Impact of age on the transmission of SARS-CoV-2 in healthcare workers : Influence of nonoccupational risk factors.

BACKGROUND: The incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV­2) infection was highest among older adults early in the COVID-19 pandemic; however, this pattern was later reversed with young adults showing the highest incidence. The aim of this study was to identify risk factors in healthcare workers (HCWs) associated with this evolution. METHODS: We conducted a survey nested within a prospective cohort study of 680 HCWs from a tertiary referral public hospital who received 2 doses of SARS-CoV­2 vaccine in January and February 2021 (VACCICO-VAO cohort). In October 2022 all participants were invited to participate in a survey. Risk factors were tested for association with COVID-19 ever, the number of COVID-19 episodes, and the time to the first episode. RESULTS: Among 350 respondents (51% response rate, 90% female, mean age 48.1 years), 323 COVID-19 episodes were diagnosed during the study period. Multivariable analysis revealed that age < 35 years vs. > 50 years (odds ratio, OR 2.12, 95% confidence interval, CI 1.27-3.51; P = 0.004) and not maintaining social distance at social events (OR: 1.82, 95% CI: 1.16-3.19; P = 0.011) were associated with a higher risk of COVID-19. Age < 35 years (hazard ratio, HR 1.70, 95% CI 1.14-2.54; P = 0.010), and not maintaining social distance (HR 1.34, 95% CI 1.05-1.72; P = 0.020) were also associated with the time to the first episode. CONCLUSIONS: The youngest HCWs had the highest incidence rate of COVID-19, which was not explained by occupational risk factors or health conditions. The increase in nonoccupational exposure since the end of the lockdowns in summer 2020 could by a key factor.

Elevated Lead, Nickel, and Bismuth Levels in the Peritoneal Fluid of a Peritoneal Endometriosis Patient without Toxic Habits or Occupational Exposure following a Vegetarian Diet.

Potentially toxic elements (PTEs), found as environmental contaminants, have been related to endometriosis disease. In this context, the peritoneal fluid (PF) matrix has been poorly studied despite its importance. PF is the environment in which endometriotic lesions reside and communicate with surrounding tissues including tissues and nerve cells. In this work, our investigation group reports the special case of a peritoneal endometriosis patient presenting elevated lead, nickel, and bismuth levels in PF. This patient reported following a vegetarian diet and no toxic habits or occupational exposure. In conclusion, the elevated levels of PTEs found may result from a vegetarian diet or an unidentified environmental exposure source. This report provides new insights regarding the possible etiology of endometriosis disease and potential biomarkers for its diagnosis in early stages, although additional research is needed.

A New Advanced and Validated Method for the Determination of Potentially Toxic Metals and Trace and Ultra-Trace Elements in Peritoneal Fluid to Assess the Health Risks of Women with Gynecological Pathologies.

Toxic metals found in the environment have been linked to female infertility and gynecological illnesses. Reliable analytical methods, such as inductively coupled plasma tandem mass spectrometry (ICP-MS/MS), are necessary to determine the elemental composition of biological samples. Currently, the multielemental profile of peritoneal fluid (PF) samples has not yet been established. Due to the complexity of the PF matrix, an ICP-MS/MS-based method has been optimized to mitigate matrix effects and spectral interferences. A dilution factor of 1:4 was the best option to mitigate matrix effects while keeping sensitivity at an appropriate level. A collision gas (He) was useful to lower the extent of spectral interferences for 56Fe, 52Cr, 63Cu, and 68Zn. An intermediate validation test was performed to evaluate accuracy, achieving recoveries ranging from 90 to 110%. The method was validated in terms of intermediate precision, reproducibility, and trueness, with an expanded uncertainty lower than 15%. Afterward, it was applied to perform the multielemental analysis of 20 PF samples. The concentrations for major analytes were up to 151 µg L-1. Meanwhile,209Bi, 111Cd, 52Cr, 55Mn, 95Mo, 60Ni, 208Pb, 118Sn, and 51V were present at concentrations included within the 1-10 µg L-1 range, while 59Co and 139La were found at concentrations below 1 µg L-1.

Occurrence and potential transmission of extended-spectrum beta-lactamase-producing extraintestinal pathogenic and enteropathogenic Escherichia coli in domestic dog faeces from Minnesota.

Interactions between humans and pets are increasingly valued in western countries, leading to more extensive contact between humans and their pets within households. Although the magnitude of the risk of transfer of Escherichia coli between humans and their companion animals is undefined, that such transmission occurs has been established and warrants attention. This study examined 186 fresh faecal samples from companion dogs visiting 22 municipal dog parks in the Minneapolis/Saint Paul metropolitan area, Minnesota, USA. Samples were processed to isolate 3rd-generation cephalosporin-resistant E. coli, which were further characterized using PCR-based virulence genotyping, antimicrobial susceptibility profiling and whole-genome sequencing. Of the 186 faecal samples, 29% yielded cephalosporin-resistant E. coli, and 2.2% yielded extended-spectrum beta-lactamase producers. Co-resistance to sulfonamides was typical (77.3% of isolates), and multidrug resistance (i.e. to ≥3 antimicrobial classes), including to combinations of tetracyclines, phenicols, quinolones and aminoglycosides, was substantial (18.9% of isolates). Identified beta-lactamase genes included blaCMY-2 , blaTEM-1B , blaTEM-1 , blaCTX-M-24 , blaCTX-M-15 and blaOXA-1 . Genome sequencing of 14 isolates identified genes typical of extraintestinal pathogenic E. coli or enteropathogenic E. coli. In three instances, closely related isolates were recovered from different dogs, within either the same park-suggesting transfer of E. coli between dogs within the park-or different parks-suggesting that dogs may be pre-disposed to carry certain E. coli types, such as those from serogroups O4, O71 and O157. This study adds to the existing evidence that companion dogs can harbour and share antimicrobial-resistant E. coli with presumed intestinal or extraintestinal pathogenic potential.

Impact of Heavy Metals on Human Male Fertility-An Overview.

Heavy metals are endocrine disruptors which interfere with processes mediated by endogenous hormones of the organism, negatively affecting endocrine functions. Some studies have correlated heavy metal exposure with male infertility. However, the number of studies conducted on humans are limited. Therefore, the aim of this study is to summarize the current knowledge on how heavy metals influence human male fertility. Hence, three distinct databases were consulted-PubMed, Scopus and Web of Science-using single keywords and combinations of them. The total number of identified articles was 636. Nevertheless, by using the inclusion and exclusion criteria, 144 articles were finally included in this work. Results display that the development of adequate instruments for heavy metal assessment may play an important function in human male fertility diagnosis and treatment. Furthermore, clinical trials could be useful to confirm the role of heavy metals in human male fertility diagnosis. Overall, further research is required to fully understand the molecular and cellular basis of the influence of environmental and occupational exposure to heavy metals on human male infertility and reproductive outcomes.

Anastrozole and levonorgrestrel-releasing intrauterine device in the treatment of endometriosis: a randomized clinical trial.

BACKGROUND: To study the effectiveness of an aromatase inhibitor (Anastrozole) associated with levonorgestrel-releasing intrauterine device (LNG-IUD, Mirena®) in the treatment of endometriosis. METHODS: Prospective, randomized clinical trial. SETTING: University Hospital (single center). Elegibility criteria: Endometriomas > 3 × 4 cm, CA-125 > 35 U/mL and endometriosis symptoms. PATIENTS: Thirty-one women randomized to anastrozole + Mirena® + Conservative Surgery(CS) (n = 8), anastrozole + Mirena® + transvaginal ultrasound-guided puncture-aspiration (TUGPA) (n = 7), Mirena® + CS (n = 9), or Mirena® + TUGPA (n = 7). INTERVENTIONS: Anastrozole 1 mg/day and/or only Mirena® for 6 months; CS (ovarian and fertility-sparing) or TUGPA of endometriomas one month after starting medical treatment. MAIN OUTCOME MEASURES: Visual analogic scale for symptoms, CA-125 levels, ultrasound findings of endometriomas and recurrences. RESULTS: A significant improvement in symptoms during the treatment (difference of 43%, 95% CI 29.9-56.2) occurred, which was maintained at 1 and 2 years. It was more significant in patients including anastrozole in their treatment (51%, 95% CI 33.3-68.7). For CA-125, the most significant decrease was observed in patients not taking anastrozole (73.8%, 95% CI 64.2-83.4 vs. 53.8%, 95% CI 25.7-81.6 under Mirena® + anastrozole). After CS for endometriosis, a reduction of ultrasound findings of endometriomas and long-term recurrence occurred, with or without anastrozole. At 4.2 ± 1.7 years (95% CI 3.57-4.85), 88% of the patients who underwent CS were asymptomatic, without medication or reoperation, compared to only 21% if TUGPA was performed, with or without anastrozole (p = 0.019). CONCLUSIONS: Dosing anastrozole for 6 months, starting one month before CS of endometriosis, reduces significantly the painful symptoms and delays recurrence, but has no other significant advantages over the single insertion of LNG-IUD (Mirena®) during the same time. Anastrozole and/or only Mirena® associated with TUGPA are not effective. TRIAL REGISTRATION: Eudra CT System of the European Medicines Agency (London, 29-Sept-2008) Nº EudraCT: 2008-005744-17 (07/11/2008). Date of enrolment of first patient: 15/01/2009.

Long-term outcomes of transvaginal ultrasound-guided aspiration versus traditional conservative surgery as treatment for endometriomas: A retrospective study of cohorts.

AIM: To evaluate if the long-term results (on fertility, need of hysterectomy and persistence of endometriosis) after a minimally invasive intervention (transvaginal ultrasound-guided puncture-aspiration [TUGPA]) for endometriomas are significantly different from performing the traditional conservative surgery (CS) by laparoscopy or laparotomy. METHODS: We performed a retrospective study of cohorts on patients undergoing surgery for ovarian endometriomas between January 1998 and April 2015. Cohort 1 consisted of 75 women whose first intervention for endometriomas had been TUGPA. For the cohort 2, we selected a randomized paired case in which the first operation for endometriomas had been CS by laparoscopic or laparotomy (another set of 75 patients). RESULTS: There were significantly more recurrences and the time to recurrence and repetition of operations were also significantly shorter in patients with TUGPA. However, there were no significant differences in overall pregnancy/delivery outcomes, in hysterectomy performances, or in endometriosis persistence at the last follow-up visit. There were no significant differences related to the symptoms or to analytical presurgical values but the application of multivariate analysis with binary logistic regression to each dependent variable adjusted for age, symptoms, and presurgical analyses showed a significant risk of recurrence and reoperation of TUGPA versus CS. CONCLUSIONS: Those patients with endometriomas who underwent TUGPA (with or without associated medications) had a significant increase in recurrence and the need for reoperation. However, in the long-term there were no significant differences in the results of pregnancy/childbirth, need for hysterectomy, or in the clinical or doubtful persistence of endometriosis.

Influence of in vitro capacitation time on structural and functional human sperm parameters.

A cascade of dramatic physiological events is linked to the sperm acrosome reaction and binding to the oocyte's zona pellucida during human sperm capacitation. However, structural and functional sperm changes during capacitation currently remain poorly defined. Here, we performed a multibiomarker approach based on the utilization of sperm concentration, motility, viability, morphology, acrosome reaction, tyrosine phosphorylation, DNA fragmentation, and lectin-binding sites to analyze the impact caused by swim-up selection times (uncapacitated, 1 h capacitated, and 4 h capacitated) on sperm function and structure in normozoospermic samples. We found that a 4 h swim-up capacitation increased sperm quality, because a large number of cells with normal morphology and lower DNA fragmentation rates were recovered. Furthermore, the long-term capacitation induced a higher percentage of cells with tyrosine phosphorylation of the principal piece as well as a redistribution of lectin-binding sites. Overall, the multivariate biomarkers analyzed showed a less variable distribution on spermatozoa recovered after 4 h capacitation than that with the shorter capacitation time. These findings stress the importance of capacitation time as a relevant factor in sperm quality with potential biological reproductive implications both for basic research and in assisted reproduction techniques.

Peritoneal fluid from women with endometriosis impairs human spermatozoa functionality.

The success of mammalian fertilization depends largely on spermatozoa physiological events. However, the manner in which endometriosis influence morpho-functional spermatozoa biomarkers is poorly defined. Here, we studied in vitro the effect of peritoneal fluid (PF) from women with endometriosis (PFE) and non-endometriosis (PFNE) on spermatozoa parameters. This research was prospective and double-blind. A total of 45 PF samples were collected from women with (n = 25) and without endometriosis (n = 20). Semen samples were obtained from normozoospermic donors (n = 15) and cultured with 20 % (v/v) of PF or commercial culture medium (controls) during 0, 24, and 48 h. The outcome measures were spermatozoa/viability, motility, tyrosine phosphorylation (TP) and spontaneous acrosomal reaction. In addition, plasma membrane sugars were characterized by lectins [Aleuria aurantia agglutinin (AAA), Concanavalin A (ConA), Peanut agglutinin (PNA), and Wheat germ agglutinin (WGA)]. After a 24 -h culture, results reported a significant decrease in motility in cells cultured with PFE compared to the control, together with differences in the AAA and WGA-binding sites. Moreover, spermatozoa in contact with PFNE presented a significantly lower level of acrosome spontaneous reaction. At 48 h, no differences were observed in the biomarkers studied between the PFNE and the control, excluding ConA-binding sites. On the other hand, cells cultured with PFE exhibited significantly less motility, TP, and differences in the relocation of spermatozoa surface sugars. Viability was not affected in any culture condition. Overall, the effects of PFE could negatively affect spermatozoa quality, contributing to explain and diagnose the infertility associated to male partners of women with endometriosis.

Epithelial ovarian cancers and endometriosis.

AIMS: To determine the prevalence of endometriosis in epithelial ovarian cancers (EOC) and the association among their histological subtypes and with endometrial carcinoma. METHODS: An observational cohort study performed in 192 patients operated on for EOC, 30 women with atypical endometriosis and 17 with p53 positive endometriosis. Data on associated endometriosis and endometrial carcinomas, histological subtypes, tumor stage, clinical and pathological characteristics and survival were analyzed. RESULTS: Twenty cases of EOC (10.4%) had also endometriosis (12.7 in borderline and 9.3% in invasive cases), being a synchronous finding in most cases. Endometriosis associated with serous or mucinous EOC was observed in 2.2 and 2.7% of cases, respectively. However, this association was observed in 50 of endometrioid and 23% of clear cell EOC. Age, parity and tumor stage were lower in endometriosis-associated EOC patients; and all associated cases were type I (Kurman and Shih's classification) and showed better results in survival rate. Endometrial carcinoma was more frequently associated with endometrioid EOC (25%). CONCLUSIONS: There is a significant association between endometriosis, including atypical forms, and endometrioid and clear cell carcinomas, but not with other EOC histotypes. The presence of endometriosis in EOC suggests a better prognosis and an intermediate stage within the progression endometriosis-carcinoma.

Is a bowel resection necessary for deep endometriosis with rectovaginal or colorectal involvement?

BACKGROUND: The purpose of this paper is to report the long-term results of surgery without bowel resection in patients suffering from deep infiltrating endometriosis with rectovaginal or colorectal involvement. METHODS: This retrospective observational study identified 42 patients suffering with deep infiltrating endometriosis who underwent surgery. Conservative surgery was performed in 23 women (only one of them with bowel resection), and 19 women underwent a hysterectomy and bilateral salpingo-oophorectomy (HBSO). In the conservative surgery group, a later HBSO was performed in eight patients as a second operation. Pregnancies, recurrences, reoperations, use of hormone replacement therapy, and outcomes during long-term follow-up were analyzed. RESULTS: The average follow-up duration was 7 ± 5.7 years in conservative surgery cases. Only one patient was treated with sigmoid bowel resection in 1997 and had complications. In this conservative surgery group, 13 patients (56%) received medical treatment after surgery, 10 patients wanted to get pregnant (of whom seven [70%] were successful), and eight patients underwent a subsequent HBSO because of recurrent symptoms and/or endometrioma. Therefore, HBSO was performed in 27 patients, of whom 14 (51.8%) used hormone replacement therapy for 5.6 ± 3.6 years. No recurrences or complications were observed in patients after HBSO with or without hormone replacement therapy. CONCLUSION: Good clinical results can be obtained by performing only conservative surgery and/or HBSO without bowel resection, an alternative that could reduce the number of colorectal resections that are performed very frequently nowadays. After HBSO, patients may use hormone replacement therapy for several years with total satisfaction and well-being.

Endometriosis: a disease that remains enigmatic.

Endometriosis, a gynecologic pathology, is defined by the presence of a tissue similar to uterine endometrium, which is located in places other than physiologically appropriate. These endometrial heterotopic islets contain glands and stroma and are functionally capable of responding to exogenous, endogenous, or local hormonal stimuli. Endometriosis affects 8%-10% of women of reproductive age; in 30% of the women, the condition is associated with primary or secondary infertility. In several instances, endometriosis persists as a minimal or mild disease, or it can resolve on its own. Other cases of endometriosis show severe symptomatology that ends when menopause occurs. Endometriosis can, however, reactivate in several postmenopausal women when iatrogenic or endogenous hormones are present. Endometriosis is occasionally accompanied by malignant ovarian tumors, especially endometrioid and clear cell carcinomas. Its pathogenesis is widely debated, and its variable morphology appears to represent a continuum of individual presentations and progressions. Endometriosis has no pathognomonic signs or symptoms; it is therefore difficult to diagnose. Because of its enigmatic etiopathogenesis, there is currently no satisfactory therapy for all patients with endometriosis. Treatments include medications, surgery, or combined therapies; currently, the only procedures that seem to cure endometriosis are hysterectomy and bilateral salpingo-oophorectomy. In this paper, we review the most controversial and enigmatic aspects of this disease.

¿Cribado de infección por citomegalovirus en embarazadas? Perfil serológico en la Comunidad de Madrid / Routine screening for cytomegalovirus in pregnancy? Serologic profile in Madrid

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Treatment of endometriosis with transvaginal ultrasound-guided drainage and recombinant interleukin-2 left in the cysts: a third clinical trial.

BACKGROUND: To analyze the therapeutic results of recombinant interleukin-2 (rIL-2) left in the cysts after transvaginal ultrasound (US)-guided drainage of endometriomas as an alternative to surgery. METHODS: Prospective and randomized clinical trial. A total of 25 consecutive patients were included. Two transvaginal US-guided punctures were performed, and 3 million IU of rIL-2 were left in the aspirated cysts once (group I) or both (group II) times according to randomization. MAIN OUTCOME MEASURES: Clinical results, prevented surgeries, and recurrences. RESULTS: Results were moderate or good in only 16% of subjects at 3 months and in 33% of subjects at 6 months after treatment in group I; these numbers were 66 and 33%, respectively, in group II. Differences were not statistically significant. However, the evolution of symptoms, endometriomas, and CA-125 revealed the low efficacy of rIL-2 left intracyst as well as a poor control of the clinical manifestations. After 1 year, 20% (group I) and 73% (group II) of patients had to be operated; after 2 years, these numbers were 55 and 82%, respectively. CONCLUSIONS: Treatment of endometriomas with transvaginal US-guided drainage and rIL-2 left in the cysts, without using endometrial suppressive therapy with GnRH analogues as done in previous studies, has low efficacy. Recurrences are even more frequent after the use of two rIL-2 doses.

Interleukin-6 and other soluble factors in peritoneal fluid and endometriomas and their relation to pain and aromatase expression.

Immunological changes and gene expression anomalies are involved in the etiopathophysiology of endometriosis, although how these alterations are connected is not well established. The aim of this study was to determine the relationship between levels of immune cell populations, cytokines and CA-125 in peritoneal fluid (PF) and 'chocolate' cyst fluid (CF), and aromatase expression in endometriotic tissue, as well as to investigate any association with symptoms or recurrence of the disease. Eutopic and ectopic endometrium, CF and PF were collected from 84 women with endometriomas and 24 with benign non-functioning ovarian tumors undergoing radical or conservative surgery. Immunohistochemistry was performed to determine aromatase expression. PF cell populations were assessed by flow cytometry, and CF and PF levels of interleukin (IL)-6, IL-8, IL-13, IL-17 and CA-125 were quantified by ELISA. These parameters were compared with aromatase expression, symptoms and recurrence of the disease. IL-6 levels in PF were higher in patients with endometriosis than in patients with benign non-functioning ovarian cysts, and correlated positively to dysmenorrhea and pelvic pain in the first group. An association between PF IL-8 and CA-125 was also observed in endometriosis. Aromatase positive patients showed higher levels of PF CA-125 and CF IL-17. Recurrence of symptoms or endometrioma occurred sooner in patients having higher IL-6 or IL-8 levels in CF, respectively. These findings suggest an association of IL-6 with pain in endometriosis, as well as a relationship between cytokine expression and recurrence of the disease. However no clear relationship between aromatase expression and other parameters was found.

The effect of intraperitoneal interleukin-2 on surgically induced endometriosis in rats.

OBJECTIVE: To evaluate the effect of interleukin-2 (IL-2) on an experimental model of endometriosis. STUDY DESIGN: Double blind and randomized experimental prospective placebo-controlled study. Experimental endometriosis was induced in 66 three-month-old female Wistar rats, by auto-transplanting fragments of endometrium to the peritoneum. After four weeks, the size of each implant was measured in millimeters by laparotomy (L2), and animals were randomly distributed for intraperitoneal administration of human-IL-2, rat-IL-2 or placebo. Four weeks later, the implants were measured (L3) and a second dose was given. After four weeks, endometriosis size was evaluated again (L4). RESULTS: We found a reduction of experimental endometriosis at L3 that was only significant in IL-2 treated groups: 20.1% and 30.3% with human-IL-2 and rat-IL-2, respectively (p<0.001 with respect to L2 size), versus a non-significant reduction of 9.0% found in placebo group, but the differences were not statistically significant between groups. The decrease after a second dose (L4) was: 49.8%, 41.8% and 11.4% with human-IL-2, rat-IL-2 and placebo, respectively (p<0.001 in IL-2 groups versus L2 and L3, and p<0.05 in both groups versus placebo at L4). CONCLUSION: Intraperitoneal administration of IL-2 reduces experimental endometriosis, and this effect is similar using rat-IL-2 or human IL-2 (non specie-specific effect).

Aromatase expression in endometriotic tissues and its relationship to clinical and analytical findings.

OBJECTIVE: To study the relationship between aromatase expression in endometriotic tissues and clinical and laboratory findings. DESIGN: Prospective basic and clinical research. SETTING: University hospital. PATIENT(S): Sixty-two women with endometriosis, and 12 without endometriosis. INTERVENTION(S): Conservative surgery, or hysterectomy and adnexectomy, along with an immunohistochemical study of aromatase in endometriotic and nonendometriotic tissues. MAIN OUTCOME MEASURE(S): Symptoms of the disease, ultrasound and surgical findings, values of tumor markers, steroids and immunoglobulins, and recurrences after surgery. RESULT(S): We observed positive immunohistochemical expression for aromatase in endometriotic tissues from 38 patients (61.3%). Aromatase expression was negative in the rest of the tissues studied and in the 12 cases without endometriosis. Aromatase-positive patients had a higher number of endometriomas, more bilaterality, and more moderate-to-severe chronic pelvic pain. Also, infertility and associated leiomyomas were more frequent in these patients, though without significant differences. There were no differences in recurrence of the disease 1 year later. Estradiol and PRL levels were significantly higher, and IgG values lower, than in aromatase-negative patients. High values of blood sedimentation rate were more frequent in aromatase-negative patients. CONCLUSION(S): Molecular alterations such as the presence of aromatase in endometriotic tissues could be involved in the development or maintenance of endometriosis. Our findings suggest major severity, activity, and chronic pelvic pain in patients with aromatase in endometriotic tissue.

Intraperitoneal recombinant interleukin-2 activates leukocytes in rat endometriosis.

The aim of this double-blinded study was to determine changes in leukocyte populations in blood, peritoneal lavage fluid, eutopic and ectopic endometrium after treatment with recombinant rat interleukin-2 (IL-2) using an in vivo experimental model of rat endometriosis. The in vivo model involved transplanting four square fragments of autologous endometrium onto the inner surface of the abdominal wall in 20 Wistar rats. The control group was constituted by 20 sham-operated rats. Both groups were randomly treated (1-month interval treatment) with 2 intraperitoneal doses of glucose solution (5%) that did or did not contain recombinant IL-2, and animals were sacrificed 4 weeks after the last dose of treatment. Blood and peritoneal lavage were obtained during the initial and final laparotomy, whereas eutopic and ectopic endometrium were collected at the end of the experiment. Endometriotic implants were measured in each laparotomy to determine any change in size. Leukocyte populations were analyzed by flow cytometry and immunofluorescence microscopy. Cytometric results were similar in blood and peritoneal lavage. CD25+ and natural killer (NK) cell levels in peripheral blood were lower in rats with endometriosis treated with IL-2, whereas NK cells increased in lavage compared to placebo group. The percentage of macrophages and dendritic cells in blood were higher in all rats treated with IL-2, as well as peritoneal dendritic cells. Implant size of these rats decreased significantly, showing a greater number of activated lymphocytes, macrophages, NK and dendritic cells inside them. In conclusion, recombinant IL-2 induced recruitment of activated leukocytes into endometriotic-like foci, and this was related to a reduction of the implant size, suggesting potential effectiveness of IL-2 as an immunomodulatory agent in this pathology.

Treatment of endometriosis with transvaginal ultrasound-guided drainage under GnRH analogues and recombinant interleukin-2 left in the cysts.

BACKGROUND: To analyze the therapeutic results of one dose of 3 million IU of recombinant interleukin-2 (rIL-2) left intracyst (group I) versus two doses with a 1-month interval (group II) after transvaginal ultrasound (US)-guided drainage of endometriomas under the effect of GnRH analogues. METHODS: Prospective and randomized clinical trial (helped by a random number table) at a University Hospital. Twenty-four consecutive patients with endometriomas initially sent to us for laparotomy and conservative surgery for endometriosis were included. INTERVENTIONS: Treatment with GnRH analogues every 28 days, 3 doses. Under their effect, one or two transvaginal US-guided punctures were performed in order to aspirate the endometriomas, and 3 million IU of rIL-2 were left in the aspirated cysts each time. CLINICAL RESULTS: two menstruations after GnRH analogues. Other secondary outcome measures were: the time until recurrence of cysts, symptoms and CA-125 >35 U/ml, and the need for further medical or surgical treatment. RESULTS: They were moderate or good in >50% of cases with one drainage and one dose of 3 million IU of rIL-2 intracyst, but were better with a second drainage and two doses of rIL-2 (25 vs. 58.3% 'good results'). There were fewer recurrences and the interval before recurrence was longer after two doses but differences were not significant. Six patients from group I (50%) and 3 from group II (25%) needed laparotomy and conservative surgery at 17.5 +/- 8.7 months (total time of follow-up = 33 +/- 8.8 months). CONCLUSIONS: Treatment of endometriomas with transvaginal US-guided drainage and rIL-2 left in the cysts under endometrial suppressive therapy with GnRH analogues has beneficial effects, improving clinical manifestations and avoiding some surgical therapies. The use of a higher dose of rIL-2 does not produce better results, whereas drainage + rIL-2 twice does.

Changes in cytokine levels of patients with ovarian endometriosis after treatment with gonadotropin-releasing hormone analogue, ultrasound-guided drainage, and intracystic recombinant interleukin-2.

OBJECTIVE: To determine the changes in cytokine levels from women with endometriomas who are treated with recombinant interleukin-2 after ultrasound-guided cyst aspiration, and to relate these changes to the clinical results observed in these patients. DESIGN: A double-blind randomized controlled trial. SETTING: University hospital. PATIENT(S): Twenty-four women with endometriosis-related symptoms and endometriomas. INTERVENTION(S): Endometriomas in women receiving GnRH analogues and undergoing transvaginal ultrasound-guided cyst aspiration were injected with dextrose that did or did not contain recombinant interleukin-2 (IL-2). Serum samples were collected before and after treatment. MAIN OUTCOME MEASURE(S): Serum samples were analyzed by enzyme immunoassay to determine the levels of IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, IL-13, and IL-17. RESULT(S): The cytokine levels after treatment with GnRH analogues and recombinant IL-2 were similar to the initial levels. The patients receiving GnRH analogues without IL-2 had higher IL-1, IL-2, IL-8, and IL-13 levels. Good clinical results were observed in 90% of the patients in the first group but in only 30% of the second one. CONCLUSION(S): Administration of recombinant IL-2 intracystically decreases cytokine production in women with endometriomas. These results have important implications for the design of future therapies based on immunomodulation, such as using higher or repeated doses of recombinant IL-2 in the cysts.