal hyperplasia (NCCAH) in girls. Data on the prevalence and the clinical phenotype of CPP associated with NCCAH are sparse. To study the clinical and laboratory characteristics that could differentiate idiopathic CPP from CPP associated with NCCAH and to determine the prevalence of NCCAH among girls with CPP. Case-control study. Tertiary pediatric endocrinology institute. From 2008 to 2017, 147 girls who had undergone stimulation tests with gonadotropin-releasing hormone and ACTH were diagnosed with CPP; of these, seven (4.8%) were eventually diagnosed with NCCAH. These seven patients together with 30 girls who presented with CPP during 1984 to 2008 and were later diagnosed with NCCAH comprised the NCCAH group. Demographic, anthropometric, clinical, and laboratory data were compared between the NCCAH group and the 140 girls with idiopathic CPP (ICPP group). No between-group differences were found in height, weight, body mass index, bone age, and Tanner stage. Mean basal levels of androstenedione, dehydroepiandrosterone-sulphate, and 17-hydroxyprogesterone were significantly higher in the NCCAH group, although ranges overlapped between the groups, and stimulated cortisol level was higher in the ICPP group. NCCAH was found in 4.8% of girls presenting with true CPP over 10 years, and no single parameter could differentiate between the diagnoses. Thus, in girls with true CPP from populations in which NCCAH is prevalent, assessment of adrenal androgens is required, and ACTH test should be considered.

Comparative evaluation of 30 and 60 minutes cortisol Levels During Short Synacthen Test for diagnosis of Adrenal Insufficiency

To assess and compare diagnostic value of 30-minute cortisol level over 60-minute level in the diagnosis of adrenal insufficiency.The comparative cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from August 2017 to May 2018, and comprised patients referred to the facility for short synacthen test with suspicion of adrenal insufficiency. Blood samples for serum cortisol were taken at time-0 and then 30 and 60 minutes after the adreno-cortico-tropic hormone injection. Total serum cortisol was measured. Adrenal insufficiency was defined as stimulated cortisol level <500 nmol/l at 30 and 60 minutes post-stimulation. SPSS 24 was used for data analysis.Of the 111 subjects, 56(50.4%) were males and 55(49.5%) were females. Overall mean age was 34±20 years. Mean basal serum cortisol level was 110±98 nmol/l in patients with adrenal insufficiency and it was 294±164 nmol/l in patients with intact adrenal functions. Cortisol level at both 30 and 60 minutes was significant (p<0.001). Receiver Operating Characteristics curve was plotted which showed area under curve of 0.83 and 0.82 for 60 and 30 minutes respectively.The 30-minute cortisol level post-stimulation carried no diagnostic value . Measuring cortisol level once at 60-minute post-stimulation would be of more value apart from being cost-effective in the diagnosis of adrenal insufficiency.

Evaluation of transsphenoidal adenomectomy outcomes in acromegaly using different remission criteria

We aimed to evaluate the results of transsphenoidal adenomectomy in acromegaly patients using various criteria for disease remission. The study included patients with newly diagnosed acromegaly who underwent transnasal transsphenoidal endoscopic adenomectomy performed by a single neurosurgeon. The surgical treatment outcomes were evaluated 6 months after operative intervention based on levels of IGF-1, OGTT, and GH. The obtained data were analyzed using different threshold values for the level of GH nadir during OGTT: criteria A <2.0 ng/ml, criteria B <1.0 ng/ml, and criteria C <0.4 ng/ml to assess acromegaly remission, along with matching of the IGF-1 level to the reference range for a given gender and age. The study included 70 patients (52 females and 18 males) with a mean age of 52.2±11.5 years (29 to 73 years). The baseline IGF-1 level exceeded the upper limit of the reference range 3.3±1.4 (1.1-7.3)-fold, on average. The baseline mean basal GH level was 34.2±41.7 (1.2-192.0) ng/ml. The mean pituitary adenoma size was 16.7±8.6 (4.3-46.0) mm; 18 (26%) out of 70 patients had pituitary microadenoma, and 52 (74%) patients had macroadenoma. Six months after surgery, acromegaly remission met criteria A in 47 (67%) patients, criteria B in 28 (40%) patients, and criteria C in 18 (26%) patients. Our findings demonstrate that evaluation of transsphenoidal adenomectomy outcomes in treatment of acromegaly patients depends on the criteria chosen for assessing remission. This feature should be considered when comparing outcomes of surgical treatment for acromegaly in different years. Probably, introduction of the 2010 criteria should be accompanied by revision of the previous remission indicators.