PI3K inhibitor "alpelisib" alleviates methotrexate induced liver injury in mice and potentiates its cytotoxic effect against MDA-MB-231 triple negative breast cancer cell line.

Hepatotoxicity is the main off-target effect of methotrexate (MTX) limiting its effective clinical use. Besides, MDA-MB231 breast cancer cells show chemoresistance, partly via PI3K/AKT pathway. Therefore, we investigated the ameliorative potentials of the PI3K inhibitor, alpelisib (ALP) on MTX-induced hepatotoxicity (in vivo) and the restraining potentials of ALP on MDA-MB231 chemoresistance to MTX (in vitro). Twenty-eight male BALB/c mice were divided into 4 groups. In treatment groups, mice were administered ALP (2.5 and 5 mg/kg) for 5 days and MTX (20 mg/kg) from day 2 till day 5. The results showed that ALP restored hepatic architecture, reduced immune cell infiltration (F4/80, Ly6G and MPO) and repressed the rise in liver enzymes (AST and ALT) induced by MTX. Additionally, ALP rectified the MTX-induced disruption of cellular oxidant status by boosting antioxidant defense systems (HO-1 and GSH) and repressing lipid peroxidation (MDA and 4-HNE). Finally, ALP curbed MTX-induced hepatocyte apoptosis (NF-κB and BAX) and shifted the cytokine milieu away from inflammation (IL-17, IL-22, IL-6 and IL- 10). The results of the in vitro experiments revealed that ALP alone and in combination with MTX, synergistically, reduced cancer cell viability (MTT assay), migration (wound healing assay) and their capacity to establish colonies (colony formation assay) as compared to MTX alone. RT-PCR revealed the antiproliferative (Bcl-2) and proapoptotic (BAX) potentials of ALP and ALP/MTX combination especially after 24 h. In conclusion, targeting PI3K/AKT pathway is a promising strategy in triple negative breast cancer patients by ameliorating hepatotoxicity and restraining chemoresistance to chemotherapy.

Bariatric Surgeon Ergonomics: A Comparison of Laparoscopy and Robotics.

INTRODUCTION: Bariatric surgery is routinely performed using laparoscopic and robotic approaches. Musculoskeletal injuries are prevalent among both robotic and laparoscopic bariatric surgeons. Studies evaluating ergonomic differences between laparoscopic and robotic bariatric surgery are limited. This study aims to analyze the ergonomic, physical, and mental workload differences among surgeons performing robotic and laparoscopic bariatric surgery. MATERIALS AND METHODS: All primary laparoscopic and robotic bariatric surgeries, Roux-en-Y gastric bypass, and sleeve gastrectomy between May and August 2022 were included in this study. Objective ergonomic analysis was performed by an observer evaluating each surgeon intraoperatively according to the validated Rapid Entire Body Assessment tool, with a higher score indicating more ergonomic strain. After each operation, surgeons subjectively evaluated their physical workload using the body part discomfort scale, and their mental workload using the surgery task load index. RESULTS: Five bariatric surgeons participated in this study. In total, 50 operative cases were observed, 37 laparoscopic and 13 robotic. The median total Rapid Entire Body Assessmentscore as a primary surgeon was significantly higher in laparoscopic (6.0) compared to robotic (3.0) cases (P < 0.01). The laparoscopic and robotic approaches had no significant differences in the surgeons' physical (body part discomfort scale) or mental workload (surgery task load index). CONCLUSIONS: This study identified low-risk ergonomic stress in surgeons performing bariatric surgery robotically compared to medium-risk stress laparoscopically. Since ergonomic stress can exist even without the perception of physical or mental stress, this highlights the importance of external observations to optimize ergonomics for surgeons in the operating room.

The Association of Preoperative Food Insecurity With Early Postoperative Outcomes After Bariatric Surgery.

INTRODUCTION: To assess the rate of food insecurity in patients undergoing bariatric surgery. To compare the rates of 30-d postoperative complications based on food security status. METHODS: Patients undergoing primary Roux-en-Y gastric bypass or sleeve gastrectomy between 7/2020 - 3/2022 were screened for food insecurity via telephone using questions from the Accountable Health Communities Health-Related Social Needs Screening Tool. Screens were matched to patient data and 30-d outcomes from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. RESULTS: In total, 213 (59%) of the 359 bariatric surgery patients were screened with 81 (38%) screening positive for food insecurity. Evaluation of preoperative variables based on food security status showed comparable age, body mass index, and comorbidity status. Food insecure patients were found to have an increased length of stay following surgery compared to food secure patients (P = 0.003). Food insecurity was not associated with higher rates of Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program reported 30-d postoperative complications including emergency department/urgent care visits (P = 0.34) and hospital readmissions (P = 0.94). CONCLUSIONS: Food insecurity was prevalent at 38% of the bariatric surgical population. Food insecure patients had a statistically longer length of stay after primary bariatric surgery but were not associated with an increased risk of 30-d complications. Future studies are needed to determine the mid-term and long-term effects of food insecurity status on bariatric surgical outcomes and the potential impact of food insecurity on length of stay.

The complete chloroplast genome of the halophyte flowering plant Suaeda monoica from Jeddah, Saudi Arabia.

The complete chloroplast genome (plastome) of the annual flowering halophyte herb Suaeda monoica Forssk. ex J. F. Gmel. family (Amaranthaceae) that grows in Jeddah, Saudi Arabia, was identified for the first time in this study. Suaeda monoica is a medicinal plant species whose taxonomic classification remains controversial. Further, studying the species is useful for current conservation and management efforts. In the current study, the full chloroplast genome S. monoica was reassembled using whole-genome next-generation sequencing and compared with the previously published chloroplast genomes of Suaeda species. The chloroplast genome size of Suaeda monoica was 151,789 bp, with a single large copy of 83,404 bp, a small single copy of 18,007 bp and two inverted repeats regions of 25,189 bp. GC content in the whole genome was 36.4%. The cp genome included 87 genes that coded for proteins, 37 genes coding for tRNA, 8 genes coding for rRNA and one non-coding pseudogene. Five chloroplast genome features were compared between S. monoica and S. japonica, S. glauca, S. salsa, S. malacosperma and S. physophora. Among Suaeda genus and equal to most angiosperms chloroplast genomes, the RSCU values were conservative. Two pseudogenes (accD and ycf1), rpl16 intron and ndhF-rpl32 intergenic spacer, were highlighted as suitable DNA barcodes for different Suaeda species. Phylogenetic analyses show Suaeda cluster into three main groups; one in which S. monoica was closer to S. salsa. The obtained result provided valuable information on the characteristics of the S. monoica chloroplast genome and the phylogenetic relationships.

Glymphatic pathway: An emerging perspective in the pathophysiology of neurodegenerative diseases.

The central nervous system (CNS) is widely recognized as the only organ system without lymphatic capillaries to promote the removal of interstitial metabolic by-products. Thus, the newly identified glymphatic system which provides a pseudolymphatic activity in the nervous system has been focus of latest research in neurosciences. Also, findings reported that, sleep stimulates the elimination actions of glymphatic system and is linked to normal brain homeostatis. The CNS is cleared of potentially hazardous compounds via the glymphatic system, particularly during sleep. Any age-related alterations in brain functioning and pathophysiology of various neurodegenerative illnesses indicates the disturbance of the brain's glymphatic system. In this context, ß-amyloid as well as tau leaves the CNS through the glymphatic system, it's functioning and CSF discharge markedly altered in elderly brains as per many findings. Thus, glymphatic failure may have a potential mechanism which may be therapeutically targetable in several neurodegenerative and age-associated cognitive diseases. Therefore, there is an urge to focus for more research into the connection among glymphatic system and several potential brain related diseases. Here, in our current review paper, we reviewed current research on the glymphatic system's involvement in a number of prevalent neurodegenerative and neuropsychiatric diseases and, we also discussed several therapeutic approaches, diet and life style modifications which might be used to acquire a more thorough performance and purpose of the glymphatic system to decipher novel prospects for clinical applicability for the management of these diseases.

Current status of resident simulation training curricula: pearls and pitfalls.

BACKGROUND: Residency programs are required to incorporate simulation into their training program. Ideally, simulation provides a safe environment for a trainee to be exposed to both common and challenging clinical scenarios. The purpose of this review is to detail the current state of the most commonly used laparoscopic, endoscopic, and robotic surgery simulation programs in general surgery residency education, including resources required for successful implementation and benchmarks for evaluation. MATERIALS AND METHODS: Members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Resident and Fellow Task Force (RAFT) Committee performed a literature review using PubMed and training websites. Information regarding the components of the most commonly used laparoscopic, endoscopic, and/or robotic simulation curriculum, including both formal and informal benchmarks for evaluating training competence, were collected. RESULTS: Laparoscopic simulation revolves around the Fundamentals of Laparoscopic Surgery (FLS). Proficiency-based as well as virtual simulation have been utilized for FLS training curricula. Challenges include less direct translation to the technical complexities that can arise in laparoscopic surgery. Endoscopic simulation focuses on the Fundamentals of Endoscopic Surgery. There are virtual reality simulation platforms that can be used for skills assessment and training. Challenges include simulator types and access, as well as structured mentoring and feedback. Robotic simulation training curricula have not been standardized. Simulation includes one primary technology, which can be prohibitive based on cost and requirements for onboarding. CONCLUSIONS: While surgical simulation seems to be a fundamental and integrated part of surgical training, it requires a significant number of resources, which can be daunting for residency training programs. Regardless of the barriers outlined, the need for surgical simulation in laparoscopy, endoscopy, and robotics at surgical education training programs is clear.

Simplification of Mobility Tests and Data Processing to Increase Applicability of Wearable Sensors as Diagnostic Tools for Parkinson's Disease.

Quantitative mobility analysis using wearable sensors, while promising as a diagnostic tool for Parkinson's disease (PD), is not commonly applied in clinical settings. Major obstacles include uncertainty regarding the best protocol for instrumented mobility testing and subsequent data processing, as well as the added workload and complexity of this multi-step process. To simplify sensor-based mobility testing in diagnosing PD, we analyzed data from 262 PD participants and 50 controls performing several motor tasks wearing a sensor on their lower back containing a triaxial accelerometer and a triaxial gyroscope. Using ensembles of heterogeneous machine learning models incorporating a range of classifiers trained on a set of sensor features, we show that our models effectively differentiate between participants with PD and controls, both for mixed-stage PD (92.6% accuracy) and a group selected for mild PD only (89.4% accuracy). Omitting algorithmic segmentation of complex mobility tasks decreased the diagnostic accuracy of our models, as did the inclusion of kinesiological features. Feature importance analysis revealed that Timed Up and Go (TUG) tasks to contribute the highest-yield predictive features, with only minor decreases in accuracy for models based on cognitive TUG as a single mobility task. Our machine learning approach facilitates major simplification of instrumented mobility testing without compromising predictive performance.

Solvent-free method for masking the bitter taste of azithromycin dihydrate using supercritical fluid technology.

INTRODUCTION AND PURPOSE: The unpleasant extremely bitter taste of the orally administered broad-spectrum antibiotic azithromycin decreases patient compliance, especially in pediatrics. This issue can be overcome by decreasing drug interaction with the tasting buds using insoluble polymers at salivary pH (6.8 - 7.4), like the cationic polymer Eudragit EPO. Supercritical fluid technology is a green synthesis method for preparing pharmaceutical preparations that replace organic solvents with safe supercritical CO2. This study aimed to mask the bitter taste of azithromycin using the supercritical fluid method and a pH-sensitive Eudragit EPO polymer. METHODS: A foaming process was investigated for preparing a formulation (TEST), which comprises treating the polymer with supercritical carbon dioxide (CO2) fluid to prepare a taste-masked dosage form without employing organic solvents or flavors. RESULTS: The use of the supercritical technique at 40 °C and 10 MPa for 2 h allowed the manufacturing of solvent-free polymeric foam with azithromycin dispersions; the average calculated percentage of apparent volume change was 62.5 ± 5.9% with an average pore diameter of 34.879 Å. The formulated sample showed low drug release in simulated salivary fluid while keeping its crystalline nature. Moreover, clinical studies on healthy subjects showed that the formula successfully masked azithromycin's bitter taste. CONCLUSIONS: Overall, it has been shown herein that the supercritical fluid technology foaming method is promising in masking the bitter taste of bitter ingredients.

Epinephrine vs. phenylephrine infusion for prophylaxis against maternal hypotension after spinal anesthesia for cesarean delivery: a randomized controlled trial.

BACKGROUND: The hemodynamic effects of relatively low-dose epinephrine and phenylephrine infusions during cesarean delivery under spinal anesthesia were compared. METHODS: This randomized controlled trial included full-term pregnant women who underwent elective cesarean delivery. After spinal anesthesia, participants received either epinephrine (0.03 mcg/kg/min) or phenylephrine (0.4 mcg/kg/min) infusion that continued until 5 min after delivery. The primary outcome was a composite outcome of the occurrence of any of hypotension, hypertension, bradycardia, and/or tachycardia. Neonatal outcomes, including umbilical artery blood gas and Apgar scores, were assessed. RESULTS: In total, 98 patients in each group were analyzed, and the number of patients with the composite outcome was comparable between the epinephrine and phenylephrine groups (30/98 [31%] vs. 31/98 [32%], respectively; P = 0.877). However, the incidence of hypotension was likely lower in the epinephrine group than in the phenylephrine group (P = 0.066), and the number of hypotensive episodes per patient was lower in the epinephrine group than in the phenylephrine group. On the other hand, the incidence of tachycardia was higher in the epinephrine group than that in the phenylephrine group. The incidence of hypertension was comparable between the two groups and none of the participants developed bradycardia. Neonatal outcomes were comparable between the two groups. CONCLUSIONS: Epinephrine and phenylephrine infusion produced comparable maternal hemodynamics and neonatal outcomes. Epinephrine was associated with a higher incidence of maternal tachycardia and likely lower incidence of maternal hypotension than phenylephrine. IRB number: MD-245-2022. CLINICAL TRIAL REGISTRATION: This study was registered on May 31, 2023 at clinicaltrials.gov registry, NCT05881915, URL: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05881915term=NCT05881915&draw=2&rank=1.

Robotic Repair: An Alternative Technique for Rectus Diastasis and Abdominal Bulge Following DIEP Flap Breast Reconstruction.

BACKGROUND: The deep inferior epigastric artery perforator (DIEP) flap is the gold standard in autologous breast reconstruction. Despite advances in perforator dissection, abdominal morbidity still occurs. Traditional rectus diastasis (RD), abdominal bulge, and hernia repair with open techniques are associated with higher complication rates and recurrence. OBJECTIVES: We present a novel case series of robotic repair of symptomatic RD and/or abdominal bulge with concurrent hernia following DIEP flap surgery. METHODS: A single-center, retrospective review was conducted of 10 patients who underwent bilateral DIEP flap breast reconstruction and subsequent robotic repair of RD and/or abdominal bulge and hernia. Preoperative demographics and postoperative clinical outcomes were reviewed. RD up to 5 cm, abdominal bulge, and any concurrent ventral/umbilical hernias were repaired robotically with retrorectus plication and macroporous mesh reinforcement. RESULTS: The average age and BMI were 49 years (range 41-63) and 31 kg/m2 (range 26-44), respectively. The average number of perforators harvested per flap was 2.5 (range 1-4). Average RD and hernia size were 3.95 cm (range 2-5) and 5.8 cm2 (1-15), respectively. Eight patients stayed 1 night in the hospital, and 2 went home the same day as the robotic repair. No patients were converted to open technique and none experienced complications within 30 days. CONCLUSIONS: For patients who experience donor site morbidity following DIEP flap breast reconstruction, minimally invasive robotic repair of RD and/or abdominal bulge with hernia can be performed with mesh reinforcement. This technique is effective, with low complication rates, and should be considered over open repair.

Candidate genes associated with reproductive traits in rabbits.

In the era of scientific advances and genetic progress, opportunities in the livestock sector are constantly growing. The application of molecular-based methods and approaches in farm animal breeding would accelerate and improve the expected results. The current work aims to comprehensively review the most important causative mutations in candidate genes that affect prolificacy traits in rabbits. Rabbits are a source of excellent-tasting meat that is high in protein and low in fat. Their early maturity and intensive growth are highly valued all over the world. However, improving reproductive traits and prolificacy in rabbits could be very tricky with traditional selection. Therefore, traditional breeding programs need new methods based on contemporary discoveries in molecular biology and genetics because of the complexity of the selection process. The study and implementation of genetic markers related to production in rabbits will help to create populations with specific productive traits that will produce the desired results in an extremely short time. Many studies worldwide showed an association between different genes and productive traits in rabbits. The study of these polymorphisms and their effects could be useful for molecular-oriented breeding, particularly marker-assisted selection programs in rabbit breeding.

LC/MS-Based Metabolomics Reveals Chemical Variations of Two Broccoli Varieties in Relation to Their Anticholinesterase Activity: In vitro and In silico Studies.

Broccoli is commonly consumed as food and as medicine. However, comprehensive metabolic profiling of two broccoli varieties, Romanesco broccoli (RB) and purple broccoli (PB), in relation to their anticholinergic activity has not been fully disclosed. A total of 110 compounds were tentatively identified using UPLC-Q-TOF-MS metabolomics. Distinctively different metabolomic profiles of the two varieties were revealed by principal component analysis (PCA). Furthermore, by volcano diagram analysis, it was found that PB had a significantly higher content of phenolic acids, flavonoids, and glucosinolates, indicating the different beneficial health potentials of PB that demonstrated higher antioxidant and anticholinergic activities. Moreover, Pearson's correlation analysis revealed 18 metabolites, mainly phenolic and sulfur compounds, as the main bioactive. The binding affinity of these biomarkers to the active sites of acetyl- and butyryl-cholinesterase enzymes was further validated using molecular docking studies. Results emphasize the broccoli significance as a functional food and nutraceutical source and highlight its beneficial effects against Alzheimer's disease.

The submergence tolerance regulator SUB1A differentially coordinates molecular adaptation to submergence in mature and growing leaves of rice (Oryza sativa L.).

A typical adaptive response to submergence regulated by SUB1A, the ethylene-responsive transcription factor gene, is the restricted elongation of the uppermost leaves. However, the molecular and physiological functions of SUB1A have been characterized using entire shoot tissues, most of which are mature leaves that do not elongate under submergence. We aimed to identify leaf-type-specific and overlapping adaptations coordinated in SUB1A-dependent and -independent manners. To this end, we compared the transcriptomic and hormonal responses to submergence between mature and growing leaves using rice genotypes with and without SUB1A. Monosaccharide, branched-chain amino acid, and nucleoside metabolism, associated with ATP synthesis, were commonly activated in both leaf types regardless of genotype. In both leaf types, pathways involved in carbohydrate and nitrogen metabolism were suppressed by SUB1A, with more severe restriction in growing leaves that have a greater energy demand if SUB1A is absent. In growing leaves, accumulation of and responsiveness to growth-regulating hormones were properly modulated by SUB1A, which correlated with restricted elongation. In mature leaves, submergence-induced auxin accumulation was suppressed by SUB1A. This study demonstrates that different sets of hormonal pathways, both of which are modulated by SUB1A, contribute to distinct adaptive responses to submergence in mature and growing rice leaves.

Phosphine-Dependent Photoinitiation of Alkyl Thiols under Near-UV Light Facilitates User-Friendly Peptide Desulfurization.

Peptides are steadily gaining importance as pharmaceutical targets, and efficient, green methods for their preparation are critically needed. A key deficiency in the synthetic toolbox is the lack of an industrially viable peptide desulfurization method. Without this tool, the powerful native chemical ligation reaction typically used to assemble polypeptides and proteins remains out of reach for industrial preparation of drug targets. Current desulfurization methods require very large excesses of phosphine reagents and thiol additives or low-abundance metal catalysts. Here, we report a phosphine-only photodesulfurization (POP) using near-UV light that is clean, high-yielding, and requires as little as 1.2 equiv phosphine. The user-friendly reaction gives complete control to the chemist, allowing solvent and reagent selection based on starting material and phosphine solubility. It can be conducted in a range of solvents, including water or buffers, on protected or unprotected peptides, in low or high dilution and on gram scale. Oxidation-prone amino acids, π-bonds, aromatic rings, thio-aminal linkages, thioesters, and glycans are all stable to the POP reaction. We highlight the utility of this approach for desulfurization of industrially relevant targets including cyclic peptides and glucagon-like peptide 1 (GLP-1(7-36)). The method is also compatible with NCL buffer, and we highlight the robustness of the approach through the one-pot disulfide reduction/multidesulfurization of linaclotide, aprotinin, and wheat protein.

Health inequity in genomic personalized medicine in underrepresented populations: a look at the current evidence.

Improvements in sequencing technology coupled with dramatic declines in the cost of genome sequencing have led to a proportional growth in the size and number of genetic datasets since the release of the human genetic sequence by The Human Genome Project (HGP) international consortium. The HGP was undeniably a significant scientific success, a turning point in human genetics and the beginning of human genomics. This burst of genetic information has led to a greater understanding of disease pathology and the potential of employing this data to deliver more precise patient care. Hence, the recognition of high-penetrance disease-causing mutations which encode drivers of disease has made the management of most diseases more specific. Nonetheless, while genetic scores are becoming more extensively used, their application in the real world is expected to be limited due to the lack of diversity in the data used to construct them. Underrepresented populations, such as racial and ethnic minorities, low-income individuals, and those living in rural areas, often experience greater health disparities and worse health outcomes compared to the general population. These disparities are often the result of systemic barriers, such as poverty, discrimination, and limited access to healthcare. Addressing health inequity in underrepresented populations requires addressing the underlying social determinants of health and implementing policies and programs which promoted health equity and reduce disparities. This can include expanding access to affordable healthcare, addressing poverty and unemployment, and promoting policies that combat discrimination and racism.

ENTERPRET: A Randomized Controlled Trial of Vedolizumab Dose Optimization in Patients With Ulcerative Colitis Who Have Early Nonresponse.

BACKGROUND & AIMS: Patients with ulcerative colitis (UC) may experience nonresponse to biologics, possibly as a result of low drug exposure. This trial assessed the efficacy of dose optimization in patients with UC who have early nonresponse to vedolizumab and high drug clearance. METHODS: ENTERPRET was a phase 4, open-label, randomized, controlled trial that included patients with moderate to severe UC who had high drug clearance at week 5 (serum concentration, <50 µg/mL) and nonresponse to standard vedolizumab treatment at week 6. At week 6, eligible patients were randomized 1:1 to receive standard dosing (300 mg every 8 weeks) or dose-optimized vedolizumab (600 mg at week 6, then 300 mg every 4 weeks; or 600 mg at week 6, then 600 mg every 4 weeks [based on week 5 serum concentration]). The primary end point was endoscopic improvement at week 30. RESULTS: Of 278 enrolled patients, 132 (47.5%) had a clinical response at week 6. From week 6, 108 patients received standard (n = 53) or dose-optimized vedolizumab (n = 55); among patients with nonresponse at week 6, 86.5% had high drug clearance. At week 30, 10 patients (18.9%) who received standard vedolizumab had endoscopic improvement vs 8 patients (14.5%) who received dose-optimized vedolizumab. Five patients (9.4%) who received standard vedolizumab had clinical remission at week 30 vs 5 patients (9.1%) who received dose-optimized vedolizumab; clinical response was observed in 17 (32.1%) and 17 patients (30.9%), respectively. Safety event rates were similar among treatment groups. CONCLUSIONS: In patients with early nonresponse and high drug clearance, vedolizumab dose optimization is probably not required. A proportion of patients benefited from continued treatment irrespective of the dose received. CLINICALTRIALS: gov: NCT03029143.

Vedolizumab, Adalimumab, and Methotrexate Combination Therapy in Crohn's Disease (EXPLORER).

BACKGROUND & AIMS: Although biologics have revolutionized the treatment of Crohn's disease (CD), an efficacy ceiling has been reached. Combining biologic therapies may improve remission rates. METHODS: EXPLORER, a phase 4, single-arm, open-label study, evaluated triple combination therapy with vedolizumab (300 mg on day 1, weeks 2 and 6, and then every 8 weeks), adalimumab (160 mg on day 2, 80 mg at week 2, then 40 mg every 2 weeks), and methotrexate (15 mg weekly) in biologic-naïve patients with newly diagnosed, moderate- to high-risk CD. Endoscopic remission at week 26 (primary end point; Simple Endoscopic Score for CD ≤2), clinical remission at weeks 10 and 26 (secondary end point; Crohn's Disease Activity Index <150), and incidences of adverse events and serious adverse events were evaluated. RESULTS: Among 55 enrolled patients, the mean CD duration was 0.4 years, the mean baseline Simple Endoscopic Score for CD was 12.6, and the mean baseline Crohn's Disease Activity Index was 265.5. At week 26, 19 patients (34.5%) were in endoscopic remission. At weeks 10 and 26, 34 (61.8%) and 30 patients (54.5%), respectively, were in clinical remission. Post hoc Bayesian analysis showed that the probabilities that triple combination therapy produced a higher endoscopic remission rate (33.5%; 95% credible interval, 22.4-45.7) than placebo (14%), vedolizumab monotherapy (27%), or adalimumab monotherapy (30%) were 99.9% or higher, 86.3%, and 71.4%, respectively. Six patients had serious adverse events. CONCLUSIONS: Combination therapy resulted in endoscopic and clinical remission at week 26 in 34.5% and 54.5% of patients, respectively, with no safety signal related to the treatment regimen. This supports further evaluation of combination therapy in CD. CLINICALTRIALS: gov number: NCT02764762.

The role of transvaginal ultrasound in the third-trimester evaluation of patients at high risk of placenta accreta spectrum at birth.

BACKGROUND: Transvaginal ultrasound imaging has become an essential tool in the prenatal evaluation of the lower uterine segment and anatomy of the cervix, but there are only limited data on the role of transvaginal ultrasound in the management of patients at high risk of placenta accreta spectrum at birth. OBJECTIVE: This study aimed to evaluate the role of transvaginal sonography in the third trimester of pregnancy in predicting outcomes in patients with a high probability of placenta accreta spectrum at birth. STUDY DESIGN: This was a retrospective analysis of prospectively collected data of patients presenting with a singleton pregnancy and a history of at least 1 previous cesarean delivery and patients diagnosed prenatally with an anterior low-lying placenta or placenta previa delivered electively after 32 weeks of gestation. All patients had a least 1 detailed ultrasound examination, including transabdominal and transvaginal scans, within 2 weeks before delivery. Of note, 2 experienced operators, blinded to the clinical data, were asked to make a judgment on the likelihood of placenta accreta spectrum as a binary, low or high-probability of placenta accreta spectrum, and to predict the main surgical outcome (conservative vs peripartum hysterectomy). The diagnosis of accreta placentation was confirmed when one or more placental cotyledons could not be digitally separated from the uterine wall at delivery or during the gross examination of the hysterectomy or partial myometrial resection specimens. RESULTS: A total of 111 patients were included in the study. Abnormal placental tissue attachment was found in 76 patients (68.5%) at birth, and histologic examination confirmed superficial villous attachment (creta) and deep villous attachment (increta) in 11 and 65 cases, respectively. Of note, 72 patients (64.9%) had a peripartum hysterectomy, including 13 cases with no evidence of placenta accreta spectrum at birth because of failure to reconstruct the lower uterine segment and/or excessive bleeding. There was a significant difference in the distribution of placental location (X2=12.66; P=.002) between transabdominal and transvaginal ultrasound examinations, but both ultrasound techniques had similar likelihood scores in identifying accreta placentation that was confirmed at birth. On transabdominal scan, only a high lacuna score was significantly associated (P=.02) with an increased chance of hysterectomy, whereas on transvaginal scan, significant associations were found between the need for hysterectomy and the thickness of the distal part of the lower uterine segment (P=.003), changes in the cervix structure (P=.01), cervix increased vascularity (P=.001), and the presence of placental lacunae (P=.005). The odds ratio for peripartum hysterectomy were 5.01 (95% confidence interval, 1.25-20.1) for a very thin (<1-mm) distal lower uterine segment and 5.62 (95% confidence interval, 1.41-22.5) for a lacuna score of 3+. CONCLUSION: Transvaginal ultrasound examination contributes to both prenatal management and the prediction of surgical outcomes in patients with a history of previous cesarean delivery with and without ultrasound signs suggestive of placenta accreta spectrum. Transvaginal ultrasound examination of the lower uterine segment and cervix should be included in clinical protocols for the preoperative evaluation of patients at risk of complex cesarean delivery.

Effectiveness of Body Mass Index-Based Prophylactic Enoxaparin Dosing in Bariatric Surgery Patients.

INTRODUCTION: Enoxaparin is administered for venous thromboembolic (VTE) prophylaxis in bariatric surgery patients. There is concern whether body mass index (BMI)-based enoxaparin dosing consistently achieves prophylactic targets in patients with severe obesity. METHODS: This retrospective study included patients who underwent bariatric surgery at an academic medical center from Jan 2015-May 2021 and had an anti-Xa level drawn 2.5-6 h after ≥3 doses of BMI-based prophylactic enoxaparin. The primary outcome was the percentage of patients who achieved a target anti-Xa level. Secondary outcomes were prevalence of venous thromboembolic and bleeding events within 30 d post-operatively. RESULTS: Overall, 137 patients were included. Mean BMI was 59.1 ± 10.4 kg/m2, mean age was 43.9 ± 13.3 y and 110 patients (80.3%) were female. Target anti-Xa levels were achieved in 116 patients (84.7%); 14 (10.2%) were above target and 7 (5.1%) were below target. Patients with above target anti-Xa levels were significantly shorter in height than those within target range (167.1 versus 159.8 cm, P = 0.003). Five patients (3.6%) had a bleeding event; no thromboembolisms occurred. Anti-Xa levels correlated more strongly with enoxaparin dose per unit estimated blood volume (EBV) than dose per unit BMI (Rho = 0.54 versus Rho = 0.33). CONCLUSIONS: Target range anti-Xa levels were achieved in 85% of patients using BMI-based enoxaparin dosing. Patients with above target anti-Xa levels were significantly shorter by nearly 3 inches, suggesting an increased risk of overdosing enoxaparin in shorter, obese patients. An EBV-based dosing regimen may better account for patient height and is supported by a greater correlation with anti-Xa levels with dosing based on EBV than BMI.

The impact of preoperative ultrasound and intraoperative findings on surgical outcomes in patients at high risk of placenta accreta spectrum.

OBJECTIVE: To assess whether preoperative ultrasound imaging and intraoperative features predict surgical outcomes in patients at high risk for placenta accreta spectrum (PAS). DESIGN: Cohort study. SETTING: Cairo University Maternity, Egypt. POPULATION OR SAMPLE: Pregnant patients with one or more prior caesarean deliveries presenting with a low-lying/placenta praevia with or without PAS confirmed by histopathology. METHODS: Logistic regression and multivariable analyses. MAIN OUTCOMES MEASURES: Need for primary caesarean hysterectomy, numbers of red blood cell (RBC) units transfused and patients requiring transfusion of >5 units. RESULTS: Ninety consecutive records were reviewed, including 58 (64.4%) PAS cases. Sixty (66.7%, 95% confidence interval (CI) 56-76) required hysterectomy. Odds of hysterectomy were significantly (p = 0.005) increased with complete praevia. Significantly higher odds of hysterectomy were associated with subplacental hypervascularity (7.23, 95% CI 2.72-19.2, p < 0.001), lacunar scores 2+ and 3+ (12.6, 95% CI 4.15-38.5, p < 0.001), lacunar feeder vessels (5.69, 95% CI 1.77-18.3, p = 0.004) or bridging vessels (2.00, 95% CI 1.29-3.10, p = 0.002) on ultrasound, and increased lower segment vascularization at laparotomy (5.42, 95% CI 2.09-14.1, p = 0.001). Transfusion >5 RBC units was associated with number of lacunae (odds ratio [OR] 1.48, 95% CI 1.14-1.93, p = 0.004) and presence of feeder vessels (OR 1.62, 95% CI 1.24-2.11, p = 0.001). The multivariable analysis indicated that parity, placental location and PAS were significantly (p = 0.007; p = 0.01; p < 0.001, respectively) associated with hysterectomy. CONCLUSIONS: Preoperative ultrasound imaging can assist in triaging and counselling patients regarding the odds of PAS, intraoperative blood losses and need for hysterectomy, and intraoperative features can assist the surgeon in evaluating the need for multidisciplinary support.