Biophysical Profile Research Articles

Dual targeting of mast cells and TSLP with a bispecific antibody

Abstract Rationale: Reduction of mast cells (MCs) through stem cell factor (SCF) neutralization combined with inhibition of the alarmin TSLP in a single molecule may result in broader efficacy in inflammatory disorders. Methods: Monoclonal antibodies (mAb) separately targeting SCF and TSLP were generated from immunized mice. A potent neutralizing antibody against each target was selected and humanized. Bispecific tetravalent antibodies (bsAbs) with specificity towards SCF and TSLP were generated. Candidate bsAbs were tested in vitro for neutralizing activity and evaluated in pilot non-human primates (NHP) studies. Results: We discovered a novel anti-SCF neutralizing mAb (SCF-12) that potently inhibits SCF-dependent KIT phosphorylation and SCF-enhanced degranulation of primary human MCs. Separately, a novel anti-TSLP mAb (1D10) inhibits TSLP receptor binding and TSLP-dependent TARC release from human monocyte-derived DCs. bsAbs combining humanized SCF-12 and 1D10 with good expression, biophysical profile and robust neutralizing activity against each target were generated. Following demonstration of MC depletion in NHPs with SCF-12, we conducted a pilot NHP study with two lead candidate bsAbs. Pharmacokinetic, pharmacodynamic and tolerability data from this study will be presented. Conclusions: SCF x TSLP bsAbs were successfully generated from antibodies that neutralize soluble SCF, leading to MC reduction in NHP, and TSLP, a key alarmin implicated in inflammatory and autoimmune disorders. Combined inhibition of these two pathways using a single molecule may be of broad utility in multiple inflammatory disorders. Celldex Therapeutics

Comparison of modified biophysical profile and doppler ultrasonography studies in predicting perinatal outcome in high-risk pregnancies

In order to improve perinatal outcomes and reduce mother and foetal morbidity and mortality especially in high-risk pregnancies, there is an immense need to do thorough antepartum surveillance test. Aims and Objectives: To compare modified biophysical profile (MBPP) and Doppler studies results for prediction of perinatal outcome and to evaluate the association between the mode of delivery and abnormal Doppler and MBPP.Methodology: This is a prospective observational and comparative study. High-risk term patients were taken in this study, following which MBPP and Doppler studies were performed within 48 to 72 hours of delivery.The study population were divided as follows and perinatal outcome was assessed:A-Normal MBPP and normal Doppler velocimetryB-Normal MBPP and abnormal Doppler velocimetryC-Abnormal MBPP and normal Doppler velocimetryD-Abnormal MBPP and abnormal Doppler velocimetry.Results: The high-risk factor for the greatest number of patients, which accounted for 39.33% of patients, was pregnancy-induced hypertension. Age was less than 25 years in 88 patients (55%). 67 patients were primigravida (44.7%), LSCS was the mode of termination of pregnancy in 127 (84.7%) patients.Greatest prenatal complications occurred in individuals who had abnormal MBPP and Doppler, with a significant P value of < 0.05., Subsequently followed by MBPP, which had a significantly higher NPV than Doppler studies (63.64% vs. 59.41%), which makes it helpful for identifying healthy new-borns.Conclusion: In our study, it was determined that better prediction of adverse perinatal outcome was observed when both Doppler studies and MBPP was done in combination followed by MBPP.

The role of umbilical artery Doppler analysis in estimating perinatal morbidity and mortality in hypertensive pregnancy

Aims: Uteroplacental (uterine artery systolic/diastolic (S/D) ratio) and fetal circulation changes (umbilical artery pulsatility Index (PI) value) can be evaluated non-invasively by using Doppler ultrasonography spectral analysis. The present study aimed to demonstrate how Doppler ultrasonography should be combined with classical well-being tests to detect perinatal morbidity and mortality in hypertensive pregnancy. Methods: This prospective research was carried out with 88 pregnant women diagnosed with high-risk pregnancy and hypertension between April 1992 and May 1994. A non-stress test (NST) was performed in all cases, and fetal distress was evaluated by a biophysical profile (BP) and/or a contraction stress test (CST) subsequent to a non-reactive NST. Following the diagnosis of hypertension, longitudinal maternal (uterine artery) and fetal (umbilical artery) Doppler analyses were initiated at 7–10-day intervals. In the study, the Acuson 128 XP 10 device (Research project No. 515/080555592 was funded by the İstanbul University Research Fund) and a 3.5-5 MHz curvilinear probe were used. No Doppler pathology was considered solely in the timing of delivery. Results: There was no case of perinatal loss, antepartum and intrapartum fetal distress, neonatal asphyxia, and oligohydramnios in the group with normal uterine and umbilical artery Doppler analyses. There was one case with umbilical artery Doppler flow pathology only, which was delivered by preterm cesarean section with the diagnosis of antepartum fetal distress. Fetus diagnosed to have a fetal growth restriction (FGR) and the findings of fetal distress, FGR, and cesarean delivery were concordant with the literature. There was also increased perinatal mortality (9.1%) among patients with pathological uterine artery Doppler and normal umbilical artery Doppler group, but there was no case of oligohydramnios in this group and the rate of neonatal asphyxia (5.min Apgar score &lt;7) was 21.7%. The antepartum loss was 27%, the neonatal loss was 23.8%, and perinatal mortality was 44.8% in the group with pathological uterine and umbilical artery Doppler findings, and this group had all cases of oligohydramnios. Conclusion: Overall, it seems reasonable to identify any pathologies with Doppler ultrasonography in hypertensive pregnant women in the early pregnancy and to follow them up with classical fetal antepartum surveillance tests at appropriate intervals related to their umbilical artery Doppler pathologies.

Ramadan fasting and pregnancy: an evidence-based guide for the obstetrician

Pregnant Muslim women may be religiously exempt from fasting during the Islamic month of Ramadan, especially if there is concern for undue hardship or harm to maternal or fetal health. However, several studies demonstrate that most women still choose to fast during pregnancy and avoid discussing fasting with their providers. A targeted literature review of published studies on fasting during Ramadan and pregnancy or maternal and fetal outcomes was performed. We generally found little to no clinically significant effect of fasting on neonatal birthweight or preterm delivery. Conflicting data exist on fasting and mode of delivery. Fasting during Ramadan has been mainly associated with signs and symptoms of maternal fatigue and dehydration, with a minimal decrease in weight gain. There is conflicting data regarding the association with gestational diabetes mellitus and insufficient data on maternal hypertension. Fasting may affect some antenatal fetal testing indices, including nonstress tests, lower amniotic fluid levels, and lower biophysical profile scores. Current literature on the long-term effects of fasting on offspring suggests possible adverse effects, but more data are required. The quality of evidence was negatively impacted by the variation in defining "fasting during Ramadan" in pregnancy, study size and design, and potential confounders. Therefore, in counseling patients, obstetricians should be prepared to discuss the nuances in the existing data while demonstrating cultural and religious awareness and sensitivity to foster a trusting relationship between patient and provider. We provide a framework for obstetricians and other prenatal care providers to aid in that effort and supplemental materials to encourage patients to seek clinical advice on fasting. Providers should engage patients in a shared decision-making process and offer them a nuanced review of the evidence (including limitations) and individualized recommendations based on clinical experience and patient history. Finally, should certain patients choose to fast while pregnant, providers should offer medical recommendations, closer observation, and support to reduce harm and hardship while fasting.

The utility of complete blood parameter indices to predict stillbirths

Objective In this study, we aimed to investigate the relationship between unexplained stillbirth (SB) cases and the complete blood parameter indices and we compared them with uncomplicated healthy cases. Methods Patients diagnosed with unexplained SB cases in a tertiary center between 2019-2022 were included in this retrospective case-control study. The gestational age threshold for SBs was accepted as births after the 20th week of pregnancy. Consecutive patients with no adverse obstetric outcomes were accepted as the control group. Patients’ complete blood parameter results at the time of the first admission to the hospital until 14 weeks were labeled as “1’’ and at the time of delivery were labeled as “2’’ and recorded. As inflammatory parameters, neutrophile-lymphocyte ratio, derivated neutrophile-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio (LMR), and hemoglobin-lymphocyte ratio (HLR) were calculated from complete blood results and recorded. Results There were statistically significant differences between the groups’ LMR1 (p = .040). Additionally, whereas HLR1 of the study group was 0.693 (0.38–2.72), it was 0.645 (0.15–1.82) in the control group (p = .026). However, the HLR2 of the study group was significantly lower than the control group (p = .021). Conclusion Necessary precautions such as fetal biophysical profile examination can be taken more frequently in the antenatal follow-up in patients considered to be at high risk of SB by using HLR. It is a novel marker that can be easily accessible and calculated from the complete blood parameters.

Diagnostic Tests in the Prediction of Neonatal Outcome in Early Placental Fetal Growth Restriction

Background and Objectives: Monitoring pregnancies with fetal growth restriction (FGR) presents a challenge, especially concerning the time of delivery in cases of early preterm pregnancies below 32 weeks. The aim of our study was to compare different diagnostic parameters in growth-restricted preterm neonates with and without morbidity/mortality and to determine sensitivity and specificity of diagnostic parameters for monitoring preterm pregnancies with early preterm fetal growth restriction below 32 weeks. Materials and Methods: Our clinical study evaluated 120 cases of early preterm deliveries, with gestational age ≤ 32 + 0 weeks, with prenatally diagnosed placental FGR. All the patients were divided into three groups of 40 cases each based on neonatal condition,: I-Neonates with morbidity/mortality (NMM); II-Neonates without morbidity with acidosis/asphyxia (NAA); III-Neonates without neonatal morbidity/acidosis/asphyxia (NWMAA). Results: Amniotic fluid index (AFI) was lower in NMM, while NWMAA had higher biophysical profile scores (BPS). UA PI was lower in NWMAA. NWMAA had higher MCA PI and CPR and fewer cases with CPR <5th percentile. NMM had higher DV PI, and more often had ductus venosus (DV) PI > 95th‱ or absent/reversed A wave, and pulsatile blood flow in umbilical vein (UV). The incidence of pathological fetal heart rate monitoring (FHRM) was higher in NMM and NAA, although the difference was not statistically significant. ROC calculated by defining a bad outcome as NMM and a good outcome as NAA and NWMAA showed the best sensitivity in DV PIi. ROC calculated by defined bad outcome in NMM and NAA and good outcome in NWMAA showed the best sensitivity in MCA PI. Conclusions: In early fetal growth restriction normal cerebral blood flow strongly predicts good outcomes, while pathological venous blood flow is associated with bad outcomes. In fetal growth restriction before 32 weeks, individualized expectant management remains the best option for the optimal timing of delivery.

Preeclampsia: Recent Advances in Predicting, Preventing, and Managing the Maternal and Fetal Life-Threatening Condition.

Preeclampsia accounts for one of the most common documented gestational complications, with a prevalence of approximately 2 to 15% of all pregnancies. Defined as gestational hypertension after 20 weeks of pregnancy and coexisting proteinuria or generalized edema, and certain forms of organ damage, it is life-threatening for both the mother and the fetus, in terms of increasing the rate of mortality and morbidity. Preeclamptic pregnancies are strongly associated with significantly higher medical costs. The maternal costs are related to the extra utility of the healthcare system, more resources used during hospitalization, and likely more surgical spending due to an elevated rate of cesarean deliveries. The infant costs also contribute to a large percentage of the expenses as the babies are prone to preterm deliveries and relevant or causative adverse events. Preeclampsia imposes a considerable financial burden on our societies. It is important for healthcare providers and policy-makers to recognize this phenomenon and allocate enough economic budgets and medical and social resources accordingly. The true cellular and molecular mechanisms underlying preeclampsia remain largely unexplained, which is assumed to be a two-stage process of impaired uteroplacental perfusion with or without prior defective trophoblast invasion (stage 1), followed by general endothelial dysfunction and vascular inflammation that lead to systemic organ damages (stage 2). Risk factors for preeclampsia including race, advanced maternal age, obesity, nulliparity, multi-fetal pregnancy, and co-existing medical disorders, can serve as warnings or markers that call for enhanced surveillance of maternal and fetal well-being. Doppler ultrasonography and biomarkers including the mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and serum pregnancy-associated plasma protein A (PAPP-A) can be used for the prediction of preeclampsia. For women perceived as high-risk individuals for developing preeclampsia, the administration of low-dose aspirin on a daily basis since early pregnancy has proven to be the most effective way to prevent preeclampsia. For preeclamptic females, relevant information, counseling, and suggestions should be provided to facilitate timely intervention or specialty referral. In pregnancies complicated with preeclampsia, closer monitoring and antepartum surveillance including the Doppler ultrasound blood flow study, biophysical profile, non-stress test, and oxytocin challenge test can be arranged. If the results are unfavorable, early intervention and aggressive therapy should be considered. Affected females should have access to higher levels of obstetric units and neonatal institutes. Before, during, and after delivery, monitoring and preparation should be intensified for affected gravidas to avoid serious complications of preeclampsia. In severe cases, delivery of the fetus and the placenta is the ultimate solution to treat preeclampsia. The current review is a summary of recent advances regarding the knowledge of preeclampsia. However, the detailed etiology, pathophysiology, and effect of preeclampsia seem complicated, and further research to address the primary etiology and pathophysiology underlying the clinical manifestations and outcomes is warranted.

Comparison between Protocols for Management of Fetal Growth Restriction.

This comprehensive review compares clinical protocols of important entities regarding the management of fetal growth restriction (FGR), published since 2015. Five protocols were chosen for data extraction. There were no relevant differences regarding the diagnosis and classification of FGR between the protocols. In general, all protocols suggest that the assessment of fetal vitality must be performed in a multimodally, associating biophysical parameters (such as cardiotocography and fetal biophysical profile) with the Doppler velocimetry parameters of the umbilical artery, middle cerebral artery, and ductus venosus. All protocols reinforce that the more severe the fetal condition, the more frequent this assessment should be made. The timely gestational age and mode of delivery to terminate the pregnancy in these cases can vary much between the protocols. Therefore, this paper presents, in a didactic way, the particularities of different protocols for monitoring FGR, in order to help obstetricians to better manage the cases.

Measurement of amniotic fluid volume

The qualitative or semi-quantitative assessment of amniotic fluid volume (AFV) is a standard component of every ultrasound in the second and third trimesters of pregnancy. AFV abnormalities are associated with various pregnancy complications. In clinical practice, ultrasound (US) assessment of AFV is used in conjunction with other clinical and sonographic parameters (biophysical profile, non-stress test, estimated fetal weight on ultrasound, clinical examination) to make effective medical decisions to maintain fetal well-being in the management of pregnancies with obstetric complications. US is the most common AFV assessment technique, in which AFV is determined on a basis of the opinion of a physician (qualitatively) or on a basis of the value of the maximum vertical pocket (MVP) and amniotic fluid index. These techniques are well suited for detecting fetuses with normal AFV; however, they have insufficient accuracy for diagnosing oligohydramnios and polyhydramnios. Furthermore, ultrasound AFV assessment in twins poorly corresponds with the reference values for oligohydramnios and polyhydramnios. Despite this, it is advisable to use qualitative and semi-quantitative (MVP) methods for AFV assessment. Results for each twin are interpreted using the same MVP criteria as those for single fetuses.

Biophysical profiling of synthetic ultra-long tear film lipids

The tear film lipid layer (TFLL) is a unique biological membrane of importance to the maintenance of ocular surface health. The underlying factors at play, e.g. the ability to retard evaporation and offer protection from the environment, are all closely connected to the properties of individual lipid components and their interplay. The TFLL contains unique ultra-long polar lipid species such as O-acyl-ω-hydroxy fatty acids, type I-St diesters and type II diesters, which are considered important for its proper function. Herein, we have synthesized model compounds from these categories and studied their biophysical and surface rheological properties at the aqueous interface. Altogether, we provide insights on the distinct biophysical profiles of these lipid classes and discuss how their interplay may affect the structure and function of the TFLL.

The Relationship Between the Full Biophysical Profile and Rapid Biophysical Profile in Antepartum Fetal Surveillance

Background: One of the best tests for the assessment of a fetus is the biophysical profile test which has a significant effect on the fetus’s health and the outcome of pregnancy. The present study was designed to determine the relationship between the full biophysical profile (FBP) and the rapid biophysical profile (RBP) tests in antepartum fetal surveillance. Methods: In this prospective study, Singleton pregnancies (n=209) with more than 34 weeks of gestational age were chosen. Both FBP and RBP tests were performed for all the patients. The main outcome is the Apgar score and neonatal intensive care unit admission analyzed by SPSS software, version 24. The sensitivity, specificity, positive predictive value, and negative predictive value of RBP were calculated. Findings: Out of 209 people who entered the study, 48 women (23.0%) had gestational diabetes, 84 women (40.2%) had hypertension pregnancy (preeclampsia), 45 people (21.5%) had intrauterine growth restriction, and 45 women (21.5%) had post-date pregnancy. For predicting adverse fetal outcomes of pregnancy, the sensitivity, specificity, positive predictive value, and negative predictive value of RBP were 95%, 73%, 52%, and 98%, respectively. Conclusion: According to the statistically significant positive correlation between RBP and FBP and its simple and rapid application, RBP might be an acceptable alternative method for primary antepartum fetal screening tests in overcrowded obstetrics centers.

OBSTETRIC AND PERINATAL ASPECTS OF METABOLIC DISORDERS IN PREGNANT WOMEN.

The aim: To determine the feasibility of using Tivortin in metabolic disorders during pregnancy and its effect on the course of pregnancy, childbirth, fetal and neonatal status. Materials and methods: We examined 210 pregnant women with metabolic disorders using clinical and laboratory data, uterine artery Doppler, determi¬nation of lipid peroxidation and antioxidant system, leptin and placental growth factor content. The fetal condition was assessed by ultrasound examination with Doppler, determination of biophysical profile, and cardiotocography. Results: Metabolic disorders in pregnant women increase the risk of obstetric and perinatal complications by activating lipid peroxidation and inhibiting the antioxidant system, reducing the content of placental growth factor and increasing the level of leptin in the blood plasma. After treatment, there was a significant decrease in leptin levels and an increase in placental growth factor levels, normalization of lipid peroxidation and antioxidant system, uterine artery pulsatility index and umbilical cord peak systolic velocity index, systolic-diastolic ratio, fetal biophysical profile and cardiotocography. The incidence of complications in childbirth decreased by 3 times, surgical interventions - by 2 times, postpartum infectious complications - by 1.7 times, and the birth of infants in a state of asphyxia - by 1.8 times. Conclusions: Metabolic disorders in pregnant women are a significant factor in the development of obstetric and perinatal complications due to the intensity of lipid peroxidation and depression of the antioxidant system, and a decrease in the content of placental growth factor. The use of Tivortin in the treatment of pregnant women with metabolic disorders has proven its safety and efficacy.

Biochemical and ultrasonographic markers in fetal surveillance

Introduction/Objective. Fetal growth restriction (FGR) is associated with increased fetal and neonatal mortality and morbidity. The study objective was to investigate the correlation of maternal blood biochemical markers routinely determined in the first and second trimester screening and ultrasound fetal surveillance parameters in the prediction of fetal growth and condition in singleton pregnancies. Methods. In the first trimester we measured serum levels of beta subunit of human chorionic gonadotropin (?HCG) and pregnancy-associated plasma protein A (PAPP-A). In the second trimester we measured values of chorionic gonadotropin (HCG), alpha fetoprotein (AFP), unconjugated estriol (E3) and inhibin A, also examined ultrasonographic biometric fetal parameters, amniotic fluid index (AFI) and Doppler resistance indexes. FGR was defined as ultrasonographically determined fetal weight and growth parameters below the 10th percentile for the gestational age. Obtained biochemical and ultrasonographic parameters were correlated. Results. Study included 104 singleton pregnancies. ?HCG in the first trimester correlated negatively with fetal growth in the second and third trimester, and the second trimester AFI. Increased PAPP-A correlated positively with elevated resistance index in medial cerebral artery, lower biophysical profile scores, and intermediate type of non-stress test. Lower values of E3 were associated with FGR. Elevated serum AFP levels were linked to oligoamnion in the third trimester. There was no correlation of inhibin A levels with fetal condition. Conclusion. First and second trimester biochemical markers of pregnancy (?HCG, PAPP-A, HCG, AFP and E3) in combination with ultrasonographic biophysical parameters of fetus have predictive value for fetal growth and development.

Putting the “f”etus back in maternal-fetal telemedicine: a prospective pilot study

Hybrid care programs bring advantages of virtual visits (cost, logistics and comfort) and in-person visits (doctor-patient relationship and extended clinical evaluation). For maternal-fetal telemedicine to become a mainstream of MFM, the virtual visits must be comprehensive, and extend beyond maternal assessment to fetal wellbeing. We sought to assess the feasibility of hybrid care for women with gestational diabetes mellitus (GDM). A prospective pilot clinical study. Women with a singleton pregnancy and GDM at ≥31 weeks of gestation were recruited. Patient journey included alternating in-person and remote visits for a duration of four weeks. The remote visit included maternal assessment - vital signs, glycemic control (documented in Datos app), urinalysis (Healthy.io), fetal heart rate assessment (INVU by Nuvo™) and ultrasound measured maximal vertical pocket (PulseNmore) yielding a modified biophysical profile (mBPP) [Figure1]. Total visit length was compared between the virtual and in-person visits. Usefulness, effectiveness, reliability, and patient satisfaction were assessed with the telehealth usability questionnaire (TUQ). 20 participants with GDM between 31-34 gestational weeks at recruitment were enrolled [Table1]. One participant withdrew consent after one virtual visit. 38/39 (97.4%) of remote visits concluded in comprehensive assessment including mBPP to the physician's satisfaction. One referral to in-person monitoring occurred due to technical difficulties. Total remote visit length was significantly shorter (65.4±21.6 min) compared to the in-person visit (171.1±21.4 min, P< 0.001). TUQ results indicate high usability of the telehealth system (6.6/7). No adverse events or safety incidents occurred. A hybrid maternal-fetal program consisting of alternating in-person and virtual visits is feasible, saves time and improves women satisfaction. Use of the service and technologies requires a learning process for both the care team and the women. Shifting maternal-fetal surveillance to women’s home or work has broad implications with many advantages.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The predictive value of amniotic fluid index for adverse perinatal outcome and its correlation to the biophysical profile and doppler velocimetery of umbilical artery and middle cerebral artery

The predictive value of amniotic fluid index for adverse perinatal outcome and its correlation to the biophysical profile and doppler velocimetery of umbilical artery and middle cerebral artery

Prevalence of Intrauterine Growth Retardation on Antenatal Ultrasound Scan in Lahore, Pakistan

Fetal growth retardation is described as infants whose weights are much less than expected. Population based norms are used to categorize abnormal growths. The objective of the study was to determine the frequency of intrauterine growth retardation on antenatal ultrasound scan. It was an observational descriptive study conducted at the Radiology Department of Fatima Memorial Hospital, Shadman Lahore. Patients visited the Ultrasound Department for Obstetric scan. The study was conducted in 6 months from January to June in 2022. The sample size of 87 was calculated for study with expected rate of 9% of pregnancies resulted in intrauterine growth retardation at 5% level of significance at 5% margin of error. The study included pregnant females in third trimesters of pregnancy. The data was analyzed using SPSS version 20. A total of 87 obstetric ultrasounds were performed during the study period. The mean age of the patients was 28.69 ±4.46 years with age range 20-42. The 87 included patients showed mean gestational age 35.29 ±2.50 weeks. The mean biparietal diameter was 8.69±0.57 cm and abdominal circumference was 29.72±3.03 cm. The mean fetal body weight is 2.52±0.59 kg. The frequency of intrauterine growth retardation was 10.3%. Fetal biometry, biophysical profile and Doppler studies were helpful in the diagnosis of intrauterine growth retardation and evaluation of ultrasound parameters in third trimester.

Cell Mass and Stiffness As Integrative Biomarkers of Cell State in Mantle Cell Lymphoma

Background: Mantle cell lymphoma (MCL) manifests extensive clinical phenotypic heterogeneity, ranging from indolent to aggressive, rapidly progressive disease. Molecular, genomic, transcriptomic, and immunophenotypic variation, as well as the presence of multiple subclones at diagnosis reflect the clinical diversity seen among MCL patients and make it challenging to define therapies that optimally align with individual patient risk. Biophysical phenotypes of cells, such as mass, density and stiffness, are valuable markers of changes in their intrinsic properties and closely associated with cellular states and functions, which have proven useful in elucidating fundamental processes in cell growth and development. We integrate single-cell biophysical features, which provide more granularity than canonical immunophenotypes, to further refine the biological characterization of MCL with the goal of defining rapid ex vivo biomarkers of clinical response or resistance. Methods: We utilize a device called suspended microchannel resonator (SMR) to perform biophysical measurements (mass, stiffness and density) of individual cells. We characterized the biophysical properties of MCL cells from representative sites, including peripheral blood, bone marrow and lymph nodes, of human clinical specimens and, additionally, spleen from six patient-derived xenografts (PDX) models of MCL. Furthermore, to identify genes that covary with lymphoma cell biophysical heterogeneity, we linked the biophysical measurements of individual MCL cells from the matched spleen, peripheral blood, bone marrow, and liver tissues of three carefully curated PDX models of MCL to downstream single-cell RNA-sequencing (SMR-scRNA-Seq). Results: We observed inter- and intra-tumor heterogeneity in mass and stiffness within each lymphoma specimen. Interestingly, these biophysical features reflect underlying histopathologic phenotypes, with higher mass and higher stiffness measured in blastoid and pleomorphic diseases as opposed to the smaller classical variant. By coupling biophysical measurement with transcriptomic profiling at single-cell resolution, we found that mass is strongly associated with the expression of genes annotated for cell division, cell cycle, and B-cell activation such as CCNB1, CDK1, CENPF, BLK, CD79A. Similarly, cell stiffness correlated with B-cell activation signatures and B-cell receptor signaling pathway activity, especially in the highly proliferative models. Functional genomics assays are ongoing to validate the contribution of these target pathways to MCL biophysical changes. To further define how B-cell activation impacts cellular biophysical properties, we profiled the biophysical properties of normal mature B-cell developmental stages from naïve B-cells to plasma cells. We found that cells at each differentiation stage possess a unique combination of mass, stiffness, and density. Highlighting the dynamic nature of these properties, B-cells undergo significant biophysical change after activation, with buoyant mass quadrupling upon activation and then rapidly decreasing by half. Preliminary data further reveal that mature B-cells lose approximately 25% of their stiffness after activation before reverting to their original stiffness after immunoglobulin class switching and even increasing in stiffness at the plasma cell stage. Most MCL cells are conventionally thought to derive from naïve pre-germinal center B cells, but our analysis revealed biophysical profiles overlapping strongly with more mature B cell states, suggesting that lymphomagenesis may entail reprogramming the machinery regulating cell mass and stiffness. We are now generating biophysical, transcriptomic, and genomic measurements within primary specimens from patients with MCL undergoing combined therapy targeting BTK, BCL2, and CD20 to assess their potential for inclusion within integrated predictive biomarkers. Conclusions: We established the biophysical landscape of MCL and non-malignant B-lymphoid cells to sharpen biological characterization and resolve tumor heterogeneity. We did so using a unique single-cell platform integrating transcriptomic and biophysical features as rapid, quantitative, and label-free measurements of live-cell state and phenotypic composition in pursuit of functionally integrated predictive biomarkers.

Efficacy, safety and tolerability of dimethylfumarate during pregnancy and breastfeeding

<h3>Background</h3> The disease course in relapsing-remitting multiple sclerosis (RRMS) is notably affected by pregnancy. Disease-modifying therapies are usually contraindicated during pregnancy and breastfeeding for safety reasons. We assessed safety and tolerability of dimethylfumarate (DMF) in women with RRMS and their infants. <h3>Methods</h3> We observed 29 pregnancies of 26 women, followed from 2015 to 2020. DMF was administered through week 24 of pregnancy and resumed one month after delivery. We followed mothers with clinical follow-up, MRI and regular ultrasounds to establish the safety and efficacy of DMF during pregnancy and lactation. Infants were monitored up to the third year for infections and developmental disorders. <h3>Results</h3> No voluntary terminations, ectopic pregnancies, miscarriages or congenital abnormalities were detected. 3 infants (10%) were born preterm. 26 and 3 newborns had an 8/8 and a 7/8 biophysical profile (BPP) score, respectively. During growth, all children resulted between the 70^th and 95^th percentile for height and weight. Only 1 serious infection was detected in a child. 22/26 mothers decided to breastfeed (interval: 4–7 months). No relapses were observed during pregnancy and during the first 6 months post-delivery. 2 relapses were observed in the 6–12-month interval. New T2 lesions were detected in 3/26 scans at 3 months, 2/26 scans at 12 months, 3/24 scans at 24 months. <h3>Conclusion</h3> All outcomes related to infant birth and development were comparable to the general population, despite DMF intake during pregnancy. DMF effectively prevented increased disease activity during puerperium. According to our data, continuing therapy while breastfeeding is also safe. <h3>Keywords</h3> Pregnancy, Breastfeeding, Case series, Dimethylfumarate, Safety, Magnetic resonance imaging <h3>Disclosures</h3> AI has received consulting fees from Janssen. GB has no conflict of interest or other disclosures to report.

Diagnostic accuracy of middle cerebral artery Doppler findings in intrauterine growth restriction taking biophysical profile as gold standard.

Objective: To find the diagnostic accuracy of middle cerebral Artery Doppler findings in Intrauterine Growth Restriction taking Biophysical Profile as Gold Standard. Study Design: Cross Sectional study. Setting: Department of Radiology, Allied Hospital Faisalabad. Period: 11 February 2021 to 30 April 2022. Material &amp; Methods: A cross-sectional study of 161 pregnant women was conducted at the radiology department of allied hospital Faisalabad. The Inclusion Criteria were 114 pregnant women with abnormal biophysical profile and with a history of previous IUGR fetus pregnancy. All women's ultrasounds were performed on color Doppler. Data was analyzed by using IBM-SPSS version 25. Results: In our study age ranged from 18-42 years with mean age of 27.2547 ± 6.46363 years. The RI of MCA ranged from 0.30-0.90 % in the IUGR patients with the mean value 0.5330 ± 0.16134, and the RI of MCA ranged from 0.60-0.70 % in the normal was 0.6632 ± 0.4828. Similarly the PI of MCA ranged from 1.00-2.00 % in the IUGR patients with the mean value 1.9825 ± 0.13187, and the PI of MCA ranged from 2.00-2.00 % in the normal was 2.0000 ± 0.00000. The biophysical profile scoring of MCA_PI with range from 0.5-0.6 was 8 in two patients while with range from 0.6-7.98 was 6 in 32 patients, and was 8 in 127 patients. Conclusion: In conclusion, the diagnostic accuracy of Color Doppler of umbilical and cerebral pulsatility is very excessive in diagnosing IUGR.

Prognostic Factors Impacting Surgical Outcomes in Patients With Cervical Spondylotic Myelopathy.

The purpose of surgical decompression in patients who have CSM is to stop the progression of symptoms and hopefully improve function. It is critical to understand prognostic factors that affect the outcome. Factors intrinsic to the patient that can adversely affect outcomes include diabetes, older age, tobacco use, the presence of mental health disease, and obesity. MRI imaging findings of T2 hyperintensity and clinical duration and severity of symptoms is also associated with poorer outcomes. Patients should be counseled regarding the efficacy of decompressive procedures for CSM and given realistic expectations based on their unique biophysical profiles.