Prevalence, Characteristics, and Treatment of Hemorrhoids During Pregnancy: A Nationwide Population-Based Cohort Study in Taiwan.

Background: Hemorrhoids, a gastrointestinal tract disorder, are common during pregnancy. However, large-scale epidemiological studies on hemorrhoids during pregnancy are limited. Therefore, this study used analyzed data from a nationwide population-based database to investigate the prevalence, characteristics, and treatment of hemorrhoids in Taiwan. Materials and Methods: This retrospective population-based study used data from the National Health Insurance Research Database and Taiwan Birth Certificate Application to collect the medical records of women who were pregnant at any time during 2009-2018. Hemorrhoids was defined by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) (455. X) and International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) (K64.X, O22.4X) with related treatment. Results: We enrolled 1,608,804 deliveries in 1,070,708 women. The proportion of hemorrhoids increased with age in both primipara and multipara women. Of the pregnant women, 31% received oral medication, and 93.2% used the topical ointment to treat their hemorrhoids. Few patients (1.8%) required procedure or surgery during pregnancy, and 41.4% of those patients underwent procedure or surgery in their first trimester. The cumulative incidence of hemorrhoids during pregnancy was significantly higher in women with a history of hemorrhoids and those with multifetal pregnancies. No significant difference in the incidence of hemorrhoids was observed between multiparous and primiparous women. Conclusion: Women with a history of hemorrhoids or those carrying multiple fetuses had an increased risk of hemorrhoids during pregnancy. The most commonly used treatment for hemorrhoids during pregnancy was topical ointments, with only a small proportion (1.8%) of patients requiring procedure or surgery.

Enhanced Oral NO Delivery through Bioinorganic Engineering of Acid-Sensitive Prodrug into a Transformer-like DNIC@MOF Microrod.

Nitric oxide (NO) is an endogenous gasotransmitter regulating alternative physiological processes in the cardiovascular system. To achieve translational application of NO, continued efforts are made on the development of orally active NO prodrugs for long-term treatment of chronic cardiovascular diseases. Herein, immobilization of NO-delivery [Fe2(µ-SCH2CH2COOH)2(NO)4] (DNIC-2) onto MIL-88B, a metal-organic framework (MOF) consisting of biocompatible Fe3+ and 1,4-benzenedicarboxylate (BDC), was performed to prepare a DNIC@MOF microrod for enhanced oral delivery of NO. In simulated gastric fluid, protonation of the BDC linker in DNIC@MOF initiates its transformation into a DNIC@tMOF microrod, which consisted of DNIC-2 well dispersed and confined within the BDC-based framework. Moreover, subsequent deprotonation of the BDC-based framework in DNIC@tMOF under simulated intestinal conditions promotes the release of DNIC-2 and NO. Of importance, this discovery of transformer-like DNIC@MOF provides a parallel insight into its stepwise transformation into DNIC@tMOF in the stomach followed by subsequent conversion into molecular DNIC-2 in the small intestine and release of NO in the bloodstream of mice. In comparison with acid-sensitive DNIC-2, oral administration of DNIC@MOF results in a 2.2-fold increase in the oral bioavailability of NO to 65.7% in mice and an effective reduction of systolic blood pressure (SBP) to a ΔSBP of 60.9 ± 4.7 mmHg in spontaneously hypertensive rats for 12 h.

Levonorgestrel intrauterine system for the treatment of intermenstrual spotting in patients with previous cesarean delivery scar defect.

AIM: To evaluate the efficacy of levonorgestrel 52 mg intrauterine system for intermenstrual bleeding in patients with previous cesarean delivery scar defects (PCDSs). METHODS: The medical records of 28 consecutive patients with previous cesarean delivery scar defect and intermenstrual bleeding who had undergone conservative treatment with levonorgestrel 52 mg intrauterine system were reviewed. The efficacy of treatment and frequency of adverse events were measured retrospectively. RESULTS: After 1 year of treatment, 22 patients (78.6%) reported an improvement in symptoms. The mean duration of menstruation were 18 and 5 days before and after treatment, respectively. No uterine perforations or pelvic inflammatory diseases occurred during or after the insertion procedures. Eighteen (64.3%) patients did not experience any adverse events, and the patients with adverse events reported that they could be managed by adjusting their medications or observation. CONCLUSION: Levonorgestrel intrauterine system may have a role in the safe and effective management of intermenstrual spotting in patients with PCDSs.

Serum ß-human chorionic gonadotropin profile and its correlations with ultrasound parameters in low-lying-implantation ectopic pregnancy in the first trimester.

AIM: Cervical pregnancy (CP) and cesarean scar pregnancy (CSP), defined as low-lying-implantation ectopic pregnancy (LLIEP), are rare conditions of aberrant implantation around the lowest portion of the uterus. This study aimed to illustrate the serum ß-human chorionic gonadotropin (ß-hCG) profile of LLIEP and to explore its implications with the clinical characteristics. METHODS: Women with LLIEP during the first trimester were retrospectively evaluated at a tertiary referral center from August 1999 to July 2016. Demographic and clinical data were recorded, including maternal age, gestational age (GA), serum ß-hCG level, maximal diameter of the gestational mass/sac (MDM/MDS) by ultrasonography and CSP implantation types. The serum ß-hCG level was measured on the day of ultrasound imaging. The significance of pretreatment the serum ß-hCG level and its correlations with the clinical characteristics were analyzed. RESULTS: A total of 88 LLIEP with 64 CSP and 24 CP was included. The mean GA at the time of diagnosis was 7 weeks (range, 5-12 weeks). The ß-hCG concentrations rapidly increased from GA 5 to 9 weeks and fluctuated thereafter. The ß-hCG levels correlated positively with GA and ultrasound MDM/MDS. In the CSP group, there was no difference in the ß-hCG level between superficial and deep implantation types. ß-hCG levels demonstrated no significant differences among simple and complicated LLIEP. CONCLUSION: This study established the serum ß-hCG profile in LLIEP in the first trimester. The exponential increase of ß-hCG levels was similar to that of normal intrauterine pregnancies. The ß-hCG levels were not associated with placentation complexity of CSP. Higher ß-hCG levels did not implicate less success in conservative surgical management.

Intestine-targeted delivery potency of O-carboxymethyl chitosan-coated layer-by-layer microcapsules: An in vitro and in vivo evaluation.

The intestine-targeted delivery performance of the gum Arabic (GA) - O-carboxymethyl chitosan (OCMC) microcapsules prepared by layer-by-layer (LbL) assembly and genipin crosslinking was evaluated by using an acid-susceptible compound omeprazole as the model. Confocal laser scanning microscope observation revealed that spherical microcapsules with the core-shell structure were successful fabricated. Genipin crosslinking did not affect the microencapsulation yield or drug load, but significantly decreased the particle size and positive charge of the microcapsules, and increased their stability against disintegration in the simulated gastric fluid. Pharmacokinetic analysis indicated that entrapment by GA - OCMC LbL assembly greatly improved the bioavailability of omeprazole and crosslinking by 0.1 mg/mL genipin led to the highest value of 8.76 relative to the control formulation. It was concluded that the GA - OCMC LbL microcapsules could be used for the oral delivery of nutraceuticals and its delivery performance could be tailored by varying the genipin crosslinking degree.

pH-Dependent intestine-targeted delivery potency of the O-carboxymethyl chitosan - gum Arabic coacervates.

Bovine serum albumin (BSA)-loaded microcapsules were prepared at pH 3.0, 4.5, and 6.0 through O-carboxymethyl (O-CMC) - gum Arabic (GA) coacervation followed by genipin crosslinking to explore the effects of coacervation acidity on the intestine-targeted delivery potency of resultant microcapsules. Confocal laser scanning microscope observation revealed that microcapsules with the multilayer structure were successfully prepared. As the coacervation pH rose from 3.0 to 6.0, the amount of O-CMC deposited on the microcapsule surface and the particle size increased accordingly. Swelling and BSA release results indicated that coacervation at higher pH conferred greater stability against simulated gastric fluid and better intestine-targeted delivery potency to the microcapsules. Circular dichroism analysis demonstrated that the structural integrity of entrapped BSA was well maintained during microencapsulation and incubation in simulated gastrointestinal fluids. Hence, genipin-crosslinked O-CMC - GA coacervates could be used to deliver nutraceuticals to the intestine and its delivery performance could be tailored by varying the coacervation pH.

Genipin-crosslinked O-carboxymethyl chitosan-gum Arabic coacervate as a pH-sensitive delivery system and microstructure characterization.

The possibility of genipin-crosslinked O-carboxymethyl chitosan-gum Arabic coacervate as a pH-sensitive delivery vehicle was investigated. O-carboxymethyl chitosan-gum Arabic coacervates separated in pH 3.0, 4.5, and 6.0 were crosslinked by genipin for different durations and the crosslinked products were subjected to crosslinking degree, swelling behavior, bovine serum albumin release profile, and microstructure characterization. Genipin-crosslinking greatly improved the stability of the coacervates against the simulated gastric solution and created certain pH-sensitivity. The coacervates displayed higher swelling ratios in the simulated gastric solution than in the simulated intestine and colon solutions; meanwhile, the coacervates prepared in pH 4.5 and 6.0 swelled more severely than the complex separated in pH 3.0. Nevertheless, the bovine serum albumin release in the simulated gastric solution from the microcapsules prepared in pH 6.0 was much lower than those prepared in pH 4.5 and 3.0, whose cumulative release percentages in the three simulated solutions were 17.14%, 55.23%, and 79.79%, respectively, in crosslinking duration 2 h. X-ray diffraction, scanning electron microscopy, and transmission electron microscopy analysis revealed that genipin-crosslinking improved the regularity and compactness of coacervate structure, whereas confocal laser scanning microscopy observation indicated that O-carboxymethyl chitosan content was possibly the major reason for the different swelling and bovine serum albumin release behavior of the coacervates. It was concluded that the genipin-crosslinked O-carboxymethyl chitosan-gum Arabic coacervate was a potential intestine-targeted delivery system and its delivery performance could be tailored by varying the crosslinking degree and coacervation acidity.

Ectopic pregnancy following in vitro fertilization with embryo transfer: A single-center experience during 15 years.

OBJECTIVE: Ectopic pregnancy is an obstetrical disease that is potentially associated with maternal death in the first trimester. It is one of the well-known complications following in vitro fertilization (IVF) with embryo transfer (ET). The incidence of ectopic pregnancy is estimated to be 2.1-8.6% of clinical pregnancy after IVF-ET, which is higher than natural conceptions (incidence rate 2%). This study aimed to re-evaluate the ectopic pregnancy rate in patients undergoing IVF-ET and to investigate the effects of embryo stage and frozen-thawed blastocyst transfer and ET during full bladder distention on ectopic pregnancy rate. MATERIALS AND METHODS: This retrospective study reviewed women who achieved a clinical pregnancy after IVF-ET at the Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital between 1999 and 2013. We compared ectopic pregnancy rate following Day 3 ET with Day 5 ET, and after fresh ET with thawed ET. Besides, multivariate analysis was used to clarify the factors affecting ectopic pregnancy after IVF-ET. RESULTS: Of the total 1213 clinical pregnancies after fresh ET, 18 (1.5%) were verified as ectopic, which is similar to the rate following natural conception. The ectopic pregnancy rates were similar for Day 3 (1.2%) and Day 5 (1.7%) ETs. The incidence of ectopic pregnancy in thawed ET cycles (0.6%) was not significantly reduced than fresh ET cycles (1.5%). Tubal ET (TET) and ET under full bladder distention had a significant effect on ectopic pregnancy. CONCLUSION: Thawed ET was not associated with a lower incidence of ectopic pregnancy than fresh ET, and embryo stage did not affect the rate of ectopic pregnancy. In addition, TET and ET under conditions of full bladder distention may increase the ectopic pregnancy rate.

Outcomes of primary surgical evacuation during the first trimester in different types of implantation in women with cesarean scar pregnancy.

OBJECTIVE: To assess the efficacy and safety of primary surgical evacuation therapy for cesarean scar pregnancy (CSP) of the first trimester, and to evaluate its possible prognostic factors. DESIGN: Retrospective consecutive cohort study. SETTING: Tertiary care university hospital. SUBJECT(S): A cohort of patients with CSP and clear ultrasound images who underwent primary surgical evacuation from January 2000 to December 2012. INTERVENTION(S): Patients fulfilling the ultrasound criteria of CSP were further classified into superficial and deep groups according to their implantation locations and extents. The final decision on the method of treatment, including methotrexate chemotherapy, surgical evacuation, and others, was made by the patients after consultation with the physician. Pretreatment patient characteristics were compared in the patients with superficial and deep implantation, as were the results after primary surgical evacuation. MAIN OUTCOME MEASURE(S): Rates of successful treatment by primary surgical evacuation of CSP and the need for salvage intervention in the patients with deep and superficial implantation. RESULT(S): Forty-eight CSP patients who had sufficient data and imaging for analysis were enrolled. Of these 48 cases, 26 in the superficial group and 14 in the deep group were willing to undergo primary surgical evacuation. Blood loss and need for salvage intervention were significantly lower in the patients with superficial implantation. Surgical evacuation was successful in 23 of 26 patients (88.5%) with superficial implantation and in 8 of 14 patients (57.1%) with deep implantation. Patients who failed primary surgical evacuation showed complete recovery, with uterus preservation, after salvage interventions, including laparoscopic surgery, angioembolization, and laparotomy. CONCLUSION(S): Preoperative determination of CSP implantation depth and extent is important in selecting candidates for surgical treatment. Primary single-step surgical evacuation was successful in most patients with superficial implantation, but patients should be informed of the possibility of salvage interventions before undergoing surgical evacuation.

[Progress in sustained-release drug delivery system for treatment of posterior segment eye diseases].

There is an urgent requirement to find effective therapeutic procedures for the treatment of refractory eye diseases of posterior segment such as posterior uveitis, proliferative vitreoretinopathy, and macular edema associated with diabetes and retinal vein occlusion. Due to systemic side effect developed from systemic drug administration and the low efficiency of topical drug administration, implantable drug devices for the treatment of posterior segment diseases have been explored. In recent years, three different intraocular implantable devices (ganciclovir, fluocinolone acetonide and dexamethasone) have been approved by FDA and showed exciting clinical efficacy. However, these devices have surgical complications and the drug-related side effects. Recently, transscleral drug delivery to the posterior segment has been investigated. Transscleral drug delivery has advantages of large scleral surface area, better safety profile, easily drug administration and could evolve into an effective route with the use of novel biomaterials and the study of drug delivery methods.

[Recent advance in pharmacological therapies for proliferative vitreoretinopathy].

Proliferative vitreoretinopathy (PVR) is a leading blinding disease, which is often associated with ocular trauma, rhegmatogenous retinal detachment and diabetic retinopathy. PVR involves the vitreous and retina and its occurrence is characterized by vitreoretinal cells migration, transformation and excessive proliferation which lead to the formation of pre- or sub-retinal membrane or membrane formation in the vitreous. The subsequent contraction of the membrane can lead to retinal detachment and loss of vision. At present, vitrectomy is the standard treatment modality for the treatment of PVR. However, this procedure is expensive and post-operative vision is often unsatisfactory. With the advances of biological studies, the pathogenesis of PRV becomes clear, and the corresponding pharmacological intervention studies targeting the relevant pathways developed rapidly. This review is aiming to highlight the new developments in pharmacological prevention and treatment for PVR.