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Introduction: Partnership is an important resource in dealing with endometriosis related chronic pain. Hence, our objective was to assess partnership in the context of endometriosis and its symptoms, considering the perspectives of both individuals involved. Methods: The study was designed as a multi-center matched case-control study in Switzerland, Germany and Austria. Altogether 381 women with surgically/histologically confirmed endometriosis and 381 control women, 250 male partners of endometriosis-affected women and 229 of control women were evaluated. Partnership quality, partnership happiness, separation thoughts, and areas of conflict were evaluated through the Partnership Questionnaire and a validated list of conflict areas. Results: Quality of partnership was rated as high by 60.1% of the women with endometriosis and 66.7% of the control women, as well as by 45.8 and 50.2% of their respective partners. Women with endometriosis mentioned separation thoughts, mostly related to sexual satisfaction, more often (34.9%/28.3%) and experienced more partnership-related conflicts than control women. Chronic pain, dyspareunia, dissatisfaction with sexuality, fatigue, and infertility were significantly associated with partnership conflicts. Fatigue and infertility but not pain experiences were related to lower partnership quality. Male partners in both groups reported separation thoughts equally often. In men, a high intensity of pain experienced by their partner was associated with reduced partnership happiness. Conclusion: Given the significance of partnership in dealing with chronic diseases and the connection between symptoms of endometriosis and a decrease in partnership quality, it is essential to incorporate strategies that alleviate the negative impacts on relationships for both partners into medical support. Clinical trial registration: identifier NCT02511626.
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Neurotransmitter:sodium symporters (NSSs) play critical roles in neural signaling by regulating neurotransmitter uptake into cells powered by sodium electrochemical gradients. Bacterial NSSs orthologs, including MhsT from Bacillus halodurans, have emerged as model systems to understand the structural motifs of alternating access in NSSs and the extent of conservation of these motifs across the family. Here, we apply a computational/experimental methodology to illuminate the conformational landscape of MhsT alternating access. Capitalizing on our recently developed method, Sampling Protein Ensembles and Conformational Heterogeneity with AlphaFold2 (SPEACH_AF), we derived clusters of MhsT models spanning the transition from inward-facing to outward-facing conformations. Systematic application of double electron-electron resonance (DEER) spectroscopy revealed ligand-dependent movements of multiple structural motifs that underpin MhsT's conformational cycle. Remarkably, comparative DEER analysis in detergent micelles and lipid nanodiscs highlights the profound effect of the environment on the energetics of conformational changes. Through experimentally derived selection of collective variables, we present a model of ion and substrate-powered transport by MhsT consistent with the conformational cycle derived from DEER. Our findings not only advance the understanding of MhsT's function but also uncover motifs of conformational dynamics conserved within the broader context of the NSS family and within the LeuT-fold class of transporters. Importantly, our methodological blueprint introduces an approach that can be applied across a diverse spectrum of transporters to describe their conformational landscapes.
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Proteínas Bacterianas , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Conformación Proteica , Bacillus/metabolismo , Sodio/metabolismo , Espectroscopía de Resonancia por Spin del Electrón/métodos , Neurotransmisores/metabolismo , Modelos MolecularesRESUMEN
RESEARCH QUESTION: Does ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), delay ovulation? DESIGN: Two-stage, proof-of-concept, controlled study, assessing the percentage of non-ovulated follicles 42 h after HCG injection in patients taking ibuprofen. The intervention group consisted of women undergoing natural cycle IVF treatment taking ibuprofen 3â¯×â¯400 mg per day. The control group consisted of women undergoing timed sexual intercourse or intrauterine insemination. The proportion of patients with non-ovulated follicles in the ibuprofen group was first compared against a reference of 50% using a one-sample binomial test, and second against the proportion observed in the control group using an adjusted logistic regression. RESULTS: A total of 26 women were recruited in the ibuprofen intervention group. Twenty-five patients were recruited in the control group. The proportion of patients with delayed ovulation observed (22/26 [84.6%]; 95% CI 65.1% to 95.6%) was significantly higher than the reference of 50% (P < 0.001). In the control group, the proportion of patients with delayed ovulation was 20.0% ([5/25], 95% CI 6.8% to 40.7%). Compared with the ibuprofen group, a significantly increased probability of a delayed ovulation was found in the ibuprofen intervention group (adjusted OR 22.72, 95% CI 5.77 to 115; P < 0.001). Of the 22 women with delayed ovulation, oocytes were retrieved in 20 women (90.9%) and all oocytes were mature (metaphase II). CONCLUSIONS: Women trying to conceive should avoid non-selective NSAIDs around the time of ovulation. Ibuprofen or other NSAID can be used to delay ovulation for several hours in assisted reproductive technology and other infertility treatments if required.
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Antiinflamatorios no Esteroideos , Gonadotropina Coriónica , Ibuprofeno , Ovulación , Humanos , Femenino , Ibuprofeno/uso terapéutico , Ibuprofeno/farmacología , Ovulación/efectos de los fármacos , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/farmacología , Gonadotropina Coriónica/administración & dosificación , Gonadotropina Coriónica/uso terapéutico , Estudios Prospectivos , Fertilización In Vitro/métodos , Inducción de la Ovulación/métodosRESUMEN
OBJECTIVE(S): The recommended mode of delivery following pelvic ring fractures with surgical fixation is unclear. The objective of this study was to assess expert opinions from orthopaedic surgeons and obstetrician gynecologists on their recommended delivery recommendations for pregnant individuals with a history of pelvic ring injury, and to see if there was any difference in recommendations between the two specialties, and what factors influenced recommendations. STUDY DESIGN: An electronic, web-based survey was administered to a convenience sample of orthopaedic surgeons and obstetrician gynecologists, via advertisement to members of the Orthopaedic Trauma Association (OTA), the Society for Maternal Fetal Medicine, and querying obstetrician gynecologists practicing within the Military Health System. The survey was administered from November 2021 to December 2022. A two-proportion z-test, Chi-square or Fisher's Exact Test, and descriptive statistics were used to analyze data. RESULTS: Survey respondents included 44 orthopaedic surgeons and 37 obstetricians. A total of 74 % obstetricians would recommend a trial of labor with hardware in place, while orthopaedic surgeon's recommendations varied based on the type of fixation. Forty four, 100 % of orthopaedic surgeons, recommended trial of labor if non-operative pelvic injury or unilateral posterior fixation only, 88 % recommended trial of labor if bilateral posterior fixation only, and 47.7 % for anterior trans-symphyseal plating only, 50 % for unilateral posterior and trans-symphyseal plating, and 43.2 % for bilateral posterior fixation with trans-symphyseal plating. CONCLUSIONS: The results of these surveys demonstrate the lack of consensus as to the most appropriate birth plan for patients with a history of pelvic ring injuries. Vaginal delivery following pelvic ring fracture and fixation is possible, yet these patients are significantly more likely to undergo cesarean section than the general population. As such, we recommend that women who become pregnant after operative treatment of a pelvic ring injury develop an in-depth birthing plan with their obstetrician to determine the best course.
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Cesárea , Fracturas Óseas , Cirujanos Ortopédicos , Huesos Pélvicos , Pautas de la Práctica en Medicina , Humanos , Femenino , Embarazo , Huesos Pélvicos/lesiones , Fracturas Óseas/cirugía , Cesárea/estadística & datos numéricos , Cirujanos Ortopédicos/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Encuestas y Cuestionarios , Obstetricia/métodos , Esfuerzo de Parto , Adulto , GinecologíaRESUMEN
BACKGROUND: Extremity amputations are associated with pain in both the residual limb and the phantom limb. This pain, which is often debilitating, may be prevented by excellent perioperative pain control. Ultrasound-guided percutaneous cryoneurolysis is an analgesic modality offering pain control for weeks or months following surgery. This treatment has not been compared to the sham procedure for large nerves (e.g., femoral and sciatic) to provide preoperative analgesia. We therefore conducted a randomized, controlled pilot study to evaluate the use of this modality for the treatment of pain following amputation to (1) determine the feasibility of and optimize the study protocol for a subsequent definitive clinical trial; and (2) estimate analgesia and opioid reduction within the first postoperative weeks. METHODS: A convenience sample of seven patients undergoing lower extremity amputation were randomized to receive either active cryoneurolysis or a sham procedure targeting the sciatic and femoral nerves in a participant-masked fashion. This was a pilot study with a relatively small number of participants, and therefore the resulting data were not analyzed statistically. RESULTS: Compared to the participants who received sham treatment (n=3), those who underwent active cryoneurolysis (n=4) reported lower pain scores and decreased opioid consumption at nearly all time points between days one and 21 following amputation. CONCLUSIONS: Ultrasound-guided percutaneous cryoneurolysis of the femoral and sciatic nerves prior to lower extremity amputation appears feasible and potentially effective. The data from this pilot study may be used to power a definitive randomized clinical trial.
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OBJECTIVE: The lateral transorbital approach (LTOA) is a relatively new minimal access skull base approach suited for addressing paramedian pathology of the anterior and middle fossa. The authors define target zones for this approach and describe a series of cases with detailed measurements of visual outcomes, including those obtained with exophthalmometry. METHODS: The authors performed a retrospective analysis of a consecutive series of LTOA patients. Seven target zones were identified: 1) the orbit, 2) the lesser sphenoid wing and anterior clinoid, 3) the middle fossa, 4) the lateral wall of the cavernous sinus and Meckel's cave, 5) the infratemporal fossa, 6) the petrous apex, and 7) the anterior fossa. The authors used volumetric analyses of preoperative and postoperative MR and CT imaging data to calculate the volume of bone and tumor removed and to provide detailed ophthalmological, neurological, and cosmetic outcomes. RESULTS: Of the 20 patients in this cohort, pathology was in zone 2 (n = 10), zone 4 (n = 6), zone 3 (n = 2), zone 1 (n = 1), and zone 5 (n = 1). Pathology was meningioma (n = 10), schwannoma (n = 2), metastasis (n = 2), epidermoid (n = 1), dermoid (n = 1), encephalocele (n = 1), adenoma (n = 1), glioblastoma (n = 1), and inflammatory lesion (n = 1). The goal was gross-total resection (GTR) in 9 patients, all of whom achieved GTR. Subtotal resection (STR) was the goal in 8 patients (5 spheno-orbital meningiomas, 1 giant cavernous sinus/Meckel's cave schwannoma, 1 cavernous sinus prolactinoma, and 1 cavernous sinus dermoid), 7 of whom achieved STR and 1 of whom achieved GTR. The goal was biopsy in 2 patient and repair of encephalocele in 1. Visual acuity was stable or improved in 18 patients and worse in 2. Transient early postoperative diplopia, ptosis, eyelid swelling, and peri-orbital numbness were common. All 9 patients with preoperative diplopia improved at their last follow-up. Seven of 8 patients with preoperative exophthalmos improved after surgery (average correction of 64%). There were no cases of clinically significant (> 2 mm) postoperative enophthalmos. The most frequent postoperative complaint was peri-orbital numbness (40%). There was 1 CSF leak. Most patients were satisfied with their ocular (84%-100% of patients provided positive satisfaction-related responses) and cosmetic (75%-100%) outcomes. CONCLUSIONS: The LTOA is a safe minimal access approach to a variety of paramedian anterior skull base pathologies in several locations. Early follow-up revealed excellent resolution of exophthalmos with little risk of clinically significant enophthalmos. Transient diplopia, ptosis, and peri-orbital numbness were common but improved. Careful case selection is critical to ensure good outcome.
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Seno Cavernoso , Quiste Dermoide , Enoftalmia , Exoftalmia , Neurilemoma , Humanos , Diplopía , Seno Cavernoso/diagnóstico por imagen , Seno Cavernoso/cirugía , Encefalocele , Hipoestesia , Estudios Retrospectivos , Exoftalmia/etiología , Exoftalmia/cirugíaRESUMEN
PURPOSE: Fracture blisters, a common soft-tissue complication of pilon fractures, are associated with post-operative wound infections, delays in definitive fixation, and alterations in surgical plan. The purpose of this study was to (1) identify the delay in surgery attributable to the presence fracture blisters and (2) investigate the relationship of fracture blisters to comorbidities and fracture severity. METHODS: Patients with pilon fractures at an urban level 1 Trauma center from 2010 to 2021 were identified. The presence or absence of fracture blisters was noted, along with location. Demographic information, time from injury to external fixator placement, and time to definitive open reduction internal fixation (ORIF) were collected. Pilon fractures were classified according to AO/OTA guidelines using CT imaging and plain radiographs. RESULTS: 314 patients with pilon fractures were available for analysis, eighty (25%) of whom were found to have fracture blisters. Patients with fracture blisters had longer time to surgery compared to those without fracture blisters (14.2 days vs 7.9 days, p < 0.001). A greater proportion of patients with fracture blisters had AO/OTA 43C fracture patterns, compared with those without fracture blisters (71.3% vs 53.8%, p = 0.03). Fractures blisters were less likely to be localized over the posterior ankle (12%, p = 0.007). CONCLUSION: The presence of fracture blisters in pilon fractures are associated with significant delays in time to definitive fixation and higher energy fracture patterns. Fracture blisters are less commonly located over the posterior ankle which may support the implementation of a staged posterolateral approach when managing these injures.
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Fracturas de Tobillo , Traumatismos del Tobillo , Fracturas de la Tibia , Humanos , Vesícula/etiología , Resultado del Tratamiento , Traumatismos del Tobillo/cirugía , Estudios Retrospectivos , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/cirugía , Fracturas de Tobillo/diagnóstico por imagen , Fracturas de Tobillo/cirugía , Fijación de Fractura/efectos adversos , Fijación de Fractura/métodos , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/métodosRESUMEN
OBJECTIVE: Olfactory groove meningiomas (OGMs) often require surgical removal. The introduction of recent keyhole approaches raises the question of whether these tumors may be better treated through a smaller cranial opening. One such approach, the supraorbital keyhole craniotomy, has never been compared with more traditional open transcranial approaches with regard to outcome. In this study, the authors compared clinical, radiographic, and functional quality of life (QOL) outcomes between the keyhole supraorbital approach (SOA) and traditional transcranial approach (TTA) for OGMs. They sought to examine the potential advantages and disadvantages of open/TTA versus keyhole SOA for the resection of OGMs in a relatively case-matched series of patients. METHODS: A retrospective, single-institution review of 57 patients undergoing a keyhole SOA or larger traditional transcranial (frontotemporal, pterional, or bifrontal) craniotomy for newly diagnosed OGMs between 2005 and 2023 was performed. Extent of resection, olfaction, length of stay (LOS), radiographic volumetric assessment of postoperative vasogenic and cytotoxic edema, and QOL (using the Anterior Skull Base Questionnaire) were assessed. RESULTS: Thirty-two SOA and 25 TTA patients were included. The mean EOR was not significantly different by approach (TTA: 99.1% vs SOA: 98.4%, p = 0.91). Olfaction was preserved or improved at similar rates (TTA: 47% vs SOA: 43%, p = 0.99). The mean LOS was significantly shorter for SOA patients (4.1 ± 2.8 days) than for TTA patients (9.4 ± 11.2 days) (p = 0.002). The authors found an association between an increase in postoperative FLAIR cerebral edema and TTA (p = 0.031). QOL as assessed by the ASQB at last follow-up did not differ significantly between groups (p = 0.74). CONCLUSIONS: The keyhole SOA was associated with a statistically significant decrease in LOS and less postoperative edema relative to traditional open approaches.
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BACKGROUND: Endometriosis, i.e., endometrial-like tissue outside the uterus, is a chronic inflammatory condition affecting physical functioning. However, the specific levels of physical activity (PA) in the context of endometriosis and different disease symptoms remain unclear. METHODS: This multi-center, cross-sectional study compared PA levels and influencing factors in endometriosis patients and non-endometriosis patients. Data were collected through questionnaires. Endometriosis was surgically confirmed. A statistical analysis was performed with appropriate tests. RESULTS: The study included 460 women with endometriosis and 460 age-matched women without this condition. The two groups did not differ significantly in terms of age, education level, or stable partnership. Women with endometriosis exhibited lower PA levels, practicing fewer hours of sports weekly and climbing fewer stairs daily compared to the control group. These differences remained significant after controlling for confounding factors. Factors such as endometriosis, current dysmenorrhea, and depression were associated with decreased PA. CONCLUSIONS: These findings suggest that women with endometriosis engage in less PA compared to those without this condition. These results highlight the need for interventions to promote increased PA in endometriosis patients and harness the associated health benefits. Further research is warranted to explore the underlying mechanisms and develop tailored exercise therapies for this population.
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Endometriosis , Deportes , Humanos , Femenino , Estudios Transversales , Ejercicio Físico , Terapia por Ejercicio , Grupos Control , Endometriosis/epidemiologíaRESUMEN
Introduction: Recent evidence shows that endometriosis, a significant cause of infertility, may already present in adolescents. Dysmenorrhea, often leading to school absences, is a key symptom of the maturing menstrual cycle but also of endometriosis. However, it is often perceived as "normal" and left untreated. In adolescents, laparoscopy, the standard procedure to diagnose endometriosis, is performed particularly cautiously. To improve reproductive health in adolescents, we evaluate associations between early menstrual experiences and endometriosis. Methods: Retrospective data on early menstrual experiences from 563 women with surgically/histologically verified endometriosis and from 563 age-matched controls were compared. Study participants were recruited in Switzerland, Germany, and Austria. Information on menstrual experiences was collected via a structured questionnaire. Results: The bivariate analysis showed that early menarche (p = 0.004), dysmenorrhea and negative memories of menarche (p < 0.001) were significantly associated with a diagnosis of endometriosis. After controlling for confounders in bivariate regression analysis occurrence of dysmenorrhea (p = <0.001, OR 5,74, 95% CI 3.82-7.22) especially with onset >3 years after menarche ((p = <0.001, OR 3.42, 95% CI 2.09-5.64) remained statistically significant predictors for diagnosis of endometriosis. Dysmenorrhea in mothers and mothers' perceived attitude towards menstruation were not associated with the occurrence of Endometriosis. Conclusions: Dysmenorrhea and onset of dysmenorrhea at menarche or several years after it are strongly associated with the development of endometriosis. As mothers perceived attitudes towards menstruation show no significant association with their daughters' experiences, physical symptoms accompanying menarche and menstrual period pain in adolescents seem to be very reliable predictors in diagnosis of endometriosis. Therefore, dysmenorrhea in adolescents requires careful investigation of possible endometriosis, especially if it does not respond to medical management. Clinical trials registration: The study was registered on ClinicalTrials.gov, identifier (NCT02511626).
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The on-call orthopaedic surgeon is faced with a wide array of orthopaedic pathology for which intra-articular aspiration, injection, and/or nerve/hematoma block may be used. Efficient use of these diagnostic and therapeutic modalities affords better patient care and a more effective on-call period. Often, these interventions are the rate limiting factor in a reduction or diagnosis. In this review, we describe joint aspirations, saline load tests, hematoma blocks, and nerve blocks in detail to include their indications, techniques, related pharmacology, pearls, and pitfalls.
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Bloqueo Nervioso , Cirujanos Ortopédicos , Ortopedia , Humanos , Bloqueo Nervioso/métodosRESUMEN
Background: While the sexuality of patients with endometriosis is an established topic in research, the possible effect of endometriosis on partnership sexuality has come to the fore only recently. To improve counseling, more information is needed on how both partners experience sexuality in the context of endometriosis. Aim: Previous research regarding endometriosis and sexuality normally focused on one partner to explore couples' intimate relations, whereas this study provides a comparison on both partners' perspectives on their common sexuality. Methods: An overall 302 couples received a questionnaire based on the Brief Index of Sexual Functioning and Sexual History Form, which was modified by endometriosis specialists to better focus on endometriosis-specific aspects. To detect different perspectives on common sexuality within the couple, the Wilcoxon test and the Pearson chi-square test were performed. Outcomes: Various aspects of couple sexuality were assessed by both partners to investigate divergent perspectives between the man and the woman within a couple. Results: On one hand, male and female partners seem to have divergent perspectives on sexual satisfaction in general, desired frequency of sexual contacts, and the question of the female partner engaging in sexual activity despite discomfort. On the other, they have similar perspectives on who takes initiative in sexual contacts, satisfaction with variety in the sexual relationship, and the impact of sexual limitations on their satisfaction within the partnership. Clinical implications: Endometriosis research addressing issues related to sexuality should include male partners; the same applies to consulting women with endometriosis in the context of their relationships rather than as individuals. Strengths and Limitations: This is the first analysis conducted on a larger scale of data from both partners in couples dealing with endometriosis. As it provides quantitative information only, some qualitative information remains unexplored. Conclusion: As both partners showed tendencies to overestimate their partners' sexual satisfaction and had different perspectives on sensitive topics in sexuality, such as the female partner engaging in sexual activity despite discomfort, addressing sexual communication could be a starting point in counseling couples dealing with endometriosis.
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BACKGROUND: San Diego County hospitals commonly care for patients injured by falls from the United States-Mexico border. From 2018 to 2019, the height of >400 miles of an existing border wall was raised. Prior work has demonstrated a 5-fold increase in traumatic border wall fall injuries after barrier expansion. We aimed to examine the impact of a barrier height increase on fracture burden and resource use. METHODS: We performed a retrospective review of patients admitted to a level 1 trauma center from 2016 to 2021 with lower extremity or pelvic fractures sustained from a border wall fall. We defined the pre-wall group as patients admitted from 2016 to 2018 and the post-wall group as those admitted from 2019 to 2021. We collected demographic and treatment data, hospital charges, weight-bearing status at discharge, and follow-up. RESULTS: A total of 320 patients (pre-wall: 45; post-wall: 275) were admitted with 951 lower extremity fractures (pre-wall: 101; post-wall: 850) due to border wall fall. Hospital resources were utilized to a greater extent post-wall: a 537% increase in hospital days, a 776% increase in intensive care unit days, and a 468% increase in operative procedures. Overall, 86% of patients were non-weight-bearing on at least 1 lower extremity at discharge; 82% were lost to follow-up. CONCLUSION: Traumatic lower extremity fractures sustained from border wall fall rapidly rose after the wall height increase. Hospital resources were used to a greater extent. Patients were frequently discharged with weight-bearing limitations and rarely received scheduled follow-up care. Policymakers should consider the costs of caring for border fall patients, and access to follow-up should be expanded.
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Fracturas Óseas , Huesos Pélvicos , Humanos , Estados Unidos , Fracturas Óseas/terapia , Hospitalización , Centros Traumatológicos , Huesos Pélvicos/lesiones , Estudios RetrospectivosRESUMEN
BACKGROUND: The most common presenting symptom in patients with both small and large Rathke cleft cysts (RCC) is headache (H/A). It is well established that patients with large RCC can have significant symptomatic improvement after cyst drainage. However, patients with small RCC (≤ 1 cm) are rarely operated on, even if they present with debilitating H/A. It is not well understood whether resection of these smaller RCCs can lead to durable H/A resolution. METHODS: A retrospective search of our institutional database for sub-centimeter RCCs presenting with intractable H/A and treated with an endoscopic endonasal approach was carried out. A detailed H/A questionnaire as well as patient chart review was conducted to assess the long-term outcome of these patients after surgical intervention. RESULTS: Ten consecutive patients with 11 endonasal surgeries met inclusion criteria. Eight responded to the questionnaire. The median cyst diameter was 6 mm (IQR 3-9). Median preoperative H/A duration was 12 months (range 2 months-15 years). H/As occurred on average for 20 days per month and all required analgesics for symptomatic control for more than 15 of these 20 days. Half of the patients also had to miss work because of H/A. Average preoperative H/A intensity was 8.7 (scale 0-10) compared with postoperative scores of 2.9 at one month, 1.6 at 3 months, and 0.9 at 1 year. There were no permanent endocrinological or other surgical complications. After a median follow-up of 2 years, one patient had radiographic and symptomatic recurrence which resolved after re-operation. CONCLUSIONS: Endoscopic fenestration of sub-centimeter RCCs provides a safe and durable treatment for patients with intractable H/A.
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Carcinoma de Células Renales , Quistes del Sistema Nervioso Central , Quistes , Neoplasias Renales , Humanos , Estudios Retrospectivos , Cefalea/etiología , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Quistes del Sistema Nervioso Central/cirugía , Quistes del Sistema Nervioso Central/complicaciones , Quistes/diagnóstico por imagen , Quistes/cirugía , Quistes/complicaciones , Resultado del TratamientoRESUMEN
Introduction: The number of frozen embryo transfers increased substantially in recent years. To increase the chances of implantation, endometrial receptivity and embryo competency must be synchronized. Maturation of the endometrium is facilitated by sequential administration of estrogens, followed by administration of progesterone prior to embryo transfer. The use of progesterone is crucial for pregnancy outcomes. This study compares the reproductive outcomes and tolerability of five different regimens of hormonal luteal phase support in artificial frozen embryo transfer cycles, with the objective of determining the best progesterone luteal phase support in this context. Design: This is a single-center retrospective cohort study of all women undergoing frozen embryo transfers between 2013 and 2019. After sufficient endometrial thickness was achieved by estradiol, luteal phase support was initiated. The following five different progesterone applications were compared: 1) oral dydrogesterone (30 mg/day), 2) vaginal micronized progesterone gel (90 mg/day), 3) dydrogesterone (20 mg/day) plus micronized progesterone gel (90 mg/day) (dydrogesterone + micronized progesterone gel), 4) micronized progesterone capsules (600 mg/day), and (5) subcutaneous injection of progesterone 25 mg/day (subcutan-P4). The vaginal micronized progesterone gel application served as the reference group. Ultrasound was performed after 12-15 days of oral estrogen (≥4 mg/day) administration. If the endometrial thickness was ≥7 mm, luteal phase support was started, up to six days before frozen embryo transfer, depending on the development of the frozen embryo. The primary outcome was the clinical pregnancy rate. Secondary outcomes included live birth rate, ongoing pregnancy, and miscarriage and biochemical pregnancy rate. Results: In total, 391 cycles were included in the study (median age of study participants 35 years; IQR 32-38 years, range 26-46 years). The proportions of blastocysts and single transferred embryos were lower in the micronized progesterone gel group. Differences among the five groups in other baseline characteristics were not significant. Multiple logistic regression analysis, adjusting for pre-defined covariates, showed that the clinical pregnancy rates were higher in the oral dydrogesterone only group (OR = 2.87, 95% CI 1.38-6.00, p=0.005) and in the dydrogesterone + micronized progesterone gel group (OR = 5.19, 95% CI 1.76-15.36, p = 0.003) compared to micronized progesterone gel alone. The live birth rate was higher in the oral dydrogesterone-only group (OR = 2.58; 95% CI 1.11-6.00; p=0.028) and showed no difference in the smaller dydrogesterone + micronized progesterone gel group (OR = 2.49; 95% CI 0.74-8.38; p=0.14) compared with the reference group. Conclusion: The application of dydrogesterone in addition to micronized progesterone gel was associated with higher clinical pregnancy rate and live birth rate and then the use of micronized progesterone gel alone. DYD should be evaluated as a promising LPS option in FET Cycles.
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Didrogesterona , Progesterona , Embarazo , Femenino , Humanos , Adulto , Fase Luteínica , Estudios Retrospectivos , Transferencia de Embrión , Resultado del Embarazo , EstrógenosRESUMEN
RESEARCH QUESTION: Does antioestrogen effect of clomiphene citrate (CC) on the endometrium reduce implantation and thereby decrease pregnancy and live birth rate per transferred embryo? METHODS: In this cohort, unstimulated IVF cycles modified with clomiphene citrate (CC-NC-IVF) and unstimulated, natural IVF cycles (NC-IVF) conducted between 2011 and 2016 were included. CC was applied in a dosage of 25mcg per day, starting on cycle day 7 until ovulation trigger day. Primary outcomes were clinical pregnancy rate, defined as amniotic sac visible in ultrasound, and live birth rate per transferred embryo. Miscarriage rate calculated as amniotic sac not ending in a live birth was secondary outcome. A modified mixed-effect Poisson regression model was applied, and adjustments were made for female age, parity, type and cause of infertility. Additionally, stratification by parity and age was performed. RESULTS: Four hundred and ninety-nine couples underwent a total of 1042 IVF cycles, 453 being NC-IVF and 589 being CC-NC-IVF cycles. Baseline characteristics of both groups did not differ. Addition of CC did neither decrease clinical pregnancy rate (aRR 0.86; 95% CI 0.67-1.12) nor live birth rate per transferred embryo (aRR 0.84; 95% CI 0.62-1.13) in comparison with NC-IVF. Miscarriage rate did not differ between CC-NC-IVF and NC-IVF (aRR 0.95; 95% CI 0.57-1.57). CONCLUSION: Low-dose CC does not reduce pregnancy or live birth rate per transferred embryo. It can be used in infertility treatment without negatively affecting the endometrium and implantation.
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Aborto Espontáneo , Infertilidad , Embarazo , Femenino , Humanos , Tasa de Natalidad , Fertilización In Vitro , Aborto Espontáneo/epidemiología , Aborto Espontáneo/tratamiento farmacológico , Estudios Retrospectivos , Clomifeno/uso terapéutico , Índice de Embarazo , Infertilidad/tratamiento farmacológico , Nacimiento Vivo , Inducción de la OvulaciónRESUMEN
Research suggests that gonadotropin stimulation in in vitro fertilization (IVF) treatment affects embryo quality and the endometrium that might influence embryo implantation, placentation and establishment of a viable pregnancy. We assessed the impact of gonadotropin stimulation on implantation, live birth and miscarriage rates per transferred embryo by comparing stimulated and unstimulated IVF treatment. In a cohort of 728 couples, 1310 IVF cycles with successful embryo transfer were analysed; 857 cycles were stimulated with gonadotropins > 75 IU/day (333 poor responder < 4 oocytes; 524 normal responders), and 453 were unstimulated. In total, 1913 fresh cleavage-stage embryos were transferred. Zygote but no embryo selection was performed, and supernumerous zygotes were vitrified. The implantation rate was defined as number of sonographically detected amniotic sacs; live birth rate as number of children born per transferred embryo. Modified mixed effect Poisson regression was used to account for the dependency of cycles and embryos within the same women and the same transfer cycle. Adjustments were made for maternal age, parity, primary or secondary infertility and indication for IVF. Per transferred embryo, implantation rates (rate ratio (RR) 1.37; 95% CI 1.04-1.81; p = 0.028; aRR 1.42; 95% CI 1.10-1.84; p = 0.008) and live birth rates (RR 1.33; 95% CI 0.95-1.86; p = 0.093; aRR 1.38; 95% CI 1.01-1.88; p = 0.044) were higher in NC-IVF compared to cIVF normal responders. Miscarriage did not differ (RR 0.99; 95% CI 0.59-1.65; p = 0.965; aRR 0.90; 95% CI 0.52-1.53 p = 0.698). Similar results were obtained in poor responders. The study suggests an impact of gonadotropin stimulation on the implantation potential of embryos.
Asunto(s)
Aborto Espontáneo , Embarazo , Humanos , Femenino , Tasa de Natalidad , Índice de Embarazo , Fertilización In Vitro/métodos , Implantación del Embrión , Gonadotropinas/uso terapéutico , Nacimiento Vivo , Estudios RetrospectivosRESUMEN
BACKGROUND: Pain plays a central role in endometriosis. The complex relationship among pain characteristics, comorbid pain disorders and daily life represents a challenge for medical support. This multicentre cross-sectional case-control study analysed the association between endometriosis-related chronic pain and functions of daily life in 510 women with endometriosis, 265 (52%) who experienced chronic pain, either from endometriosis alone (N = 134, 26.3%) or in association with additional pain disorders (N = 131, 25.7%). METHODS: Self-administered questionnaires from the Brief Pain Inventory and the Pain Disability Index were used to investigate associations between pain characteristics (frequency, duration, intensity) and daily life. Also, associations between different endometriosis characteristics (rASRM stage, presence of adhesions, localisation of lesions) and pain were evaluated. RESULTS: Chronic pain is negatively associated with almost all (12/14) aspects of daily life investigated, including standing, walking, sitting, defaecation, sleep, sports activities, family and domestic responsibilities, sexuality, social functioning, professional life, mood, and joy of life. Altogether, 33.7% of women with chronic pain reported moderate and 27.5% severe limitations. Comorbid pain disorders resulted in significantly more limitations. The length of pain episodes showed a particularly important influence, especially for family/domestic responsibilities (OR 22.94, p < 0.001), professional life (OR 16.56, p < 0.001) and social functioning (OR 41.03, p < 0.001). CONCLUSIONS: Our data confirm that despite treatment, about 50% of women experience pain. Pain was associated with at least moderate negative effects on almost all areas of daily life; additional pain comorbidities increased limitations. Improving pain management is essential for improving quality of life in women with endometriosis. SIGNIFICANCE: The study provides an accurate overview of the impact of endometriosis-associated pain on daily life. This is important because pain plays a central role in women living with endometriosis, and despite modern therapies, many women continue to suffer from chronic pain. The detailed analysis of its impact with a comprehensive survey of all aspects of daily life in a very large study population is unique. We expect an improved understanding of consequences of pain to significantly advance medical support in these patients.