Covering Hierarchical Dirichlet Mixture Models on binary data to enhance genomic stratifications in onco-hematology.

Onco-hematological studies are increasingly adopting statistical mixture models to support the advancement of the genomically-driven classification systems for blood cancer. Targeting enhanced patients stratification based on the sole role of molecular biology attracted much interest and contributes to bring personalized medicine closer to reality. In onco-hematology, Hierarchical Dirichlet Mixture Models (HDMM) have become one of the preferred method to cluster the genomics data, that include the presence or absence of gene mutations and cytogenetics anomalies, into components. This work unfolds the standard workflow used in onco-hematology to improve patient stratification and proposes alternative approaches to characterize the components and to assign patient to them, as they are crucial tasks usually supported by a priori clinical knowledge. We propose (a) to compute the parameters of the multinomial components of the HDMM or (b) to estimate the parameters of the HDMM components as if they were Multivariate Fisher's Non-Central Hypergeometric (MFNCH) distributions. Then, our approach to perform patients assignments to the HDMM components is designed to essentially determine for each patient its most likely component. We show on simulated data that the patients assignment using the MFNCH-based approach can be superior, if not comparable, to using the multinomial-based approach. Lastly, we illustrate on real Acute Myeloid Leukemia data how the utilization of MFNCH-based approach emerges as a good trade-off between the rigorous multinomial-based characterization of the HDMM components and the common refinement of them based on a priori clinical knowledge.

A dynamic time-to-event model for prediction of acute graft-versus-host disease in patients after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Acute graft-versus-host disease (aGvHD) is a major cause of death for patients following allogeneic hematopoietic stem cell transplantation (HSCT). Effective management of moderate to severe aGvHD remains challenging despite recent advances in HSCT, emphasizing the importance of prophylaxis and risk factor identification. METHODS: In this study, we analyzed data from 1479 adults who underwent HSCT between 2005 and 2017 to investigate the effects of aGvHD prophylaxis and time-dependent risk factors on the development of grades II-IV aGvHD within 100 days post-HSCT. RESULTS: Using a dynamic longitudinal time-to-event model, we observed a non-monotonic baseline hazard overtime with a low hazard during the first few days and a maximum hazard at day 17, described by Bateman function with a mean transit time of approximately 11 days. Multivariable analysis revealed significant time-dependent effects of white blood cell counts and cyclosporine A exposure as well as static effects of female donors for male recipients, patients with matched related donors, conditioning regimen consisting of fludarabine plus total body irradiation, and patient age in recipients of grafts from related donors on the risk to develop grades II-IV aGvHD. Additionally, we found that higher cumulative hazard on day 7 after allo-HSCT are associated with an increased incidence of grades II-IV aGvHD within 100 days indicating that an individual assessment of the cumulative hazard on day 7 could potentially serve as valuable predictor for later grades II-IV aGvHD development. Using the final model, stochastic simulations were performed to explore covariate effects on the cumulative incidence over time and to estimate risk ratios. CONCLUSION: Overall, the presented model showed good descriptive and predictive performance and provides valuable insights into the interplay of multiple static and time-dependent risk factors for the prediction of aGvHD.

Data-driven grading of acute graft-versus-host disease.

Despite advances in allogeneic hematopoietic cell transplantation, acute graft-versus-host disease (aGVHD) remains its leading complication, yet with heterogeneous outcomes. Here, we analyzed aGVHD phenotypes and clinical classifications in depth in large, multicenter cohorts involving 3019 patients and addressed prevailing gaps by developing data-driven models. We compared, tested and verified these along with all conventional classifications in independent cohorts and found that data-driven grading outperformed conventional grading in Akaike information criterion and concordance index metrics. Data-driven classifications refined aGVHD assessment with up to 12 severity grades, which were associated with distinct nonrelapse mortality (NRM) and confirmed the key role of intestinal aGVHD. We developed an online calculator for physicians to implement principal component-derived grading (PC1). These results provide substantial insight into the evaluation of aGVHD phenotypes and multiorgan involvement, which relegates the exclusive reporting of overall aGVHD severity grades in transplant registries and clinical trials. Data-driven aGVHD grading provides an expandable platform to refine classification and transplant risk assessment.

Effect of Eco-Friendly Application of Bee Honey Solution on Yield, Physio-Chemical, Antioxidants, and Enzyme Gene Expressions in Excessive Nitrogen-Stressed Common Bean (Phaseolus vulgaris L.) Plants.

Excessive use of nitrogen (N) pollutes the environment and causes greenhouse gas emissions; however, the application of eco-friendly plant biostimulators (BSs) can overcome these issues. Therefore, this paper aimed to explore the role of diluted bee honey solution (DHS) in attenuating the adverse impacts of N toxicity on Phaseolus vulgaris growth, yield quality, physio-chemical properties, and defense systems. For this purpose, the soil was fertilized with 100, 125, and 150% of the recommended N dose (RND), and the plants were sprayed with 1.5% DHS. Trials were arranged in a two-factor split-plot design (N levels occupied main plots × DH- occupied subplots). Excess N (150% RND) caused a significant decline in plant growth, yield quality, photosynthesis, and antioxidants, while significantly increasing oxidants and oxidative damage [hydrogen peroxide (H2O2), superoxide (O2•-), nitrate, electrolyte leakage (EL), and malondialdehyde (MDA) levels]. However, DHS significantly improved antioxidant activities (glutathione and nitrate reductases, catalase, ascorbate peroxidase, superoxide dismutase, proline, ascorbate, α-tocopherol, and glutathione) and osmoregulatory levels (soluble protein, glycine betaine, and soluble sugars). Enzyme gene expressions showed the same trend as enzyme activities. Additionally, H2O2, O2•-, EL, MDA, and nitrate levels were significantly declined, reflecting enhanced growth, yield, fruit quality, and photosynthetic efficiency. The results demonstrate that DHS can be used as an eco-friendly approach to overcome the harmful impacts of N toxicity on P. vulgaris plants.

Optimizing platelet transfusion through a personalized deep learning risk assessment system for demand management.

ABSTRACT: Platelet demand management (PDM) is a resource-consuming task for physicians and transfusion managers of large hospitals. Inpatient numbers and institutional standards play significant roles in PDM. However, reliance on these factors alone commonly results in platelet shortages. Using data from multiple sources, we developed, validated, tested, and implemented a patient-specific approach to support PDM that uses a deep learning-based risk score to forecast platelet transfusions for each hospitalized patient in the next 24 hours. The models were developed using retrospective electronic health record data of 34 809 patients treated between 2017 and 2022. Static and time-dependent features included demographics, diagnoses, procedures, blood counts, past transfusions, hematotoxic medications, and hospitalization duration. Using an expanding window approach, we created a training and live-prediction pipeline with a 30-day input and 24-hour forecast. Hyperparameter tuning determined the best validation area under the precision-recall curve (AUC-PR) score for long short-term memory deep learning models, which were then tested on independent data sets from the same hospital. The model tailored for hematology and oncology patients exhibited the best performance (AUC-PR, 0.84; area under the receiver operating characteristic curve [ROC-AUC], 0.98), followed by a multispecialty model covering all other patients (AUC-PR, 0.73). The model specific to cardiothoracic surgery had the lowest performance (AUC-PR, 0.42), likely because of unexpected intrasurgery bleedings. To our knowledge, this is the first deep learning-based platelet transfusion predictor enabling individualized 24-hour risk assessments at high AUC-PR. Implemented as a decision-support system, deep-learning forecasts might improve patient care by detecting platelet demand earlier and preventing critical transfusion shortages.

Genome-Wide Analysis and Expression Profiling of DUF668 Genes in Glycine max under Salt Stress.

The DUF668 gene performs a critical role in mitigating the impact of abiotic stress factors. In this study, we identified 30 DUF668 genes in a soybean genome, distributed across fifteen chromosomes. The phylogenetic analysis classified the DUF668 genes into three groups (group I, group II, and group III). Interestingly, gene structure analysis illustrated that several GmDUF668 genes were without introns. Furthermore, the subcellular localization results suggested that GmDUF668 proteins were present in the nucleus, mitochondria, cytoplasm, and plasma membrane. GmDUF668 promoters were analyzed in silico to gain insight into the presence of regulatory sequences for TFs binding. The expression profiling illustrated that GmDUF668 genes showed expression in leaves, roots, nodules, and flowers. To investigate their response to salt stress, we utilized the RNA sequencing data of GmDUF668 genes. The results unveiled that GmDUF668-8, GmDUF668-20, and GmDUF668-30 genes were upregulated against salt stress treatment. We further validated these findings using qRT-PCR analysis. These findings provide a scientific basis to explore the functions of GmDUF668 genes against different stress conditions.

Evaluating the genotoxicity of salinity stress and secondary products gene manipulation in lime, Citrus aurantifolia, plants.

Salinity is a significant abiotic stress that has a profound effect on growth, the content of secondary products, and the genotoxicity of cells. Lime, Citrus aurantifolia, is a popular plant belonging to the family Rutaceae. The interest in cultivating this plant is due to the importance of its volatile oil, which is included in many pharmaceutical industries, but C. aurantifolia plants are affected by the NaCl salinity levels. In the present study, a comet assay test has been applied to evaluate the genotoxic impact of salinity at 0, 50, 100, and 200 mM of NaCl on C. aurantifolia tissue-cultured plants. Furthermore, terpene gene expression was investigated using a semi-quantitative real-time polymerase chain reaction. Results from the two analyses revealed that 200 mM of NaCl stress resulted in high levels of severe damage to the C. aurantifolia plants' DNA tail 21.8%, tail length 6.56 µm, and tail moment 3.19 Unit. The relative highest expression of RtHK and TAT genes was 2.08, and 1.693, respectively, when plants were exposed to 200 mM of NaCl, whereas pv4CL2RT expressed 1.50 in plants subjected to 100 mM of NaCl. The accumulation of transcripts for the RTMYB was 0.951 when plants were treated with NaCl at 50 mM, and RtGPPS gene was significantly decreased to 0.446 during saline exposure at 100 mM. We conclude that the comet assay test offers an appropriate tool to detect DNA damage as well as RtHK, TAT, and pv4CL2RT genes having post-transcriptional regulation in C. aurantifolia plant cells under salinity stress. Future studies are needed to assess the application of gene expression and comet assay technologies using another set of genes that show vulnerability to different stresses on lime and other plants.

Omics-assisted characterization of two-component system genes from Gossypium Raimondii in response to salinity and molecular interaction with abscisic acid.

The two-component system (TCS) genes are involved in a wide range of physiological processes in prokaryotes and eukaryotes. In plants, the TCS elements help in a variety of functions, including cell proliferation, response to abiotic and biotic stresses, leaf senescence, nutritional signaling, and division of chloroplasts. Three different kinds of proteins make up the TCS system in plants. These are known as HKs (histidine kinases), HPs (histidine phosphotransfer), and RRs (response regulators). We investigated the genome of Gossypium raimondii and discovered a total of 59 GrTCS candidates, which include 23 members of the HK family, 8 members of the HP family, and 28 members of the RR family. RR candidates are further classified as type-A (6 members), type-B (11 members), type-C (2 members), and pseudo-RRs (9 members). The GrTCS genes were analyzed in comparison with the TCS components of other plant species such as Arabidopsis thaliana, Cicer arietinum, Sorghum bicolor, Glycine max, and Oryza sativa. This analysis revealed both conservation and changes in their structures. We identified 5 pairs of GrTCS syntenic homologs in the G. raimondii genome. All 59 TCS genes in G. raimondii are located on all thirteen chromosomes. The GrTCS promoter regions have several cis-regulatory elements, which function as switches and respond to a wide variety of abiotic stresses. RNA-seq and real-time qPCR analysis showed that the majority of GrTCS genes are differentially regulated in response to salt and cold stress. 3D structures of GrTCS proteins were predicted to reveal the specific function. GrTCSs were docked with abscisic acid to assess their binding interactions. This research establishes the groundwork for future functional studies of TCS elements in G. raimondii, which will further focus on stress resistance and overall development.

Evaluation of Radiological and Functional Outcome of Intra-articular Proximal Tibia Plateau Fracture Treated with Plating.

Introduction: Proximal tibial plateau fractures are one of the major problems in orthopaedic surgery and are associated with high complication rates. Intra-articular proximal tibia plateau fractures represent approximately 1% of fractures in adults. Various modalities of proximal tibial plateau fracture management have been considered, ranging from simple external fixators in impending compartment syndrome to periarticular proximal tibia plates and inter-locking nails with poller screws. Purpose of this study is to determine clinical outcomes of proximal tibial plateau fractures treated with plate. Materials and methods: We did this study of proximal tibial plateau fracture according to Schatzker's classification treated with proximal tibial periarticular plates in 53 patients prospectively admitted at the author's institute from June 2018 to May 2020 with follow-up period of 6 months. Results: In our study, the average knee score was 89.30 (ranging from 79 to 93) and functional knee score was 97.92 (ranging from 75 to 100). Fifty-one (51) patients (96.23%) showed excellent results and 2 patients (3.77%) showed good results according to Knee Society Score, which suggest that internal fixation of proximal tibia plateau fracture with plating provides better results. Out of 53 patients, 9 patients had post-operative complications. Average radiological union was seen at 14 weeks. Conclusion: Locking compression plate in proximal tibia plateau fractures act as a good biological fixation provide stable fixation, articular reduction and limb alignment even in difficult fracture situations. Fixation of proximal tibia plateau fractures with plate gives excellent to good knee society score, with satisfactory functional and radiological outcome.

Time series clustering of T cell subsets dissects heterogeneity in immune reconstitution and clinical outcomes among MUD-HCT patients receiving ATG or PTCy.

Introduction: Anti-T-lymphocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy) prevent graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT), yet individual patients benefit differentially. Methods: Given the sparse comparative data on the impact of cellular immune reconstitution in this setting, we studied flow cytometry and clinical outcomes in 339 recipients of 10/10 matched-unrelated donor (MUD) HCT using either ATG (n=304) or PTCy (n=35) for in vivo T cell manipulation along with a haploidentical PTCy control cohort (n=45). Longitudinal cellular immune reconstitution data were analyzed conventionally and with a data science approach using clustering with dynamic time warping to determine the similarity between time-series of T cell subsets. Results: Consistent with published studies, no significant differences in clinical outcomes were observed at the cohort level between MUD-ATG and MUD-PTCy. However, cellular reconstitution revealed preferences for distinct T cell subpopulations associating with GVHD protection in each setting. Starting early after HCT, MUD-PTCy patients had higher regulatory T cell levels after HCT (p <0.0001), while MUD-ATG patients presented with higher levels of γδ T- or NKT cells (both p <0.0001). Time-series clustering further dissected the patient population's heterogeneity revealing distinct immune reconstitution clusters. Importantly, it identified phenotypes that reproducibly associated with impaired clinical outcomes within the same in vivo T cell manipulation platform. Exemplarily, patients with lower activated- and αß T cell counts had significantly higher NRM (p=0.032) and relapse rates (p =0.01). Discussion: The improved understanding of the heterogeneity of cellular reconstitution in MUD patients with T cell manipulation both at the cohort and individual level may support clinicians in managing HCT complications.

Pelvic pain and venous congestion revisited: examining relationship between chronic pelvic pain and uterine venous size and blood flow.

OBJECTIVE: To investigate the relationship between increased uterine venous plexus diameter and chronic pelvic pain in women attending a gynecology clinic. METHODS: This was a retrospective study of patients attending a tertiary university hospital in London, UK. Women presenting to the gynecology clinic undergoing transvaginal ultrasound examination were recruited into the study. The largest trunk of the uterine venous plexus was measured on each side. Blood flow within the uterine veins was categorized into continuous or interrupted flow and evaluated using color and spectral Doppler ultrasound during normal respiration and on Valsalva maneuver to demonstrate the presence of venous reflux. The largest uterine vein diameter and its blood flow were used for the analysis. The main variables of interest were chronic pelvic pain, uterine vein diameter and type of blood flow. RESULTS: We included 1500 women in the study, of whom 584 (38.9% (95% CI, 36.5-41.5%)) reported chronic pelvic pain. Dysmenorrhea was the most common type of pelvic pain. Age (P < 0.001), menopausal status (P = 0.02), varicose veins (P = 0.01), adenomyosis (P < 0.001) and endometriosis (P < 0.001) were found to be independently associated with the occurrence of pain on multiple logistic regression analysis. There was no difference in uterine vein diameter between women with and those without pain (P = 0.10). Neither uterine vein diameter (P = 0.47) nor type of blood flow (P = 0.07) was significantly associated with the occurrence of pelvic pain on multiple logistic regression. CONCLUSIONS: Our findings show that uterine vein diameter is not associated with pelvic pain. However, we found other important clinical and demographic factors that are associated with chronic pelvic pain. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of chronic graft-versus-host-disease on intensive care outcome in allogeneic hematopoietic stem cell recipients.

Chronic graft-vs-host-disease (cGvHD) is the most relevant long-term complication after allogeneic stem cell transplantation (HSCT) with major impact on non-relapse mortality, but data on intensive care unit (ICU) outcome are missing. In this retrospective, multicenter study we analyzed 174 adult HSCT recipients with cGvHD requiring intensive care treatment. Skin, pulmonary, liver, and intestinal involvement were present in 76.7%, 47.1%, 38.1% and 24.1%, respectively, and a total of 63.2% had severe cGvHD. Main reasons for ICU admission were respiratory failure (69.7%) and sepsis (34.3%). Hospital- and 3-year OS rates were 51.7% and 28.6%, respectively. Global severity of cGvHD did not impact short- and long-term survival. However, patients with severe liver cGvHD or the overlap subtype had a reduced hospital survival, while severe pulmonary cGvHD was associated with worse long-term survival. In multivariate analysis need for invasive ventilation (HR 1.08 (95% CI 1.02-1.14)) or hemodialysis (HR 1.73 (95% CI 1.14-2.62)) and <1 year since HSCT (HR 1.56 (95% CI 1.03-2.39)) were independently associated with a poorer survival. While the global severity of cGvHD does not per se affect patients' survival after intensive care treatment, pre-existing severe hepatic, intestinal or pulmonary cGvHD is associated with worse outcomes.

Reproductive outcome in 326 women with unicornuate uterus.

OBJECTIVES: To study the reproductive outcomes of women with a unicornuate uterus and compare them to those of women with no congenital uterine anomaly. METHODS: This was a single-center, retrospective cohort study. Cases were women aged at least 16 years who were diagnosed with a unicornuate uterus on transvaginal/transrectal ultrasound between January 2008 and September 2021. Controls were women with no congenital uterine anomaly matched 1:1 by age and body mass index. The primary outcome was live-birth rate. Secondary outcomes were pregnancy loss (miscarriage, ectopic pregnancy, termination of pregnancy), preterm delivery, mode of delivery and concomitant gynecological abnormalities (endometriosis, adenomyosis, fibroids). RESULTS: Included in the study were 326 cases and 326 controls. Women with a unicornuate uterus had a significantly lower live-birth rate (184/388 (47.4%) vs 229/396 (57.8%); P = 0.004) and higher rates of overall miscarriage (178/424 (42.0%) vs 155/465 (33.3%); adjusted odds ratio (aOR), 2.21 (95% CI, 1.42-3.42), P < 0.001), ectopic pregnancy (26/424 (6.1%) vs 11/465 (2.4%); aOR, 2.52 (95% CI, 1.22-5.22), P = 0.01), preterm delivery (45/184 (24.5%) vs 17/229 (7.4%); aOR, 3.04 (95% CI, 1.52-5.97), P = 0.001) and Cesarean delivery (116/184 (63.0%) vs 70/229 (30.6%); aOR, 2.54 (95% CI, 1.67-3.88), P < 0.001). Rudimentary-horn pregnancies accounted for 7/26 (26.9%) ectopic pregnancies in the study group. Women with a unicornuate uterus were more likely to have endometriosis (17.5% vs 10.7%; P = 0.018) and adenomyosis (26.7% vs 15.6%; P = 0.001), but were not more likely to have fibroids compared with controls. Women with a functional rudimentary horn were more likely to have pelvic endometriosis compared to those without (odds ratio, 2.4 (95% CI, 1.4-4.1), P = 0.002). CONCLUSIONS: Pregnant women with a unicornuate uterus should be classified as high risk. Removal of a functional rudimentary horn should be discussed with the patient to prevent a rudimentary-horn ectopic pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Time-dependent prediction of mortality and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation using machine learning.

Allogeneic hematopoietic cell transplantation (HCT) effectively treats high-risk hematologic diseases but can entail HCT-specific complications, which may be minimized by appropriate patient management, supported by accurate, individual risk estimation. However, almost all HCT risk scores are limited to a single risk assessment before HCT without incorporation of additional data. We developed machine learning models that integrate both baseline patient data and time-dependent laboratory measurements to individually predict mortality and cytomegalovirus (CMV) reactivation after HCT at multiple time points per patient. These gradient boosting machine models provide well-calibrated, time-dependent risk predictions and achieved areas under the receiver-operating characteristic of 0.92 and 0.83 and areas under the precision-recall curve of 0.58 and 0.62 for prediction of mortality and CMV reactivation, respectively, in a 21-day time window. Both models were successfully validated in a prospective, non-interventional study and performed on par with expert hematologists in a pilot comparison.

Sorghum Allelopathy: Alternative Weed Management Strategy and Its Impact on Mung Bean Productivity and Soil Rhizosphere Properties.

The reduction of herbicide use and herbicide-resistant weeds through allelopathy can be a sustainable strategy to combat the concerns of environmental degradation. Allelopathic crop residues carry great potential both as weed suppressers and soil quality enhancers. The influence of sorghum crop residues and water extracts on the weed population, soil enzyme activities, the microbial community, and mung bean crop productivity was investigated in a two-year experiment at the Student Research Farm, University of Agriculture Faisalabad. The experimental treatments comprised two levels of sorghum water extract (10 and 20 L ha-1) and two residue application rates (4 and 6 t ha-1), and no sorghum water extract and residues were used as the control. The results indicated that the incorporation of sorghum water extract and residue resulted in significant changes in weed dynamics and the soil quality indices. Significant reduction in weed density (62%) and in the dry weight of weeds (65%) was observed in T5. After the harvest, better soil quality indices in terms of the microbial population (72-90%) and microbial activity (32-50%) were observed in the rhizosphere (0-15 cm) by the same treatment. After cropping, improved soil properties in terms of available potassium, available phosphorus soil organic matter, and total nitrogen were higher after the treatment of residue was incorporated, i.e., 52-65%, 29-45%, 62-84%, and 59-91%, respectively. In the case of soil enzymes, alkaline phosphatase and dehydrogenase levels in the soil were 35-41% and 52-77% higher, respectively. However, residue incorporation at 6 t ha-1 had the greatest effect in improving the soil quality indices, mung bean productivity, and reduction of weed density. In conclusion, the incorporation of 6 t ha-1 sorghum residues may be opted to improve soil quality indices, suppress weeds, harvest a better seed yield (37%), and achieve higher profitability (306 $ ha-1) by weed suppression, yield, and rhizospheric properties of spring-planted mung beans. This strategy can provide a probable substitute for instigating sustainable weed control and significant improvement of soil properties in the mung bean crop, which can be a part of eco-friendly and sustainable agriculture.

Early report on the severity of COVID-19 in hematologic patients infected with the SARS-CoV2 omicron variant.

INTRODUCTION: Patients with hematologic disease are at high risk of morbidity and mortality from COVID-19 due to disease-inherent and therapy-related immunodeficiency. Whether infection with the SARS-CoV2 omicron variant leads to attenuated disease severity in these patients is currently unknown. METHODS: We assessed clinical and laboratory parameters in 61 patients with underlying hematologic conditions with a SARS-CoV2 omicron variant infection confirmed by nucleic acid amplification testing. RESULTS: Fifty patients reported symptoms of COVID-19, most commonly fatigue (37 patients, 60.66%) and cough (32 patients, 52.46%). 39.34% of patients reported fever. Dyspnea was reported by 10 patients and 7 patients (11.48%) required oxygen therapy. Anosmia and ageusia were relatively rare, occurring in less than 10% of patients. Severity of SARS-CoV2 infection could be assessed in 60 patients. Five cases of critical illness leading to ICU admission occurred during the observation period. Overall mortality was 9.84% in this patient cohort, with heterogeneous causes of death. The majority of omicron-infected hematologic patients experienced mild symptoms or remained asymptomatic. DISCUSSION: In this study, symptoms of COVID-19 tended to be milder than described for previous SARS-CoV2 variants. However, the extent to which attenuated severity of omicron-variant SARS-CoV2 infection is caused by altered viral pathogenicity or pre-existing host immunity cannot be inferred from our data and should be investigated in larger prospective studies.

Impact of CMV reactivation on relapse of acute myeloid leukemia after HCT is dependent on disease stage and ATG.

Cytomegalovirus (CMV) reactivation is a frequent complication after allogeneic hematopoietic cell transplantation (HCT), whose impact on clinical outcome, in particular on leukemic relapse, is controversial. We retrospectively analyzed 687 HCT recipients with acute myeloid leukemia (AML) and ciclosporin-based immunosuppression to better understand the differential impact of CMV on transplant outcomes depending on AML disease stage and in vivo T cell depletion with antithymocyte globulin (ATG). Without ATG, CMV reactivation associated with significantly reduced relapse, yet its effect was more pronounced for advanced disease AML (P = .0002) than for patients in first complete remission (CR1, P = .0169). Depending on the disease stage, ATG exposure abrogated relapse protection following CMV reactivation in advanced stages (P = .796), while it inverted its effect into increased relapse for CR1 patients (P = .0428). CMV reactivation was associated with significantly increased nonrelapse mortality in CR1 patients without ATG (P = .0187) but not in those with advanced disease and ATG. Following CMV reactivation, only patients with advanced disease had significantly higher event-free survival rates as compared with patients without CMV. Overall, our data suggest that both ATG and disease stage modulate the impact of post-HCT CMV reactivation in opposite directions, revealing a level of complexity that warrants future studies regarding the interplay between antivirus and antitumor immunity.

Efficacy of transrectal ultrasound in assessing endometrium of postmenopausal women with axial uterus.

OBJECTIVE: To evaluate the acceptance and efficacy of transrectal ultrasound (TRS) in assessing the endometrium in postmenopausal women with an axial uterus. METHODS: This was a prospective cross-sectional study conducted between October 2015 and October 2018 of consecutive postmenopausal women with an axial uterus on transvaginal ultrasound (TVS). Women with a known diagnosis of gynecological malignancy were excluded. TRS was offered immediately after TVS without prior bowel preparation. A single operator determined subjectively whether the endometrium was visualized satisfactorily on TVS and TRS. In women with postmenopausal bleeding (PMB), endometrial thickness (ET) was measured and endometrial morphology was categorized as atrophic, uniformly thickened, benign endometrial polyp or endometrial cancer, based on subjective pattern recognition. All women with PMB and a non-atrophic endometrium underwent outpatient endometrial biopsy, hysteroscopy or hysterectomy. The success rate of TRS in assessing satisfactorily the endometrium was compared with that of TVS. In patients with PMB, ET measurements and subjective diagnosis of endometrial cancer on TVS vs TRS were compared. RESULTS: Of the 1553 women who underwent TVS examination, 103 (6.6%) had an axial uterus, of whom 76 (73.8%) presented with PMB. TRS was accepted by 66/103 (64.1%) women with an axial uterus. TRS assessed satisfactorily a significantly higher proportion of endometria compared with TVS (90.9% vs 62.1%; χ2 = 14.1, P < 0.001). In 50 women with PMB and an axial uterus who underwent both TVS and TRS, TVS failed to visualize the endometrium satisfactorily in 15 (30.0%) women, whilst TRS provided satisfactory images in all cases. Among the 35 women with PMB and a satisfactory endometrial assessment on TVS and TRS, measurements of ET on TRS were significantly lower compared to those on TVS (median difference, -1.2 (interquartile range, -3.0 to -0.4) mm). The overall agreement of TVS and TRS on the presence or absence of endometrial cancer using subjective pattern recognition was 30/35 (85.7%; 95% CI, 74.1-97.3%). While all seven cases of histologically confirmed endometrial cancer were diagnosed correctly on TRS, four were misdiagnosed on TVS as benign polyps or uniformly thickened endometrium. CONCLUSIONS: TRS is an acceptable and effective way to assess the endometrium in postmenopausal women with an axial uterus. Among women presenting additionally with PMB, TRS is associated with a higher proportion of satisfactory endometrial assessments and fewer misdiagnoses of endometrial cancer by subjective pattern recognition compared with TVS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.