Fetal Medicine Foundation

The current outbreak of Zika virus (ZIKV) infection has been associated with an apparent increased risk of congenital microcephaly. We describe a case of a pregnant woman and her fetus infected with ZIKV during the 11th gestational week. The fetal head circumference decreased from the 47th percentile to the 24th percentile between 16 and 20 weeks of gestation. ZIKV RNA was identified in maternal serum at 16 and 21 weeks of gestation. At 19 and 20 weeks of gestation, substantial brain abnormalities were detected on ultrasonography and magnetic resonance imaging (MRI) without the presence of microcephaly or intracranial calcifications. On postmortem analysis of the fetal brain, diffuse cerebral cortical thinning, high ZIKV RNA loads, and viral particles were detected, and ZIKV was subsequently isolated.

Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disability and cardiovascular and metabolic disease later in life. Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only 'cure' for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials.

BACKGROUND: Experimental and clinical data suggest that fetal endoscopic tracheal occlusion to induce lung growth may improve the outcome of severe congenital diaphragmatic hernia. We performed a randomized, controlled trial comparing fetal tracheal occlusion with standard postnatal care. METHODS: Women carrying fetuses that were between 22 and 27 weeks of gestation and that had severe, left-sided congenital diaphragmatic hernia (liver herniation and a lung-to-head ratio below 1.4), with no other detectable anomalies, were randomly assigned to fetal endoscopic tracheal occlusion or standard care. The primary outcome was survival at the age of 90 days; the secondary outcomes were measures of maternal and neonatal morbidity. RESULTS: Of 28 women who met the entry criteria, 24 agreed to randomization. Enrollment was stopped after 24 patients had been enrolled because of the unexpectedly high survival rate with standard care and the conclusion of the data safety monitoring board that further recruitment would not result in significant differences between the groups. Eight of 11 fetuses (73 percent) in the tracheal-occlusion group and 10 of 13 (77 percent) in the group that received standard care survived to 90 days of age (P=1.00). The severity of the congenital diaphragmatic hernia at randomization, as measured by the lung-to-head ratio, was inversely related to survival in both groups. Premature rupture of the membranes and preterm delivery were more common in the group receiving the intervention than in the group receiving standard care (mean [+/-SD] gestational age at delivery, 30.8+/-2.0 weeks vs. 37.0+/-1.5 weeks; P<0.001). The rates of neonatal morbidity did not differ between the groups. CONCLUSIONS: Tracheal occlusion did not improve survival or morbidity rates in this cohort of fetuses with congenital diaphragmatic hernia.

Environmental context Plastic, and particularly microplastic, pollution is a growing environmental concern worldwide. Research regarding marine environments has led to a substantial increase in knowledge, yet little is known as regards the situation in freshwater environments. Although the occurrence of microplastics was demonstrated in Lake Geneva in 2012, the present research aims at confirming this pollution and expanding the data set for other lakes and environments of Switzerland. Abstract Marine microplastic (&amp;lt;5 mm) water pollution has met growing public and scientific interest in the last few years. The situation in freshwater environments remains largely unknown, although it appears that they play an important role as part of the origin of marine pollution. Apart from the physical impacts on biota, chemical effects are to be expected as well, especially with smaller particles. This study aims at assessing plastic abundance in Lakes Geneva, Constance, Neuchâtel, Maggiore, Zurich and Brienz, and identifying the nature of the particles, potential ingestion by birds and fishes, and the associated pollutants. Lake surface transects and a few rivers were sampled using a floating manta net, and beach sediments were analysed. Plastics were sorted by type (fragments, pellets, cosmetic beads, lines, fibres, films, foams) and composition (polypropylene, polyethylene, polystyrene, etc.); fish and water birds were dissected to assess their potential exposure, and analyses were conducted on the hydrophobic micropollutants adsorbed to the microplastics as well as some potentially toxic additives they contained. Evidence of this pollution is shown for all lakes, microplastics of all types and diverse composition having been found in all samples. Birds and fish are prone to microplastic ingestion, and all the tested chemicals (both adsorbed micropollutants and contained additives) were found above the detection limit, and often the quantification limit. The sources and their respective contribution need to be confirmed and quantified, and the ecotoxicological effects need further investigation. Other questions remain open, including the transport and fate of plastic particles in the environment.

STUDY DESIGN: A 5-year longitudinal interview and questionnaire-based survey of back pain in adolescents. OBJECTIVES: To determine the natural history of back pain during adolescence in boys and girls and to explore the influence of sports participation and lumbar flexibility. SUMMARY OF BACKGROUND DATA: Previous data on low back pain and flexibility in adolescents have come largely from cross-sectional studies with differing definitions and age groups. A longitudinal study would offer a more detailed description of aspects of the natural history of back pain. METHODS: A cohort of 216 11-year-old children was given a structured questionnaire about back pain. Follow-up evaluation was annual for 4 more years. Lumbar sagittal mobility was measured in first and last years. Life-table analysis was the chosen statistical method. RESULTS: Annual incidence rose from 11.8% at age 12+ to 21.5% at 15+ years. Lifetime prevalence rose from 11.6% at age 11+ to 50.4% at age 15+ years. Experience of back pain was frequently forgotten. Recurrent pain was common, usually manifesting as such rather than as progression from a single episode; few children required treatment. Back pain was more common in boys than girls, especially by age 15 years. There was a positive link between sports and back pain only for boys. Severity and flexibility were not related to sex, treatment, or sport. CONCLUSIONS: Back pain in adolescents is common; it increases with age and is recurrent, but in general does not deteriorate with time. Much of the symptomatology may be considered a normal life experience, probably unrelated to adult disabling trouble.

STUDY DESIGN: Range of motion, neutral zone, and stiffness parameters of the complete cervical, thoracic, and lumbar sheep spine were determined in flexion and extension, axial left/right rotation, and right/left lateral bending. OBJECTIVES: To determine quantitative biomechanical properties of the sheep spine and compare them with those from the human spine. SUMMARY OF BACKGROUND DATA: Sheep spines often serve as a model for experimental in vivo and in vitro studies in spine research, but few quantitative biomechanical data from sheep spines for comparison with human specimens are available. METHODS: Complete spines were sectioned into single-joint segments and tested in a spine tester under pure moments in the three main anatomic planes. RESULTS: The craniocaudal variation in range of motion in all load directions was qualitatively similar between sheep spines and values reported in the literature for human specimens. CONCLUSIONS: Based on the biomechanical similarities of sheep and human spines demonstrated in this study, it appears that the use of the sheep spine, which already includes evaluation of surgical techniques and bone healing processes, might be extended to spinal implants.

STUDY DESIGN: A Cochrane review of randomized controlled trials. OBJECTIVES: To collate the scientific evidence on surgical management for lumbar-disc prolapse and degenerative lumbar spondylosis. SUMMARY OF BACKGROUND DATA: Surgical investigations and interventions account for as much as one third of the health care costs for spinal disorders, but the scientific evidence for most procedures still is unclear. METHODS: A highly sensitive search strategy identified all published randomized controlled trials. Cochrane methodology was used for meta-analysis of the results. RESULTS: Twenty-six randomized controlled trials of surgery for lumbar disc prolapse and 14 trials of surgery for degenerative lumbar spondylosis were identified. Methodologic weaknesses were found in many of the trials. Only one trial directly compared discectomy and conservative management. Meta-analyses showed that surgical discectomy produces better clinical outcomes than chemonucleolysis, which is better than placebo. Three trials showed no difference in clinical outcomes between microdiscectomy and standard discectomy, but in three other studies, both produced better results than percutaneous discectomy. Three trials showed that inserting an interposition membrane after discectomy does not significantly reduce scar formation or alter clinical outcomes. Five heterogeneous trials on spinal stenosis and degenerative spondylolisthesis permit very limited conclusions. There were nine trials of instrumented versus noninstrumented fusion: Meta-analysis showed that instrumentation may facilitate fusion but does not improve clinical outcomes. CONCLUSIONS: There is now strong evidence on the relative effectiveness of surgical discectomy versus chemonucleolysis versus placebo. There is considerable evidence on the clinical effectiveness of discectomy for carefully selected patients with sciatica caused by lumbar disc prolapse that fails to resolve with conservative management. There is no scientific evidence on the effectiveness of any form of surgical decompression or fusion for degenerative lumbar spondylosis compared with natural history, placebo, or conservative management. The Cochrane reviews will be updated continuously as other trials become available.

Monochorionic twins share a single placenta with intertwin vascular anastomoses, allowing the transfer of blood from one fetus to the other and vice versa. These anastomoses are the essential anatomical substrate for the development of several complications, including twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). TTTS and TAPS are both chronic forms of fetofetal transfusion. TTTS is characterized by the twin oligopolyhydramnios sequence, whereas TAPS is characterized by large intertwin hemoglobin differences in the absence of amniotic fluid discordances. TAPS may occur spontaneously in up to 5% of monochorionic twins and may also develop after incomplete laser treatment in TTTS cases. This review focuses on the pathogenesis, incidence, diagnostic criteria, management options and outcome in TAPS. In addition, we propose a classification system for antenatal and postnatal TAPS.

STUDY DESIGN: Radiographic analysis, outcomes analysis (pain scale, Oswestry, SRS-24), and accumulation of complications. Outcomes and complications collected prospectively. Radiographic analysis performed retrospectively. OBJECTIVES: To assess the benefits and stress complications of pedicle subtraction osteotomies for patients with fixed sagittal imbalance. SUMMARY OF BACKGROUND DATA: Few reports on pedicle subtraction osteotomies exist in the peer-review literature for conditions other than trauma and ankylosing spondylitis. MATERIALS AND METHODS: Thirty-three consecutive patients with sagittal imbalance treated with lumbar pedicle subtraction osteotomy at one institution (minimum 2-year follow-up) were analyzed. Complications were also analyzed for the entire group of consecutive pedicle subtraction osteotomies done at our institution to date (n = 66). RESULTS: For the 33 patients with minimum 2-year follow-up, there were significant improvements in the overall Oswestry score (P 0.0001) and pain score (P = 0.0001). Most patients reported improvement in pain and self-image and reported overall satisfaction based on ultimate SRS-24 questionnaire. There was one pseudarthrosis in the lumbar spine through an area of pedicle subtraction osteotomy (area of previous laminectomy and nonunion), and six patients had thoracic pseudarthroses (levels other than the osteotomy level) and one patient had a pseudarthrosis at L5-S1. Two patients had acute angular kyphosis at the thoracolumbar junction at the proximal end of the construct. Five patients who experienced transient neurologic deficits resolved their deficits after central canal enlargement. CONCLUSIONS: The clinical result with pedicle subtraction osteotomy is reduced with pseudarthrosis in the thoracic or lumbar spine and subsequent breakdown adjacent to the fusion. For patients with a degenerative sagittal imbalance etiology the results were worse and the complications were higher. Central canal enlargement is critical.

Spatio-temporal image correlation (STIC) is a new approach for clinical assessment of the fetal heart. It offers an easy to use technique to acquire data from the fetal heart and to aid in visualization with both two-dimensional and three-dimensional (3D) cine sequences. The acquisition is performed in two steps: first, images are acquired by a single, automatic volume sweep. Second, the system analyzes the image data according to their spatial and temporal domain and processes an online dynamic 3D image sequence that is displayed in a multiplanar reformatted cross-sectional display and/or a surface rendered display. The examiner can navigate within the heart, re-slice, and produce all of the standard image planes necessary for a comprehensive diagnosis. The advantages of STIC for use in evaluation of the fetal heart are as follows: the technique delivers a temporal resolution which corresponds to a B-mode frame rate of approximately 80 frames/s; it provides the examiner with an unlimited number of images for review; it allows for correlation between image planes that are perpendicular to the main image acquisition plane; it may shorten the evaluation time when complex heart defects are suspected; it enables the reconstruction of a 3D rendered image that contains depth and volume which may provide additional information that is not available from the thin multiplanar image slices (e.g. for pulmonary veins, septal thickness); it lends itself to storage and review of volume data by the examiner or by experts at a remote site; it provides the examiner with the ability to review all images in a looped cine sequence.

STUDY DESIGN: This is an analysis of consecutive cases of flatback deformity (fixed sagittal imbalance), treated by one of two surgeons at a university hospital. OBJECTIVE: To define factors that contribute to results with treatment of flatback syndrome, classify types of sagittal deformities, and discuss complications. SUMMARY OF BACKGROUND DATA: There are few reports that detail the results and complications of current instrumentation and osteotomy techniques for correction of fixed sagittal deformities. METHODS: Twenty-eight patients treated with osteotomies for sagittal imbalance were eligible for 2-year minimum follow-up (average, 3.6 years). Patients were classified (segmental imbalance, Type 1; or global imbalance, Type 2) and evaluated by upright radiographs, chart review, and a questionnaire. RESULTS: Twenty-eight (100%) patients returned the questionnaire, and 28 had current radiographs. Five treatment groups were evaluated based on osteotomy type (anterior, posterior [Smith-Petersen], both, or pedicle subtraction) and use of anterior structural grafting. All patients were treated with modern bilateral hook-rod-screw constructs. Mean correction at the osteotomy levels was 25 degrees for Type 1 deformities and 30 degrees for Type 2 (P < 0.05). Sagittal correction averaged 6.6 cm in Type 2 deformities (P < 0.05). Questionnaire analysis showed a significant and persistent reduction in subjective pain level. There were seven patients with 11 total complications and no neurologic deficits. Associations among patients who were not satisfied with their results (n = 4) included insufficient sagittal correction (P = 0.045), pseudarthrosis (P = 0.045), coronal imbalance, and four or more medical comorbidities (P = 0.03). CONCLUSIONS: Satisfaction with the results of treatment may be reduced in patients with four or more major co-existent medical problems, insufficient sagittal correction, and resultant pseudarthrosis.

STUDY DESIGN: A retrospective review of all patients surgically treated with a two-level anterior cervical discectomy and fusion with and without anterior plate fixation by a single surgeon. OBJECTIVES: To compare the clinical and radiographic success of two-level discectomy and the effect of anterior cervical plate fixation. SUMMARY OF BACKGROUND DATA: Prior studies of multisegment fusions have shown decreased fusion rates correlating with the number of increased levels. The use of anterior plates for single-level cervical fusions is controversial. However, their use in multilevel fusions may be warranted because of the increased pseudarthrosis rates. METHODS: Over a 6-year period, 60 patients were treated surgically with a two-level anterior cervical discectomy and fusion by the senior author. Thirty-two patients had cervical plates, and 28 underwent fusions without plates. These patients were followed for an average of 2.7 years. Clinical and radiographic follow-up evaluations were performed. RESULTS: Of the 60 patients, 7 had a pseudarthrosis. The pseudarthrosis rates were 0% for patients with plating and 25% for those with no plating. This difference was statistically significant (P = 0.003). No correlation of pseudarthrosis with gender, age, level of surgery, history of tobacco use, or the presence of prior anterior surgery was found. There was significantly less graft collapse (P = 0.0001) in the patients without plates in whom pseudarthrosis developed (1.4 mm) than in those who had fusions with plates (0.3 mm). The amount of kyphotic deformity of the fused segment was 0.4 degree in patients with plating compared with 4.9 degrees in those without plating who developed a pseudarthrosis (P = 0.0001). CONCLUSIONS: The addition of plate fixation for two-level anterior cervical discectomy and fusion is a safe procedure with no significant increase in complication rates. The pseudarthrosis rates are significantly higher in patients treated without plate fixation. No nonunions occurred in the patients treated with plate fixation. There was significantly less disc space collapse and kyphotic deformity with the plated fusions than with the nonplated fusions, in which a pseudarthrosis developed. The complication rates for plated fusions are extremely low and do not differ from those for nonplated fusions.

STUDY DESIGN: A randomized controlled design superimposed on treatment as usual was used to compare the effects of a cognitive-behavior intervention aimed at preventing chronicity with two different forms of information. OBJECTIVE: To develop a coping-oriented preventive intervention applicable in primary care, and to compare its impact with educational information. SUMMARY OF BACKGROUND DATA: Preventing long-term disability resulting from spinal pain has proved difficult. The information provided by health care professions and early interventions aimed at preventing long-term disability may be important, but little scientific evidence exists concerning their use. METHODS: A protocol for a six-session cognitive-behavior group intervention was developed on the basis of earlier research. The main focus was to prevent long-term disability by changing patients' behaviors and beliefs so they can cope better with their problems. Comparison groups received either a pamphlet shown earlier to have an effect, or a more extensive information package consisting of six installments. All the groups continued to receive treatment as usual in primary care. There were 243 patients with acute or subacute spinal pain who perceived that they were at risk for developing a chronic problem. These patients were randomized to the cognitive-behavioral intervention or one of the two information groups. Because the aim was to prevent long-term disability, the key outcome variables at the 1-year follow-up assessment were sick absenteeism and health care use. Other variables were pain, function, fear-avoidance beliefs, and cognitions. RESULTS: The comparison groups reported benefits. However, the risk for a long-term sick absence developing was lowered ninefold for the cognitive-behavior intervention group as compared with the risk for the information groups (relative risk, 9.3). Participants in the cognitive-behavior group also reported a significant decrease in perceived risk. In addition, the cognitive-behavior group demonstrated a significant decrease in physician and physical therapy use as compared with two groups receiving information, in which such use increased. All three groups tended to improve on the variables of pain, fear-avoidance, and cognitions. CONCLUSIONS: This study demonstrates that a cognitive-behavior group intervention can lower the risk of a long-term disability developing. These findings underscore the significance of early interventions that specifically aim to prevent chronic problems. This approach might be applied to primary care settings.

STUDY DESIGN: A retrospective case-control study evaluating risk factors for infection, causative organisms, and results of treatment in patients with cerebral palsy or myelomeningocele who underwent fusion for scoliosis was performed. OBJECTIVES: To identify risk factors for infection, and to characterize the infections in terms of infecting organisms and response to treatment. SUMMARY OF BACKGROUND DATA: No previous studies have analyzed risk factors or causative organisms, nor have they indicated results of treatment for infections in this group of patients. METHODS: After a 10-year retrospective review of 210 surgically treated patients, deep wound infections developed in 16 patients with myelomeningocele and 9 patients with cerebral palsy. These patients were studied extensively for possible risk factors, along with 50 uninfected patients matched for age, diagnosis, and year of surgery. Statistical testing was performed to identify risk factors. The courses of the infections were characterized in terms of organisms isolated and response to treatment. Treatment was performed in a stepwise fashion and classified in terms of the most successful step: debridement and closure, granulation over rods, or instrumentation removal. RESULTS: Of the 10 risk factors tested, 2 were found to be significant: degree of cognitive impairment and use of allograft. Findings showed that 52% of the infections were polymicrobial. Gram-negative organisms were isolated as commonly as gram-positive organisms. The most common organisms were coagulase-negative Staphylococcus, Enterobacter, Enterococcus, and Escherichia coli.- Debridement and closure were successful in 11 of 25 patients with deep wound infection. Of the 14 patients with infection not resolved by serial debridements and closure, 2 were managed successfully by allowing the wound to granulate over rods, and 7 required rod removal for persistent wound drainage. There were three symptomatic pseudarthroses. Infections resulting from gram-positive organisms were most often managed successfully with debridement and closure (P = 0.012). CONCLUSIONS: Patients with cerebral palsy or myelomeningocele who have severe cognitive impairment, and those who received allograft may be at increased risk for infection. Infections are more often polymicrobial and caused by gram-negative organisms than is typical for elective orthopedic procedures. This suggests an enteric source. Treatment with debridement and closure was not always successful. Patients in whom infection develops are then at increased risk for pseudarthrosis.

STUDY DESIGN: Retrospective study of 184 autologous iliac crest bone grafts used for anterior cervical fusion in 144 procedures. OBJECTIVES: To evaluate the effect of autologous iliac crest bone graft harvest site on operation and recovery and to identify patients at risk for harvest morbidity. SUMMARY OF BACKGROUND DATA: Although autologous iliac crest bone graft is considered the most successful grafting material, concerns about harvest morbidity provide a rationale for considering allograft. Data about the use of autograft therefore would assist spinal surgeons in selecting the appropriate substrates for fusion after anterior cervical decompression. METHODS: Statistical analysis based on patient gender, smoking history, obesity, and medical or pharmacologic risk factors for wound healing was used to evaluate morbidity after patient interviews and examinations. Limited assessment of radiographic outcome also was performed. RESULTS: A second operation because of donor site morbidity was performed in four patients (2.8%), but only one (0.7%) with meralgia paresthetica had permanent sequelae. Superficial wound infection or dehiscence occurred in 5.6% of patients, with a disproportionate number of women, obese patients, and those with medical risk represented. Protracted wound symptoms of pain and poor cosmesis were reported in 2.8% and 3.5% of patients, respectively, and also were found in a significant number of female and obese patients. Evidence of fusion was present in 97% of cases. CONCLUSION: Autologous iliac crest bone graft harvest results in minimal major morbidity when regional anatomy is respected and careful technique is observed. The identification of patients at risk for minor complications suggests that allograft may be appropriate in these patients; however, prospective comparison is required to identify whether graft material or technical factors determine fusion success and relative benefit.

BACKGROUND: Endometriosis is associated with pain and infertility. Surgical interventions aim to remove visible areas of endometriosis and restore the anatomy. OBJECTIVES: To assess the effectiveness and safety of laparoscopic surgery in the treatment of pain and infertility associated with endometriosis. SEARCH METHODS: This review has drawn on the search strategy developed by the Cochrane Gynaecology and Fertility Group including searching the Cochrane Gynaecology and Fertility Group's specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, reference lists for relevant trials, and trial registries from inception to April 2020. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) that compared the effectiveness and safety of laparoscopic surgery with any other laparoscopic or robotic intervention, holistic or medical treatment, or diagnostic laparoscopy only. DATA COLLECTION AND ANALYSIS: Two review authors independently performed selection of studies, assessment of trial quality and extraction of relevant data with disagreements resolved by a third review author. We collected data for the core outcome set for endometriosis. Primary outcomes included overall pain and live birth. We evaluated the quality of evidence using GRADE methods. MAIN RESULTS: We included 14 RCTs. The studies randomised 1563 women with endometriosis. Four RCTs compared laparoscopic ablation or excision with diagnostic laparoscopy only. Two RCTs compared laparoscopic excision with diagnostic laparoscopy only. One RCT compared laparoscopic ablation or excision with laparoscopic ablation or excision and uterine suspension. Two RCTs compared laparoscopic ablation and uterine nerve transection with diagnostic laparoscopy only. One RCT compared laparoscopic ablation with diagnostic laparoscopy and gonadotropin-releasing hormone (GnRH) analogues. Two RCTs compared laparoscopic ablation with laparoscopic excision. One RCT compared laparoscopic ablation or excision with helium thermal coagulator with laparoscopic ablation or excision with electrodiathermy. One RCT compared conservative laparoscopic surgery with laparoscopic colorectal resection of deep endometriosis infiltrating the rectum. Common limitations in the primary studies included lack of clearly described blinding, failure to fully describe methods of randomisation and allocation concealment, and poor reporting of outcome data. Laparoscopic treatment versus diagnostic laparoscopy We are uncertain of the effect of laparoscopic treatment on overall pain scores compared to diagnostic laparoscopy only at six months (mean difference (MD) 0.90, 95% confidence interval (CI) 0.31 to 1.49; 1 RCT, 16 participants; very low quality evidence) and at 12 months (MD 1.65, 95% CI 1.11 to 2.19; 1 RCT, 16 participants; very low quality evidence), where a positive value means pain relief (the higher the score, the more pain relief) and a negative value reflects pain increase (the lower the score, the worse the increase in pain). No studies looked at live birth. We are uncertain of the effect of laparoscopic treatment on quality of life compared to diagnostic laparoscopy only: EuroQol-5D index summary at six months (MD 0.03, 95% CI -0.12 to 0.18; 1 RCT, 39 participants; low quality evidence), 12-item Short Form (SF-12) mental health component (MD 2.30, 95% CI -4.50 to 9.10; 1 RCT, 39 participants; low quality evidence) and SF-12 physical health component (MD 2.70, 95% CI -2.90 to 8.30; 1 RCT, 39 participants; low quality evidence). Laparoscopic treatment probably improves viable intrauterine pregnancy rate compared to diagnostic laparoscopy only (odds ratio (OR) 1.89, 95% CI 1.25 to 2.86; 3 RCTs, 528 participants; I2 = 0%; moderate quality evidence). We are uncertain of the effect of laparoscopic treatment compared to diagnostic laparoscopy only on ectopic pregnancy (MD 1.18, 95% CI 0.10 to 13.48; 1 RCT, 100 participants; low quality evidence) and miscarriage (MD 0.94, 95% CI 0.35 to 2.54; 2 RCTs, 112 participants; low quality evidence). There was limited reporting of adverse events. No conversions to laparotomy were reported in both groups (1 RCT, 341 participants). Laparoscopic ablation and uterine nerve transection versus diagnostic laparoscopy We are uncertain of the effect of laparoscopic ablation and uterine nerve transection on adverse events (more specifically vascular injury) compared to diagnostic laparoscopy only (OR 0.33, 95% CI 0.01 to 8.32; 1 RCT, 141 participants; low quality evidence). No studies looked at overall pain scores (at six and 12 months), live birth, quality of life, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy and miscarriage. Laparoscopic ablation versus laparoscopic excision There was insufficient evidence to determine whether there was a difference in overall pain, measured at 12 months, for laparoscopic ablation compared with laparoscopic excision (MD 0.00, 95% CI -1.22 to 1.22; 1 RCT, 103 participants; very low quality evidence). No studies looked at overall pain scores at six months, live birth, quality of life, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy, miscarriage and adverse events. Helium thermal coagulator versus electrodiathermy We are uncertain whether helium thermal coagulator compared to electrodiathermy improves quality of life using the 30-item Endometriosis Health Profile (EHP-30) at nine months, when considering the components: pain (MD 6.68, 95% CI -3.07 to 16.43; 1 RCT, 119 participants; very low quality evidence), control and powerlessness (MD 4.79, 95% CI -6.92 to 16.50; 1 RCT, 119 participants; very low quality evidence), emotional well-being (MD 6.17, 95% CI -3.95 to 16.29; 1 RCT, 119 participants; very low quality evidence) and social support (MD 5.62, 95% CI -6.21 to 17.45; 1 RCT, 119 participants; very low quality evidence). Adverse events were not estimable. No studies looked at overall pain scores (at six and 12 months), live birth, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy and miscarriage. AUTHORS' CONCLUSIONS: Compared to diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis. No data were reported on live birth. There is moderate quality evidence that laparoscopic surgery increases viable intrauterine pregnancy rates confirmed by ultrasound compared to diagnostic laparoscopy only. No studies were found that looked at live birth for any of the comparisons. Further research is needed considering the management of different subtypes of endometriosis and comparing laparoscopic interventions with lifestyle and medical interventions. There was insufficient evidence on adverse events to allow any conclusions to be drawn regarding safety.

The outcome of spinal cord injury depends on the extent of secondary damage produced by a series of cellular and molecular events initiated by the primary trauma. This article reviews the evidence that secondary spinal cord injury involves the apoptotic as well as necrotic death of neurons and glial cells. Also discussed are the major factors that can contribute to cell death, such as glutamatergic excitotoxicity, free radical damage, cytokines, and inflammation. The development of innovative therapeutic strategies to reduce secondary spinal cord injury depends on an increased understanding of secondary injury mechanisms at the molecular and biochemical level. Such therapeutic interventions may include the use of antiapoptotic drugs, free radical scavengers, and anti-inflammatory agents. These could be targeted to block key reactions on cellular and molecular injury cascades, thus reducing secondary tissue damage, minimizing side effects, and improving functional recovery.

Prenatal stress has been widely associated with a number of short- and long-term pathological outcomes. Epigenetic mechanisms are thought to partially mediate these environmental insults into the fetal physiology. One of the main targets of developmental programming is the hypothalamic-pituitary-adrenal (HPA) axis as it is the main regulator of the stress response. Accordingly, an increasing number of researchers have recently focused on the putative association between DNA methylation at the glucocorticoid receptor gene (NR3C1) and prenatal stress, among other types of psychosocial stress. The current study aims to systematically review and meta-analyze the existing evidence linking several forms of prenatal stress with DNA methylation at the region 1F of the NR3C1 gene. The inclusion of relevant articles allowed combining empirical evidence from 977 individuals by meta-analytic techniques, whose methylation assessments showed overlap across 5 consecutive CpG sites (GRCh37/hg19 chr5:142,783,607-142,783,639). From this information, methylation levels at CpG site 36 displayed a significant correlation to prenatal stress (r = 0.14, 95% CI: 0.05-0.23, P = 0.002). This result supports the proposed association between a specific CpG site located at the NR3C1 promoter and prenatal stress. Several confounders, such as gender, methylation at other glucocorticoid-related genes, and adjustment for pharmacological treatments during pregnancy, should be taken into account in further studies.

STUDY DESIGN: A spine tumor database of patients with solitary sites of spine involvement from solid tumors was retrospectively reviewed. OBJECTIVES: To analyze the long-term survival, neurologic outcome, and results of surgery in a well-defined subset of patients who had spinal metastases with epidural extension to define future treatment strategies. SUMMARY OF BACKGROUND DATA: Currently accepted indications for surgical treatment of spinal metastases include histologic diagnosis, neurologic palliation in those who have failed prior irradiation, and spinal stabilization. In all others, external irradiation is considered the mainstay of therapy. Several studies have shown that prior irradiation increases the frequency of complications from surgery and affects functional outcome. METHODS: A retrospective review of 80 consecutive patients with solitary sites of spine involvement from solid tumors with varying degrees of epidural extension was performed. Complete clinical and radiologic follow-up assessment was available for all the patients. Clinical parameters, neurologic grade, preoperative pain, radiologic evaluation, and outcome measures were analyzed. Survival analysis was performed using the Kaplan-Meier product limit method, and differences between subgroups were analyzed using chi2. Prognostic factors for long-term survival also were evaluated. RESULTS: The overall median survival after surgery was 30 months, with 18% surviving 5 years or more. Survival varied by tumor type, with the best prognosis noted in patients with breast or kidney cancer. The surgical morbidity was significantly higher in those receiving prior irritation (P < 0.03), and the local recurrence rate also increased in patients who had received prior irradiation. CONCLUSIONS: Patients with solitary sites of spine involvement from solid tumors represent a biologically favorable subgroup with potential for long-term survival. In this group, complete surgical excision before irradiation should be considered to increase the prospects of long-term palliation and possible cure.

OBJECTIVE: To report the performance of massively parallel sequencing (MPS) based prenatal noninvasive fetal trisomy test based on cell-free DNA sequencing from maternal plasma in a routine clinical setting in China. METHOD: The MPS-based test was offered as a prenatal screening test for trisomies 21 and 18 to pregnant women in 49 medical centers over 2 years. A total of 11,263 participants were recruited and the MPS-based test was performed in 11,105 pregnancies. Fetal outcome data were obtained after the expected date of confinement. RESULTS: One hundred ninety cases were classified as positive, including 143 cases of trisomy 21 and 47 cases of trisomy 18. With the karyotyping results and the feedback of fetal outcome data, we observed one false positive case of trisomy 21, one false positive case of trisomy 18 and no false negative cases, indicating 100% sensitivity and 99.96% specificity for the detection of trisomies 21 and 18. CONCLUSION: Our large-scale multicenter study proved that the MPS-based test is of high sensitivity and specificity in detecting fetal trisomies 21 and 18. The introduction of this screening test into a routine clinical setting could avoid about 98% of invasive prenatal diagnostic procedures.