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1.
Reprod Sci ; 30(12): 3623-3628, 2023 12.
Article in English | MEDLINE | ID: mdl-37563479

ABSTRACT

Our primary objective is to verify or refute a 2013 study by Connolly et al. which showed that in early pregnancy, a gestational sac was visualized 99% of the time on transvaginal ultrasound when the HCG level reached 3510 mIU/mL. Our secondary objective was to make clinical correlations by assessing the relationship between human chorionic gonadotropin (HCG) level in early pregnancy when a gestational sac is not seen and pregnancy outcomes of live birth, spontaneous abortion, and ectopic pregnancy. This retrospective study includes 144 pregnancies with an outcome of live birth, 87 pregnancies with an outcome of spontaneous abortion, and 59 ectopic pregnancies. Logistic regression is used to determine the probability of visualizing a gestational sac and/or yolk sac based on the HCG level. A gestational sac is predicted to be visualized 50% of the time at an HCG level of 979 mIU/mL, 90% at 2421 mIU/mL, and 99% of the time at 3994 mIU/mL. A yolk sac was predicted to be visualized 50% of the time at an HCG level of 4626 mIU/mL, 90% at 12,892 mIU/mL, and 99% at 39,454 mIU/mL. A total of 90% of ectopic pregnancies presented with an HCG level below 3994 mIU/mL. These results are in agreement with the study by Connolly et al. Since most early ectopic pregnancies had an HCG value below the discriminatory level for gestational sac visualization, other methods for the evaluation of pregnancy of unknown location such as repeat HCG values are clinically important.


Subject(s)
Abortion, Spontaneous , Pregnancy, Ectopic , Pregnancy , Female , Humans , Chorionic Gonadotropin , Abortion, Spontaneous/diagnostic imaging , Gestational Sac/diagnostic imaging , Retrospective Studies , Pregnancy, Ectopic/diagnostic imaging
2.
Perm J ; 27(3): 37-48, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37337673

ABSTRACT

Background Deciding when to pursue parenthood can be difficult for medical trainees and infertility is more common in the physician population. However, few studies have examined the views of very early career trainees. The goal of this study was to assess premedical and medical student plans for family building, knowledge of fertility, and thoughts on assisted reproductive technology, as well as institutional support for parenthood in medical school and fertility curriculum. Methods Web-based cross-sectional survey on Qualtrics distributed through social media and school organization-based networks. Responses were reported as frequency and percent and compared across subgroups of population with χ2 tests. Results The study had a total of 605 premedical and medical students respondents. Most students (78%) do not have children but plan to have children in the future. Almost two-thirds (63%) of students would consider using assisted reproductive technology. More than 80% of respondents have considered or would consider oocyte cryopreservation for themselves or their partners. A majority (95%) of students are worried about balancing parenthood and a career in medicine and about their fertility declining while they complete medical training (84%). The most frequently cited barriers to family planning during medical school and residency were: limited time off during training (84%), demands of training (82%), cost of having a child (59%), and stigma of having a child during training (45%). Less than half of medical students had formal education on infertility. Conclusions Premedical and medical students are worried about fertility declining in training and about balancing parenthood and medical careers, but gaps in knowledge and institutional support exist.


Subject(s)
Infertility , Students, Medical , Child , Humans , Family Planning Services , Schools, Medical , Cross-Sectional Studies , Fertility , Infertility/therapy , Surveys and Questionnaires
3.
Int J Gynecol Cancer ; 32(11): 1433-1442, 2022 11 07.
Article in English | MEDLINE | ID: mdl-36167437

ABSTRACT

OBJECTIVE: Surgery for placenta accreta spectrum is associated with significant maternal morbidity and mortality. The role of gynecologic oncologists in the surgical management of placenta accreta spectrum is currently under investigation. This study examined the practices, experiences, and interests of gynecologic oncologists in placenta accreta spectrum surgeries. METHODS: The intervention was an anonymous, cross-sectional, 20-question survey sent to 1084 members of the Society of Gynecologic Oncology in the USA. RESULTS: A total of 184 gynecologic oncologists responded to the survey (response rate 17.0%). Most participating gynecologic oncologists have been practicing for >10 years after fellowship (53.2%), practice in urban-teaching hospitals (84.8%) with delivery volumes ≥3000/year (54.3%), and have a multidisciplinary approach (82.5%). Three-quarters (78.7%) feel that the rate of placenta accreta spectrum is increasing over time. One-third (35.5%) perform ≥6 hysterectomies for placenta accreta spectrum yearly. Less than half (45.5%) practice conservative management. Approximately half are involved from the beginning of the case (49.7%) and perform the surgery in the main operating room (59.4%). Almost three-quarters (71.6%) have experienced surgical blood loss >5 L and one-third (36.6%) have experienced cases with blood loss >10 L. About half (50.3%) of participants are interested in placenta accreta spectrum surgery for future practice. Gynecologic oncologists engaging in a multidisciplinary approach are more likely to practice in an urban-teaching hospital, have higher surgical volume, be involved from the beginning of the case, and be interested in placenta accreta spectrum surgery. Those >10 years post-training and in the Southern US region are more likely to practice conservative management or delayed hysterectomy. CONCLUSION: This society-based cross-sectional survey suggests that gynecologic oncologists are actively involved in the surgical management of placenta accreta spectrum in the USA. Nearly half of gynecologic oncologists who responded to the survey expressed interest in surgery for placenta accreta spectrum.


Subject(s)
Oncologists , Placenta Accreta , Pregnancy , Female , Humans , Placenta Accreta/surgery , Cross-Sectional Studies , Retrospective Studies , Hysterectomy
5.
Arch Gynecol Obstet ; 305(1): 1-5, 2022 01.
Article in English | MEDLINE | ID: mdl-34609593

ABSTRACT

Placenta accreta spectrum (PAS) encompasses a range of disorders of placental trophoblastic tissue that is morbidly adherent to the underlying gravid uterus. Women with PAS commonly undergo surgical treatment with hysterectomy at cesarean delivery that is associated with significant surgical morbidity and mortality. Increased vascularity due to gestational change and the abnormally enlarged lower uterine segment due to the location of placenta make the surgery complex and morbid. Here, we propose a simple 2-hand technique that can be used to improve surgical outcomes of cesarean hysterectomy for PAS. Unlike the ordinary hysterectomy where the transection of the cardinal ligament is started at the isthmus below the low uterine segment, the proposed 2-hand technique allows transection of the cardinal ligament at the level of the lower uterine segment below the placental bed. This minimizes blood loss that may be associated with serial transection of cardinal ligament which occurs when it is transected at or above the placenta level. This surgical approach starts with demarcation of 3 anatomical landmarks [rectum (posterior aspect), ureters (lateral aspect), and bladder (anterior aspect)] in postero-anterior progression. Complete de-serosalization of posterior low uterine segment allows lateralization of the ureter and enables the uterus to be mobilized antero-caudally where the surgeon's hand can reach below the placental bed. After the bladder flap creation to the level of endopelvic fascia, the surgeon's two hands are placed antero-posteriorly at low uterine segment below the placental bed. The fingertips of both hands meet at the cardinal ligament below placenta at the level of the upper cervix. At this point the two hands are gently moved upwards, carrying the placenta-containing low uterine segment. This step enables creation of a safe anatomical distance from surrounding structures and isolation of the cardinal ligament where surgical clamp can be applied to transect the cardinal ligament.


Subject(s)
Placenta Accreta , Cesarean Section , Female , Humans , Hysterectomy/methods , Placenta/surgery , Placenta Accreta/surgery , Pregnancy , Retrospective Studies , Uterus/surgery
6.
Reprod Sci ; 29(7): 1988-2000, 2022 07.
Article in English | MEDLINE | ID: mdl-34716538

ABSTRACT

Placenta accreta spectrum (PAS) refers to the spectrum of diagnoses involving abnormally and morbidly adherent trophoblastic tissue to the gravid uterus. These disorders are associated with significant maternal morbidity and mortality. While race/ethnicity is known to impact pregnancy outcomes, racial disparities have not been previously examined in women with PAS. The objective of current study was to compare patient characteristics and perioperative outcomes of women with PAS who underwent cesarean delivery across race/ethnicity. This is a comparative study that retrospectively queried the National Inpatient Sample, a hospital-based inpatient database in the USA. The study cohort was women diagnosed with PAS who underwent cesarean delivery from 10/2015 to 12/2018. The exposure group was race/ethnicity. Main outcomes were (i) patient/pregnancy characteristics and (ii) surgical morbidity for cesarean delivery, assessed in multivariable analysis. A total of 10,535 women comprised the study cohort (White n = 5,230 [49.6%], Black n = 2,045 [19.4%], Hispanic n = 2,540 [24.1%], and Asian n = 720 [6.8%]). Patient demographics, pregnancy characteristics, and hospital factors for the non-White groups significantly differed compared to the White group. Older age, obesity, diabetes, placenta previa, percreta, non-elective surgery, lower median household income, and Medicaid particularly represented the non-White groups. When perioperative outcomes were compared, non-White women were more likely to have any measured complications, hemorrhage/transfusion, and shock/coagulopathy compared to White women. Various sensitivity analyses redemonstrated the main cohort results. In conclusion, this study suggests that there were significant disparities in patient characteristics and outcomes of women with PAS across race/ethnicity.


Subject(s)
Placenta Accreta , Placenta Previa , Ethnicity , Female , Humans , Hysterectomy/methods , Male , Placenta Accreta/diagnosis , Placenta Accreta/surgery , Placenta Previa/surgery , Pregnancy , Retrospective Studies , United States/epidemiology
7.
Acta Obstet Gynecol Scand ; 100(12): 2234-2243, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34622939

ABSTRACT

INTRODUCTION: This study examined national-level trends, characteristics, and perioperative outcomes of women who had intra-arterial balloon occlusion at cesarean hysterectomy for placenta accreta spectrum (PAS). MATERIAL AND METHODS: This was a population-based retrospective observational study that queried the National Inpatient Sample from October 2015 to December 2018. Study population was women who underwent hysterectomy at cesarean delivery for PAS (n = 6440 in 806 centers). Exposure allocation was the use of intra-arterial balloon occlusion. Main outcome measures were (a) characteristics associated with intra-arterial balloon occlusion use, and (b) perioperative outcome including hemorrhage, blood transfusion, coagulopathy, shock, urinary tract injury, intra-arterial balloon occlusion-related complication (arterial injury, arterial thrombosis, and lower extremities ischemia), and death, assessed in multivariable analysis. RESULTS: Intra-arterial balloon occlusion was used in 420 (6.5%) women in 64 (7.9%) centers. Utilization of intra-arterial balloon occlusion during cesarean hysterectomy for placenta accreta decreased significantly over time (from 6.3% to 3.1%, p < 0.001), but not in placenta increta (from 12.8% to 9.3%, p = 0.204) or placenta percreta (from 21.3% to 17.5%, p = 0.344). In a multivariable analysis, patient factors (younger age, earlier year, obesity, diabetes mellitus), pregnancy factors (placenta increta/percreta, previous cesarean delivery, placenta previa, and early gestational age), and facility factors (large bed capacity, urban teaching status, and Northeast/West regions) represented the independent characteristics for using the intra-arterial balloon occlusion (all, p < 0.05). In a classification-tree model, the absolute difference in intra-arterial balloon occlusion use among 18 utilization patterns was 48% (range, 0%-48%). In perioperative outcome analysis, women who received intra-arterial balloon occlusion were more likely to have coagulopathy (adjusted odds ratio [aOR] 3.43) and arterial thrombosis (aOR 9.82) in placenta accreta, but less likely to have hemorrhage (aOR 0.25) in placenta increta, and blood transfusion (aOR 0.60) and urinary tract injury (aOR 0.28) in placenta percreta compared with those who did not (all, p < 0.05). CONCLUSIONS: There is a wide range in the utilization of intra-arterial balloon occlusion at cesarean hysterectomy for PAS based on patient, pregnancy, and facility factors, which implies that there is a lack of universal practice guidelines in this surgical procedure. Whether the use of intra-arterial balloon occlusion in the severe forms of PAS improves surgical outcome merits further investigation.


Subject(s)
Balloon Occlusion , Cesarean Section , Hysterectomy , Placenta Accreta/surgery , Adult , Blood Loss, Surgical , Female , Humans , Postoperative Complications , Pregnancy , Pregnancy Trimesters , Retrospective Studies , Treatment Outcome
8.
Reprod Biomed Online ; 43(3): 395-403, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34332901

ABSTRACT

RESEARCH QUESTION: What impact does maternal age and embryo morphology have on sustained implantation rates of euploid blastocysts? DESIGN: This was a retrospective analysis of sustained implantation rates of euploid blastocysts stratified by maternal age and morphology. The primary analysis included 208 embryo transfers with a total of 229 embryos transferred from January 2017 through August 2020. RESULTS: For all ages the sustained implantation rates for day 5 good quality blastocysts were higher than for day 5 fair, day 5 poor and day 6 blastocysts. At a maternal age of 36 years the best-fit sustained implantation rates were 86% for day 5 good quality blastocysts, 64% for day 5 fair, 63% for day 5 poor, and 51% for all day 6 blastocysts analysed as one group. When controlling for morphology and day of biopsy, there were higher sustained implantation rates for euploid embryos of younger patients compared with older patients. The best-fit sustained implantation rates for age 33 compared to age 39 years were 86% versus 80% for day 5 good, 71% versus 62% for day 5 fair, 59% versus 55% for day 5 poor, and 81% versus 46% for all day 6. CONCLUSIONS: There was a clinically significant higher sustained implantation rate at all ages for euploid day 5 good quality embryos compared with day 5 fair, day 5 poor and day 6 embryos.


Subject(s)
Blastocyst/cytology , Embryo Implantation/physiology , Embryo Transfer , Maternal Age , Adult , Age Factors , Cell Size , Embryo Transfer/methods , Embryo Transfer/statistics & numerical data , Embryonic Development/physiology , Female , Fertilization in Vitro/methods , Fertilization in Vitro/statistics & numerical data , Humans , Infertility/diagnosis , Infertility/epidemiology , Infertility/therapy , Ploidies , Pregnancy , Pregnancy Outcome/epidemiology , Retrospective Studies , Treatment Outcome
9.
Case Rep Obstet Gynecol ; 2021: 9912271, 2021.
Article in English | MEDLINE | ID: mdl-34104501

ABSTRACT

Septate uteri have been associated with adverse pregnancy outcomes including spontaneous abortion, preterm delivery, and malpresentation. It is unclear if uterine septa are associated with infertility. Although some studies have shown improved pregnancy outcomes after septum resection, indications for resection are not well established. We describe a case of a woman with a large partial uterine septum diagnosed during workup for infertility who conceived without septum resection. Both of her subsequent pregnancies were initially breech presentations for which the patient underwent external cephalic version followed by full-term vaginal deliveries. This case adds evidence that an unresected uterine septum should not be considered a contraindication to external cephalic version.

11.
Am J Obstet Gynecol ; 225(5): 534.e1-534.e38, 2021 11.
Article in English | MEDLINE | ID: mdl-33894149

ABSTRACT

BACKGROUND: Although an infrequent occurrence, the placenta can adhere abnormally to the gravid uterus leading to significantly high maternal morbidity and mortality during cesarean delivery. Contemporary national statistics related to a morbidly adherent placenta, referred to as placenta accreta spectrum, are needed. OBJECTIVE: This study aimed to examine national trends, characteristics, and perioperative outcomes of women who underwent cesarean delivery for placenta accreta spectrum in the United States. STUDY DESIGN: This is a population-based retrospective, observational study querying the National Inpatient Sample. The study cohort included women who underwent cesarean delivery from October 2015 to December 2017 and had a diagnosis of placenta accreta spectrum. The main outcome measures were patient characteristics and surgical outcomes related to placenta accreta spectrum assessed by the generalized estimating equation on multivariable analysis. The temporal trend of placenta accreta spectrum was also assessed by linear segmented regression with log transformation. RESULTS: Of 2,727,477 cases who underwent cesarean delivery during the study period, 8030 (0.29%) had the diagnosis of placenta accreta spectrum. Placenta accreta was the most common diagnosis (n=6205, 0.23%), followed by percreta (n=1060, 0.04%) and increta (n=765, 0.03%). The number of placenta accreta spectrum cases increased by 2.1% every quarter year from 0.27% to 0.32% (P=.004). On multivariable analysis, (1) patient demographics (older age, tobacco use, recent diagnosis, higher comorbidity, and use of assisted reproductive technology), (2) pregnancy characteristics (placenta previa, previous cesarean delivery, breech presentation, and grand multiparity), and (3) hospital factors (urban teaching center and large bed capacity hospital) represented the independent characteristics related to placenta accreta spectrum (all, P<.05). The median gestational age at cesarean delivery was 36 weeks for placenta accreta and 34 weeks for both placenta increta and percreta vs 39 weeks for non-placenta accreta spectrum cases (P<.001). On multivariable analysis, cesarean delivery complicated by placenta accreta spectrum was associated with increased risk of any surgical morbidities (78.3% vs 10.6%), Centers for Disease Control and Prevention-defined severe maternal morbidity (60.3% vs 3.1%), hemorrhage (54.1% vs 3.9%), coagulopathy (5.3% vs 0.3%), shock (5.0% vs 0.1%), urinary tract injury (8.3% vs 0.2%), and death (0.25% vs 0.01%) compared with cesarean delivery without placenta accreta spectrum. When further analyzed by subtype, cesarean delivery for placenta increta and percreta was associated with higher likelihood of hysterectomy (0.4% for non-placenta accreta spectrum, 45.8% for accreta, 82.4% for increta, 78.3% for percreta; P<.001) and urinary tract injury (0.2% for non-placenta accreta spectrum, 5.2% for accreta, 11.8% for increta, 24.5% for percreta; P<.001). Moreover, women in the placenta increta and percreta groups had markedly increased risks of surgical mortality compared with those without placenta accreta spectrum (increta, odds ratio, 19.9; and percreta, odds ratio, 32.1). CONCLUSION: Patient characteristics and outcomes differ across the placenta accreta spectrum subtypes, and women with placenta increta and percreta have considerably high surgical morbidity and mortality risks. Notably, 1 in 313 women undergoing cesarean delivery had a diagnosis of placenta accreta spectrum by the end of 2017, and the incidence seems to be higher than reported in previous studies.


Subject(s)
Placenta Accreta/epidemiology , Adult , Age Factors , Aged , Blood Coagulation Disorders/epidemiology , Breech Presentation , Cesarean Section/statistics & numerical data , Comorbidity , Databases, Factual , Female , Hospital Bed Capacity , Hospital Mortality , Hospitals, Teaching , Hospitals, Urban , Humans , Hysterectomy/statistics & numerical data , Length of Stay/economics , Middle Aged , Multivariate Analysis , Parity , Placenta Accreta/surgery , Postpartum Hemorrhage/epidemiology , Pregnancy , Reproductive Techniques, Assisted , Retrospective Studies , Tobacco Use/epidemiology , United States/epidemiology , Urinary Tract/injuries
12.
JBRA Assist Reprod ; 25(3): 373-382, 2021 07 21.
Article in English | MEDLINE | ID: mdl-33565291

ABSTRACT

OBJECTIVE: To determine the rate of live birth per blastocyst based on morphology and oocyte age using data from a single center. METHODS: This is a mathematical analysis and model building study of autologous blastocyst stage embryo transfers at a University-affiliated center. A total of 448 blastocyst stage embryos were transferred in 244 fresh and frozen embryo transfers from May 2015 through April 2018. Blastocyst morphology was divided into good, fair, and poor overall morphology grades. Each embryo transfer was modeled as an equation equating the sum of the unknown live birth rates of the transferred embryos to the number of live births that resulted. The least squares solution to the system of embryo transfer equations was determined using linear algebra. RESULTS: Trophectoderm morphology was a better predictor of live birth rate than inner cell mass morphology. Embryos graded AA/AB/BA (good) had the highest live birth rates followed by BB/CB (fair), and BC/CC (poor). In our youngest age group (25-32 years) live birth rates per embryo were 51% for good, 39% for fair, and 25% for poor quality embryos. In our oldest age group (40-44 years) the live birth rates per embryo were 22% for good, 14% for fair, and 8% for poor quality embryos. CONCLUSIONS: These techniques can help analyze small datasets such as those from individual clinics to aid in determining the ideal number of embryos to transfer to achieve live birth while limiting the risk of multiple gestations.


Subject(s)
Birth Rate , Fertilization in Vitro , Adult , Blastocyst , Embryo Transfer , Female , Humans , Live Birth/epidemiology , Pregnancy , Retrospective Studies
13.
Reprod Sci ; 28(1): 43-51, 2021 01.
Article in English | MEDLINE | ID: mdl-32648121

ABSTRACT

Accurate knowledge of the live birth rate for cleavage stage embryos is essential to determine an appropriate number of embryos to transfer at once. Results from previous studies lack details needed for practical use. This is a mathematical analysis and model building study of day 3 cleavage stage embryo transfers. A total of 996 embryos were transferred in 274 fresh and 83 frozen embryo transfers. Embryo morphology was divided into 4 groups based on number of cells and fragmentation percentage. Each embryo transfer was modeled as an equation equating the sum of the live birth rates of the transferred embryos to the number of live births that resulted. The least squares solution to the system of embryo transfer equations was determined using linear algebra. This analysis was repeated for ages 35 to 42 years old at oocyte retrieval. The best fit live birth rates per embryo in the age group centered on 35 years old were 29%, 13%, 10%, and 9% for embryos in the 8-cell with ≤ 5% fragmentation, 8-cell with > 5% fragmentation, 9-12 cell, and 6-7 cell groups, respectively. Cleavage stage embryos with fewer than 6 cells on day 3 had very low best fit live birth rates close to 0% at age 39 years and were excluded from the primary analysis to prevent overfitting. These live birth rates can be used with a simple embryo transfer model to predict rates of single and multiple gestation prior to a planned cleavage stage embryo transfer.


Subject(s)
Cleavage Stage, Ovum/transplantation , Embryo Transfer , Fertilization in Vitro , Infertility/therapy , Adult , Cleavage Stage, Ovum/pathology , Decision Support Techniques , Embryo Transfer/adverse effects , Female , Fertility , Fertilization in Vitro/adverse effects , Humans , Infertility/diagnosis , Infertility/physiopathology , Live Birth , Maternal Age , Models, Theoretical , Pregnancy , Pregnancy Rate , Treatment Outcome
14.
Acad Emerg Med ; 26(12): 1346-1356, 2019 12.
Article in English | MEDLINE | ID: mdl-31183919

ABSTRACT

BACKGROUND: Resuscitation with crystalloid fluid is a cornerstone of pediatric septic shock treatment. However, the optimal type of crystalloid fluid is unknown. We aimed to determine the feasibility of conducting a pragmatic randomized trial to compare balanced (lactated Ringer's [LR]) with 0.9% normal saline (NS) fluid resuscitation in children with suspected septic shock. METHODS: Open-label pragmatic randomized controlled trial at a single academic children's hospital from January to August 2018. Eligible patients were >6 months to <18 years old who were treated in the emergency department for suspected septic shock, operationalized as blood culture, parenteral antibiotics, and fluid resuscitation for abnormal perfusion. Screening, enrollment, and randomization were carried out by the clinical team as part of routine care. Patients were randomized to receive either LR or NS for up to 48 hours following randomization. Other than fluid type, all treatment decisions were at the clinical team's discretion. Feasibility outcomes included proportion of eligible patients enrolled, acceptability of enrollment via the U.S. federal exception from informed consent (EFIC) regulations, and adherence to randomized study fluid administration. RESULTS: Of 59 eligible patients, 50 (85%) were enrolled and randomized. Twenty-four were randomized to LR and 26 to NS. Only one (2%) of 44 patients enrolled using EFIC withdrew before study completion. Total median (interquartile range [IQR]) crystalloid fluid volume received during the intervention window was 107 (60 to 155) mL/kg and 98 (63 to 128) mL/kg in the LR and NS arms, respectively (p = 0.50). Patients randomized to LR received a median (IQR) of only 20% (13 to 32) of all study fluid as NS compared to 99% (64% to 100%) of study fluid as NS in the NS arm (absolute difference = 79%, 95% CI = 48% to 85%). CONCLUSIONS: A pragmatic study design proved feasible to study comparative effectiveness of LR versus NS fluid resuscitation for pediatric septic shock.


Subject(s)
Fluid Therapy/methods , Resuscitation/methods , Ringer's Lactate/therapeutic use , Shock, Septic/drug therapy , Adolescent , Child , Child, Preschool , Emergency Service, Hospital , Feasibility Studies , Female , Humans , Infant , Male , Pilot Projects , Pragmatic Clinical Trials as Topic , Saline Solution/therapeutic use , Shock, Septic/diagnosis
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