Maternal rest improves growth in small-for-gestational-age fetuses (\u3c10th percentile).

BACKGROUND: Optimal management of fetuses diagnosed as small for gestational age based on an estimated fetal weight of \u3c 10th percentile represents a major clinical problem. The standard approach is to increase fetal surveillance with serial biometry and antepartum testing to assess fetal well-being and timing of delivery. Observational studies have indicated that maternal rest in the left lateral position improves maternal cardiac output and uterine blood flow. However, maternal bed rest has not been recommended based on the results of a randomized clinical trial that showed that maternal rest does not improve fetal growth in small-for-gestational-age fetuses. This study was conducted to revisit this question. OBJECTIVE: This study aimed to determine whether maternal bed rest was associated with an increase in the fetal biometric parameters that reflect growth after the diagnosis of a small-for-gestational-age fetus. STUDY DESIGN: A retrospective study was conducted on fetuses who were diagnosed as small for gestational age because of an estimated fetal weight of \u3c 10th percentile for gestational age. The mothers were asked to rest in the left lateral recumbent position. Fetal biometry was performed 2 weeks after the diagnosis. All fetuses before entry into the study had a previous ultrasound that demonstrated an estimated fetal weight of \u3e10th percentile. To assess the response to bed rest, the change in fetal biometric parameters (estimated fetal weight, head circumference, abdominal circumference, and femur length) after the recommendation of bed rest was computed for 2 periods: (1) before the diagnosis of a weight of \u3c 10th percentile vs at the time of diagnosis of a weight of \u3c 10th percentile and (2) at the time of diagnosis of a weight of \u3c 10th percentile vs 2 weeks after maternal bed rest. For repeated measures, proportions were compared using the McNemar test, and percentile values were compared using the Bonferroni Multiple Comparison Test. A P value of \u3c .05 was considered significant. To describe changes in the estimated fetal weight without bed rest, 2 control groups in which the mothers were not placed on bed rest after the diagnosis of a small-for-gestational-age fetus were included. RESULTS: A total of 265 fetuses were observed before and after maternal bed rest. The following were observed in this study: (1) after 2 weeks of maternal rest, 199 of 265 fetuses (75%) had a fetal weight of \u3e10th percentile; (2) the median fetal weight percentile increased from 6.8 (interquartile range, 4.4-8.4) to 18.0 (interquartile range, 9.5-29.5) after 2 weeks of bed rest; (3) similar trends were noted for the head circumference, abdominal circumference, and femur length. In the groups of patients who were not asked to be on bed rest, a reassignment to a weight of \u3e10th percentile at a follow-up examination only occurred in 7 of 37 patients (19%) in the Texas-Michigan group and 13 of 111 patients (12%) in the Colorado group compared with the bed rest group (199/265 [75%]) (P\u3c .001). CONCLUSION: Patients who were prescribed 2 weeks of bed rest after the diagnosis of a fetal weight of \u3c 10th percentile had an increase in weight of \u3e10th percentile in 199 of 265 fetuses (75%). This increase in fetal weight was significantly higher than that in the 2 control groups in which bed rest was not prescribed. This observation suggests that bed rest improves fetal growth in a subset of patients

Molecular drivers in CNS metastatic disease.

The incidence and prevalence of CNS metastases of systemic cancer is only increasing worldwide, especially as our available systemic therapies have improved, resulting in longer survival and more time to allow for CNS progression. Fortunately, we have made substantial therapeutic advances in drug development in the last decade, with newer agents demonstrating significant penetration into the nervous system and notable efficacy. Treatments specifically targeted for certain mutations in the cancer pathway have been especially successful in aborting the onward trajectory and growth of cancer cells in the nervous system. In this review, we provide an overview and update of the drugs that have demonstrated benefit in achieving intracranial control (at times including leptomeningeal disease), many of which have already received or are pending regulatory approval. We also provide a brief look into the landscape of ongoing clinical research including challenges in the field

Radiation Induces Pericyte-Myofibroblast Transition.

PURPOSE: Radiation not only kills cancer cells directly through DNA damage but also indirectly by inducing vascular changes. The effects of radiation on tumor vasculature are critical for therapeutic efficacy; however, its impact on pericytes remains largely unknown. In this study, we investigated the effect of radiation on pericytes and sought to elucidate the mechanism by which radiation affects pericytes. METHODS AND MATERIALS: C3H10T1/2 (10T1/2) mouse embryonic mesenchymal pericyte precursor cells and human pericytes from placenta (hPC-PL) cells were irradiated to study the effects of radiation on pericyte differentiation, maturation, and transition of pericytes into myofibroblasts by flow cytometry, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and immunofluorescence. Phospho-kinase array, Western blot, and reactive oxygen species (ROS) detection assay were conducted to elucidate the signaling pathways activated by radiation in pericytes. To investigate the pericyte-myofibroblast transition in vivo, MC38 tumor cells were implanted in NG2DsRedBAC (NG2DsRed) transgenic mice whose pericytes express DsRed. Tumors harvested 3, 5, and 7 days after radiation were assessed for myofibroblast markers in DsRed RESULTS: Radiation promoted pericyte differentiation and increased the expression of adhesion molecules in both 10T1/2 and hPC-PL cells. Permeability and leukocyte adhesion were altered by radiation via an effect on endothelial cells, not pericytes. Radiation increased the expression of myofibroblast markers and induced morphologic changes. Phospho-kinase array indicated radiation activates the Akt signaling pathway, and inhibitors of Akt and ROS suppressed the expression of myofibroblast markers increased by radiation. MC38 tumors implanted in NG2DsRed transgenic mice harvested 3 days after radiation exhibited increased expression of myofibroblast markers in DsRed CONCLUSIONS: Our data suggest radiation promotes pericyte maturation and transition into myofibroblasts via Akt signaling

Outcomes among patients with coronary bifurcation lesions undergoing Impella-supported high-risk percutaneous coronary intervention.

BACKGROUND: Coronary bifurcation lesions (CBL) are associated with lower procedural success, worse postprocedural outcomes, and greater unplanned repeat revascularization. We sought to better understand the impact of Impella support in patients undergoing percutaneous coronary intervention (PCI) of CBLs. METHODS: We used data from the cVAD PROTECT III study (NCT04136392), an FDA-audited, single-arm study of patients undergoing high-risk PCI with Impella support, to examine the outcomes of patients undergoing PCI of CBLs. Patients with a Medina classification of 1.1.1, 1.0.1, or 0.1.1 were considered to have a true CBL, and were compared to patients with nontrue CBLs and/or no CBLs. The primary outcome was the rate of CEC-adjudicated major adverse cardiac and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization) at 90 days. Cox proportional hazards regression models were adjusted for age, sex, left main disease, and triple vessel disease. RESULTS: Of 1,044 patients, 523 had at least one true CBL treated. Baseline characteristics were comparable between groups except for age which was higher in patients with CBLs. Patients with CBLs had a significantly higher pre-PCI SYNTAX scores and number of treated lesions, more left main disease and triple vessel disease, and longer procedure duration. There was no difference in post-PCI SYNTAX score, PCI-related complications, or failure to achieve angiographic success. After adjustment for potential confounders, patients with CBLs had similar rates of 90-day MACCE. CONCLUSIONS: While patients with CBLs undergoing Impella-supported high-risk PCI had higher complexity, there were similar rates of PCI-related complications and 90-day MACCE