A follow up on the feasibility after national implementation of magnesium sulfate for neuroprotection prior to preterm birth.

INTRODUCTION: The risk for brain injury manifested as cerebral palsy is higher in very preterm born children than in term. Prenatal administration of magnesium sulfate (MgSO4 ) has been shown to be neuroprotective and reduces the proportion of very preterm born children later diagnosed with cerebral palsy. A Swedish national clinical practice guideline was implemented in March 2020, stipulating the administration of a single intravenous dose of 6 g MgSO4 1-24 h prior to delivery before gestational age 32+0, aiming for 90% treatment coverage. The aim of this study was to evaluate the feasibility of this new clinical practice guideline in the first year of its implementation. MATERIAL AND METHODS: Data on MgSO4 treatment were collected by reviewing the medical charts of women who gave birth to live born children in gestational age 22+0-31+6 during the period of March 1, 2020 to February 28, 2021, at five Swedish university hospitals. Women with pre-eclampsia, eclampsia, or high elevated liver enzymes low platelets (HELLP) were excluded. RESULTS: A total of 388 women were eligible and 79% received treatment with MgSO4 . Of the 21% not receiving treatment, 9% did not receive treatment due to lack of knowledge about the clinical practice guideline, 9% were not possible to treat and 3% had missing data. The proportion treated increased from 72% to 87% from the first to the last 3 months. Of those treated, 81% received the drug within the stipulated timeframe (mean 8.7 h, median 3.4 h). CONCLUSIONS: There was a positive trend over time in the proportion of women receiving MgSO4 treatment, but the a priori target of 90% was not reached during the first year of implementation. Our findings indicate that this target could be reached with additional information to clinicians.

Cell-free circulating ALU repeats in serum have a prognostic value for colorectal cancer patients.

BACKGROUND: Carcinoembryonic antigen (CEA) is the only established serum biomarker for colorectal cancer (CRC). To facilitate therapy decisions and improve the overall survival of CRC patients, prognostic biomarkers are required. OBJECTIVE: We studied the prognostic value of five different cell free circulating DNA (fcDNA) fragments. The potential markers were ALU115, ALU247, LINE1-79, LINE1-300 and ND1-mt. METHODS: The copy numbers of the DNA fragments were measured in the peripheral blood serum of 268 CRC patients using qPCR, the results were compared to common and previously described markers. RESULTS: We found that ALU115 and ALU247 fcDNA levels correlate significantly with several clinicopathological parameters. An increased amount of ALU115 and ALU247 fcDNA fragments coincides with methylation of HPP1 (P< 0.001; P< 0.01), which proved to be a prognostic marker itself in former studies and also with increased CEA level (both P< 0.001). ALU115 and ALU247 can define patients with poor survival in UICC stage IV (ALU115: HR = 2.9; 95% Cl 1.8-4.8, P< 0.001; ALU247: HR = 2.2; 95% Cl 1.3-3.6; P= 0.001). Combining ALU115 and HPP1, the prognostic value in UICC stage IV is highly significant (P< 0.001). CONCLUSIONS: This study shows that an increased level of ALU fcDNA is an independent prognostic biomarker for advanced colorectal cancer disease.

CTG interpretation templates affect residents' decision making.

OBJECTIVE: To study whether a revision of CTG guidelines and educational program influenced the perceived need for intervention by residents in obstetrics and gynecology. A secondary aim was to study the sensitivity and specificity of the classification pathological after classification by residents using two different guidelines in identifying neonates with acidemia. STUDY DESIGN: Cardiotocograms, CTGs, from 223 neonates with acidemia at birth (cord blood pH < 7.05 at vaginal birth or second stage cesarean, or pH < 7.10 at first stage cesarean) were included, as well as 223 CTGs from neonates with cord blood pH ≥ 7.15. Two separate groups of residents, who each were educated in and had clinical experience only from either of the two different guidelines, SWE09 and SWE17, classified the patterns according to the at the time current template and judged whether the patterns indicated an intervention. Sensitivity, specificity, and agreement were calculated. RESULTS: Residents using SWE09 found indication to intervene in a higher proportion of neonates with acidemia (84.8%) than residents using SWE17 (75.8%; p = 0.002), as well as in cases without acidemia (29.6% vs 22.4%; p = 0.038). Among residents using SWE09 the perceived need for intervention had a sensitivity of 85% and a specificity of 70% to identify acidemia. With SWE17 the corresponding rates were 76% and 78%. The sensitivity to identify neonates with acidemia by classification pathological was 91% with SWE09 and 72% with SWE17. The specificity was 53% and 76% respectively. The agreement rate between perception of indication to intervene and classification pathological using the SWE09 was κ 0.73, moderate, and with the SWE17 κ 0.77, moderate. The agreement on subjective perception of necessity to intervene between users of the two templates was weak to moderate, κ 0.60, and on classification pathological weak, κ 0.47. CONCLUSION: The perceived need for intervention by residents interpreting CTGs was significantly affected by the guidelines in use. The difference in decisions were less pronounced than the difference in classification. The sensitivity for both perceived need for intervention and for classification pathological to identify acidosis was higher with SWE09, and the specificity higher with SWE17, when assessed by the two comparable groups of residents.

Outpatient vs inpatient induction of labor with oral misoprostol: A retrospective study.

INTRODUCTION: Induction of labor is one of the most common obstetrical procedures today, with a successively rising rate. With a limited number of hospital beds, the option of starting induction at home has gained increasing attention. The primary aim of this study was to compare the proportion of women achieving vaginal delivery and the duration of hospital stay before delivery in induction of labor with oral misoprostol starting at home and induction with oral misoprostol at the hospital, in a low-risk population. MATERIAL AND METHODS: Women with home induction (n = 282) were individually matched to controls induced at the hospital during the same time period regarding parity, age, body mass index, labor unit and indication for induction. RESULTS: The rates of vaginal birth were similar in outpatients and inpatients (84.8% vs 86.2%; p = 0.5). Time from hospital admission to delivery in the outpatient group was significantly shorter than in the inpatient group (12.8 vs 20.6 h; p < 0.001), as was total hospital stay (2 vs 3 days; p < 0.001). There were no significant differences between the groups in neonatal or maternal outcomes. One patient undergoing outpatient induction had an unplanned home birth. CONCLUSIONS: Starting induction at home reduced the time spent in hospital without affecting the vaginal delivery rate. Although underpowered to assess safety, this study did not show any differences in adverse maternal and perinatal outcomes between inpatients and outpatients. Further research is needed to evaluate the safety of outpatient induction of labor with misoprostol.

Sporadic accelerations during labor strongly indicate normal pH, whereas periodic accelerations do not: a case-control study.

PURPOSE: To determine the association between the occurrence of sporadic and periodic fetal heart rate accelerations during labor and acidemia at birth. MATERIALS AND METHODS: This is a case-control study of fetal heart rate patterns from 364 neonates with acidemia at birth (cord blood pH <7.05 at vaginal birth, or pH <7.10 at birth after first stage cesarean delivery) and 731 controls with pH ≥7.15. The last 30-60 min of the cardiotocographic traces before birth from the neonates born with acidemia and from the corresponding stage in labor for the controls were scrutinized. Odds ratios (OR) with 95% confidence interval for acidemia at birth were determined. RESULTS: During the first stage, ≥2 sporadic accelerations were present in 16% of cases and 78% of controls; OR for acidemia (compared to 0-1 accelerations) 0.05 (0.02-0.10). In the second stage, the corresponding rates were 13% and 60%, OR 0.09 (0.06-0.14). Isolated periodic accelerations were infrequent. A weak negative association between ≥2 periodic accelerations and acidemia (compared with 0-1 accelerations) was found in the second stage, OR 0.51 (0.30-0.86), but was not significant in the first stage, OR 0.24 (0.04-1.4). Even among fetuses with normal fetal heart rate variability (5-25 beats per minute) the occurrence of less than two sporadic accelerations was associated with an increased risk of acidemia, OR 10.3 (7.2-14.8). CONCLUSIONS: Sporadic accelerations indicate a very low probability of acidosis but are absent in 40% of fetuses with normal pH during a 30-60 min second-stage recording.

Multi-scenario pear tree inflorescence detection based on improved YOLOv7 object detection algorithm.

Efficient and precise thinning during the orchard blossom period is a crucial factor in enhancing both fruit yield and quality. The accurate recognition of inflorescence is the cornerstone of intelligent blossom equipment. To advance the process of intelligent blossom thinning, this paper addresses the issue of suboptimal performance of current inflorescence recognition algorithms in detecting dense inflorescence at a long distance. It introduces an inflorescence recognition algorithm, YOLOv7-E, based on the YOLOv7 neural network model. YOLOv7 incorporates an efficient multi-scale attention mechanism (EMA) to enable cross-channel feature interaction through parallel processing strategies, thereby maximizing the retention of pixel-level features and positional information on the feature maps. Additionally, the SPPCSPC module is optimized to preserve target area features as much as possible under different receptive fields, and the Soft-NMS algorithm is employed to reduce the likelihood of missing detections in overlapping regions. The model is trained on a diverse dataset collected from real-world field settings. Upon validation, the improved YOLOv7-E object detection algorithm achieves an average precision and recall of 91.4% and 89.8%, respectively, in inflorescence detection under various time periods, distances, and weather conditions. The detection time for a single image is 80.9 ms, and the model size is 37.6 Mb. In comparison to the original YOLOv7 algorithm, it boasts a 4.9% increase in detection accuracy and a 5.3% improvement in recall rate, with a mere 1.8% increase in model parameters. The YOLOv7-E object detection algorithm presented in this study enables precise inflorescence detection and localization across an entire tree at varying distances, offering robust technical support for differentiated and precise blossom thinning operations by thinning machinery in the future.

Sublingual misoprostol vs. oral misoprostol solution for induction of labor: A retrospective study.

Introduction: Induction of labor (IOL) is one of the most common obstetrical procedures, with an increasing rate. The prostaglandin E1 analogue misoprostol is frequently used as a primary method of labor induction. The optimal dose and route of administration is yet to be ascertained. Aim: To compare efficiacy and safety between a regimen of sublingually administered misoprostol and a regimen of orally administered misoprostol, with cesarean delivery as primary outcome. Methods: A retrospective study was conducted including women carrying a live, singleton fetus in a cephalic position with labor induced at >37 + 0 gestational weeks at Skåne University hospital, Lund, between January 1st 2013 to December 31st 2017. Data was obtained from computerized obstetrical charts. Results: Totally 2,404 women were included; 974 induced with sublingual misoprostol and 1,430 with oral solution. In primiparous women the cesarean delivery rate was lower in primiparous women induced with oral compared to sublingual misoprostol (20.5% vs. 28.6%, p < 0.001), whereas in parous women the rates did not differ significantly 4.9% vs. 7.5%; NS). The increased risk of caesarean remained after controlling for potential confounding factors (adjusted odds ratio 1.49 (1.14-1.95). Women induced with sublingual misoprostol had a shorter time to vaginal delivery when compared to oral solution (primiparous median 16.7 h vs. 21.7 h; p < 0.001, parous median 9.9 h vs. 13.3 h; p = 0.01), and a higher rate of vaginal delivery within 24 h (primiparas 77.7% vs. 63.3%, p < 0.001, parous 93.2% vs. 84.2%; p = 0.01). Conclusion: IOL with oral misoprostol solution was associated with a significantly higher vaginal delivery rate when compared to sublingual misoprostol, whereas sublingual misoprostol was associated with a significantly shorter time from induction to vaginal delivery. Oral administration is considered the most safe and efficient administration of misoprostol, although more studies are needed to find the optimal route and dosage of misoprostol for IOL.

Relation between perinatal outcome and gestational duration in term primiparous pregnancies stratified by body mass index.

INTRODUCTION: There is growing evidence that induction of labor at 41 completed weeks improves neonatal outcome, at least among primiparous women. This study was performed to investigate whether maternal body mass index (BMI) should be considered when deciding on timing of intervention in term pregnancies. MATERIAL AND METHODS: The study design was a historical cohort study using data from the Swedish Medical Birth Register, singletons in cephalic presentation with births 39+0 to 41+6 weeks, with available information on maternal BMI 2005-2017 (n = 352 567). Modified Poisson regression analyses were used to investigate the association between gestational duration and stillbirth or death before 45 postmenstrual weeks (primary outcome) and Apgar score <7 at 5 minutes (secondary outcome) by BMI, respectively. Adjustments were made for maternal age, smoking, country of birth and educational level. RESULTS: The adjusted relative risk (ARR) of stillbirth or death before 45 weeks among infants born at 41+0 to 41+6 vs 40+0 to 40+6 weeks, was 1.26 with a 95% confidence interval (CI) of 1.07-1.48. Among women with BMI ≥30, the offspring mortality risk in pregnancies lasting 39+0 to 39+2 weeks was significantly above the corresponding risk among women of normal BMI who delivered at 41+0 to 41+2 weeks (ARR = 1.95; 95% CI 1.07-3.56) but no statistically significant heterogeneity was found regarding the magnitude of the association between gestational duration and offspring mortality. The ARR, for Apgar <7 at 5 minutes (41+0 to 41+6 vs 40+0 to 40+6 weeks, regardless of BMI), was 1.36 (95% CI 1.27-1.45). The risk for low Apgar score at 41+0 weeks was 1.5% among all children regardless of maternal BMI. Among children to women with BMI ≥30, this magnitude of risk was found already at 39+3 weeks. CONCLUSIONS: In primiparous women with obesity the risk of stillbirth or death before 45 postmenstrual weeks were increased throughout all full-term gestational age categories, compared with women with overweight or normal BMI. Children to obese women had the same risk for Apgar scores <7 at 5 minutes compared with women overall at earlier gestational age. The results suggest that maternal BMI needs to be considered when discussing timing of elective induction in term healthy pregnancies of primiparous women.

Loss of DRO1/CCDC80 in the tumor microenvironment promotes carcinogenesis.

Tumors are composed of the tumor cells and the surrounding microenvironment. Both are closely interwoven and interact by a complex and multifaceted cross-talk which plays an integral part in tumor initiation, growth, and progression. Dro1/Ccdc80 has been shown to be a potent suppressor of colorectal cancer and ubiquitous inactivation of Dro1/Ccdc80 strongly promoted colorectal carcinogenesis in ApcMin/+ mice and in a chemically-induced colorectal cancer model. The aim of the present study was to investigate whether Dro1/Ccdc80's tumor suppressive function is tumor-cell-autonomous. Expression of Dro1/Ccdc80 in cancer cells had no effect on both colon tumor development in ApcMin/+ mice and formation of xenograft tumors. In contrast, DRO1/CCDC80 loss in the microenvironment strongly increased tumor growth in xenograft models, inhibited cancer cell apoptosis, and promoted intestinal epithelial cell migration. Moreover, stromal Dro1/Ccdc80 inactivation facilitated formation of intestinal epithelial organoids. Expression analyses showed Dro1/Ccdc80 to be significantly down-regulated in murine gastric cancer associated fibroblasts, in ApcMin/+ colon tumor primary stromal cells and in microdissected stroma from human colorectal cancer compared to normal, non-tumor stroma. Our results demonstrate epithelial derived DRO1/CCDC80 to be dispensable for intestinal tissue homeostasis and identify Dro1/Ccdc80 as tumor suppressor in the tumor microenvironment.

Strategies to increase the rate of vaginal deliveries after cesarean without negative impact on outcomes.

OBJECTIVE: To compare the rate of vaginal birth after cesarean section (VBAC), including the maternal and perinatal outcomes, in two historical cohorts before and after the implementation of specific changes in the clinical practice. DESIGN: A retrospective cohort study. SETTING: Skåne University Hospital in Malmö, Sweden. PARTICIPANTS: including all women with one previous cesarean section (CS), who delivered during two 4-year periods: 2005-2008 (Group I) and 2013-2016 (Group II). METHODS: Medical records were retrieved from the hospital's computerized medical system. The surgical reports of all women delivered by repeat CS were reviewed and the appearance of the lower uterine segment at CS was assessed. The primary outcome was VBAC. Secondary maternal outcomes were uterine rupture/dehiscence, hysterectomy and blood loss. The secondary perinatal outcomes were cord blood pH < 7.05 and perinatal mortality rate. Differences for categorical data were studied using the chi-square test and Fisher's exact test. To assess differences for continuous data t-tests were used. To determine which factors predicted VBAC both univariate and multivariate logistic regression analysis with the likelihood ratio test were performed. A two-tailed P-value < 0.05 was considered statistically significant FINDINGS: 2017 patients were included to the study: 792 patients in Group I and 1225 in Group II. The rate of trial of labor after cesarean (TOLAC) was 65.0% and 76.9% and the VBAC rate was 49.8% and 62.0% in Group I and II respectively (p < 0.0001). Maternal and perinatal adverse outcomes were not statistically different between the two groups. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Appropriate management of women with one previous CS might increase the VBAC rate without a negative impact on maternal or perinatal outcomes. The antenatal teamwork has the greatest contribution to VBAC rate by increasing the number of women undergoing TOLAC.

Impaired validity of the new FIGO and Swedish CTG classification templates to identify fetal acidosis in the first stage of labor.

INTRODUCTION: Cardiotocography (CTG) is the main method of intrapartum fetal surveillance. In 2015 a new guideline was introduced by the International Federation of Gynecology and Obstetrics (FIGO), FIGO-15. In Sweden it was adjusted to SWE-17, replacing the previous national template, SWE-09. This study, conducted at one university hospital and one regional hospital in southern Sweden, evaluated the diagnostic validity of these three templates to detect fetal acidosis during the first stage of labor. MATERIAL AND METHODS: A total of 73 neonates with pH <7.1 in umbilical cord artery or vein at cesarean delivery during the first stage of labor were identified retrospectively. For each acidotic neonate, three non-acidemic neonates, with a pH ≥7.2 in cord artery and vein, and Apgar scores ≥9 at five and ten minutes, in all 219 neonates, were selected. The CTG tracings before birth in acidemic neonates, and tracings at the same cervical dilatation in the non-acidemic neonates, were independently assessed by three professionals from the obstetric staff, blinded to group and clinical data. Based on their categorizations of the included variables (baseline, variability, accelerations, decelerations and contraction rate), each CTG tracing was systematically classified according to the three templates. The sensitivity and specificity to identify acidemia by the classification pathological were determined for each template. Interobserver agreement in the assessments of tracings as pathological or not was analyzed, using free-marginal Kappa index. RESULTS: The sensitivity for patterns classified as pathological to identify acidemia was similar for FIGO-15 (71%) and SWE-17 (77%, p = .13), and the specificity was 97% for both. SWE-09 had a significantly higher sensitivity (95%, p < .001) albeit with a lower specificity (90%, p < .001) than the other two templates. Among acidemic neonates, the fraction of tracings classified as normal was higher with SWE-17 (9.6%) than with SWE-09 (0%; p = .01) and FIGO-15 (1.4%; p = .06). For tracings from neonates with acidemia, agreement for three independent assessors was strong (κ 0.85) with SWE-09, and weak for FIGO-15 (κ 0.47), and SWE-17 (κ 0.51). For tracings from neonates without acidemia, the agreement was almost perfect for FIGO-15 (κ 0.91), strong withSWE-17 (κ 0.90) and moderate with SWE-09 (κ 0.78). CONCLUSIONS: The ability of FIGO-15 and SWE-17 to identify fetal acidosis is considered insufficient. The combination of a high sensitivity and a high specificity makes SWE-09 the most discriminatory template during the first stage of labor.

Time to reconsider: Have the 2015 FIGO and 2017 Swedish intrapartum cardiotocogram classifications led us from Charybdis to Scylla?

In 2015, FIGO revised the 1987 intrapartum cardiotocography (CTG) classification (FIGO1987). A less radical FIGO2015 version was introduced in Sweden 2017 (SWE2017). Now, post hoc simulation studies show that FIGO2015 and SWE2017 are less reliable than (a modified) FIGO1987. FIGO2015 shows significantly better interobserver agreement for normal CTG traces than FIGO1987, but significantly worse for pathological traces. Agreements between templates are moderate to good, but different classifications of mainly variable decelerations and tachycardia cause significant heterogeneities. FIGO2015 shows insufficient sensitivity to identify fetal acidemia compared with FIGO1987. In connection with fetal electrocardiogram ST analysis, one study showed no template was superior in identifying fetal acidemia, but in a series of only academia, FIGO1987 had significantly higher sensitivity than FIGO2015 (73% vs. 43%) and set of an alarm for fetal acidemia considerably earlier. With SWE2017, operative interventions declined significantly in Sweden but several adverse neonatal outcomes increased significantly. It remains to investigate the development with FIGO2015.

Assessment of spray deposition, drift and mass balance from unmanned aerial vehicle sprayer using an artificial vineyard.

Under the rapid development of unmanned aerial vehicle (UAV) plant protection products (PPP) application in Asian countries, the drift risk of UAV sprayer operation in orchard or vineyard is fairly high because of the much finer droplets generated and the higher height than ground sprayers, increasing threats to non-targeted crop, human and environment. However, there is few of comprehensive experimental study on the effects of UAV type and nozzle type on spray deposition and drift from UAV sprayer. The objectives of this study were to compare the spray performance of three different typical commercial UAV types (helicopter, 6-rotor and 8-rotor) with two nozzles types (hollow cone nozzle, HCN and air-injector flat fan nozzle, AIN) in vineyard. An artificial vineyard and three vertical collection frames, designed and built by ourselves, were applied for collecting droplets together with PVC collectors, petri dishes and rotary samples. The characteristics of deposition, drift and mass balance of UAV aerial spraying in vineyard were analyzed. As a result, under the crosswind speed of 3.11-3.79 m/s, AIN promoted spray deposition and uniformity and reduced drift significantly compared to HCN for all tested UAVs, improving of the utilization of PPP. The fitted regression functions of the sedimenting and airborne drift were obtained, respectively, and the drift percentage reduction values of AIN compared to HCN determined based on those functions varied from 81% to 95%. With HCN, 49.3%-73.4% of measured droplets drifted into non-targeted area and the highest proportion of drift loss was found for the airborne spray drift. According to the principle of more deposition and less drift, the spray performance of the three UAVs can be ranked in an order of 6-rotor, 8-rotor and helicopter, and two main reasons causing the difference in spray performance were the vortex airflow and the nozzle arrangement.

Low sensitivity of the new FIGO classification system for electronic fetal monitoring to identify fetal acidosis in the second stage of labor.

OBJECTIVE: In 2015, new FIGO guidelines for CTG interpretation were presented (FIGO-15). In 2017, the previous Swedish guidelines (SWE-09) were replaced with guidelines adapted to FIGOs (SWE-17). The performance of these three templates had not been scientifically evaluated before its clinical implementation. The objective of this study was to compare the sensitivity and specificity to detect fetal acidosis at birth using these three templates during the second stage of labor. STUDY DESIGN: This case-control study included 295 neonates with cord blood pH < 7.05 and 591 controls with pH ≥ 7.15, born 2012-2017. Tracings from the last 30-80 min of labor were classified independently by three assessors (midwives, residents and obstetricians), blinded to group and outcome. RESULTS: The classification pathological using FIGO-15 had a sensitivity of 50 % and specificity of 88 % in detecting fetuses with acidosis. For SWE-17, the sensitivity was 62 % and the specificity 85 %. For SWE-09 the sensitivity was 87 % and the specificity 56 %.By combining suspicious and pathological patterns the sensitivity for FIGO-15 increased to 97 %, and for SWE-17 to 83 %, whereas the specificity decreased to 23 % and 68 % respectively. CONCLUSIONS: The FIGO classification seemed to be insufficiently discriminative in the second stage of labor; most patterns in acidotic cases were classified as merely suspicious with this template, and the sensitivity of pathological patterns was low at 50 %. Combined pathological and suspicious patterns detected fetal acidosis at a specificity that was too low to be useful (23 %). SWE-09 showed the best ability to detect acidosis with pathological patterns (sensitivity 87 %). SWE-17 reached almost the same sensitivity (83 %) with the combination of suspicious and pathological patterns, and at a higher specificity (68 %).

Serial Circulating Tumor DNA Mutational Status in Patients with KRAS-Mutant Metastatic Colorectal Cancer from the Phase 3 AIO KRK0207 Trial.

BACKGROUND: We assessed the usefulness of circulating tumor DNA (ctDNA) pre- or post-treatment initiation for outcome prediction and treatment monitoring in metastatic colorectal cancer (mCRC). METHODS: Droplet digital PCR was used to measure absolute mutant V-Ki-ras2 Kirsten rat sarcoma viral oncogene ((mut)KRAS) ctDNA concentrations in 214 healthy controls (plasma and sera) and in 151 tissue-based mutKRAS positive patients with mCRC from the prospective multicenter phase 3 trial AIO KRK0207. Serial mutKRAS ctDNA was analyzed prior to and 2-3 weeks after first-line chemotherapy initiation with fluoropyrimidine, oxaliplatin, and bevacizumab in patients with mCRC and correlated with clinical parameters. RESULTS: mut KRAS ctDNA was detected in 74.8% (113/151) of patients at baseline and in 59.6% (90/151) at follow-up. mutKRAS ctDNA at baseline and follow-up was associated with poor overall survival (OS) (hazard ratio [HR] =1.88, 95% confidence interval [CI] 1.20-2.95; HR = 2.15, 95% CI 1.47-3.15) and progression-free survival (PFS) (HR = 2.53, 95% CI 1.44-4.46; HR = 1.90, 95% CI 1.23-2.95), respectively. mutKRAS ctDNA clearance at follow-up conferred better disease control (P = 0.0075), better OS (log-rank P = 0.0018), and PFS (log-rank P = 0.0018). Measurable positive mutKRAS ctDNA at follow-up was the strongest and most significant independent prognostic factor on OS in multivariable analysis (HR = 2.31, 95% CI 1.40-3.25). CONCLUSIONS: Serial analysis of circulating mutKRAS concentrations in mCRC has prognostic value. Post treatment mutKRAS concentrations 2 weeks after treatment initiation were associated with therapeutic response in multivariable analysis and may be an early response predictor in patients receiving first-line combination chemotherapy. CLINICALTRIALSGOV IDENTIFIER: NCT00973609.

Complicated COVID-19 in pregnancy: a case report with severe liver and coagulation dysfunction promptly improved by delivery.

BACKGROUND: It has been proposed that pregnant women and their fetuses may be particularly at risk for poor outcomes due to the coronavirus (COVID-19) pandemic. From the few case series that are available in the literature, women with high risk pregnancies have been associated with higher morbidity. It has been suggested that pregnancy induced immune responses and cardio-vascular changes can exaggerate the course of the COVID-19 infection. CASE PRESENTATION: A 26-year old Somalian woman (G2P1) presented with a nine-day history of shortness of breath, dry cough, myalgia, nausea, abdominal pain and fever. A nasopharyngeal swab returned positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Her condition rapidly worsened leading to severe liver and coagulation impairment. An emergency Caesarean section was performed at gestational week 32 + 6 after which the patient made a rapid recovery. Severe COVID-19 promptly improved by the termination of the pregnancy or atypical HELLP (Hemolysis, Elevated Liver Enzymes and Low Platelet Count) exacerbated by concomitant COVID-19 infection could not be ruled out. There was no evidence of vertical transmission. CONCLUSIONS: This case adds to the growing body of evidence which raises concerns about the possible negative maternal outcomes of COVID-19 infection during pregnancy and advocates for pregnant women to be recognized as a vulnerable group during the current pandemic.

Obstetric and intensive-care strategies in a high-risk pregnancy with critical respiratory failure due to COVID-19: A case report.

BACKGROUND: With the disease burden increasing daily, there is a lack of evidence regarding the impact of COVID-19 in pregnancy. Healthy pregnant women are still not regarded as a susceptible group despite physiological changes that make pregnant women more vulnerable to severe infection. However, high-risk pregnancies may be associated with severe COVID-19 disease with respiratory failure, as outlined in this report. We discuss the importance of timely delivery and antenatal steroid administration in a critically ill patient. CASE: A 27-year-old pregnant woman (gravida 2, para 1) with type I diabetes, morbid obesity, hypothyroidism and a previous Caesarean section presented with critical respiratory failure secondary to COVID-19 at 32 weeks of gestation. A preterm emergency Caesarean section was performed, after steroid treatment for foetal lung maturation. The patient benefited from prone positioning; however, transient acute renal injury, rhabdomyolysis and sepsis led to prolonged intensive care and mechanical ventilation for 30 days. The baby had an uncomplicated recovery. CONCLUSION: COVID-19 infection in high-risk pregnancies may result in severe maternal and neonatal outcomes such as critical respiratory failure requiring mechanical ventilation and premature termination of the pregnancy. Antenatal steroids may be of benefit for foetal lung maturation but should not delay delivery in severe cases.

Normal vaginal delivery at term after expectant management of heterotopic caesarean scar pregnancy: a case report.

BACKGROUND: Heterotopic pregnancy with a combination of a caesarean scar pregnancy and an intrauterine pregnancy is rare and has potentially life-threatening complications. CASE PRESENTATION: We describe the case of a 27-year-old white woman who had experienced an emergency caesarean delivery at 39 weeks for fetal distress with no postpartum complications. This is a report of the successful expectant management of a heterotopic scar pregnancy. The gestational sac implanted into the scar area was non-viable. The woman was treated expectantly and had a normal vaginal delivery at 37 weeks of gestation. CONCLUSION: Expectant management under close monitoring can be appropriate in small non-viable heterotopic caesarean scar pregnancies.