Safety and feasibility of colonoscopy in nonagenarians: A systematic review, meta-analysis and meta-regression analysis.

AIM: The aim of this work was to evaluate the safety and feasibility of performing colonoscopy in patients aged 90 years or over. METHOD: In compliance with PRISMA statement standards, a systematic review of studies reporting the outcomes of colonoscopy in patients aged ≥90 years was conducted. A proportional meta-analysis model was constructed to quantify the risk of outcomes and a direct comparison meta-analysis model was constructed to compare outcomes between nonagenarians and patients aged between 50 and 89 years via random-effects models. RESULTS: Seven studies enrolling 1304 patients (1342 colonoscopies) were included. Analyses showed that complications related to bowel preparation occurred in 0.7% (95% CI 0.1%-1.6%), procedural complications in 0.6% (0.00%-1.7%), 30-day complications in 1.5% (0.6%-2.7%), procedural mortality in 0.3% (0.0%-1.1%) and 30-day mortality in 1.1% (0.3%-2.2%). Adequate bowel preparation and colonoscopy completion were achieved in 81.3% (73.8%-87.9%) and 92.1% (86.7%-96.3%), respectively. No difference was found in bowel preparation-related complications [risk difference (RD) 0.00, p = 0.78], procedural complications (RD 0.00, p = 0.60), 30-day complications (RD 0.01, p = 0.20), procedural mortality (RD 0.00, p = 1.00) or 30-day mortality (RD 0.01, p = 0.34) between nonagenarians and patients aged between 50 and 89 years. The colorectal cancer detection rate was 14.3% (9.8%-19.5%), resulting in therapeutic intervention in 65.9% (54.5%-76.6%). CONCLUSIONS: Although the evidence is limited to a selected group of nonagenarians, it may be fair to conclude that if a colonoscopy is indicated in a nonagenarian with good performance status (based on initial less-invasive investigations), the level 2 evidence supports its safety and feasibility. Age on its own should not be a reason for failing to offer colonoscopy to a nonagenarian.

'I was able to make a better decision about my health.' Wahine experiences of colposcopy at a marae-based health clinic: A qualitative study.

BACKGROUND: Equitable access to colposcopy services is required if we are to realise the benefit of the introduction of human papilloma virus (HPV) screening in Aotearoa New Zealand. We piloted a community colposcopy clinic, co-located at an urban marae health clinic. AIM: To describe the experiences of wahine (women) attending the marae-based colposcopy clinic. METHODS: An in-depth reflexive thematic analysis from 34 people's accounts was undertaken. RESULTS: Five themes were identified from the experiences of wahine attending the clinic. Three themes related to how having a local clinic supported access: everyone was welcoming and friendly, the environment was familiar and non-clinical and the clinic was accessible. The fourth theme related to how this contributed to agency. A fifth theme relates to wahine views about informing the ongoing provision of colposcopy services. The experiences reflected the principles and values practised at the marae health clinic. Wahine described feeling cared for as soon as they entered the clinic. As the clinic was local, and for some based at their marae, it was a known space where they knew the experience would be safe. Whanau were welcome with spaces for children to play. Being local meant there were fewer logistics to manage, all of which supported access. DISCUSSION: Prioritising wahine through the provision of culturally safe and accessible colposcopy is feasible. It has the potential to contribute to the elimination of cervical cancer in Aotearoa, New Zealand.

A prospective proof-of-concept trial on the effect of personalized dosages of follitropin delta in intrauterine insemination.

RESEARCH QUESTION: What is the efficacy and safety of individualized follitropin delta dosing for ovarian stimulation in intrauterine insemination (IUI)? DESIGN: This single-centre, prospective, open-label, single-cohort study involving 106 patients established an original dosing regimen based on body weight and anti-Müllerian hormone (AMH) concentrations, with adjustments based on the ovarian response from the previous IUI cycle. Each participant was enrolled in a maximum of three IUI cycles. RESULTS: Mean age was 34.5 ± 4.5 years, mean weight 69.2 ± 11.2 kg, mean AMH 15.7 ± 8.6 pmol/l, mean FSH 6.3 ± 2.6 IU/l and mean antral follicle count 16.4 ± 8.2. The percentage of patients who produced more than three mature follicles was 1.9%, 0% and 1.5%, respectively, for the three IUI cycles. The percentage of patients with two or three mature follicles was 34.0%, 36.9% and 47.1% for the three IUI cycles. The clinical pregnancy rate per IUI cycle was 17.9%, 14.3% and 17.6% for the three cycles, with a cumulative clinical pregnancy rate of 40.6%. Out of 258 cycles, 43 (16.7%) resulted in clinical pregnancy, with six of those resulting in multiple pregnancies (14.0%). Two resulted in spontaneous reduction within the first trimester and four resulted in live twin births, representing only 1.6% of the total cycles. CONCLUSIONS: This study is the first to utilize follitropin delta for stimulation in IUI. It demonstrates that individualized dosing is both effective and safe, resulting in satisfactory cumulative pregnancy rates and an acceptable multiple pregnancy rate, thus achieving the primary objectives of the research.

Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes.

The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014-12/2021). Primary outcomes included live birth, miscarriage, or transfer failure. We documented IVIg side effects and maternal/fetal outcomes. Logistic regression analysis was used to assess for association of IVIg exposure with outcomes and adjust for confounders. The study included 143 patients, with a 2:1 ratio of controls to patients receiving IVIg treatment. Patient characteristics were similar between groups. There was higher live birth rate (LBR) in patients receiving IVIg (32/49; 65.3%) compared to controls (32/94; 34%); p < 0.001). When stratifying patients into moderate and severe uRIF (respectively 3-4 and [Formula: see text] 5 previous good quality blastocyst transfer failures), only patients with severe uRIF benefited from IVIg (LBR (20/29 (69%) versus 5/25 (20%) for controls, p = 0.0004). In the logistic regression analysis, IVIg was associated with higher odds of live birth (OR 3.64; 95% CI 1.78-7.67; p = 0.0004). There were no serious adverse events with IVIg. IVIg can be considered in well selected patients with [Formula: see text] 5 previous unexplained, high quality blastocyst transfer failures. A randomized controlled trial is needed to confirm these findings.

The association between the type of progesterone supplementation and miscarriage risk in women who have had a positive pregnancy test following embryo transfer: a retrospective cohort study.

PURPOSE: The purpose of this study was to identify if switching from intramuscular (IM) to vaginal progesterone compared to staying on IM progesterone after a positive pregnancy test following embryo transfer (ET) is associated with miscarriage risk. METHODS: A retrospective cohort study was performed in a private university-affiliated fertility clinic and included women aged 18-50 years with a positive pregnancy test following ET. The two groups studied were: women who stayed on IM progesterone following a positive pregnancy test and those who switched to vaginal progesterone after a positive test. The main outcome measured was risk of miscarriage < 24 weeks gestation as a proportion of non-biochemical pregnancies. RESULTS: 1988 women were included in the analysis. Among the baseline characteristics, the presence of prior miscarriages as well as prior failed ETs, and frozen cycles (vs fresh) as type of transfer were associated with IM progesterone use (p values ≤ 0.01). As per miscarriage risk < 24 weeks, 22.4% (274/1221) of patients in the IM progesterone group experienced a miscarriage compared with 20.7% (159/767) in the vaginal progesterone group (OR 0.90; 95% CI 0.73-1.13). A multivariable logistic regression model revealed an adjusted OR (aOR) of 0.97 (95% CI 0.77-1.22). CONCLUSION: This study suggests that switching from IM to vaginal progesterone after a positive pregnancy test following an ET is not associated with miscarriage risk. Considering that IM progesterone imposes substantial discomfort, this study offers reassurance and some flexibility in treatment protocols. Further prospective studies are necessary to corroborate the results of this study.

Testicular Sperm Aspiration (TESA) or Microdissection Testicular Sperm Extraction (Micro-tese): Which Approach is better in Men with Cryptozoospermia and Severe Oligozoospermia?

OBJECTIVES: To evaluate and compare sperm retrieval outcomes by testicular sperm aspiration (TESA) and micro-dissection testicular sperm extraction (micro-TESE) in non-azoospermic men. METHODS: We conducted a retrospective study of 145 consecutive testicular sperm retrievals in men with cryptozoospermia (n = 56) or severe oligozoospermia (n = 84). The decision to perform a TESA or a micro-TESE was made after thorough discussion of the pros and cons of these procedures with the couple. Final assessment of sperm recovery, on the day of ICSI, was reported either as successful (available sperm for ICSI) or unsuccessful (no sperm for ICSI). RESULTS: Mean sperm concentration, sperm motility, testicular volume and serum FSH level of men undergoing TESA were not significantly different from those of men undergoing micro-TESE. In men with severe oligozoospermia (<5 million/ml), sperm recovery was successful in 95% (18/19) of those who underwent micro-TESE and in 92% (60/65) of those who underwent TESA (P > 0.05). In men with cryptozoospermia, sperm recovery was successful in 88% (42/48) of men who underwent micro-TESE and 25% (2/8) of men who underwent TESA (P < .001). CONCLUSIONS: These data indicate that in men with severe oligozoospermia, TESA and micro-TESE are equally successful sperm retrieval techniques. However, in men with cryptozoospermia, sperm retrieval rates are significantly higher with micro-TESE than TESA.

Risk factors for the development of endometrial fluid in women undergoing IVF: A retrospective cohort study✰.

RESEARCH QUESTION: Presence of endometrial fluid (EF) is a poorly understood pathology and remains a challenge for clinicians, as very little data exists to explain its consequences and treatment. Our objective was to investigate risk factors for EF during IVF. DESIGN: This retrospective cohort study included all women with a freeze all embryos cycle (FAE) for EF between 2010 and 2016 at a university-affiliated private IVF center. Controls (2:1) were randomly selected out of the database of our fresh autologous IVF cycles during the same period. Main outcome measures were possible risk factors for EF, comprising polycystic ovarian syndrome (PCOS), ovarian hyperstimulation syndrome (OHSS), previous pelvic or endometrial surgery (polypectomy or synechia removal), cesarean section, myomas and severe endometriosis. A logistic regression model was used to assess independent risk factors for EF. RESULTS: Out of 9000 IVF cycles, 1204 were FAE cycles, among which we identified 86 EF cases. We then selected 171 controls. Independent risk factors for presence of EF were a history of previous myomectomy (adjusted odds ratio (aOR) 19.77, 95%CI [4.01-97.53]), severe endometriosis (aOR 5.97, 95%CI [2.09-17.05]), PCOS (aOR 5.72, 95%CI [2.66-12.33]) and previous cesarean section (aOR 5.17, 95%CI [1.84-14.49]). CONCLUSIONS: Our results are not only confirming the association between PCOS, severe endometriosis, previous cesarean procedure and EF, but also reporting for the first time an association between previous myomectomy and EF.

Implementation of Perioperative Point-of-Care Platelet Function Analyses Reduces Transfusion Requirements in Cardiac Surgery: A Retrospective Cohort Study.

BACKGROUND: Platelet dysfunction is a common cause of bleeding, perioperative blood transfusion, and surgical re-exploration in cardiac surgical patients. We evaluated the effect of incorporating a platelet function analyzer utilizing impedance aggregometry (Multiplate, Roche, Munich, Germany) into our local transfusion algorithm on the rate of platelet transfusion and postoperative blood loss in patients undergoing coronary artery bypass grafting (CABG) surgery. METHODS: Data were collected on patients undergoing CABG surgery from January 2015 to April 2017. Patients who underwent surgery before and after introduction of this algorithm were classified into prealgorithm and postalgorithm groups, respectively. The primary outcome was the rate of platelet transfusion before and after implementation of the Multiplate-based transfusion algorithm. Secondary outcomes included transfusion rate of packed red blood cells, postoperative blood loss at 12 and 24 hours, length of stay in the intensive care unit, and the hospital and mortality. RESULTS: A total of 726 patients were included in this analysis with 360 and 366 patients in the pre- and postalgorithm groups, respectively. Transfusion rates of platelets (p = 0.01) and packed red blood cells (p = 0.0004) were significantly lower following introduction of the algorithm in patients (n = 257) who had insufficient time to withhold antiplatelet agents. Receiver operating characteristic curves defined optimal cutoff points of arachidonic acid and adenosine diphosphate assays on the Multiplate to predict future platelet transfusion were 23AU and 43AU, respectively. CONCLUSIONS: The introduction of a Multiplate-based platelet transfusion algorithm showed a statistically significant reduction in the administration of platelets to patients undergoing urgent CABG surgery.

In freeze-all embryo cycles due to endometrial fluid (EF), live birth rates are comparable to those of controls, despite high rates of EF recurrence and cycle cancellation.

RESEARCH QUESTION: Do cumulative live birth rates (CLBRs) differ between women who have had a freeze-all embryo cycle (FAE) for endometrial fluid (EF) and controls? DESIGN: This retrospective cohort study included 83 women who had a FAE cycle due to the presence of EF between 2010 and 2016 at a university-affiliated private IVF center. The controls were 219 women who had FAE for other indications during the same period and were randomly selected. The main outcome measures were CLBRs, EF recurrence, cancellation and pregnancy loss rates. RESULTS: Population characteristics were comparable between the two groups. The CLBR was not significantly different between the EF and the control group: 39.8 % vs. 47.0 %, respectively, p=0.26. Cancellation rates in the two first FETs were higher in the EF group than the control group: 18.1 % vs. 4.1 % (p<0.001) and 22.9 % vs. 8.5 % (p=0.02). After FAE for EF, we observed a significant risk of EF recurrence (32/177 cycles, 18.1 %), allowing us to identify a poor prognosis subgroup. When EF was detected, the LBR per transfer was 7.1 % (1/14) when the transfer was finally performed (after EF aspiration or EF disappearance), compared to 25 % (32/128) in cycles without EF recurrence (p<0.05). Conversely, in the absence of EF recurrence (145/177, 81.9 %), the LBR was comparable to that of the control group. The type of endometrial preparation does not seem to be associated with EF recurrence. CONCLUSION: Despite higher rates of EF recurrence and cycle cancellation, women with FAE for EF ultimately have comparable LBRs to those who have had a FAE for other indications. However, women presenting with at least one EF recurrence during FETs seem to have a lower LBR.

Exploring UK medical school differences: the MedDifs study of selection, teaching, student and F1 perceptions, postgraduate outcomes and fitness to practise.

BACKGROUND: Medical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors. METHOD: Aggregated data were collected for 50 measures across 29 UK medical schools. Data include institutional history (e.g. rate of production of hospital and GP specialists in the past), curricular influences (e.g. PBL schools, spend per student, staff-student ratio), selection measures (e.g. entry grades), teaching and assessment (e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores, Foundation satisfaction, postgraduate examination performance and fitness to practise (postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail. RESULTS: Medical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant with p < 0.05, and 201 (16.4%) reached a Tukey-adjusted criterion of p < 0.0025. Problem-based learning (PBL) schools differ on many measures, including lower performance on postgraduate assessments. While these are in part explained by lower entry grades, a surprising finding is that schools such as PBL schools which reported greater student satisfaction with feedback also showed lower performance at postgraduate examinations. More medical school teaching of psychiatry, surgery and anaesthetics did not result in more specialist trainees. Schools that taught more general practice did have more graduates entering GP training, but those graduates performed less well in MRCGP examinations, the negative correlation resulting from numbers of GP trainees and exam outcomes being affected both by non-traditional teaching and by greater historical production of GPs. Postgraduate exam outcomes were also higher in schools with more self-regulated learning, but lower in larger medical schools. A path model for 29 measures found a complex causal nexus, most measures causing or being caused by other measures. Postgraduate exam performance was influenced by earlier attainment, at entry to Foundation and entry to medical school (the so-called academic backbone), and by self-regulated learning. Foundation measures of satisfaction, including preparedness, had no subsequent influence on outcomes. Fitness to practise issues were more frequent in schools producing more male graduates and more GPs. CONCLUSIONS: Medical schools differ in large numbers of ways that are causally interconnected. Differences between schools in postgraduate examination performance, training problems and GMC sanctions have important implications for the quality of patient care and patient safety.

The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning.

BACKGROUND: What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL). METHOD: The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times. RESULTS: A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content. DISCUSSION: UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training.

Cancer Antigen Discovery Is Enabled by RNA Sequencing of Highly Purified Malignant and Nonmalignant Cells.

PURPOSE: Broadly expressed, highly differentiated tumor-associated antigens (TAA) can elicit antitumor immunity. However, vaccines targeting TAAs have demonstrated disappointing clinical results, reflecting poor antigen selection and/or immunosuppressive mechanisms. EXPERIMENTAL DESIGN: Here, a panel of widely expressed, novel colorectal TAAs were identified by performing RNA sequencing of highly purified colorectal tumor cells in comparison with patient-matched colonic epithelial cells; tumor cell purification was essential to reveal these genes. Candidate TAA protein expression was confirmed by IHC, and preexisting T-cell immunogenicity toward these antigens tested. RESULTS: The most promising candidate for further development is DNAJB7 [DnaJ heat shock protein family (Hsp40) member B7], identified here as a novel cancer-testis antigen. It is expressed in many tumors and is strongly immunogenic in patients with cancers originating from a variety of sites. DNAJB7-specific T cells were capable of killing colorectal tumor lines in vitro, and the IFNγ+ response was markedly magnified by control of immunosuppression with cyclophosphamide in patients with cancer. CONCLUSIONS: This study highlights how prior methods that sequence whole tumor fractions (i.e., inclusive of alive/dead stromal cells) for antigen identification may have limitations. Through tumor cell purification and sequencing, novel candidate TAAs have been identified for future immunotherapeutic targeting.

Use of testicular sperm in couples with SCSA-defined high sperm DNA fragmentation and failed intracytoplasmic sperm injection using ejaculated sperm.

Sperm DNA fragmentation (SDF) has been linked with male infertility, and previous studies suggest that SDF can have negative influence on pregnancy outcomes with assisted reproduction. We performed a retrospective review of consecutive couples with a high SDF level that had intracytoplasmic sperm injection (ICSI) using testicular sperm (T-ICSI). We compared the T-ICSI outcomes to that of two control groups: 87 couples with failed first ICSI cycle and who had a second ICSI cycle using ejaculated sperm (Ej-ICSI), and 48 consecutive couples with high sperm chromatin structure assay (SCSA)-defined SDF (>15%) that underwent an ICSI cycle using ejaculated sperm after one or more failed ICSI cycles (Ej-ICSI-high SDF). The mean number of oocytes that were retrieved and the total number of embryos were not different among the three groups. The mean number of transferred embryos in the T-ICSI group was higher than the Ej-ICSI group but not significantly different than the Ej-ICSI-high SDF group (1.4, 1.2, and 1.3, respectively, P < 0.05). Clinical pregnancy rate in the T-ICSI group was not significantly different than the Ej-ICSI and Ej-ICSI-high SDF groups (48.6%, 48.2%, and 38.7%, respectively, P > 0.05). No significant difference was found in live birth rate when comparing T-ICSI to Ej-ICSI and Ej-ICSI-high SDF groups. The results suggest that pregnancy outcomes and live birth rates with T-ICSI are not significantly superior to Ej-ICSI in patients with an elevated SCSA-defined sperm DNA fragmentation and prior ICSI failure(s).

Structural Analysis, Molecular Modelling and Preliminary Competition Binding Studies of AM-DAN as a NMDA Receptor PCP-Site Fluorescent Ligand.

Excitotoxicity related to the dysfunction of the N-methyl-d-aspartate receptor (NMDAR) has been indicated to play an integral role in the pathophysiology of multiple disease states, including neurodegenerative disorders such as Parkinson's disease. There is a notable gap in the market for novel NMDAR antagonists, however current methods to analyse potential antagonists rely on indirect measurements of calcium flux and hazardous radioligand binding assays. Recently, a fluorescent NMDAR ligand, N-adamantan-1-yl-dimethylamino-1-naphthalenesulfonic acid, known as AM-DAN was developed by our group. Additional studies on this ligand is necessary to evaluate its potential as a biological tool in NMDAR research. Therefore, this study was aimed at conducting structural analyses, fluorescence experiments, high-accuracy NMDAR molecular modelling and NMDAR phencyclidine (PCP) site competition binding studies using AM-DAN. Results revealed that AM-DAN has appropriate structural properties, significant fluorescent ability in various solvents and is able to bind selectively and compete for the PCP-binding site of the NMDAR. Therefore, AM-DAN holds promise as a novel fluorescent ligand to measure the affinity of prospective drugs binding at the NMDAR PCP-site and may circumvent the use of radioligands.

Cryopreserved embryo replacement is associated with higher birthweight compared with fresh embryo: multicentric sibling embryo cohort study.

Birth weight (BW) is higher after frozen embryo transfer (FET) than after fresh embryo replacement. No study has compared the BW of siblings conceived using the same oocyte/embryo cohort. The aim of this study was to determine whether the freezing-thawing procedure is involved in such difference. Multicenter study at Montpellier University Hospital, Clinique Ovo, Canada and Grenoble-Alpes University Hospital. The first cohort (Fresh/FET) included in vitro fertilization (IVF) cycles where the older was born after fresh embryo transfer (n = 158) and the younger after transfer of frozen supernumerary embryos (n = 158). The second cohort (FET/FET) included IVF cycles where older and younger were born after FET of embryos from the same cohort. The mean adjusted BW of the FET group was higher than that of the fresh group (3508.9 ± 452.4 g vs 3237.7 ± 463.3 g; p < 0.01). In the FET/FET cohort, the mean adjusted BW was higher for the younger by 93.1 g but this difference is not significant (3430.2 ± 347.6 g vs 3337.1 ± 391.9 g; p = 0.3789). Our results strongly suggest that cryopreservation is directly involved in the BW variation. Comparing BW difference between Fresh/FET cohort and FET/FET one, it suggests that parity is not the only responsible, increasing the role of cryopreservation step in BW variation.

Live birth rates remain stable in modified natural IVF despite low anti-Müllerian hormone: analysis of 638 cycles.

RESEARCH QUESTION: Do live birth rates (LBR) following modified natural IVF (mnIVF) differ according to serum anti-Müllerian hormone (AMH) concentration? DESIGN: Retrospective cohort study including 638 women aged ≤39 years starting their first mnIVF cycle at a university-affiliated private IVF centre. Patients were divided into three groups, by concentration of AMH: ≤0.5 ng/ml (25th percentile), 0.51-2.03 ng/ml (25-75th percentile, reference) and 2.04-6.56 ng/ml (75th percentile). Analyses were stratified by AMH percentile and the age of patients (<35, 35-39 years). Logistic regression assessed the impact of age and AMH percentile on outcomes. LBR was the primary outcome measure. RESULTS: LBR per started cycle were comparable across AMH percentiles (11.6%, 12.4% and 17.0% for the 25th, 25-75th and 75th percentile, respectively). No statistically significant difference was found between the three AMH groups with respect to cancellation, successful egg retrieval, embryo transfer, or biochemical and clinical pregnancy rates. Logistic regression analysis did not identify AMH percentile as a significant predictor of live birth. Compared with the reference group, the odds ratios (OR [95% confidence interval, CI]) for live birth in the <25th and >75th AMH percentile groups were 0.97 (0.54-1.76) and 1.41 (0.82-2.41), respectively. The results were the same regardless of age group (<35 years, 35-39 years). CONCLUSIONS: Serum AMH cannot be used to predict mnIVF outcomes. Patients in lower/upper AMH percentiles showed pregnancy and LBR comparable to patients with normal AMH.

Rescue of a submerged convulsing diver.

In 2018, the Medical Panel of the NATO Underwater Diving Working Group (UDWG) discussed the question of the rescue and management of a submerged unresponsive compressed-gas diver. The Panel reviewed the 2012 recommendation by the UHMS Diving Committee with respect to the specific recommendation in a convulsing diver using a half-face mask and separate mouthpiece, to delay surfacing until the clonic phase had subsided if the mouthpiece was in place. There is a paucity of scientific, epidemiological, experimental and observational human studies to substantiate this guidance. Experimental animal studies suggest that the likelihood of a complete airway obstruction during an ongoing seizure is low and that there is a high likelihood of surviving pulmonary barotrauma caused by complete airway closure. Airway management and control is an essential step in the management of the unresponsive diver and would be challenging to achieve in the underwater environment. Even in the military setting, it will be difficult to provide sufficient training to enable divers to handle such a situation. In this very rare scenario it is considered that emergency guidelines should be clear, concise and easy to follow. The UDWG therefore recommends that all unconscious military divers in this situation should be rescued to surface without waiting for clonic seizures to subside. Training organizations for recreational and occupational divers should consider whether this guidance should be applied for civilian divers as well.

Structure-based development of new RAS-effector inhibitors from a combination of active and inactive RAS-binding compounds.

The RAS gene family is frequently mutated in human cancers, and the quest for compounds that bind to mutant RAS remains a major goal, as it also does for inhibitors of protein-protein interactions. We have refined crystallization conditions for KRAS169Q61H-yielding crystals suitable for soaking with compounds and exploited this to assess new RAS-binding compounds selected by screening a protein-protein interaction-focused compound library using surface plasmon resonance. Two compounds, referred to as PPIN-1 and PPIN-2, with related structures from 30 initial RAS binders showed binding to a pocket where compounds had been previously developed, including RAS effector protein-protein interaction inhibitors selected using an intracellular antibody fragment (called Abd compounds). Unlike the Abd series of RAS binders, PPIN-1 and PPIN-2 compounds were not competed by the inhibitory anti-RAS intracellular antibody fragment and did not show any RAS-effector inhibition properties. By fusing the common, anchoring part from the two new compounds with the inhibitory substituents of the Abd series, we have created a set of compounds that inhibit RAS-effector interactions with increased potency. These fused compounds add to the growing catalog of RAS protein-protein inhibitors and show that building a chemical series by crossing over two chemical series is a strategy to create RAS-binding small molecules.

Autologous endometrial cell co-culture improves human embryo development to high-quality blastocysts: a randomized controlled trial.

RESEARCH QUESTION: Does autologous endometrial cell co-culture (AECC) improve the number of good-quality blastocysts obtained by IVF/intracytoplasmic sperm injection (ICSI), compared with conventional embryo culture medium in a broad group of patients referred to assisted reproductive technology (ART)? DESIGN: This interventional, randomized, double-blind study took place at Clinique Ovo from March 2013 to October 2015 and included 207 healthy patients undergoing an IVF or ICSI protocol, of which 71 were excluded before randomization. On the previous cycle, all participants underwent an endometrial biopsy at D5 to D7 post-ovulation, following which the endometrial cells were prepared for AECC. RESULTS: The data demonstrated that AECC significantly increased the incidence of good-quality blastocysts compared with culture in conventional media (42.6% vs 28.4%, P < 0.001). No significant differences were found in pregnancy and live birth rates. CONCLUSION: This study demonstrated the benefits of AECC on blastocyst quality compared with conventional embryo culture medium, in a broader category of patients referred to ART as opposed to other studies that concentrated on specific causes of infertility only. However, limitations of the study design should be taken into consideration; the analysis was performed using embryos rather than patients and a follow-up of children born following the treatments could not be conducted.