Prediction of Postoperative Day 1 Hemoglobin Level after Cesarean Delivery.

OBJECTIVE: To create a prediction model for postoperative hemoglobin levels after cesarean delivery, which could reduce routine use of postoperative laboratory test. STUDY DESIGN: This was a secondary analysis of a retrospective cohort study of all women who underwent cesarean delivery (primary or repeat) at or more than 23 weeks' gestation at a single academic center. The cohort was randomly divided into a training cohort to develop a prediction model and a validation cohort to test the model in a 2:1 ratio. Variables with p-value <0.10 were considered for the mixed multivariable linear regression model in a backward stepwise fashion. We obtained the best cut-off point of the predicted hemoglobin level to detect severe anemia (postoperative hemoglobin level less than 7.0 g/dL) in the training cohort. A receiver operating characteristic curve with the area under a curve was created. We calculated the sensitivity and specificity of the model in the validation cohort using the best cut-off point obtained in the training cohort as well as postoperative hemoglobin of 10.0 g/dL. RESULTS: Of 2,930 women, 1,954 (66.6%) and 976 (33.3%) were randomly allocated to training and validation cohorts. The final model included preoperative hemoglobin level, preoperative platelet level, quantitative blood loss, height, weight, magnesium administration, labor, and general anesthesia. The best cut-off to predict severe anemia was predicted hemoglobin level of 8.57 g/dL in the training cohort. Using this cut-off, the sensitivity and specificity in the validation cohort were 77% (95% confidence interval [CI]: 56-91%) and 87% (95% CI: 85-89%), respectively. The use of postpartum hemorrhage yielded the sensitivity of 58% (95% CI: 37-77%) and specificity 79% (95% CI: 76-81%), respectively. CONCLUSION: We developed a validated model to predict the postoperative day 1 hemoglobin levels after cesarean delivery that could assist with identifying women who may not need postoperative laboratory tests. KEY POINTS: · Postoperative laboratory tests are routine.. · A prediction model may allow reduce routine tests.. · We developed an accurate mathematical model..

Treatment and Management of Xiphoidalgia.

Xiphodynia is a rare but debilitating condition that can be described as a form of pain on the xiphisternal joint or any related structures that are anchored to the xiphoid process. Although xiphodynia is a musculoskeletal pain in nature, the pain located in the anterior chest can commonly mislead physicians into pursuing other diagnoses such as cardiac diseases. This leads to a prolonged duration of pain before receiving treatment. In the attempt to alleviate pain resulting from this condition, physicians have previously utilized a range of treatment options, including conservative management, injections, or in severe cases, xiphoidectomy. In this review, we aim to give a brief overview of xiphodynia, including clinical diagnoses and current treatment modalities. Key Summary Points: 1. Xiphodynia can be described as pain radiating from an irritated xiphoid process that can travel to the chest, abdomen, throat, and arms2. Risk factors for developing secondary xiphoidalgia include GERD, gall-bladder disease, angina pectoris, and coronary-artery disease3. The treatment of xiphodynia can range from conservative management to injections or a xiphoidectomy4. Further research is required to develop a standardized treatment protocol and currently the choice of treatment depends on the patient's individual case and the degree of severity.

Measuring intrauterine growth in healthy pregnancies using quantitative magnetic resonance imaging.

OBJECTIVE: The aim of this study was to determine in utero fetal-placental growth patterns using in vivo three-dimensional (3D) quantitative magnetic resonance imaging (qMRI). STUDY DESIGN: Healthy women with singleton pregnancies underwent fetal MRI to measure fetal body, placenta, and amniotic space volumes. The fetal-placental ratio (FPR) was derived using 3D fetal body and placental volumes (PV). Descriptive statistics were used to describe the association of each measurement with increasing gestational age (GA) at MRI. RESULTS: Fifty-eight (58) women underwent fetal MRI between 16 and 38 completed weeks gestation (mean = 28.12 ± 6.33). PV and FPR varied linearly with GA at MRI (rPV,GA = 0.83, rFPR,GA = 0.89, p value < 0.001). Fetal volume varied non-linearly with GA (p value < 0.01). CONCLUSIONS: We describe in-utero growth trajectories of fetal-placental volumes in healthy pregnancies using qMRI. Understanding healthy in utero development can establish normative benchmarks where departures from normal may identify early in utero placental failure prior to the onset of fetal harm.

Evaluation of blood transfusion rates by blood loss estimation techniques.

BACKGROUND: Postpartum hemorrhage is a major cause of maternal morbidity and mortality. Though the American College of Obstetricians and Gynecologists and quality improvement initiatives recommend the use of a quantitative measurement of blood loss, it is not known if the quantitative measurement compared to visual estimation of blood loss improves maternal outcomes. OBJECTIVE: To compare rates of red blood cell transfusion between a quantitative measurement and visual estimation of blood loss. STUDY DESIGN: This was a retrospective cohort study of all women who underwent cesarean delivery at a single academic institution from January 2012 to June 2018. Women were excluded if they received a preoperative transfusion or had missing data. Our institution implemented a quantitative measurement of blood loss in September 2015. Our primary outcome was red blood cell transfusion (intraoperative or postoperative). Women who had the quantitative measurement of blood loss (October 2015 to June 2018) were compared with those who had a visual estimation of blood loss (January 2012 to August 2015). Coarsened Exact Matching with a k-to-k solution was performed using predefined variables. RESULTS: In total, 4068 had a visual estimation of blood loss and 3117 had the quantitative measurement of blood loss; 1101 women with the quantitative measurement of blood loss were matched to 1101 women with a visual estimation of blood loss. In the unmatched cohort, women who had the quantitative measurement of blood loss compared to those who had a visual estimation of blood loss were more likely to have an increased amount of blood loss (734 ml vs. 700 ml, p < .001) and red blood cell transfusion (7.2% [223/3117] vs. 5.4% [221/4068]; crude odds ratio 1.34; 95% confidence interval 1.11-1.63). This increase in the amount of blood loss (717 ml vs. 700 ml, p < .05) and the rate of red blood cell transfusion (4.5% [49/1101] vs. 2.7% [30/1101]; crude odds ratio 1.66; 95% confidence interval 1.05-2.64) remained statically significant after matching. CONCLUSION: Women who had the quantitative measurement compared with those who had a visual estimation of blood loss were more likely to have an increased amount of blood loss and red blood cell transfusion.

Utilization of Magnesium for the Treatment of Chronic Pain.

CONTEXT: The International Association for the Study of Pain (IASP) defines chronic pain as pain that persists or recurs for longer than 3 months. Chronic pain has a significant global disease burden with profound effects on health, quality of life, and socioeconomic costs. EVIDENCE ACQUISITION: Narrative review. RESULTS: There are several treatment options, including pharmacological therapy, physical rehabilitation, psychological therapies, and surgical interventions, for chronic pain management. Magnesium has been FDA-approved for several indications including hypomagnesemia, arrhythmia, prevention of seizures in eclampsia/preeclampsia, and constipation. Magnesium has been used for numerous off-label uses, notably for acute and chronic pain management. The mechanism of magnesium in pain management is primarily through its action as a voltage-gated antagonist of NMDA receptors, which are involved in pain transduction. CONCLUSIONS: This narrative review will focus on the current evidence and data surrounding the utilization of magnesium as a treatment option for chronic pain.

Prenatal origins of neuropsychiatric diseases.

AIM: The main objective is to review the available evidence in the literature for developmental origins of neuropsychiatric diseases and their underlying mechanisms. We also probe emerging cutting-edge prenatal MR imaging tools and their future role in advancing our understanding the prenatal footprints of neuropsychiatric disorders. OBSERVATIONS: Both human and animal studies support early intrauterine origins of neuropsychiatric disease, particularly autism spectrum disorders (ASD), attention and hyperactivity disorders, schizophrenia, depression, anxiety and mood disorders. Specific mechanisms of intrauterine injury include infection, inflammation, hypoxia, hypoperfusion, ischaemia polysubstance use/abuse, maternal mental health and placental dysfunction. CONCLUSIONS AND RELEVANCE: There is ample evidence to suggest developmental vulnerability of the foetal brain to intrauterine exposures that increases and individual's risk for neuropsychiatric disease, especially the risk of ASD, depression and anxiety. Elucidating the exact timing and mechanisms of injury can be difficult and require novel, non-invasive approaches to the study emerging structural and functional brain development of the foetus. Clinical care should both emphasise maternal health during pregnancy, as well as close, continued monitoring for at risk offspring throughout young adulthood for the early identification and treatment of neuropsychiatric diseases.

The utilization of buprenorphine in chronic pain.

Reclassification of chronic pain as a disease may be helpful because patients with chronic pain require significant treatment and rehabilitation with a clear diagnosis. This can help address critical factors including suffering, quality of life, participation, and with family and social life, which continue to become more important in evaluating the quality of the health care we give our patients today. During the past decade of the opioid epidemic, methadone was the primary treatment for opioid addiction until buprenorphine was approved. Buprenorphine's high-affinity partial agonist properties make it a good alternative to methadone due to lower abuse potential and safer adverse effect profile while maintaining significant efficacy. Expanded out-patient prescribing options have allowed physician and physician extenders such as physician assistants and nurse practitioners to treat these patients that otherwise would have been required to utilize methadone. With unique pharmacological properties, buprenorphine is a safe and effective analgesic for chronic pain. The literature for buprenorphine shows great potential for its utilization in the treatment of chronic pain.

A Review of Patisiran (ONPATTRO®) for the Treatment of Polyneuropathy in People with Hereditary Transthyretin Amyloidosis.

Hereditary variant transthyretin amyloidosis (ATTRv) is a rare genetic defect that affects about 5000-10,000 people worldwide, causing amyloidosis secondary to misfolding of mutant transthyretin (TTR) protein fibrils. TTR mutations can cause protein deposits in many extracellular regions of organs, but those deposits in cardiac and axonal cells are the primary cause of this clinical syndrome. Treatment options are limited, but new drugs are being developed. Patisiran, a novel drug, is a liposomal siRNA against TTR that specifically targets this protein, reducing the accumulation of TTR in tissues, with subsequent improvement in both neuropathy and cardiac function. Patisiran is likely to serve as a prototype for the development of further intelligent drug solutions for use in targeted therapy. In this review we summarize the evidence currently available on the treatment of polyneuropathy in people with ATTRv with patisiran. We review the evidence on its efficacy, safety, and indications of use, citing novel and seminal papers on these subjects.

Systematic review of viscoelastic testing (TEG/ROTEM) in obstetrics and recommendations from the women's SSC of the ISTH.

Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are point-of-care viscoelastic devices that use whole blood samples to assess coagulation and fibrinolysis. These devices have been studied extensively in cardiac surgery, but there is limited robust evidence supporting its use in obstetrics. The hesitancy toward its routine use in obstetrics may be due to the current lack of randomized controlled trials and large observational studies. The study aims to systematically review studies that investigated TEG/ROTEM use in pregnancy or peripartum, and to provide recommendations for future studies to fill current research gaps. We performed a systematic review of studies on viscoelastic testing in obstetrics. Included studies were original research, used TEG or ROTEM during pregnancy or peripartum, and published in English. Ninety-three studies, spanning 31 years from 1989 to 2020 and with a total of 32,817 participants, were included. Sixty-two (66.7%) of the studies used TEG and 31 (33.3%) used ROTEM. To date, there are a total of two randomized controlled trials on TEG/ROTEM use in obstetrics. ROTEM may be used to guide transfusion therapy for postpartum hemorrhage. TEG and ROTEM can detect the hypercoagulable changes associated with pregnancy. Variability between study protocols and results suggests the need for future large prospective high-quality studies with standardized protocols to investigate the utility of TEG/ROTEM in assessing risk for thrombosis and hemorrhage as well as in guiding prophylaxis and treatment in obstetric patients. This review identifies the gaps and provides concrete recommendations for future studies to fill those gaps.

Hemostatic laboratory derangements in COVID-19 with a focus on platelet count.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease in 2019 (COVID-19) which rapidly evolved from an outbreak in Wuhan, China into a pandemic that has resulted in over millions of infections and over hundreds of thousands of mortalities worldwide. Various coagulopathies have been reported in association with COVID-19, including disseminated intravascular coagulation (DIC), sepsis-induced coagulopathy (SIC), local microthrombi, venous thromboembolism (VTE), arterial thrombotic complications, and thrombo-inflammation. There is a plethora of publications and conflicting data on hematological and hemostatic derangements in COVID-19 with some data suggesting the link to disease progress, severity and/or mortality. There is also growing evidence of potentially useful clinical biomarkers to predict COVID-19 progression and disease outcomes. Of those, a link between thrombocytopenia and COVID-19 severity or mortality was suggested. In this opinion report, we examine the published evidence of hematological and hemostatic laboratory derangements in COVID-19 and the interrelated SARS-CoV-2 induced inflammation, with a focussed discussion on platelet count alterations. We explore whether thrombocytopenia could be a potential disease biomarker and we provide recommendations for future studies in this regard.

An Evidence-Based Review of Fremanezumab for the Treatment of Migraine.

Migraine headache is a common, chronic, debilitating disease with a complex etiology. Current therapy for migraine headache comprises either treatments targeting acute migraine pain or prophylactic therapy aimed at increasing the length of time between migraine episodes. Recent evidence suggests that calcium gene-related peptide (CGRP) is a critical component in the pathogenesis of migraines. Fremanezumab, a monoclonal antibody against CGRP, was recently approved by the Food and Drug Administration (FDA) after multiple studies showed that it was well-tolerated, safe, and effective in the treatment of migraines. Further research is needed to elucidate the long-term effects of fremanezumab and CGRP-antagonists in general, and additional data is required in less healthy patients to estimate its effects in these populations and potentially increase the eligible group of recipients. This is a comprehensive review of the current literature on the efficacy and safety of fremanezumab for the treatment of chronic migraine. In this review we provide an update on the epidemiology, pathogenesis, diagnosis, and current treatment of migraine, and summarize the evidence for fremanezumab as a treatment for migraine.

A comprehensive review of the treatment and management of Charcot spine.

Charcot spine arthropathy (CSA), a result of reduced afferent innervation, is an occurrence of Charcot joint, a progressive, degenerative disorder in vertebral joints, related mostly to spinal cord injury. The repeated microtrauma is a result of a lack of muscle protection and destroys cartilage, ligaments, and disc spaces, leading to vertebrae destruction, joint instability, subluxation, and dislocation. Joint destruction compresses nerve roots, resulting in pain, paresthesia, sensory loss, dysautonomia, and spasticity. CSA presents with back pain, spinal deformity and instability, and audible spine noises during movement. Autonomic dysfunction includes bowel and bladder dysfunction. It is slowly progressive and usually diagnosed at a late stage, usually, on average, 20 years after the first initial insult. Diagnosis is rarely clinical related to the nature of nonspecific symptoms and requires imaging with computed tomography (CT) and magnetic resonance imaging (MRI). Conservative management focuses on the prevention of fractures and the progression of deformities. This includes bed rest, orthoses, and braces. These could be useful in elderly or frail patients who are not candidates for surgical treatment, or in minimally symptomatic patients, such as patients with spontaneous fusion leading to a stable spine. Symptomatic treatment is offered for autonomic dysfunction, such as anticholinergics for bladder control. Most patients require surgical treatment. Spinal fusion is achieved with open, minimally-open (MOA) or minimally-invasive (MIS) approaches. The gold standard is open circumferential fusion; data is lacking to determine the superiority of open or MIS approaches. Patients usually improve after surgery; however, the rarity of the condition makes it difficult to estimate outcomes. This is a review of the latest and seminal literature about the treatment and chronic management of Charcot spine. The review includes the background of the syndrome, clinical presentation, and diagnosis, and compares the different treatment options that are currently available.

Opposing role for Egr3 in nucleus accumbens cell subtypes in cocaine action.

An imbalance in molecular signaling cascades and transcriptional regulation in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine D1 versus D2 receptors, is implicated in the behavioral responses to psychostimulants. To provide further insight into the molecular mechanisms occurring in MSN subtypes by cocaine, we examined the transcription factor early growth response 3 (Egr3). We evaluated Egr3 because it is a target of critical cocaine-mediated signaling pathways and because Egr3-binding sites are found on promoters of key cocaine-associated molecules. We first used a RiboTag approach to obtain ribosome-associated transcriptomes from each MSN subtype and found that repeated cocaine administration induced Egr3 ribosome-associated mRNA in NAc D1-MSNs while reducing Egr3 in D2-MSNs. Using Cre-inducible adeno-associated viruses combined with D1-Cre and D2-Cre mouse lines, we observed that Egr3 overexpression in D1-MSNs enhances rewarding and locomotor responses to cocaine, whereas overexpression in D2-MSNs blunts these behaviors. miRNA knock-down of Egr3 in MSN subtypes produced opposite behavioral responses from those observed with overexpression. Finally, we found that repeated cocaine administration altered Egr3 binding to promoters of genes that are important for cocaine-mediated cellular and behavioral plasticity. Genes with increased Egr3 binding to promoters, Camk2α, CREB, FosB, Nr4a2, and Sirt1, displayed increased mRNA in D1-MSNs and, in some cases, a reduction in D2-MSNs. Histone and the DNA methylation enzymes G9a and Dnmt3a displayed reduced Egr3 binding to their promoters and reduced mRNA in D1-MSNs. Our study provides novel insight into an opposing role of Egr3 in select NAc MSN subtypes in cocaine action.