Improving Care Beyond Birth: A Qualitative Study of Postpartum Care After High-Risk Pregnancy.

Background: The postpartum period is a window to engage birthing people in their long-term health and facilitate connections to comprehensive care. However, postpartum systems often fail to transition high-risk patients from obstetric to primary care. Exploring patient experiences can be helpful for optimizing systems of postpartum care. Methods: This is a qualitative study of high-risk pregnant and postpartum individuals. We conducted in-depth interviews with 20 high-risk pregnant or postpartum people. Interviews explored personal experiences of postpartum care planning, coordination of care between providers, and patients' perception of ideal care transitions. We performed thematic analysis using the Capability, Opportunity, Motivation, Behavior (COM-B) model of behavior change as a framework. COM-B allowed for a formal structure to assess participants' ability to access postpartum care and primary care reengagement after delivery. Results: Participants universally identified difficulty accessing primary care in the postpartum period, with the most frequently reported barriers being lack of knowledge and supportive environments. Insufficient preparation, inadequate prenatal counseling, and lack of standardized care transitions were the most significant barriers to primary care reengagement. Participants who most successfully engaged in primary care had postpartum care plans, coordination between obstetric and primary care, and access to material resources. Conclusions: High-risk postpartum individuals do not receive effective counseling on the importance of primary care engagement after delivery. System-level challenges and lack of care coordination also hinder access to primary care. Future interventions should include prenatal education on the benefits of primary care follow-up, structured postpartum planning, and system-level improvements in obstetric and primary care provider communication.

A Comprehensive Prediction Model for Futile Recanalization in AIS Patients Post-Endovascular Therapy: Integrating Clinical, Imaging, and No-Reflow Biomarkers.

Our study aimed to construct a predictive model for identifying instances of futile recanalization in patients with anterior circulation occlusion acute ischemic stroke (AIS) who achieved complete reperfusion following endovascular therapy. We included 173 AIS patients who attained complete reperfusion, as indicated by a Modified Thrombolysis in Cerebral Infarction (mTICI) scale score of 3. Our approach involved a thorough analysis of clinical factors, imaging biomarkers, and potential no-reflow biomarkers through both univariate and multivariate analyses to identify predictors of futile recanalization. The comprehensive model includes clinical factors such as age, presence of diabetes, admission NIHSS score, and the number of stent retriever passes; imaging biomarkers like poor collaterals; and potential no-reflow biomarkers, notably disrupted blood-brain barrier (OR 4.321, 95% CI 1.794-10.405; p = 0.001), neutrophil-to-lymphocyte ratio (NLR; OR 1.095, 95% CI 1.009-1.188; p = 0.030), and D-dimer (OR 1.134, 95% CI 1.017-1.266; p = 0.024). The model demonstrated high predictive accuracy, with a C-index of 0.901 (95% CI 0.855-0.947) and 0.911 (95% CI 0.863-0.954) in the original and bootstrapping validation samples, respectively. Notably, the comprehensive model showed significantly improved predictive performance over models that did not include no-reflow biomarkers, evidenced by an integrated discrimination improvement of 8.86% (95% CI 4.34%-13.39%; p < 0.001) and a categorized reclassification improvement of 18.38% (95% CI 3.53%-33.23%; p = 0.015). This model, which leverages the potential of no-reflow biomarkers, could be especially beneficial in healthcare settings with limited resources. It provides a valuable tool for predicting futile recanalization, thereby informing clinical decision-making. Future research could explore further refinements to this model and its application in diverse clinical settings.

Abdominal Aortic Occlusion and the Inflammatory Effects in Heart and Brain.

Background: Abdominal aortic occlusion (AAO) occurs frequently and causes ischemia/reperfusion (I/R) injury to distant organs. In this study, we aimed to investigate whether AAO induced I/R injury and subsequent damage in cardiac and neurologic tissue. We also aimed to investigate the how length of ischemic time in AAO influences reactive oxygen species (ROS) production and inflammatory marker levels in the heart, brain, and serum. Methods: Sixty male C57BL/6 mice were used in this study. The mice were randomly divided into either sham group or AAO group. The AAO group was further subdivided into 1-4 hr groups of aortic occlusion times. The infrarenal abdominal aorta was clamped for 1-4 hr depending on the AAO group and was then reperfused for 24 hr after clamp removal. Serum, hippocampus, and left ventricle tissue samples were then subjected to biochemical and histopathological analyses. Results: AAO-induced I/R injury had no effect on cell necrosis, cell apoptosis, or ROS production. However, serum and hippocampus levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) increased in AAO groups when compared to sham group. Superoxide dismutase and total antioxidant capacity decreased in the serum, hippocampus, and left ventricle. In the serum, AAO increased the level of inducible nitric oxide synthase (iNOS) and decreased the levels of anti-inflammatory factors (such as arginase-1), transforming growth factor- ß1 (TGF-ß1), interleukin 4 (IL-4), and interleukin 10 (IL-10). In the hippocampus, AAO increased the levels of tumor necrosis factor (TNF-α), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), IL-4, and IL-6, and decreased the level of TGF-ß1. In the left ventricle, AAO increased the level of iNOS and decreased the levels of TGF-ß1, IL-4, and IL-10. Conclusions: AAO did not induce cell necrosis or apoptosis in cardiac or neurologic tissue, but it can cause inflammation in the serum, brain, and heart.

Predictors of nonadherence to breast cancer screening guidelines in a United States urban comprehensive cancer center.

BACKGROUND: This study aimed to identify predictors of nonadherence to breast cancer screening guidelines in an urban screening clinic among high- and average-risk women in the United States. METHODS: We reviewed records of 6090 women who received ≥2 screening mammograms over 2 years at the Karmanos Cancer Institute to examine how breast cancer risk and breast density were associated with guideline-concordant screening. Incongruent screening was defined as receiving supplemental imaging between screening mammograms for average-risk women, and as not receiving recommended supplemental imaging for high-risk women. We used t-tests and chi-square tests to examine bivariate associations with guideline-congruent screening, and probit regression to regress guideline-congruence unto breast cancer risk, breast density, and their interaction, controlling for age and race. RESULTS: Incongruent screening was more likely among high- versus average-risk women (97.7% vs. 0.9%, p < 0.01). Among average-risk women, incongruent screening was more likely among those with dense versus nondense breasts (2.0% vs. 0.1%, p < 0.01). Among high-risk women, incongruent screening was more likely among those with nondense versus dense breasts (99.5% vs. 95.2%, p < 0.01). The significant main effects of density and high-risk on increased incongruent screening were qualified by a density by high-risk interaction, showing a weaker association between risk and incongruent screening among women with dense breasts (simple slope = 3.71, p < 0.01) versus nondense breasts (simple slope = 5.79, p < 0.01). Age and race were not associated with incongruent screening. CONCLUSIONS: Lack of adherence to evidence-based screening guidelines has led to underutilization of supplementary imaging for high-risk women and potential overutilization for women with dense breasts without other risk factors.

Hypoxia-Preconditioned Bone Marrow Mesenchymal Stem Cells Improved Cerebral Collateral Circulation and Stroke Outcome in Mice.

BACKGROUND: Adequate collateral circulation can remarkably improve patient prognoses for patients experiencing ischemic stroke. Hypoxic preconditioning enhances the regenerative properties of bone marrow mesenchymal stem cells (BMSCs). Rabep2 (RAB GTPase binding effector protein 2) is a key protein in collateral remodeling. We investigated whether BMSCs and hypoxia-preconditioned BMSCs (H-BMSCs) augment collateral circulation poststroke, particularly through Rabep2 regulation. METHODS: BMSCs or H-BMSCs (1×106) were delivered intranasally in ischemic mice with distal middle cerebral artery occlusion at 6 hours poststroke. Two-photon microscopic imaging and vessel painting methods were used to analyze collateral remodeling. Blood flow, vascular density, infarct volume, and gait analysis were assessed to evaluate poststroke outcomes. Expressions of proangiogenic marker VEGF (vascular endothelial growth factor) and Rabep2 were determined by Western blotting. Western blot, EdU (5-ethynyl-2'-deoxyuridine) incorporation, and tube formation assays were conducted on cultured endothelial cells treated with BMSCs. RESULTS: BMSCs were more effectively transplanted in the ischemic brain after hypoxic preconditioning. The ipsilateral collateral diameter was increased by BMSCs and strengthened by H-BMSCs (P<0.05). BMSCs increased peri-infarct blood flow and vascular density and reduced infarct volume, gait deficits (P<0.05), and furthermore by H-BMSCs (P<0.05). VEGF and Rabep2 protein expression was increased by BMSCs (P<0.05), which was enhanced by preconditioning (P<0.01). Additionally, BMSCs increased Rabep2 expression, proliferation, and tube formation of endothelial cells in vitro (P<0.05). H-BMSCs enhanced these effects (P<0.05), which were annulled by Rabep2 knockdown. CONCLUSIONS: BMSCs increased collateral circulation and improved poststroke outcomes, through the upregulation of Rabep2. These effects were enhanced by hypoxic preconditioning.

Cerebral Glucose Metabolism and Potential Effects on Endoplasmic Reticulum Stress in Stroke.

Ischemic stroke is an extremely common pathology with strikingly high morbidity and mortality rates. The endoplasmic reticulum (ER) is the primary organelle responsible for conducting protein synthesis and trafficking as well as preserving intracellular Ca2+ homeostasis. Mounting evidence shows that ER stress contributes to stroke pathophysiology. Moreover, insufficient circulation to the brain after stroke causes suppression of ATP production. Glucose metabolism disorder is an important pathological process after stroke. Here, we discuss the relationship between ER stress and stroke and treatment and intervention of ER stress after stroke. We also discuss the role of glucose metabolism, particularly glycolysis and gluconeogenesis, post-stroke. Based on recent studies, we speculate about the potential relationship and crosstalk between glucose metabolism and ER stress. In conclusion, we describe ER stress, glycolysis, and gluconeogenesis in the context of stroke and explore how the interplay between ER stress and glucose metabolism contributes to the pathophysiology of stroke.

COVID-19-induced thrombotic microangiopathy: A great mimicker of thrombotic thrombocytopenic purpura (TTP).

We present a unique case of a 68-year-old male who was diagnosed with COVID-19. His hospital course was complicated by widespread thrombosis, renal failure, and thrombocytopenia. Thrombotic thrombocytopenic purpura was initially suspected, yet plasma exchange and steroids did not improve his disease. Ultimately, he was diagnosed with COVID-19-induced thrombotic microangiopathy.

Mobilizing the fourth trimester to improve population health: interventions for postpartum transitions of care.

Birthing people in the United States, particularly those from marginalized communities, experience an unexpectedly high rate of morbidity and mortality. Optimal postpartum care is an opportunity to address immediate maternal health concerns while providing a connection to further high-value primary care. However, postpartum care in the United States is fragmented and incomplete. In response to this failure, the American College of Obstetricians and Gynecologists has called for obstetricians to develop individualized care plans that facilitate transitions from obstetrical to primary care after delivery. In this clinical opinion, we review previous interventions that have aimed to increase postpartum care engagement and bridge gaps in care. Although numerous interventions have been trialed, few have been both successful and scalable. We provide recommendations on ways to reimagine equitable and effective postpartum care interventions with multidisciplinary collaboration.

The Key Role of Initiation Timing on Stroke Rehabilitation by Remote Ischemic Conditioning with Exercise (RICE).

OBJECTIVE: Physical therapy is an integral part of post-stroke rehabilitation. Remote ischemic conditioning (RIC) induces neuroprotection within 24 hours after stroke, during which exercise is unsafe and ineffective. We combined RIC with exercise to establish a novel rehabilitation strategy, RICE (RIC+Exercise). The aim of this study was to optimize the RICE protocol in neurorehabilitation. METHODS: Thirty-two adult male Sprague-Dawley rats were placed in one of four groups: stroke with no rehabilitation or stroke with various RICE protocols. To further understand the mechanisms underlying neurorehabilitation, sixteen adult male Sprague-Dawley were added, each placed in one of two groups: stroke with exerciseor RIC  . Long-term functional outcomes were determined by beam balance, rota-rod, grid walk, forelimb placing, and Morris water maze tests up to 28 days after stroke (p < 0.05). Changes in neuroplasticity including synaptogenesis (assessed by measuring synaptophysin, post-synaptic density protein-95, and brain-derived neutrophic factor), angiogenesis (via vascular endothelial growth factor, Angiopoietin-1, and Angiopoietin-2), and regulatory molecules (including hypoxia inducible factor-1α, phospholipase D2 and the mechanistic target of rapamycin pathway), were all measured at both mRNA and protein levels (p < 0.05). RESULTS: All rehabilitation groups showed significant improvement in functional outcomes and levels of synaptogenesis and angiogenesis. 5 day RICE groups, in which RIC was started five days prior to exercise, demonstrated the greatest improvement among these parameters. The results also suggested that the HIF-1α/PLD2/mTOR signaling pathway may be implicated in post-stroke neuroplasticity. CONCLUSIONS: RICE, particularly RIC initiation at hour 6 post-reperfusion followed by exercise on day 5, enhanced post-stroke rehabilitation in rats.

Arterial Glyceryl Trinitrate in Acute Ischemic Stroke after Thrombectomy for Neuroprotection (AGAIN): Rationale, design and protocol for a prospective randomized controlled trial.

BACKGROUND: Although endovascular recanalization therapy demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all victims of these cerebrovascular accidents can benefit from it and achieve a favorable prognosis after successful reperfusion. Therefore, alternative neuroprotective strategies are urgently needed for AIS patients after vessel recanalization. Nitric oxide (NO) levels are low after AIS and NO donor drugs may be neuroprotective against cerebral ischemia-reperfusion injury. Glyceryl trinitrate (GTN), often used in the clinic as a NO donor, may provide a novel neuroprotective strategy. This rationale, design, and protocol for a prospective pilot study plans to explore the preliminary safety, feasibility, and neuroprotective benefits of Arterial Glyceryl Trinitrate in Acute Ischemic Stroke after Thrombectomy for Neuroprotection (AGAIN). METHODS: AGAIN, a prospective RCT, is proposed for AIS patients after mechanical thrombectomy. Subjects will be randomly assigned in a 1:1 fashion (n = 40) to either the control group or the intervention group. Participants assigned to the intervention group will be administered 800 µg GTN in the catheter immediately after recanalization, whereas those in the control group will be administered the same volume of normal saline. All participants from either group will be given concurrent treatment with standard of care therapies in accordance with the current guidelines for stroke management. The primary outcome is safety [symptomatic intracranial hemorrhage (ICH), hypotension, neurological deterioration, ICH, fatal ICH, as well as headache, tachycardia, emesis, and seizures], whereas secondary outcomes included changes in poststroke functional outcomes, infarction volumes, and blood nitrate index detection. DISCUSSIONS: This study is a prospective randomized controlled trial to test the safety and efficacy of intra-arterial GTN in AIS patients after endovascular therapy. The results from this study will give insight for future GTN studies and new neuroprotective strategies for future AIS treatment strategies. TRIAL REGISTRATION NUMBER: ChiCTR2100045254. Registered on March 21, 2021.

Chlorpromazine and Promethazine (C+P) Reduce Brain Injury after Ischemic Stroke through the PKC-δ/NOX/MnSOD Pathway.

Cerebral ischemia-reperfusion (I/R) incites neurologic damage through a myriad of complex pathophysiological mechanisms, most notably, inflammation and oxidative stress. In I/R injury, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) produces reactive oxygen species (ROS), which promote inflammatory and apoptotic pathways, augmenting ROS production and promoting cell death. Inhibiting ischemia-induced oxidative stress would be beneficial for reducing neuroinflammation and promoting neuronal cell survival. Studies have demonstrated that chlorpromazine and promethazine (C+P) induce neuroprotection. This study investigated how C+P minimizes oxidative stress triggered by ischemic injury. Adult male Sprague-Dawley rats were subject to middle cerebral artery occlusion (MCAO) and subsequent reperfusion. 8 mg/kg of C+P was injected into the rats when reperfusion was initiated. Neurologic damage was evaluated using infarct volumes, neurological deficit scoring, and TUNEL assays. NOX enzymatic activity, ROS production, protein expression of NOX subunits, manganese superoxide dismutase (MnSOD), and phosphorylation of PKC-δ were assessed. Neural SHSY5Y cells underwent oxygen-glucose deprivation (OGD) and subsequent reoxygenation and C+P treatment. We also evaluated ROS levels and NOX protein subunit expression, MnSOD, and p-PKC-δ/PKC-δ. Additionally, we measured PKC-δ membrane translocation and the level of interaction between NOX subunit (p47phox) and PKC-δ via coimmunoprecipitation. As hypothesized, treatment with C+P therapy decreased levels of neurologic damage. ROS production, NOX subunit expression, NOX activity, and p-PKC-δ/PKC-δ were all significantly decreased in subjects treated with C+P. C+P decreased membrane translocation of PKC-δ and lowered the level of interaction between p47phox and PKC-δ. This study suggests that C+P induces neuroprotective effects in ischemic stroke through inhibiting oxidative stress. Our findings also indicate that PKC-δ, NOX, and MnSOD are vital regulators of oxidative processes, suggesting that C+P may serve as an antioxidant.

Updates on Selective Brain Hypothermia: Studies From Bench Work to Clinical Trials.

Thrombectomy or thrombolysis are the current standards of care for acute ischemic stroke (AIS), however, due to time constraints regarding operations and a multitude of contraindications, AIS remains one of the leading causes of death and chronic disability worldwide. In recent years, therapeutic hypothermia has been explored as an adjuvant therapy for AIS treatment and has shown potential to improve outcomes in patients with AIS. In particular, selective therapeutic hypothermia has shown to markedly reduce infarct volumes and have neuroprotective effects, while also minimizing many systemic side effects seen with systemic therapeutic hypothermia. Both preclinical and clinical trials have demonstrated that selective therapeutic hypothermia is a safe and feasible therapy for patients who have suffered an AIS. In this review, we summarize the current update on selective hypothermia through major studies that have been conducted in rodents, large animals, and clinical trials, and briefly discuss the prospects of selective hypothermic research. We hope this review helps facilitate the exploration of other possible adjuvant treatment modalities in the neuroprotection of ischemic stroke, whether upon symptom onset or after vascular recanalization.

Uptake of genetic counseling and testing in a clinic-based population of women with breast cancer.

BACKGROUND: The study was conducted to evaluate racial differences in referral and uptake of genetic counseling (GC) in a clinic-based population of women with breast cancer. METHODS: Medical records of 150 breast cancer patients at the Karmanos Cancer Institute were reviewed to determine eligibility for GC according to National Comprehensive Cancer Network guidelines, GC referral rates, and appointment completion rates. Logistic regression was used to assess the relationship between demographic and clinical factors and GC eligibility and referral. RESULTS: The mean age at diagnosis was 57.1 (SD 12.6) and 66% of the women were Black. There were 91 women (60.7%) eligible for GC and of those, 54 (61.4%) were referred. After multivariable analyses, factors associated with reduced eligibility were older age at diagnosis (OR = 0.91, 95% CI [0.87,0.95]) and Black race (OR = 0.37, 95% CI [0.15, 0.96]). After additional multivariable analysis, eligibility was associated with an increased likelihood of referral (OR = 5.97, 95% CI [2.29, 15.56]), however, Medicare versus private insurance was associated with a lower likelihood for referral (OR = 0.32, 95% CI [0.12-0.80]. Of those referred, 49 (76.6%) completed an appointment, and 47 had genetic testing. Women with Medicare were also less likely to complete an appointment. Race had no impact on referral or appointment completion. CONCLUSIONS: There were no racial differences in GC referral or appointment completion in a clinic-based sample of women with breast cancer. Further interventions are needed to promote increased referral and appointment completion for women with breast cancer who are eligible for GC.