Clinical outcomes of anterior tibiofibular ligament’s distal fascicle transfer versus ligament reconstruction with InternalBrace™ for chronic ankle instability patients

Purpose Treatment of chronic ankle instability (CAI) for ankle sprain patients remains a challenge. If initial treatments fail, surgical stabilization techniques including ligament reconstruction should be performed. Anterior tibiofibular ligament (ATiFL) distal fascicle transfer for CAI was recently introduced. The goal of the study is to assess the 1-year clinical effectiveness of ATiFL’s distal fascicle transfer versus ligament reconstruction with InternalBrace™ (Fa. Arthrex, Naples). Methods Between October 2019 and February 2021, 25 patients (14 males and 11 females) scheduled for ligament reconstruction treatment of CAI were enrolled after propensity score matching. Twelve underwent ligament reconstruction with InternalBrace™ (InternalBrace™ group) and thirteen underwent ATiFL’s distal fascicle transfer (ATiFL’s distal fascicle transfer group). We recorded the American Orthopedic Foot & Ankle Society (AOFAS) score, Visual Analogue Scale (VAS), anterior drawer test grade, patient satisfaction and complications. All results of this study were retrospectively analyzed. Results Statistically significant (p = 0.0251, independent-samples t test) differences in the AOFAS can be found between the ATiFL’s distal fascicle transfer group and the InternalBrace™ group. No substantial changes in the VAS (p = 0.1778, independent-samples t test), patient satisfaction (p = 0.1800, independent-samples t test) and anterior drawer test grade (p = 0.9600, independent-samples t test) were found between the two groups. There was one patient with superficial wound infection and one patient with sural nerve injury in the InternalBrace™ group and ATiFL’s distal fascicle transfer group, respectively. Conclusion This is the first study that assessed a cohort of CAI patients and suggests that the ATiFL’s distal fascicle transfer operation has the potential to attain good-to-excellent clinical outcomes after 1-year recovery. The AOFAS scores were significantly higher for patients with ATiFL’s distal fascicle transfer, indicating that this technique may be considered a viable option for both patients and their surgeon, while long-term outcomes should be investigated in the future.

Tumor Cell Distinguishable Nanomedicine Integrating Chemotherapeutic Sensitization and Protection

Theoretically, with a high enough drug dosage, cancer cells could be eliminated. However, the dosages that can be administered are limited by the therapeutic efficacy and side effects of the given drug. Herein, a nanomedicine integrating chemotherapeutic sensitization and protection was developed to relieve the limitation of administration dosage and to improve the efficacy of chemotherapy. The nanomedicine was endowed with the function of synergistically controlled release of CO and drugs under near-infrared (NIR) light irradiation. CO photo-induced release system (COPIRS) was synthesized by constructing an electron excitation–electron transfer group–electron-induced CO release structure and was used as the hydrophobic part, and then hydrophilic polymer (polyethylene glycol; PEG) was introduced by a thermal-responsive groups (DA group), forming a near-infrared-induced burst-release nanocarrier. In vitro and in vivo experiments showed that the nanomedicine can distinguish between tumor and normal cells and regulates the resistance of these different cells through the controlled release of carbonic oxide (CO), simultaneously enhancing the efficacy of chemotherapy drugs on tumor cells and chemotherapeutic protection on normal cells. This strategy could solve the current limitations on dosages due to toxicity and provide a solution for tumor cure by chemotherapy.

Chromosomal Analysis of 129 Miscarried Conceptuses: A Retrospective Study

Background Embryonic chromosomal abnormality is one of the significant causative factors of pregnancy loss. Our goal was to investigate the differences of chromosomal abnormality between different conception modes in miscarried products of conception (POCs). Methods A retrospective study included 129 miscarried POCs from 81 women undergoing assisted reproductive technology (ART) and 48 spontaneous pregnant (SP) women during March 2019 to March 2021 in Renmin Hospital of Wuhan University. Subgroups were divided according to age, fertilization method, types of embryo transfer. The profiles of cytogenetic abnormalities in the miscarried POCs were measured via next-generation sequencing. Results The total chromosomal abnormality rate was 65.1%. No significant difference was found in the rate of chromosomal abnormalities between ART and SP group (63% vs. 68.8%, P = 0.505). However, the rate of chromosomal structural abnormalities was significantly increased in ART group (P = 0.02). There was no significant difference in the rate of chromosomal abnormalities when stratified by age (62.9% vs. 71.9%, P = 0.355) and frequency of abortion (66.7% vs. 63.2%, P = 0.678). In the patients aged < 35 years, the ART group had more frequent structural abnormality than SP group (P = 0.006). In the patients aged ≥ 35 years, numerical chromosomal abnormality was predominated in both groups (P = 0.655). Compared with the IVF fertilization subgroup, microdeletion was more frequent in the ICSI fertilization subgroup (80% vs.28.6%, P = 0.013). The rate of chromosomal abnormality in the fresh embryo transfer group was significantly higher than that in the frozen embryo transfer group (92.3% vs.50%, P = 0.0001), especially the structural abnormality (46.2% vs. 15.4%, P = 0.016). Conclusion Chromosomal abnormality is the main cause of spontaneous abortion, whether in SP or in ART patients. The incidence of structural abnormalities in miscarried POCs from ART patients was significantly increased and fresh cycles had higher frequency of chromosomal abnormalities than the frozen cycles, hints us that “freezing all” should be considered in the process of assisted reproduction if encountered hyper ovarian stimulation, to avoid the negative effect of high estrogen environment on embryo development.

Sequential cleavage and blastocyst embryo transfer and IVF outcomes: a systematic review

Background Sequential embryo transfer has been proposed as a way to improve embryo implantation in women for in vitro fertilization (IVF), but the effect on pregnancy outcomes remains ambiguous. This systematic review was conducted to investigate the efficacy of sequential embryo transfer on IVF outcomes. Methods A literature search was performed in the PubMed, Web of Science, Cochrane Library, ScienceDirect and Wanfang databases. Data were pooled using a random- or fixed-effects model according to study heterogeneity. The results are expressed as relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was evaluated by the I2 statistic. The study protocol was registered prospectively on INPLASY, ID: INPLASY202180019. Results Ten eligible studies with 2658 participants compared sequential embryo transfer and cleavage transfer, while four studies with 513 participants compared sequential embryo transfer and blastocyst transfer. The synthesis results showed that the clinical pregnancy rate was higher in the sequential embryo transfer group than in the cleavage embryo transfer group (RR 1.42, 95% CI 1.26–1.60, P< 0.01) for both women who did experience repeated implantation failure (RIF) (RR 1.58, 95% CI 1.17–2.13, P< 0.01) and did not experience RIF (Non-RIF) (RR 1.44, 95% CI 1.20–1.66, P< 0.01). However, sequential embryo transfer showed no significant benefit over blastocyst embryo transfer. Conclusion The current systematic review demonstrates that sequential cleavage and blastocyst embryo transfer improve the clinical pregnancy rate over conventional cleavage embryo transfer. For women with adequate embryos, sequential transfer could be attempted following careful consideration. More high-grade evidence from prospective randomized studies is warranted.

P–281 Is it worth to go to blastocyst when there are less than 4 embryos on day 3?

Study question Are pregnancy rates similar with blastocyst transfer compared to D3 transfer for patient with a poor embryo yield. Summary answer In poor prognosis patients, more D3 embryos are needed to result in similar outcome compared to single blastocyst and it increases the multiple pregnancy risk. What is known already Good prognosis patients benefit from a blastocyst transfer rather than cleavage-stage embryo because day 3 morphology has limited predictive value for subsequent developmental. A Cochrane meta-analysis in 2016 found a higher live birth rate per transfer in the blastocyst group compared to cleavage-stage and no difference in miscarriage and multiple pregnancies. However, in unselected patients, studies have yielded conflicting results and especially in poor prognosis patients at risk of transfer cancellation. A threshold of four good embryos on the third day has been previously correlated with blastocyst yield and live birth rate compared with cleavage-stage embryo transfer. Study design, size, duration We analyzed the outcome of 1115 cycles with less than 4 embryos during 2019–2020 and compared the results between two groups of D3 and D5 transfers. Participants/materials, setting, methods Amongst 1115 study cycles, in 691 cycles a D3 transfer was performed and in 424 cycles a D5 transfer was performed. We compared transfer cancellation rates, mean number of transferred embryos and ongoing pregnancy rates between the two groups and also in subgroups with female age &lt;37 and female age &gt;37. The statistical analyses were done by Chi square and t-test for paired samples. Main results and the role of chance In the overall study population, the mean female age was 36.3 ± 4.3 years, the mean number of obtained embryos was 2.4 ± 1.0, the mean number of transferred embryos was 1.4 ± 0.8. 17.2% of the cycles resulted in transfer cancellation (6.2% in D3 transfer group and 35.0% in D5 transfer group). After D3 transfer the ongoing pregnancy rate (OPR) per transfer was 21.5% compared to 39.7% in D5 transfers (p &lt; 0.05). A similar pattern was observed in subgroups of age &lt;37 years and &gt;37 years with OPR per transfer significantly higher when D5 transfer was performed. Notably more embryos were transferred on D3 compared to D5 (mean number 1.4 for D3 and 1 for D5). Nonetheless, OPR were similar per cycle in both groups and subgroups of different ages. Limitations, reasons for caution A prospective randomized controlled trial is needed to confirm these results that are consistent with previously reports on retrospective and observational studies. Wider implications of the findings: In poor prognosis patients with low embryo yield, D3 and D5 transfers result in similar OPR per cycle. Transferring at blastocyst stage is not inferior to D3, despite the high cancellation rate, and appears safer permitting a single embryo transfer to avoid multiple pregnancy. Trial registration number Not applicable

P–515 Clinical outcome of mosaic-blastocyst transfer versus euploid-blastocyst transfer in single frozen blastocyst transfer cycles

Study question What is the clinical outcome of transferring a mosaic blastocyst versus a euploid blastocyst in single frozen blastocyst transfer (sFBT) cycles? Summary answer Single mosaic blastocyst transfer has similar clinical outcome to single euploid blastocyst transfer. What is known already Embryonic mosaicism occurs when there are two or more distinct cell lines found in preimplantation embryos derived from IVF. Data from recent studies show that mosaic blastocysts have the potential to implant and can result in healthy live births. As a result, patients now have the option of transferring mosaic blastocyst when they do not have any euploid blastocyst available for transfer. However, the clinical outcome of transferring mosaic blastocyst has not been definitively reported. Thus, a retrospective study was conducted to compare the clinical outcome of mosaic sFBT and euploid sFBT. Study design, size, duration A total of 602 patients underwent frozen blastocyst transfer in Alpha IVF from January to October 2019 and had their blastocysts screened for aneuploidy. These patients were divided into 2 groups: 26 patients with mosaic blastocysts transferred (Group A, age ranged 19–44), and 576 patients with euploid blastocysts transferred (Group B, age ranged 21–44). The mean age of patients from Group A and B were 34.0 and 32.8 respectively (p &gt; 0.05). Participants/materials, setting, methods All samples had their DNA libraries constructed for sequencing using Next Generation Sequencing according to manufacturer’s specification (IonTorrent, USA). All blastocysts were frozen for subsequent sFBT cycle (Cryotech, Japan). All thawed blastocysts for sFBT survived with morphologically intact inner cell mass and trophectoderm cells. The importance of antenatal confirmation of the fetal chromosome status was emphasized in patients from Group A. The clinical outcomes of both groups were analysed and compared. Main results and the role of chance No significant differences were seen in the clinical pregnancy and implantation rate of Group A and B (65.4% vs 63.0%; p &gt; 0.05). The miscarriage rate of Group A and B were 23.5% and 14.0% respectively. Albeit the higher miscarriage rate in Group A, there was no statistical significance between these two groups (p &gt; 0.05). Group A was further divided into two subgroups, Subgroup A1: low risk mosaic blastocyst transfer; Subgroup A2: high risk mosaic blastocyst transfer. In the comparison of Group A subgroups, the clinical pregnancy and implantation of Group A1 is higher than Group A2 (76.9% vs 44.4%). In addition, the miscarriage rate of Group A1 and A2 were 23.1% and 0.0% respectively. Interestingly, there was no statistical significance in clinical pregnancy rate, implantation rate and miscarriage rate between these two subgroups. Limitations, reasons for caution This is a retrospective study and the sample size was comparatively smaller in the mosaic blastocyst transfer group than the euploid blastocyst transfer group. Further studies with a larger sample size should be carried out to ascertain the clinical outcome. Wider implications of the findings: Single mosaic blastocyst transfer has similar clinical outcome to single euploid blastocyst transfer. Thus, mosaic blastocyst can be considered for transfer when no euploid blastocyst are available. Nevertheless, stringent antenatal surveillance for chromosomal abnormalities to confirm the chromosomal status of the fetus must be followed. Trial registration number Not applicable

P–692 Are live birth rate and obstetric outcomes different between immediate and delayed embryo transfers following a freeze-all cycle? A retrospective study combined with a meta-analysis

Study question Do livebirth rate (LBR), obstetric and perinatal outcomes vary between frozen embryo transfers (FET) in the first or subsequent menstrual cycles following a freeze-all approach? Summary answer Immediate FET has a higher LBR and similar perinatal outcomes than delayed FET. Quantitative synthesis of available literature shows an increased LBR with immediate transfer. What is known already Whether FET should be done in the first menstrual cycle following oocyte collection (OC) is controversial and the duration of a possible detrimental effect of supraphysiological sex steroid levels on pregnancy outcome is unknown. A multinational survey centers showed that, 61% of clinicians prefer to wait for a washout period before proceeding to FET, even after a failed fresh embryo transfer. Limited number of studies compared FET in the first menstrual cycle with delayed FET in a subsequent cycle with varying results. There is limited data on obstetric outcomes of pregnancies resulting from FET in the first menstrual cycle. Study design, size, duration 198 women who underwent a freeze-all cycle followed by FET between July 2017 and June 2020 were included. 119 FET in the first menstrual cycle (&lt;30 days from oocyte collection) and 79 FET in subsequent cycles (&gt;30 days from oocyte collection) were retrospectively compared. MEDLINE was searched on 01 January 2021 using relevant keywords. Cohort studies comparing immediate versus delayed transfer following freeze all cycles were included and quantitative summary for LBR was obtained. Participants/materials, setting, methods Freeze-all was undertaken when (i) the woman is deemed to be at high risk for OHSS, (ii)serum progesterone level is &gt; 1.5 ng/ml on the day of trigger, (iii)preimplantation genetic testing is planned, (iv)the woman will undergo surgery prior to ET, (v)couple preference. Main results and the role of chance Baseline characteristics were similar between the groups except for antral follicle count (22 vs 18, MD = 5, 95% CI = 0 to 8), and number of metaphase-two oocytes (13 vs 10, MD = 3, 95% CI = 1 to 6) all of which were significantly higher in the immediate transfer group. Clinical pregnancy rate (CPR) per ET was similar in two groups (50.4% vs 44.3%, RR = 1.14, 95% CI = 0.84 to 1.54). Miscarriage rate per pregnancy was significantly lower (12.3 vs 31.1, RR = 0.40, 95% CI = 0.19 to 0.84) and LBR per ET was significantly higher (42.9 vs 26.6, RR = 1.61, 95% CI = 1.06 to 2.46) in the immediate transfer group. Median gestational age at delivery was similar (267.5 (262.5–273) vs 268 (260–271.5) days, MD = 1.00, 95% CI= –4.00 to 5.00). Median birthweight was significantly higher in the delayed transfer group (3520 vs 3195 grams, MD= –300, 95% CI= –660 to –20 grams). Birthweight percentile, height at birth and head circumference were similar between groups. Literature search revealed 1712 studies from which nine were eligible for quantitative summary. Cumulative risk ratio showed a 10% increase in LBR with immediate transfer compared to delayed transfer (RR = 1.10, 95% CI = 1.01 – 1.20, I2=67%, 17369 embryo transfers). Limitations, reasons for caution Our study is limited by its retrospective design and relatively limited sample size for multivariate analyses. Yet, it is reassuring that the majority of our findings are consistent with previous publications. Wider implications of the findings: The hypotheses generated by our retrospective findings, i.e., FET in the immediate menstrual cycle resembling fresh ETs with strong trends towards lower birthweight and lower incidence of preeclampsia is noteworthy for the design of future studies, and these outcomes should be followed and reported. Trial registration number None

Impact of Inter-Hospital Transfer on Outcomes in Patients Undergoing Emergency Abdominal Surgery: A Tertiary Referral Center’s Perspective

Background In trauma patients, the impact of inter-hospital transfer has been widely studied. However, for patients undergoing emergency abdominal surgery (EAS), the effect of inter-hospital transfer on outcomes is largely unknown. Methods This is a single-center, retrospective observational study. Outcomes of transferred patients undergoing EAS were compared to patients primarily admitted to a tertiary care hospital from 01/2016 to 12/2018 using univariable and multivariable analyses. The primary outcome was in-hospital mortality. Results Some 973 patients with a median (IQR) age of 58.1 (39.4–72.2) years and a median body mass index of 25.8 (22.5–29.3) kg/m2 were included. The transfer group comprised 258 (26.3%) individuals and the non-transfer group 715 (72.7%). The population was stratified in three subgroups: (1) patients with low surgical stress (n = 483, 49.6%), (2) with hollow viscus perforation (n = 188, 19.3%) and (3) with potential bowel ischemia (n = 302, 31.1%). Neither in the low surgical stress nor in the hollow viscus perforation group was the transfer status associated with mortality. However, in the potential bowel ischemia group inter-hospital transfer was a predictor for mortality (OR 3.54, 95%CI 1.03–12.12, p = 0.045). Moreover, in the hollow viscus perforation group inter-hospital transfer was a predictor for reduced hospital length of stay (RC -10.02, 95%CI −18.14/−1.90, p = 0.016) and reduced severe complications (OR 0.38, 95%CI 0.18–0.77, p = 0.008). Conclusion Other than in patients with low surgical stress or hollow viscus perforation, in patients with potential bowel ischemia inter-hospital transfer was an independent predictor for higher mortality. Taking into account the time sensitiveness of bowel ischemia, efforts should be made to avoid inter-hospital transfer in this vulnerable subgroup of patients.

Cytogenetic Analysis of the Products of Conception After Spontaneous Abortion in the First Trimester

In the present study, we retrospectively recruited 340 patients who underwent spontaneous abortions to investigate chromosomal abnormalities of the conception products in the first trimester. We also performed a relevant analysis of clinical factors. Of these patients, 165 had conception products with chromosomal abnormalities, including 135 aneuploidies, 11 triploidies, 10 complex abnormalities, and 9 segmental aneuploidies. The most common abnormal chromosomes were chromosome 16 in the embryo-transfer group and sex chromosomes in the natural-conception group. The most common abnormal chromosomes in all analyzed maternal age groups were sex chromosomes, 16, and 22. The chromosomal abnormality incidence was related to age and number of spontaneous abortions (both <i>p</i> &#x3c; 0.05), but not to number of pregnancies, deliveries, induced abortions, or methods of conception (all <i>p</i> &#x3e; 0.05). The rates of abnormality for chromosomes 12, 15, 20, and 22 increased with age, while the rates for chromosomes 6, 7, 13, and X decreased. In all age groups, aneuploidy was by far the most common abnormality; however, the low-incidence distributions of chromosomal abnormalities were entirely different. Overall, chromosomal aneuploidy was the primary cause of pregnancy loss in the first trimester, and low-frequency abnormalities differed across age subgroups. Chromosomal aberrations were found to be related to maternal age and spontaneous abortion, but not all chromosomal abnormalities increased with age.

Cash transfers may increase the no-show rate for surgical patients in low-resource settings: A randomized trial

Background: Over two-thirds of the world's population cannot access surgery when needed. Interventions to address this gap have primarily focused on surgical training and ministry-level surgical planning. However, patients more commonly cite cost--rather than governance or surgeon availability--as their primary access barrier. We undertook a randomized, controlled trial (RCT) to evaluate the effect on compliance with scheduled surgical appointments of addressing this barrier through a cash transfer. Methods: 453 patients who were deemed surgical candidates by a nursing screening team in Guinea, West Africa, were randomized into three study arms: control, conditional cash transfer, and labeled unconditional cash transfer. Arrival to a scheduled surgical appointment was the primary outcome. The study was performed in conjunction with Mercy Ships. Results: The overall no-show rate was five-fold lower in Guinea than previously published estimates, leading to an underpowered study. In a post-hoc analysis, which included non-randomized patients, patients in the control group and the conditional cash transfer group demonstrated no effect from the cash transfer. Patients in the unconditional cash transfer group were significantly less likely to arrive for their scheduled appointment. Subgroup analysis suggested that actual receipt of the unconditional cash transfer, instead of a lapse in the transfer mechanism, was associated with failure to show. Conclusion: We find that cash transfers are feasible for surgical patients in a low-resource setting, but that unconditional transfers may have negative effects on compliance. Although demand-side barriers are large for surgical patients in low-resource settings, interventions to address them must be designed with care.