Postconceptual Neonatal Dating by Transmastoid Ultrasound of Transcerebellar Diameter-Comparison to Crown Rump Length Measurement: A Proof of Concept Paper.

OBJECTIVES: Transcerebellar diameter (TCD) has been utilized prenatally as a tool to estimate gestational age (GA) when fetal growth aberrations are suspected. Traditionally, first trimester ultrasound (1TUS) has been the gold standard of dating a pregnancy in spontaneous pregnancies. We sought to determine if neonatal TCD measurement was as accurate as 1TUS in the estimation of postconceptual gestational age (PCGA). METHODS: A retrospective cohort from a registry of high-quality transmastoid views of consecutive patients from July 2019 to November 2020, delivered from 24 to 34 weeks GA, and with a 1TUS were included. The reference PCGA was the sum of the GA at delivery by 1TUS and day of life. The PCGA by TCD was calculated from Chang et al for GA by TCD. Reference and experimental values were compared by correlation, agreement within 7 days, and Bland-Altman analysis. RESULTS: Of the 154 individual patients in the registry of high-quality transmastoid views during the study period, 62 met inclusion and exclusion criteria. PCGA by 1TUS and TCD were highly correlated (r = 0.86, P < .001; κ = 47% agreement within 7 days of PCGA). The bias of PCGA by TCD was 4.6 days earlier than the PCGA by 1TUS (95% confidence interval of agreement: -29.2, 20). CONCLUSIONS: PCGA estimation by neonatal transmastoid TCD was highly correlated with that of 1TUS. It generally underestimates GA by 4.6 days. This relationship warrants further investigation to determine if this method of estimating PCGA in undated gestations is generalizable.

Efficacy and Safety of Anti-Tumor Necrosis Factor Alpha in Very Early Onset Inflammatory Bowel Disease.

BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) is defined as disease onset in patients younger than 6 years. Challenges in treatment of VEOIBD include lack of approved therapies and increased incidence of monogenic immunodeficiencies. We report on patterns of anti-TNF use, efficacy, and safety in a large cohort of patients with VEOIBD. METHODS: Very early onset inflammatory bowel disease patients receiving care at a single center were prospectively enrolled in a data registry and biorepository starting in 2012. Whole exome sequencing was available to all patients. Clinical data including IBD medication use and response were extracted from the medical record. We examined antitumor necrosis factor (anti-TNF) cumulative exposure and time to failure and evaluated the effect of covariates on anti-TNF failure using Cox proportional hazard regression. RESULTS: In this cohort of 216 VEOIBD patients with median 5.8-year follow-up, 116 (53.7%) were TNF-exposed. Sixty-two TNF-exposed patients (53.4%) received their first dose at younger than 6 years. Cumulative exposure to anti-TNF was 23.6% at 1 year, 38.4% at 3 years, and 43.4% at 5 years after diagnosis. Cumulative exposure was greater in patients with Crohn's disease (P = .0004) and in those diagnosed in 2012 or later (P < .0001). Tumor necrosis factor failure occurred in 50.9% of those exposed. Features predictive of anti-TNF failure included ulcerative colitis/IBD-unclassified (hazard ratio, 1.94; P = .03), stricturing (hazard ratio, 2.20; P = .04), and younger age at diagnosis (hazard ratio, 1.25; P = .01). Adverse events occurred in 22.6% of infliximab-exposed and 14.3% of adalimumab-exposed. CONCLUSIONS: Efficacy and safety of anti-TNFs in VEOIBD is comparable to what has previously been reported in older patients.

Half of VEOIBD patients followed for a median 5.8 years used anti-TNF. Anti-TNF failure occurred in half of those exposed. Stricturing, UC/IBD-U, and younger age at diagnosis were predictors of failure. Adverse events were similar to those reported in older patients.

A Systematic Review of Vitamin D and Fibroids: Pathophysiology, Prevention, and Treatment.

Uterine fibroids are the most common tumor of reproductive-age women worldwide and cause significant morbidity in affected women. Vitamin D has emerged as a potential therapy for uterine fibroids based on experimental and epidemiologic evidence. The objective of this systematic review was to evaluate the role of vitamin D in the pathophysiology of uterine fibroids and its efficacy for prevention and treatment of fibroids. A comprehensive search was conducted of Cochrane Library, Embase, PubMed, Scopus, and Web of Science from inception to March 2022. English-language publications that evaluated vitamin D and uterine fibroids in humans, whether experimental or clinical, were considered. The search yielded 960 publications, and 89 publications met inclusion criteria: 23 preclinical studies, 25 clinical studies, and 41 review articles. Preclinical studies indicated that the vitamin D receptor was decreased in fibroid cells. Vitamin D treatment of fibroid cells decreased proliferation, extracellular matrix protein expression, and Wnt/ß-catenin signaling. Fourteen clinical studies (n = 3535 participants) assessed serum vitamin D level in women with ultrasound-proven fibroids, and all found an inverse correlation between serum vitamin D level and presence of fibroids. Five clinical studies (n = 472 patients) evaluated treatment of fibroids with vitamin D. Four of five studies showed vitamin D significantly inhibited fibroid growth. One pilot study (n = 109 patients) of vitamin D for secondary prevention of fibroids demonstrated smaller recurrent fibroids in the treated group. These studies provide evidence for vitamin D as a therapy for uterine fibroids and underscore the need for well-designed, randomized, placebo-controlled clinical trials.

Perception of pain and the oocyte donor experience: a retrospective analysis of commercial US donors.

RESEARCH QUESTION: What is the relationship between oocyte donor characteristics and their pain perception, their expectation and experience of pain, and the interaction between pain and overall satisfaction with the donation process? DESIGN: Institutional Review Board approved, retrospective survey of commercial, US oocyte donors was emailed to recent donors recruited through Donor Egg Bank USA before 2020. RESULTS: Of the 503 opened emails, 246 individuals responded (48.9%). Most donors ranked their pain between minimal and moderate at all time points analysed. Altruistically motivated donors and parous donors were less likely to experience unexpected levels of pain. A high proportion (93.9%) of donors reported being informed of the risk of pain. Those who recalled being informed of the risk of pain were less likely to report higher levels of pain than expected. Although 94.2% of donors reported having an average to positive experience overall, 92.3% (12 out of 13 donors) in the group reporting a negative overall experience said they felt more pain than expected. CONCLUSIONS: Donors were well informed about the risk of pain. Altruistically motivated donors and parous donors were less likely to experience unexpected levels of pain. Report of unexpected levels of pain was highly related to low donor satisfaction.

Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2.

While there is SARS-CoV-2 multiorgan tropism in severely infected COVID-19 patients, it's unclear if this occurs in healthy young individuals. In addition, for antibodies that target the spike protein (SP), it's unclear if these reduce SARS-CoV-2/SP multiorgan tropism equally. We used fluorescently labeled SP-NIRF to study viral behavior, using an in vivo dynamic imaging system and ex in vivo tissue analysis, in young mice. We found a SP body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. SP uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or CSF. Thus, the brain vascular barriers were effective in restricting the entry of SP into brain parenchyma in young healthy mice. While both anti-ACE2 and anti-SP antibodies suppressed SP biodistribution and organ uptake, anti-SP antibody was more effective. By extension, our data support the efficacy of these antibodies on SARS-CoV-2 multiorgan tropism, which could determine COVID-19 organ-specific outcomes.

Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging.

BACKGROUND: Continuous circulation and drainage of cerebrospinal fluid (CSF) are essential for the elimination of CSF-borne metabolic products and neuronal function. While multiple CSF drainage pathways have been identified, the significance of each to normal drainage and whether there are differential changes at CSF outflow regions in the aging brain are unclear. METHODS: Dynamic in vivo imaging of near infrared fluorescently-labeled albumin was used to simultaneously visualize the flow of CSF at outflow regions on the dorsal side (transcranial and -spinal) of the central nervous system. This was followed by kinetic analysis, which included the elimination rate constants for these regions. In addition, tracer distribution in ex vivo tissues were assessed, including the nasal/cribriform region, dorsal and ventral surfaces of the brain, spinal cord, cranial dura, skull base, optic and trigeminal nerves and cervical lymph nodes. RESULTS: Based on the in vivo data, there was evidence of CSF elimination, as determined by the rate of clearance, from the nasal route across the cribriform plate and spinal subarachnoid space, but not from the dorsal dural regions. Using ex vivo tissue samples, the presence of tracer was confirmed in the cribriform area and olfactory regions, around pial blood vessels, spinal subarachnoid space, spinal cord and cervical lymph nodes but not for the dorsal dura, skull base or the other cranial nerves. Also, ex vivo tissues showed retention of tracer along brain fissures and regions associated with cisterns on the brain surfaces, but not in the brain parenchyma. Aging reduced CSF elimination across the cribriform plate but not that from the spinal SAS nor retention on the brain surfaces. CONCLUSIONS: Collectively, these data show that the main CSF outflow sites were the nasal region across the cribriform plate and from the spinal regions in mice. In young adult mice, the contribution of the nasal and cribriform route to outflow was much higher than from the spinal regions. In older mice, the contribution of the nasal route to CSF outflow was reduced significantly but not for the spinal routes. This kinetic approach may have significance in determining early changes in CSF drainage in neurological disorder, age-related cognitive decline and brain diseases.