RESUMEN
RESEARCH QUESTION: Is sphingosine 1-phosphate (S1P) pathway involved in the process of fibrosis in adenomyosis? DESIGN: RNA was extracted from paraffin-embedded slices collected from the ectopic endometrium of patients with nodular adenomyosis (nâ¯=â¯27) and eutopic endometrium of healthy controls women (nâ¯=â¯29). Expression of genes involved in the metabolism and signalling of S1P, and actin-alpha-2 smooth muscle, encoded by ACTA2 gene, a gene involved in fibrogenesis, was evaluated by real-time polymerase chain reaction analysis. RESULTS: In adenomyotic samples, the expression of sphingosine kinase 1 (SPHK1), the enzyme responsible for the synthesis of S1P, and of S1P phosphatase 2 (SGPP2), the enzyme responsible for the conversion of S1P back to sphingosine, was lower (Pâ¯=â¯0.0006; Pâ¯=â¯0.0015), whereas that of calcium and integrin-binding protein 1, responsible for membrane translocation of SPHK1, was higher (Pâ¯=â¯0.0001) compared with healthy controls. In S1P signalling, a higher expression of S1P receptor S1P3 (Pâ¯=â¯0.001), and a lower expression of S1P2 (Pâ¯=â¯0.0019) mRNA levels, were found compared with healthy endometrium. In adenomyotic nodules, a higher expression of ACTA2 mRNA levels were observed (Pâ¯=â¯0.0001), which correlated with S1P3 levels (Pâ¯=â¯0.0138). CONCLUSION: Present data show a profound dysregulation of the S1P signalling axis in adenomyosis. This study also highlights that the bioactive sphingolipid might be involved in the fibrotic tract of the disease, correlated with the expression of ACTA2, suggesting its role as novel potential biomarker of adenomyosis.
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Adenomiosis , Esfingosina , Adenomiosis/genética , Adenomiosis/metabolismo , Femenino , Fibrosis , Humanos , Lisofosfolípidos/genética , Lisofosfolípidos/metabolismo , ARN Mensajero , Esfingosina/análogos & derivados , Esfingosina/genética , Esfingosina/metabolismoRESUMEN
OBJECTIVE: To evaluate the different effects of a progestin-only contraceptive with desogestrel (DSG) vs combined oral contraceptives (COCs) for a first line long-term treatment of endometriosis-related pain among patients seeking hormonal contraception. METHODS: An observational retrospective cohort study was conducted in collaboration with a local outpatient clinic for endometriosis among a group of nulliparous young women (n = 216) with endometriosis-related pain and seeking contraception. The cohort was subdivided into a group (n = 73) treated as first line by DSG and another group (n = 75) treated by a COC. During the study, clinical symptoms, side effects and possible changes in OC type use were recorded. RESULTS: No significant difference was found between the two groups in terms of clinical characteristics and pain scores before treatment. After 6 months both treatments were effective in reducing endometriosis-related pain, and those treated with DSG showed lower levels of dysmenorrhea, dyspareunia and nonmenstrual pelvic pain than COCs group (p < .01). After 12 months, in DSG Group some patients (15%) switched from DSG to a COC for breakthrough bleeding, whereas in COC Group 48% of patients switched to another type of COC for reduced efficacy on pain and/or for side effects. After 3 years of OC treatment, in DSG Group 79% of patients maintained the same therapy, whereas in COC Group only 14% continued the same COC type, 37% switched to another COC and 47% to DSG. CONCLUSIONS: A progestin-only contraceptive with DSG is a valid option for long term management of endometriosis-related pain in patients seeking hormonal contraception.
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Endometriosis , Anticoncepción , Anticonceptivos Orales Combinados/efectos adversos , Desogestrel/efectos adversos , Endometriosis/complicaciones , Endometriosis/tratamiento farmacológico , Etinilestradiol/uso terapéutico , Femenino , Anticoncepción Hormonal , Humanos , Masculino , Dolor Pélvico/tratamiento farmacológico , Dolor Pélvico/etiología , Congéneres de la Progesterona , Progestinas/uso terapéutico , Estudios RetrospectivosRESUMEN
STUDY OBJECTIVE: To investigate the clinical and surgical predictors of urinary tract endometriosis (UTE) relapse. DESIGN: Retrospective single institutional study. SETTING: Italian multidisciplinary referral center for endometriosis. PATIENTS: Consecutive patients affected by UTE and surgically treated between January 2016 and March 2020. INTERVENTION: Surgical excision for UTE. Uni- and multivariate logistic regression analyses were fitted to evaluate clinical and surgical predictors of recurrence. MEASUREMENTS AND MAIN RESULTS: A total of 105 female age-reproductive patients were enrolled. Median age was 32 years (interquartile range, 24-37). Ureteral involvement was recorded in 53 patients (50.5%), being unilateral and bilateral in 46 patients (43.8%) and 7 patients (6.7%), respectively. Bladder involvement occurred in 52 patients (49.5%). Open surgical approach was performed in 24 cases (22.9%), whereas 30 patients (28.5%) and 51 patients (48.6%) were treated with laparoscopic and robot-assisted approach, respectively. Overall, 53 patients (50.5%) received adjuvant hormonal therapy. At a median follow-up of 39 months (interquartile range, 22-51), 30 patients (28.6%) experienced disease relapse, with 14 recurrences (13.3%) recorded at the level of the urinary tract. At multivariable analysis, age at first surgery <25 years (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.10-1.84; p = .02) and the presence of a concomitant autoimmune disease (OR, 1.45; 95% CI, 1.24-2.17; p = .02) were found as predictors of deep infiltrating endometriosis recurrence, whereas adjuvant postsurgical therapy showed a protective role (OR, 0.83; 95% CI, 0.53-0.98; p = .01). CONCLUSIONS: Young age (<25 years) and the presence of autoimmune diseases were significant predictors for the development of disease recurrence, whereas adjuvant hormonal therapy showed a protective role.
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Endometriosis , Laparoscopía , Enfermedades Ureterales , Sistema Urinario , Adulto , Endometriosis/complicaciones , Endometriosis/cirugía , Femenino , Humanos , Laparoscopía/efectos adversos , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Enfermedades Ureterales/prevención & control , Enfermedades Ureterales/cirugíaRESUMEN
RESEARCH QUESTION: How effective is medical hormonal treatment in preventing endometriosis recurrence and in improving women's clinical symptoms and quality of life? DESIGN: This observational cross-sectional study evaluated the effects of hormonal medical treatment (progestins, gonadotrophin-releasing hormone analogues or continuous oral contraceptives) on endometriosis recurrence, current clinical symptoms and quality of life in three groups of patients: Group A (n = 34), no hormonal treatment either before or after the first endometriosis surgery; Group B (n = 76), on hormonal treatment after the first endometriosis surgery; and Group C (n = 75), on hormonal treatment both before and after the first endometriosis surgery. RESULTS: Group C patients were characterized by a lower rate of endometriosis reoperation (P = 0.011) and a lower rate of dysmenorrhoea (P = 0.006). Women who experienced repetitive endometriosis surgery showed worse physical (P = 0.004) and mental (P = 0.012) status than those who received a single surgery, independent of the treatment. CONCLUSION: Hormonal treatments represent a valid cornerstone of endometriosis management and may be useful as an alternative to surgery, but also before surgery, to plan better, and after surgery in order to reduce the risk of recurrence. Medical counselling is very helpful in choosing the correct and individualized endometriosis treatment. In fact, the gold standard for modern endometriosis management is the individualized approach and surgery should be considered, depending on the clinical situation and a patient's symptoms.
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Endometriosis/tratamiento farmacológico , Procedimientos Quirúrgicos Ginecológicos/estadística & datos numéricos , Hormonas/administración & dosificación , Reoperación/estadística & datos numéricos , Prevención Secundaria/estadística & datos numéricos , Adulto , Estudios Transversales , Endometriosis/cirugía , Femenino , Humanos , Adulto JovenRESUMEN
Primary dysmenorrhea (PD) is the most common gynecologic disorder during adolescence and it is characterized by crampy lower abdominal pain that occurs during menstruation. Secondary dysmenorrhea, in contrast, has the same clinical features but occurs in women with a disease that could account for their symptoms (endometriosis, adenomyosis, uterine fibroids, pelvic inflammatory disease). Endometriosis is the most common cause of secondary dysmenorrhea and it should be considered in patients with persistent and clinically significant dysmenorrhea despite treatment. It is often diagnosed after a long delay, increasing the likelihood of pain chronicity and fertility problems at a later age. Women who suffer from dysmenorrhea in adolescence have higher risk of endometriosis in future. The open question is if endometriosis was already present at the onset of dysmenorrhea but undiagnosed or if PD favors subsequent development of endometriosis-associated pain. Since PD is associated with higher risk for developing chronic pain state and shares some of the same pain pathways of endometriosis (prostaglandins overproduction, inflammation, peripheral sensitization, central sensitization and abnormal stress responses), a correlation between PD and endometriosis is suggested. To know whether it is a risk factor for the development of endometriosis-associated pain may provide an opportunity for early intervention and prevention. The present review aims to investigate the clinical and pathogenetic features of PD and endometriosis in order to identify a possible association between the two conditions.
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Dismenorrea/fisiopatología , Endometriosis/fisiopatología , Inflamación/fisiopatología , Anticonceptivos Orales Combinados/uso terapéutico , Dismenorrea/inmunología , Endometriosis/inmunología , Femenino , Humanos , Inflamación/inmunología , Dolor Pélvico/inmunología , Dolor Pélvico/fisiopatología , Factores de RiesgoRESUMEN
Endometriosis is a gynecological disease characterized by pain and infertility. The diagnosis is very often made during the infertility work-up, together with other reproductive diseases and uterine disorders. A retrospective cohort study was conducted on infertile women with clinical or ultrasound suspect of endometriosis, undergoing an ultrasound (US) evaluation by a team of expert sonographers (n = 419), with the aim to evaluate the prevalence of concomitant uterine disorders. The US coexistence of endometriosis with uterine fibroids and/or adenomyosis was investigated according to three age intervals (<35years; 35 ≥ years <45; ≥45 years) and to endometriosis phenotypes: ovarian endometriosis (OMA), deep infiltrating endometriosis (DIE), or both. The US diagnosis of fibroids was made in 3.1% of cases, adenomyosis was found in 21.2%, and the co-existence of both uterine disorders with endometriosis was reported in 14.6% of patients. When analyzed according to age, patients aged >35 years were more likely to be affected by uterine fibroids (p = .003), adenomyosis (p = .030) and both adenomyosis and fibroids (p < .0001). No statistically significant association was found between endometriosis phenotypes and myometrial pathologies. Uterine disorders coexistence should be considered in the assessment of women with endometriosis, in order to better define a treatment strategy for infertility, especially in women older than 35 years.
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Endometriosis/diagnóstico , Infertilidad Femenina/diagnóstico , Enfermedades Peritoneales/diagnóstico , Enfermedades Uterinas/diagnóstico , Útero/diagnóstico por imagen , Adenomiosis/complicaciones , Adenomiosis/diagnóstico , Adenomiosis/epidemiología , Adulto , Estudios de Cohortes , Comorbilidad , Endometriosis/complicaciones , Endometriosis/epidemiología , Femenino , Humanos , Infertilidad Femenina/complicaciones , Infertilidad Femenina/epidemiología , Leiomioma/complicaciones , Leiomioma/diagnóstico , Leiomioma/epidemiología , Persona de Mediana Edad , Enfermedades Peritoneales/complicaciones , Enfermedades Peritoneales/epidemiología , Estudios Retrospectivos , Ultrasonografía , Enfermedades Uterinas/complicaciones , Enfermedades Uterinas/epidemiología , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/epidemiología , Útero/patologíaRESUMEN
We assessed the outcome of pregnancy in women with a history of recurrent pregnancy loss (RPL) following treatment with low-dose human menopausal gonadotropin (HMG)+progesterone or progesterone alone. This single-center retrospective cohort study included data from women diagnosed with RPL and treated between February 2005 and December 2012 with one cycle of HMG + progesterone or progesterone alone. Primary endpoint was the rate of ongoing pregnancies and losses by treatment, age (<38 vs. ≥38 years) and in the subgroup with unexplained RPL. Of 169 RPL patients, 35.5% (n = 60) received HMG + progesterone and 64.5% (n = 109) progesterone alone. Compared to progesterone alone, HMG + progesterone led to a lower, although not significant, frequency of losses (3.3% vs. 11.9%, p = .09) and a twofold higher rate of ongoing pregnancies (41.7% vs. 19.3%, p = .002). Similar results were obtained in the subgroup of patients with unexplained RPL (ongoing pregnancies: 48.1% upon HMG + progesterone vs. 21.3% upon progesterone, p = .03; losses: 0% vs. 8.5%, respectively, p = .29) and in those <38 years (ongoing pregnancies: 47.4% vs. 18.8%, respectively, p = .003; losses: 5.3% vs. 10.9% respectively, p = .47). These findings suggest that HMG in women with RPL may reduce the rate of miscarriages and increase that of live births regardless of RPL cause and in women aged <38 years.
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Aborto Habitual , Infertilidad Femenina , Menotropinas/administración & dosificación , Inducción de la Ovulación/métodos , Progesterona/administración & dosificación , Adolescente , Adulto , Femenino , Humanos , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: The objective of the study was to evaluate the correlation between endometrioma-associated pain and lesion vascularization as measured with 3-dimensional power Doppler transvaginal sonography. METHODS: Endometriomas were examined, and 4 indices were obtained: mean grayness, flow index, vascularization index, and vascularization-flow index. Dysmenorrhea, chronic pelvic pain, and dyspareunia were analyzed in terms of severity, presence/absence, and duration. RESULTS: Twenty-nine women were selected. The univariable association of painful symptoms in terms of presence/absence and duration was low with the exception of mean grayness with the presence of chronic pelvic pain (ß = -0.106; P = .047; 95% confidence interval, 0.810 to 0.998). The R2 value increased to 0.226 for dysmenorrhea (ß = -0.475; P = .029) when analyzing the association between the vascularization index and the severity of painful symptoms. The visual analog scale scores for chronic pelvic pain and dyspareunia were higher (R2 = 0.300; ß = -0.547 and -0.548, respectively; P = .028 and .053). CONCLUSIONS: We observed an inverse association between the severity of pain and endometrioma vascularization. Further larger studies are required to confirm our findings.
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Endometriosis/complicaciones , Endometriosis/diagnóstico por imagen , Imagenología Tridimensional/métodos , Enfermedades del Ovario/diagnóstico por imagen , Dolor Pélvico/etiología , Ultrasonografía Doppler/métodos , Adulto , Femenino , Humanos , Enfermedades del Ovario/complicaciones , Ovario/diagnóstico por imagen , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
We report a rare case of rectus abdominis muscle endometriosis excised under ultrasound guidance. A 36-year-old woman came to our observation presenting an abdominal nodule located in the right side of the umbilical area. Ultrasound of the abdominal wall showed two hypoechogenic nodules in the context of the right rectus abdominis muscle and a fine-needle aspiration, performed under ultrasound guidance, confirmed the diagnosis of endometriosis. The patient underwent surgical excision of the lesions. Intraoperative localization was performed through ultrasonography. In our case, the diagnosis was essentially based on ultrasound scan. Computed tomography and magnetic resonance imaging were not performed. A high-resolution ultrasound is a simple, inexpensive and safe method and is sufficient for indicating surgery. Furthermore, the use of intraoperative ultrasound allowed adequate margins of excision.
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Endometriosis/cirugía , Enfermedades Musculares/cirugía , Recto del Abdomen/cirugía , Adulto , Endometriosis/diagnóstico por imagen , Femenino , Humanos , Enfermedades Musculares/diagnóstico por imagen , Recto del Abdomen/diagnóstico por imagen , UltrasonografíaRESUMEN
PURPOSE: Adnexal masses represent a common finding among both premenopausal and postmenopausal women. This article will concentrate on the importance of an accurate preoperative diagnosis of adnexal masses that may be encountered in the course of an assessment of the female pelvis. The ultrasonographic modalities including two-dimensional, Doppler, three-dimensional and real-time four-dimensional approach, the accuracy of the technique, and the role of second-level exam will be discussed. METHODS: In this review, we searched for the most relevant articles on the topic with a special focus on the importance of an accurate preoperative diagnosis of adnexal masses, the different ultrasonographic modalities, and the role of second-level exam. RESULTS: The primary goal of diagnostic evaluation is to exclude malignancy. Furthermore, differentiation among pelvic masses with non-malignant features is relevant as well since suitable counseling and treatment depend on the suspected histology. Ultrasound represents the first-line modality for assessing adnexal masses and showed a very accurate examination. Ultrasound, performed by experienced operators, is effective in the morphologic evaluation of the adnexal masses and is useful in discriminating between benign and malignant lesions. Second-level exams may include assessment by an experienced ultrasound examiner, magnetic resonance imaging, and computed tomography. CONCLUSION: Ultrasound represents the first-line modality for assessing adnexal masses. Predicting the nature of an adnexal mass is essential regarding counseling, clinical management and surgical planning in such patients. Pattern recognition can accurately diagnose the majority of the benign masses and malignancies.
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Enfermedades de los Anexos/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Femenino , Humanos , Cuidados Preoperatorios/métodos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
The present narrative review aims to discuss the available data on the incidence and the risk factors of uterine fibroids (UFs) recurrence after different types of conservative surgical or radiologic procedures in women wishing to preserve their uterus. UFs are the most common benign tumors in women all over the world. Clinical presentation, including abnormal uterine bleeding (AUB), pelvic pain, bulky symptoms, and infertility affect patients' quality of life, and a large variety of conservative treatments are available especially for those with desire of pregnancy. Fertility sparing surgery, by either laparoscopy, hysteroscopy or laparotomy, or radiological interventions (uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound), are the most common therapeutic approaches. However, the genetic or acquired predisposition to UFs remain despite the treatments, and the recurrences are frequently described in a large percentage of patients. The most relevant risk factors for recurrence of UFs are young age at the first surgery, incomplete fibroid resection, the presence of multiple lesions, an enlarged uterus, and the coexistence with other pelvic diseases. The discussion on the possible medical strategy to reduce the recurrence is an open field of clinical investigation, in particular by using hormonal drugs.
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Leiomioma , Recurrencia Local de Neoplasia , Neoplasias Uterinas , Humanos , Femenino , Leiomioma/cirugía , Leiomioma/diagnóstico por imagen , Neoplasias Uterinas/cirugía , Factores de Riesgo , Embolización de la Arteria UterinaRESUMEN
Diaphragmatic endometriosis (DpE) is a rare disease localization which represents an important clinical challenge. The main criticisms toward the proper DpE management consist of poor consensus on both surgical indications and the choice between different surgical techniques available to treat the disease. Furthermore, only weak recommendations are provided by current guidelines and surgical management is mostly based on surgeon's experience. As consequence, the lack of standardization about the surgical treatment led to the risk of under- or over-treatments in patients suffering from this form of endometriosis. The latest evidence-based data suggest to adopt a lesion-oriented surgical approach serving as a guide in daily surgical activities, in order to ensure a tailored radicality and reduce the rate of surgery-related complications. Diaphragmatic endometriosis surgery should be performed only by expert surgeons with an extensive oncogynecologic expertise since it represents a technically demanding procedure. A multidisciplinary approach is also mandatory in order to adequately select and treat these patients by minimizing the risk of additional morbidity.
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Diafragma , Endometriosis , Humanos , Endometriosis/cirugía , Femenino , Diafragma/cirugíaRESUMEN
Adenomyosis is a common benign uterine disorders and patients may present dysmenorrhea, dyspareunia, abnormal uterine bleeding (AUB) and infertility. The treatment is very complex, including medical, surgical or radiological approaches. Hormonal drugs represent the first line therapy of adenomyosis, highly effective on symptoms and uterine volume reduction. Radiological procedures (UAE and HIFU), RFA and hysteroscopy may be proposed in those cases in which medical therapy is ineffective. Considering surgical treatment, hysterectomy remains the only existing definitive treatment but in the last decades the desire of uterus preservation is becoming more and more diffuse. On the other hand, surgical conservative treatments of adenomyosis are very effective in ameliorating AUB and pelvic pain and in reducing uterine volume, with some post-operative risks and obstetrics complications. Cytoreductive surgery for adenomyosis may be very complex, therefore it should be performed by experienced surgeons in dedicated centers, above all in case of concomitant endometriosis.
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Adenomiosis , Tratamiento Conservador , Humanos , Femenino , Adenomiosis/cirugía , Tratamiento Conservador/métodos , Histeroscopía/métodos , Útero/cirugía , Útero/diagnóstico por imagen , Histerectomía/métodos , Tratamientos Conservadores del Órgano/métodosRESUMEN
Deep endometriosis (DE) can be localized in the parametrium, a complex bilateral anatomical structure, sometimes necessitating intricate surgical intervention due to the potential involvement of autonomic nerves, uterine artery, and ureter. If endometriotic ovarian cysts have been considered metaphorically representative of "the tip of the iceberg" concerning concealed DE lesions, it is reasonable to assert that parametrial lesions should be construed as the most profound region of this iceberg. Also, based on a subdual clinical presentation, a comprehensive diagnostic parametrial evaluation becomes imperative to strategize optimal management for patients with suspected DE. Recently, the ULTRAPARAMETRENDO studies aimed to evaluate the role of transvaginal ultrasound for parametrial endometriosis, showing distinctive features, such as a mild hypoechoic appearance, starry morphology, irregular margins, and limited vascularization. The impact of medical therapy on parametrial lesions has not been described in the current literature, primarily due to the lack of adequate detection at imaging. The extension of DE into the parametrium poses significant challenges during the surgical approach, thereby increasing the risk of intra- and postoperative complications, mainly if performed by centers with low expertise and following multiple surgical procedures where parametrial involvement has gone unrecognized. Over time, the principles of nerve-sparing surgery have been incorporated into the surgical DE treatment to minimize iatrogenic damage and potentially reduce the risk of functional complications.
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Endometriosis , Endometriosis/patología , Endometriosis/diagnóstico por imagen , Endometriosis/cirugía , Humanos , Femenino , UltrasonografíaRESUMEN
Background: In February 2021, a few cases of unusual, severe thrombotic events associated with thrombocytopenia reported after vaccination with ChAdOx1 nCoV-19 (Vaxzevria) or with Johnson & Johnson's Janssen vaccine raise concern about safety. The vaccine-induced thrombotic thrombocytopenia (VITT) has been related to the presence of platelet-activating antibodies directed against platelet Factor 4. Objectives: We investigated VITT subject genetic background by a high-throughput whole exome sequencing (WES) approach in order to investigate VITT genetic predisposition. Methods: Six consecutive patients (females of Caucasian origin with a mean age of 64 years) were referred to the Atherothrombotic Diseases Center (Department of Experimental and Clinical Medicine, Azienda Ospedaliero-Universitaria Careggi, Florence) with a diagnosis of definite VITT underwent WES analysis. WES analysis was performed on the Illumina NextSeq500 platform. Results:WES analysis revealed a total of 140,563 genetic variants. Due to VITT's rare occurrence, we focused attention on rare variants. The global analysis of all high-quality rare variants did not reveal a significant enrichment of mutated genes in biological/functional pathways common to patients analyzed. Afterwards, we focused on rare variants in genes associated with blood coagulation and fibrinolysis, platelet activation and aggregation, integrin-mediated signaling pathway, and inflammation with particular attention to those involved in vascular damage, as well as autoimmune thrombocytopenia. According to ACMG criteria, 47/194 (24.2%) rare variants were classified as uncertain significance variants (VUS), whereas the remaining were likely benign/benign. Conclusion: WES analysis identifies rare variants possibly favoring the prothrombotic state triggered by the exposure to the vaccine. Functional studies and/or extensions to a larger number of patients might allow a more comprehensive definition of these molecular pathways.
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Secuenciación del Exoma , Humanos , Persona de Mediana Edad , Femenino , Anciano , Trombocitopenia/genética , Trombocitopenia/inducido químicamente , ChAdOx1 nCoV-19/efectos adversos , Trombosis/genética , Predisposición Genética a la Enfermedad , Factor Plaquetario 4/genética , Masculino , Vacunación/efectos adversosRESUMEN
Estrogen dependence and progesterone resistance play a crucial role in the origin and development of endometriosis. Therefore, hormonal therapies are currently the most effective treatment. Progestins are considered the first-line approach, especially for a long-term management. Progestins are synthetic compounds that mimic the effects of progesterone by binding progesterone receptors. Continuous use of progestins leads to the suppression of ovarian steroidogenesis with anovulation and low serum levels of ovarian steroids, causing endometrial pseudodecidualization. Moreover, they act by interfering on several endometriosis pathogenetic pathways, decreasing inflammation, provoking apoptosis in endometriotic cells, stimulating atrophy or regression of endometrial lesions, inhibiting angiogenesis, and decreasing expression of metalloproteinases, thus diminishing the invasiveness of endometriotic implants. Progestins are effective for pain relief and improvement of the quality of life (QoL). The side effects are limited, and the compounds are available in different formulations and routes of administration and represent, in most cases, an inexpensive treatment option. Dienogest, Medroxyprogesterone acetate and Norethisterone acetate are the labeled progestins for endometriosis, but other progestins, such as Dyhidrogesterone, Levonorgestrel and Desogestrel, have been shown to be effective in the treatment of endometriosis-associated pain. The present review aims to describe the available and emerging evidences on progestins used for the treatment of endometriosis.
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Endometriosis , Progestinas , Femenino , Humanos , Progestinas/uso terapéutico , Progestinas/farmacología , Endometriosis/tratamiento farmacológico , Endometriosis/patología , Receptores de Progesterona/metabolismo , Calidad de Vida , Ligandos , Dolor/inducido químicamente , Dolor/tratamiento farmacológicoRESUMEN
BACKGROUND: The purpose of the present study was to compare the effectiveness of intrathecal injection of morphine, inserted in the protocols of multimodal analgesia, versus intravenous morphine in the control of postoperative pain and course in women undergoing gynecological surgery. METHODS: An observational, single-center, retrospective and case-controlled study was performed. Data were collected in a group of women (N.=80) who underwent to gynecological surgery. Women were divided into two groups: group A (40 patients) laparoscopic hysterectomy and group B (N.=40) performing laparotomic myomectomy. In both groups 20 patients underwent administration of intrathecal morphine (125 mcg in 5 mL) and 20 patients underwent to intravenous morphine (1 mg maximum every 10 minutes). The primary endpoint collected was the mean VAS Score during the first 3 days after surgery, while secondary endpoints were opioid consumed during the same period, nausea, vomitus and pruritus. Among the exploratory objectives, length of hospital stay, canalization and feeding time were collected. RESULTS: In group A, patients performing intrathecal morphine presented a significantly lowest VAS on postoperative day 1 and 3 compared to patients performing intravenous morphine while in group B mean VAS was statistically significant lower only on the first day. The emergence of pruritus was significantly higher in patients performing intrathecal morphine. The day of complete canalization was different in Group A patients in favor of intrathecal morphine as well as the length of stay. CONCLUSIONS: The present study showed that intrathecal morphine allows to achieve important management goals with minimal side effects and complications, in particular in case of laparoscopic hysterectomy.
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Analgesia , Morfina , Humanos , Femenino , Morfina/uso terapéutico , Morfina/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Analgesia/métodos , Prurito/inducido químicamente , Prurito/tratamiento farmacológico , Procedimientos Quirúrgicos Ginecológicos/efectos adversosRESUMEN
Background: Sexual health is a major concern in women with endometriosis, however only a few controlled studies have examined this with validated instruments. The effect of hormonal treatments on sexual function in endometriosis is also an underrated topic. The aim of this study was to investigate sexual function of patients with endometriosis by a specific tool to better evaluate their sexual function (including different domains), and the influence of hormonal treatment or surgery on these parameters. Methods: An observational, cross-sectional, multicentre study was conducted in a group (n=194) of sexually active, women aged 25-45 years old, with surgical or ultrasonographic diagnosis of endometriosis, referred to the Endometriosis Center of Careggi University Hospital or Negrar di Valpolicella. Sexual function was assessed by administering the Female Sexual Function Index (FSFI), which assesses the domains of desire, arousal, lubrication, orgasm, satisfaction and pain. FSFI scores were compared to those of a control group (n=58) and according to the treatment received by patients with endometriosis. Results: Ovarian endometriosis was present in 50 patients (25.8%), deep infiltrating endometriosis in 65 patients (33.5%) and both in 79 patients (40.7%). Adenomyosis coexisted in 102 patients (52.6%). Women with endometriosis reported a mean total FSFI score of 18.3 [4.2-25.8] (< 26.55), indicating female sexual dysfunction (FSD) in all patients. At multivariate analysis, after adjusting for confounders (BMI and hormonal therapy), women with endometriosis presented significantly lower scores than controls in all the FSFI (p<0.001). Patients with endometriosis under hormonal treatments (n=124; 64%), regardless of the type, had significantly lower scores in all FSFI subscales and total score, even after adjusting for confounders-age, BMI and history of surgery. Conclusions: Patients with endometriosis are at risk for FSD, encompassing not only dyspareunia, but all domains of sexual function. Hormonal treatments do not result in improvement in sexual symptoms.
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Endometriosis , Disfunciones Sexuales Fisiológicas , Humanos , Femenino , Endometriosis/cirugía , Endometriosis/tratamiento farmacológico , Endometriosis/complicaciones , Estudios Transversales , Adulto , Persona de Mediana EdadRESUMEN
In the past, the primary approach for the treatment of endometriosis was represented by surgery; however, after the introduction of non-invasive diagnosis of endometriosis with the development of imaging technologies, medical treatment became the preferred approach, particularly in young patients. Hormonal drugs, by blocking menstruation, are the most effective for the treatment of endometriosis-related pain, independently of phenotype (ovarian, deep, or superficial endometriosis). Gonadotropin-releasing hormone analogs and oral antagonists act on hypothalamus-pituitary-ovary axis inducing iatrogenic menopause, thus reducing dysmenorrhea and all pain symptoms. The side effects, such as hot flushes and bone loss, may be reduced by an add-back therapy. However, the cost in terms of women's health remains high in view of a long-term treatment. Progestins are considered the first-line treatment, highly effective, and with reduced side effects. In addition to the well-known and largely used Norethisterone acetate and Medroxyprogesterone acetate, recently Dienogest has become one of the most used drugs in all endometriosis phenotypes for long-term treatment. Besides, Intrauterine levornogestrel or subcutaneous etonogestrel are valid alternative for long-term treatment.
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Endometriosis , Humanos , Femenino , Endometriosis/tratamiento farmacológico , Endometriosis/diagnóstico , Endometriosis/cirugía , Hormona Liberadora de Gonadotropina/uso terapéutico , Progestinas/efectos adversos , Dolor/tratamiento farmacológicoRESUMEN
INTRODUCTION: Endometriosis is an estrogen-dependent disease on the background of progesterone resistance. Increased estrogen production, low estrogen metabolization, and altered estrogen receptors (ERs) expression contribute to the hyperestrogenic milieu within endometriotic lesions. Since estrogens play a crucial role in the pathogenesis of the disease, inhibition of estrogen production is one of the main targets of available and emerging drugs. AREAS COVERED: Firstly, we described the molecular alterations responsible for estrogen dependence. Secondly, we reviewed available and emerging treatments that interfere, through central (gonadotropin-releasing hormone analogs (GnRH-a), GnRH antagonists) or local mechanisms (aromatase inhibitors (AIs), inhibitors of steroid sulfatase (STS) and hydroxysteroid dehydrogenase type 1 (17ß-HSD1)), with estrogen dependence. Finally, we focused on emerging treatments targeting ERs (selective estrogen receptor modulators (SERMs), estrogen receptors agonists, and antagonists). EXPERT OPINION: Available treatments interfering with estrogen pathways exert a contraceptive effect, have hypoestrogenic side effects, and cannot prevent or definitively treat the disease. Preclinical and animal studies are focusing on emerging drugs targeting ERs in order to overcome limitations of available treatments. These treatments may represent a promising option, as they may produce a more specific inhibition of disease activity within endometriotic implants, avoiding prolonged hypoestrogenic status and limiting systemic side effects.