An evidence-based definition of anemia for singleton, uncomplicated pregnancies

Background The definition for anemia in pregnancy is outdated, derived from Scandinavian studies in the 1970’s to 1980’s. To identity women at risk of blood transfusion, a common cause of Severe Maternal Morbidity, a standard definition of anemia in pregnancy in a modern, healthy United States cohort is needed. Objective To define anemia in pregnancy in a United States population including a large county vs. private hospital population using uncomplicated patients. Materials and methods Inclusion criteria were healthy women with the first prenatal visit before 20 weeks. Exclusion criteria included preterm birth, preeclampsia, hypertension, diabetes, short interval pregnancy (<18 months), multiple gestation, abruption, and fetal demise. All women had iron fortification (Ferrous sulfate 325 mg daily) recommended. The presentation to care and pre-delivery hematocrits were obtained, and the percentiles determined. A total of 2000 patients were included, 1000 from the public county hospital and 1000 from the private hospital. Each cohort had 250 patients in each 2011, 2013, 2015, and 2018. The cohorts were compared for differences in the fifth percentile for each antepartum epoch. Student’s t-test and chi-squared statistical tests were used for analysis, p-value of ≤0.05 was considered significant. Results In the public and private populations, 777 and 785 women presented in the first trimester while 223 and 215 presented in the second. The women at the private hospital were more likely to be older, Caucasian race, nulliparous, and present earlier to care. The fifth percentile was compared between the women in the private and public hospitals and were clinically indistinguishable. When combining the cohorts, the fifth percentile for hemoglobin/hematocrit was 11 g/dL/32.8% in the first trimester, 10.3 g/dL/30.6% in the second trimester, and 10.0 g/dL/30.2% pre-delivery. Conclusions Fifth percentile determinations were made from a combined cohort of normal, uncomplicated pregnancies to define anemia in pregnancy. Comparison of two different cohorts confirms that the same definition for anemia is appropriate regardless of demographics or patient mix.

A Machine Learning Ensemble Based on Radiomics to Predict BI-RADS Category and Reduce the Biopsy Rate of Ultrasound-Detected Suspicious Breast Masses

We developed a machine learning model based on radiomics to predict the BI-RADS category of ultrasound-detected suspicious breast lesions and support medical decision-making towards short-interval follow-up versus tissue sampling. From a retrospective 2015–2019 series of ultrasound-guided core needle biopsies performed by four board-certified breast radiologists using six ultrasound systems from three vendors, we collected 821 images of 834 suspicious breast masses from 819 patients, 404 malignant and 430 benign according to histopathology. A balanced image set of biopsy-proven benign (n = 299) and malignant (n = 299) lesions was used for training and cross-validation of ensembles of machine learning algorithms supervised during learning by histopathological diagnosis as a reference standard. Based on a majority vote (over 80% of the votes to have a valid prediction of benign lesion), an ensemble of support vector machines showed an ability to reduce the biopsy rate of benign lesions by 15% to 18%, always keeping a sensitivity over 94%, when externally tested on 236 images from two image sets: (1) 123 lesions (51 malignant and 72 benign) obtained from two ultrasound systems used for training and from a different one, resulting in a positive predictive value (PPV) of 45.9% (95% confidence interval 36.3–55.7%) versus a radiologists’ PPV of 41.5% (p < 0.005), combined with a 98.0% sensitivity (89.6–99.9%); (2) 113 lesions (54 malignant and 59 benign) obtained from two ultrasound systems from vendors different from those used for training, resulting into a 50.5% PPV (40.4–60.6%) versus a radiologists’ PPV of 47.8% (p < 0.005), combined with a 94.4% sensitivity (84.6–98.8%). Errors in BI-RADS 3 category (i.e., assigned by the model as BI-RADS 4) were 0.8% and 2.7% in the Testing set I and II, respectively. The board-certified breast radiologist accepted the BI-RADS classes assigned by the model in 114 masses (92.7%) and modified the BI-RADS classes of 9 breast masses (7.3%). In six of nine cases, the model performed better than the radiologist did, since it assigned a BI-RADS 3 classification to histopathology-confirmed benign masses that were classified as BI-RADS 4 by the radiologist.

Motor Cortical Plasticity Induced by Volitional Muscle Activity-Triggered Transcranial Magnetic Stimulation and Median Nerve Stimulation

Bilateral motor training is a useful method for modifying corticospinal excitability. The effects of bilateral movement that are caused by artificial stimulation on corticospinal excitability have not been reported. We compared motor-evoked potentials (MEPs) of the primary motor cortex (M1) after conventional bilateral motor training and artificial bilateral movements generated by electromyogram activity of abductor pollicis brevis (APB) muscle-triggered peripheral nerve stimulation (c-MNS) and transcranial magnetic stimulation of the ipsilateral M1 (i-TMS). A total of three protocols with different interventions—bilateral finger training, APB-triggered c-MNS, and APB-triggered i-TMS—were administered to 12 healthy participants. Each protocol consisted of 360 trials of 30 min for each trial. MEPs that were induced by single-pulse TMS, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) that were induced by paired-pulse TMS were assessed as outcome measures at baseline and at 0, 20, 40, and 60 min after intervention. MEP amplitude significantly increased up to 40 min post-intervention in all protocols compared to that at the baseline, although there were some differences in the changing pattern of ICF and SICI in each protocol. These findings suggest that artificial bilateral movement has the potential to increase the ipsilateral cortical excitability of the moving finger.

Early PSA Change after [177Lu]PSMA-617 Radioligand Therapy as a Predicator of Biochemical Response and Overall Survival

Purpose: Radioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCPRP). This study assessed the prognostic value of early PSA measurements during PSMA-RLT. Methods: 27 patients with mCRPC scheduled for PSMA-RLT were prospectively enrolled for a serial short-interval PSA-assessment. Change in PSA (∆%PSA) during two treatment cycles was correlated with biochemical response (BR) and change in tumor volume on PET (TV) after 16 weeks (w16), as well as overall survival (OS). PCWG3 criteria and the recently recommended threshold of ∆%PSA ≤ −30% were assessed for their predictive value. Results: ∆%PSA first correlated with BR, TV and OS after 4 weeks (c1w4). At c1w4, ∆%PSA ≤ −30% was associated with the biochemical response at w16 (p = 0.003) and a longer median OS (p = 0.025), whereas the PCWG3-derived threshold of ∆%PSA ≤ −50% showed no such correlation. In contrast, ∆%PSA ≥ 25% at c1w4 was associated with biochemical progression at w16 (p = 0.003) and a shorter median OS (p < 0.001). Conclusion: PSA changes as early as four weeks after PSMA-RLT allow a significant prediction of later biochemical and PET-based imaging response, as well as OS. At this early time point, a more lenient threshold for a PSA decrease of at least 30% appears better-suited for the prediction of a positive biochemical response and longer OS. In contrast, the PCWG3-derived threshold for PSA increase (+25%) reliably anticipates biochemical progression and shorter OS.

SARS-CoV-2 Omicron Spike recognition by plasma from individuals receiving BNT162b2 mRNA vaccination with a 16-weeks interval between doses

Continuous emergence of SARS-CoV-2 variants of concern (VOC) is fueling the COVID-19 pandemic. Omicron (B.1.1.529), is rapidly spreading worldwide. The large number of mutations in its Spike raised concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses was shown to elicit antibodies that efficiently recognize Spikes from different VOCs. Here we evaluated the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naive and previously-infected individuals that received their BNT162b2 mRNA vaccine 16-weeks apart. Omicron Spike was recognized less efficiently than D614G, Alpha, Beta, Gamma and Delta Spikes. We compared to plasma activity from participants receiving a short (4-weeks) interval regimen. Plasma from individuals of the long interval cohort neutralized better the Omicron Spike compared to those that received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.

Deep Eutectic Solvent Dyeing of Cellulose Acetate Nanofibers With Disperse Dyes: Kinetics, Isotherm and Thermodynamic Studies

Deep Eutectic Solvents (DES) was introduced more than a decade ago and has been used in variety of applications based on their unique chemical and physical properties. Recently, they have shown a considerable attention in various sectors including nanotechnology because they have distinctive features as “New green solvents”. Within this scope of work, we introduced choline chloride (CC) as a DES which is nontoxic, inexpensive and has tendency to improve color yield properties of disperse dyes on the nanofibers membrane. Cellulose acetate nanofibers (CANF) were electrospun and dyed with Color Index Disperse Red 277, Color Index Disperse Blue 165:1, and Color Index Disperse Yellow 211 in Choline chloride:Ethylene glycol (CC:EG) media and Choline chloride:Urea (CC:Urea) media by using high-temperature exhaust method. Results revealed that dyeing of CANF by CC:EG media has good color fixation properties than CC:Urea media. The dyed samples were characterized by FTIR and SEM. Further, the thermodynamic, standard affinities, and kinetic parameters have also been analyzed. The proposed dyeing of CANF with DES showed excellent calorimetric properties within a short interval of time as compared to conventional dyeing process.