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.

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.

Permissive HLA-DPB1 mismatches in HCT depend on immunopeptidome divergence and editing by HLA-DM.

In hematopoietic cell transplantation (HCT), permissive HLA-DPB1 mismatches between patients and their unrelated donors are associated with improved outcomes compared with nonpermissive mismatches, but the underlying mechanism is incompletely understood. Here, we used mass spectrometry, T-cell receptor-ß (TCRß) deep sequencing, and cellular in vitro models of alloreactivity to interrogate the HLA-DP immunopeptidome and its role in alloreactive T-cell responses. We find that permissive HLA-DPB1 mismatches display significantly higher peptide repertoire overlaps compared with their nonpermissive counterparts, resulting in lower frequency and diversity of alloreactive TCRß clonotypes in healthy individuals and transplanted patients. Permissiveness can be reversed by the absence of the peptide editor HLA-DM or the presence of its antagonist, HLA-DO, through significant broadening of the peptide repertoire. Our data establish the degree of immunopeptidome divergence between donor and recipient as the mechanistic basis for the clinically relevant permissive HLA-DPB1 mismatches in HCT and show that permissiveness is dependent on HLA-DM-mediated peptide editing. Its key role for harnessing T-cell alloreactivity to HLA-DP highlights HLA-DM as a potential novel target for cellular and immunotherapy of leukemia.

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.

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.

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.

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.

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.

Cytomegalovirus kinetics after hematopoietic cell transplantation reveal peak titers with differential impact on mortality, relapse and immune reconstitution.

Even in the era of PCR-based monitoring, prophylaxis, and preemptive therapy, Cytomegalovirus (CMV) viremia remains a relevant cause of non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT). However, studies using binary analysis (presence/absence of CMV) reported contradicting data for NRM, overall survival and leukemia relapse. Here, we analyzed CMV replication kinetics in 11 508 whole blood PCR samples of 705 patients with HCT between 2012 and 2017. Using two independent models based on CMV peak titers and on the time point of first CMV reactivation, we stratified patients into risk cohorts. Each cohort had distinct cellular immune reconstitution profiles and differentiated for relevant clinical outcomes. Patients with high CMV peak titers had significantly reduced overall survival (HR 2.13, 95% CI 1.53-2.96; p < .0001), due to high NRM. Early impaired T cell reconstitution was a risk factor for high CMV peak titers, however relevant CMV viremia also related to boosted T cell reconstitution. Importantly, intermediate CMV peak titers associated with a significantly reduced relapse probability (HR 0.53, 95% CI 0.31-0.91; p = .022). In short, CMV kinetics models distinguished relevant clinical outcome cohorts beyond the R+ serostatus with distinct immune reconstitution patterns and resolve in part contradicting results of previous studies exclusively focused on the presence or absence of CMV.

Ultrasound diagnosis of endometrial cancer by subjective pattern recognition in women with postmenopausal bleeding: prospective inter-rater agreement and reliability study.

OBJECTIVES: To assess the inter-rater agreement and reliability of using subjective pattern recognition for diagnosing endometrial cancer (EC) on ultrasound in women with postmenopausal bleeding (PMB). METHODS: This was a prospective cross-sectional study conducted at a gynecological rapid-access clinic, between October 2016 and December 2017, in which consecutive women with PMB and endometrial thickness of ≥ 4.5 mm on transvaginal ultrasound examination were included. Women on hormone replacement therapy or tamoxifen and those with a history of primary gynecological malignancy were excluded. Two raters independently performed ultrasound examinations, blinded to each other's findings, and classified women as having uniformly thickened endometrium, benign endometrial polyp or EC, using subjective pattern recognition. Inter-rater reliability of ultrasound diagnosis was assessed using Cohen's kappa (κ) statistic. All women subsequently underwent either outpatient endometrial biopsy, hysteroscopy or hysterectomy. RESULTS: Forty women were included in the study, with a median age of 61 (interquartile range (IQR), 57-69) years and a median endometrial thickness of 11.0 (IQR, 6.2-20.3) mm. Final histological analysis confirmed 16 (40%) women with EC, 16 (40%) with benign endometrial polyp, four (10%) with atrophic endometrium, three (8%) with proliferative endometrium and one (3%) with endometrial hyperplasia. Inter-rater agreement for the ultrasound diagnoses of uniformly thickened endometrium, benign endometrial polyp and EC was 14/16 (87.5%), 22/30 (73.3%) and 28/34 (82.4%), respectively; inter-rater reliability was good (κ = 0.69; 95% CI, 0.49-0.88). When the ultrasound diagnoses were grouped as either cancer or no cancer, inter-rater agreement was 85% and inter-rater reliability was good (κ = 0.78; 95% CI, 0.61-0.95). Rater A correctly identified 14/16 cases of EC and Rater B identified 15/16. EC was misdiagnosed as benign polyps on ultrasound in two women by Rater A and in one woman by Rater B. The overall accuracies of Rater A and Rater B in differentiating between benign endometrial pathologies and malignancy were 90% and 90%, respectively. CONCLUSIONS: Our results show good inter-rater reliability of subjective pattern recognition in diagnosing uniformly thickened endometrium, benign endometrial polyp and EC on ultrasound in women with PMB. Our findings should facilitate wider use of subjective pattern recognition in routine clinical practice. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Real-world efficacy of docetaxel plus nintedanib after chemo-immunotherapy failure in advanced pulmonary adenocarcinoma.

Aim: This real-world analysis evaluated docetaxel plus nintedanib in patients with advanced pulmonary adenocarcinoma after chemotherapy and immune checkpoint inhibitor failure, for whom treatment options are limited. Methods: Data were sourced retrospectively from seven German centers. Results: Of 93 patients, overall response rate was 41.4% (disease control rate: 75.9%). Of 57 patients given third-line docetaxel plus nintedanib, overall response rate was 50.0% (disease control rate: 82.7%). Median overall survival following third-line docetaxel plus nintedanib was 8.4 months. Adverse events were consistent with the known safety profile of docetaxel plus nintedanib. Conclusion: To date, this was the largest retrospective, real-world analysis of docetaxel plus nintedanib after chemotherapy-immunotherapy failure, indicating that docetaxel plus nintedanib offers meaningful clinical benefits in this setting.

Lay abstract The standard of care for patients with lung adenocarcinoma has advanced with the introduction of immunotherapy in the first-line setting. However, limited clinical data are available to help guide treatment decisions after failure of chemotherapy and immunotherapy. Nintedanib is an oral antiangiogenic agent that is approved in the EU and other countries in combination with docetaxel for the treatment of patients with advanced/metastatic lung adenocarcinoma after first-line chemotherapy. This study is a retrospective, real-world analysis of docetaxel plus nintedanib in 93 patients with advanced lung adenocarcinoma who progressed on immunotherapy (either in sequence or in combination with chemotherapy). The results suggest that docetaxel plus nintedanib offers a meaningful clinical benefit in this setting. Safety findings were generally consistent with the known safety profile of docetaxel plus nintedanib.

A bi-centric experience of extracorporeal carbon dioxide removal (ECCO2 R) for acute hypercapnic respiratory failure following allogeneic hematopoietic stem cell transplantation.

Acute respiratory failure (ARF) is the main reason for ICU admission following allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal CO2 removal (ECCO2 R) can be used as an adjunct to mechanical ventilation in patients with severe hypercapnia but has not been assessed in HSCT recipients. Retrospective analysis of all allogeneic HSCT recipients ≥18 years treated with ECCO2 R at two HSCT centers. 11 patients (m:f = 4:7, median age: 45 [IQR: 32-58] years) were analyzed. Acute leukemia was the underlying hematologic malignancy in all patients. The time from HSCT to ICU admission was 37 [8-79] months, and 9/11 (82%) suffered from chronic graft-versus-host disease (GVHD) with lung involvement. Pneumonia was the most frequent reason for ventilatory decompensation (n = 9). ECCO2 R was initiated for severe hypercapnia (Pa CO2 : 96 [84-115] mm Hg; pH: 7.13 [7.09-7.27]) despite aggressive mechanical ventilation (invasive, n = 9; non-invasive, n = 2). ECCO2 R effectively resolved blood gas disturbances in all patients, but only 2/11 (18%) could be weaned off ventilatory support, and one (9%) patient survived hospital discharge. Progressive respiratory and multiorgan dysfunction were the main reasons for treatment failure. ECCO2 R was technically feasible but resulted in a low survival rate in our cohort. A better understanding of the prognosis of ARF in patients with chronic GVHD and lung involvement is necessary before its use can be reconsidered in this setting.

Optimizing anti-T-lymphocyte globulin dosing to improve long-term outcome after unrelated hematopoietic cell transplantation for hematologic malignancies.

Prophylaxis of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HCT) remains challenging. Because prospective randomized trials of in-vivo T cell depletion using anti-T-lymphocyte globulin (ATLG) in addition to a calcineurin inhibitor and methotrexate (MTX) led to conflicting outcome results, we evaluated the impact of ATLG on clinical outcome, lymphocyte- and immune reconstitution survival models. In total, 1500 consecutive patients with hematologic malignancies received matched unrelated donor (MUD) HCT with cyclosporin and MTX (N = 723, 48%) or with additional ATLG (N = 777, 52%). In the ATLG cohort, grades III-IV acute (12% vs 23%) and extensive chronic GVHD (18% vs 34%) incidences were significantly reduced (P < .0001). Nonrelapse mortality (27% vs 45%) and relapse (30% vs 22%) differed also significantly. Event-free and overall survival estimates at 10 years were 44% and 51% with ATLG and 33% and 35% without ATLG (P < .002 and <.0001). A dose-dependent ATLG effect on lymphocyte- and neutrophil reconstitution was observed. At ATLG exposure, lymphocyte counts and survival associated through a logarithmically increasing function. In this survival model, the lymphocyte count optimum range at exposure was between 0.4 and 1.45/nL (P = .001). This study supports additional ATLG immune prophylaxis and is the first study to associate optimal lymphocyte counts with survival after MUD-HCT.

Platelet number and graft function predict intensive care survival in allogeneic stem cell transplantation patients.

Despite significant advances in the treatment of complications requiring intensive care unit (ICU) admission, ICU mortality remains high for patients after allogeneic stem cell transplantation. We evaluated the role of thrombocytopenia and poor graft function in allogeneic stem cell recipients receiving ICU treatments along with established prognostic ICU markers in order to identify patients at risk for severe complications. At ICU admission, clinical and laboratory data of 108 allogeneic stem cell transplanted ICU patients were collected and retrospectively analyzed. Platelet counts (≤ 50,000/µl, p < 0.0005), hemoglobin levels (≤ 8.5 mg/dl, p = 0.019), and leukocyte count (≤ 1500/µl, p = 0.025) along with sepsis (p = 0.002) and acute myeloid leukemia (p < 0.0005) correlated significantly with survival. Multivariate analysis confirmed thrombocytopenia (hazard ratio (HR) 2.79 (1.58-4.92, 95% confidence interval (CI)) and anemia (HR 1.82, 1.06-3.11, 95% CI) as independent mortality risk factors. Predominant ICU diagnoses were acute respiratory failure (75%), acute kidney injury (47%), and septic shock (30%). Acute graft versus host disease was diagnosed in 42% of patients, and 47% required vasopressors. Low platelet (≤ 50,000/µl) and poor graft function are independent prognostic factors for impaired survival in critically ill stem cell transplanted patients. The underlying pathophysiology of poor graft function is not fully understood and currently under investigation. High-risk patients may be identified and ICU treatments stratified according to allogeneic stem cell patients' individual risk profiles. In contrast to previous studies involving medical or surgical ICU patients, the fraction of thrombocytopenic patients was larger and low platelets were a better differentiating factor in multivariate analysis than any other parameter.

Correction to: Platelet number and graft function predict intensive care survival in allogeneic stem cell transplantation patients.

The author name Philipp Wohlfarth was incorrectly spelled as Philipp Wohlfahrth in the original version of this article.

Ileostomy for steroid-resistant acute graft-versus-host disease of the gastrointestinal tract.

Steroid-resistant acute graft-versus-host disease (GVHD) of the gastrointestinal tract associates with important morbidity and mortality. While high-dose steroids are the established first-line therapy in GVHD, no second-line therapy is generally accepted. In this analysis of 65 consecutive patients with severe, steroid-resistant, intestinal GVHD (92% stage 4), additional ileostomy surgery significantly reduced overall mortality (hazard ratio 0.54; 95% confidence interval, 0.36-0.81; p = 0.003) compared to conventional GVHD therapy. Median overall survival was 16 months in the ileostomy cohort compared to 4 months in the conventional therapy cohort. In the ileostomy cohort, both infectious- and GVHD-associated mortality were reduced (40% versus 77%). Significantly declined fecal volumes (p = 0.001) after surgery provide evidence of intestinal adaptation following ileostomy. Correlative studies indicated ileostomy-induced immune-modulation with a > 50% decrease of activated T cells (p = 0.04) and an increase in regulatory T cells. The observed alterations of the patients' gut microbiota may also contribute to ileostomy's therapeutic effect. These data show that ileostomy induced significant clinical responses in patients with steroid-resistant GVHD along with a reduction of pro-inflammatory immune cells and changes of the intestinal microbiota. Ileostomy is a treatment option for steroid-resistant acute GVHD of the gastrointestinal tract that needs further validation in a prospective clinical trial.

Immunosuppressive therapy (IST) in adult patients with acquired aplastic anemia (AA): A single-center experience over the past 15 years.

OBJECTIVE: Immunosuppressive therapy (IST) with horse anti-thymocyte globulin (hATG) and cyclosporine (CsA) is considered one of the first-line therapies in patients (pts) with acquired aplastic anemia (AA). METHODS: In our single-center, retrospective analysis response rates (RRs) to ATG/CsA at a minimum of 6 mo were evaluated in 67 treatment-naïve (TN) AA pts (52.2% (35/67) females; median age 45 y (range 18-89 y)) being treated at the West German Cancer Center at the Department of Hematology at the University Hospital of Essen between April 2000 and December 2015. RESULTS: Overall 6 mo RRs in TN pts following ATG/CsA were 67.2% (45/67) (5-year OS: 79.5%). In TN hATG-treated pts 6 mo RRs were 75.5% (37/49) (5-year OS: 81%) compared to 44.4% (8/18) (5-year OS 73.5%) following rabbit ATG (rATG). Response to ATG/CsA was dependent of age, absolute reticulocyte count (ARC), and disease severity. Six mo RRs to salvage ATG/CsA in relapsed/refractory (R/R) pts were 37.5% (6/16). CONCLUSION: Our data independently confirm the findings of previous studies that hATG/CsA is superior to rATG/CsA in TN pts. The lack of hATG availability should not result in abstaining it from an indicated ATG therapy, even though ATGAM® is not registered in Germany.

Reference ranges for uterine vein dimensions in non-pregnant women with normal pelvic organs.

OBJECTIVE: To establish reference ranges for uterine vein (UtV) diameters in non-pregnant women with normal pelvic organs. METHODS: This was a prospective study of all women attending the general gynecological clinic of a university teaching hospital in the UK, between August 2015 and December 2016. All women aged ≥ 18 years underwent a transvaginal ultrasound examination in accordance with the study protocol. In women with normal pelvic organs, the largest trunk of the uterine venous plexus was identified in the transverse plane on each side. The maximum anteroposterior vessel diameter was measured by placing the calipers on the inner walls of the vein, and the mean of three measurements was used as the representative value. Inter- and intraobserver variability was assessed in a subgroup of 30 women. Maximum UtV diameter was compared between right and left UtVs and between pre- and postmenopausal women. Factors associated with UtV diameter were assessed and reference ranges were constructed. RESULTS: Of 1500 women examined, 486 (32%) had normal pelvic organs on ultrasound scan and were included in the final analysis. In all women, the uterine venous trunk was clearly visualized and there was no significant difference between the maximum median left and right UtV diameters (P = 0.37). UtV diameters were generally lower in postmenopausal, compared with premenopausal, women, with the difference being statistically significant for the right UtV and the average of left and right UtVs. There was a gradual increase in UtV diameter with advancing age, with a peak observed in women aged 41-50 years and decreasing values in older age groups. Univariable analysis showed that parity, menopausal status and age were associated significantly with UtV diameters (P < 0.01). On multivariable analysis, only higher parity was significantly associated with increasing venous size in both pre- and postmenopausal women. Reference ranges were constructed separately for nulliparous and parous premenopausal women aged between 18 and 45 years. CONCLUSION: UtVs can be identified and measured consistently in all women with normal pelvic organs using transvaginal ultrasound. Parity was the main factor influencing the maximum mean UtV diameter, which had to be taken into account when constructing reference ranges. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Microbiologic Diagnostic Workup of Acute Respiratory Failure with Pulmonary Infiltrates after Allogeneic Hematopoietic Stem Cell Transplantation: Findings in the Era of Molecular- and Biomarker-Based Assays.

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients frequently develop acute respiratory failure (ARF) with pulmonary infiltrates. Molecular- and biomarker-based assays enhance pathogen detection, but data on their yield in this population are scarce. This was a retrospective single-center study of 156 consecutive HSCT recipients admitted to the intensive care unit (ICU) between May 2013 and July 2017. Findings from a microbiologic diagnostic workup using currently available methods on bronchoalveolar lavage (BAL) and blood samples from 66 patients (age, 58 years [range, 45 to 64]; HSCT to ICU, 176 days [range, 85 to 407]) with ARF and pulmonary infiltrates were analyzed. In 47 patients (71%) a causative pathogen was identified (fungal, n = 28; viral, n = 26; bacterial, n = 18). Polymicrobial findings involving several pathogen groups occurred in 20 patients (30%). Culture (12/16, 75%), galactomannan (13/15, 87%), and Aspergillus-PCR (8/9, 89%) from BAL but not serum galactomannan (6/14, 43%) helped to diagnose invasive aspergillosis (n = 16, 24%). Aspergillus-PCR detected azole resistance in 2 cases. Mucorales was found in 7 patients (11%; BAL culture, n = 6; Mucorales-PCR, n = 1). Patients with identified pathogens had higher Simplified Acute Physiology Score II scores (P = .049) and inferior ICU survival (6% versus 37%, P < .01), which largely related to the presence of an invasive fungal infection. Eight patients (12%) had 1 or more viruses with uncertain lung pathogenicity as the sole microbiologic finding. A diagnostic microbiologic workup incorporating molecular- and biomarker-based assays identified pathogens in most HSCT recipients with ARF and pulmonary infiltrates admitted to the ICU. Implications of polymicrobial infection and pathogen patterns in these patients warrant further investigation.

How to measure size of tubal ectopic pregnancy on ultrasound.

OBJECTIVE: To identify the preoperative ultrasound parameters for assessing the size of tubal ectopic pregnancy that correlate best with findings at surgery. METHODS: This was a prospective study of all women attending our center who had a conclusive transvaginal ultrasound diagnosis of tubal ectopic pregnancy over a 10-month period. In each case, the total size of the ectopic pregnancy was measured by placing the calipers on the outer edges of the visible trophoblastic tissue. In ectopic pregnancies presenting with a well-defined gestational sac, the size of the celomic (chorionic) cavity was also measured using the inner borders of the trophoblastic ring as reference points. In women with signs of intra-abdominal bleeding, the size of the hematosalpinx and/or hemoperitoneum was measured. Surgeons were blinded to the ultrasound measurements and were asked to estimate the size of the ectopic pregnancy and the amount of hemoperitoneum intraoperatively. RESULTS: A total of 105 women were diagnosed with a tubal ectopic pregnancy on ultrasound examination, of whom 71 (67.6%) were managed surgically. A significant (P < 0.01) positive correlation was found between all ultrasound measurements and the size of the tubal ectopic pregnancy as reported during surgery. In the absence of hematosalpinx, the mean total outer diameter of the ectopic pregnancy had the highest positive correlation with the size of the tubal ectopic pregnancy at surgery (r = 0.65, P < 0.001). In cases complicated by hematosalpinx, the mean diameter of the tube was the only variable that correlated significantly with the estimated size of the ectopic pregnancy at surgery (P < 0.001). There was a significant positive association between the amount of hemoperitoneum on ultrasound and the estimated volume of intraperitoneal blood at surgery (P < 0.001). CONCLUSIONS: The mean size of a hematosalpinx and the total outer mean diameter of an ectopic pregnancy on ultrasound correlate better with the surgical findings than does the size of the celomic cavity. Our findings show that the standard approach of measuring the size of an intrauterine pregnancy on ultrasound should be adapted to include these additional measurements in women diagnosed with a tubal ectopic pregnancy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.