Exercise testing unmasks exaggerated blood pressure independent of fibrinolytic response in Black but not White postmenopausal females.

Exercise testing unmasks more exaggerated systolic blood pressure responses (SBP) in Black compared with White male adults. Such responses, if translatable to females, may detect racial disparities particularly relevant during menopause. Given the endothelial involvement in BP regulation and as a source of fibrinolytic markers, it follows that fibrinolytic and BP response to exercise could be linked. Thus, we examined BP and fibrinolytic responses to exercise testing in Black and White postmenopausal females. Postmenopausal females (Black = 40; White = 41; 51-70 yr) performed maximal treadmill exercise. BP and blood draws were conducted before and immediately after exercise. Plasma samples, using minimal stasis, were analyzed for tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) activity and antigen, respectively. Resting SBP and fibrinolytic potential were similar between races. Black females exhibited greater increases in SBP during exercise [change (d)=75, 95% CI: 64-86 mmHg, P < 0.001] than White females (d = 60, 95% CI: 48-71 mmHg, P < 0.001). Black compared with White females had smaller changes in tPA (d = 3.27, 95% CI: 2.28-4.27 IU/mL, P < 0.001 vs. d = 5.55, 95% CI: 4.58-6.53, P < 0.001) and PAI-1 (d = -2.89, 95% CI: -4.39 to -1.40 IU/mL, P < 0.001 vs. d = -5.08, 95% CI: -6.59 to -3.61, P < 0.001) activities after exercise. SBP exercise-induced changes were not associated with tPA (r = -0.10, P = 0.42) or PAI-1 (r = 0.13, P = 0.30), without any influence of race (P > 0.05). Our findings show that maximal exercise unmasks risk factors for cardiovascular disease in Black postmenopausal females.NEW & NOTEWORTHY Exaggerated SBP responses to exercise testing are more frequent in Black than in White male adults. Such responses, if translatable to females, may detect early racial disparities arriving during menopause. Because the endothelium regulates BP and fibrinolytic responses, these could be linked during exercise. At peak exercise, Black but not White postmenopausal females had more exaggerated SPB responses regardless of reduced fibrinolytic potential. Maximal exercise unmasked risk factors for cardiovascular disease in Black postmenopausal females.

Hospitalization in pregnancy due to human respiratory syncytial virus associated disease.

Background: Despite pregnancy being a state of physiologic immune alteration, it has not previously been described as a risk factor for hospitalization due to human respiratory syncytial virus (RSV). Case: This retrospective case series describes two cases of hospitalization due to RSV associated illness in pregnancy. Conclusion: It remains to be determined if the current RSV surge is more dangerous to pregnant patients than those in seasons past. These cases support the importance of maintaining RSV on the differential for respiratory illness in pregnancy.

Hyaline protoplasmic astrocytopathy in epilepsy.

Hyaline protoplasmic astrocytopathy (HPA) describes a rare histologic finding of eosinophilic, hyaline cytoplasmic inclusions in astrocytes, predominantly in the cerebral cortex. It has mainly been observed in children and adults with a history of developmental delay and epilepsy, frequently with focal cortical dysplasia (FCD), but the nature and significance of these inclusions are unclear. In this study, we review the clinical and pathologic features of HPA and characterize the inclusions and brain tissue in which they are seen in surgical resection specimens from five patients with intractable epilepsy and HPA compared to five patients with intractable epilepsy without HPA using immunohistochemistry for filamin A, previously shown to label these inclusions, and a variety of astrocytic markers including aldehyde dehydrogenase 1 family member L1 (ALDH1L1), SRY-Box Transcription Factor 9 (SOX9), and glutamate transporter 1/excitatory amino acid transporter 2 (GLT-1/EAAT2) proteins. The inclusions were positive for ALDH1L1 with increased ALDH1L1 expression in areas of gliosis. SOX9 was also positive in the inclusions, although to a lesser intensity than the astrocyte nuclei. Filamin A labeled the inclusions but also labeled reactive astrocytes in a subset of patients. The immunoreactivity of the inclusions for various astrocytic markers and filamin A as well as the positivity of filamin A in reactive astrocytes raise the possibility that these astrocytic inclusions may be the result of an uncommon reactive or degenerative phenomenon.

Brain pathology in patients with congenital heart disease.

INTRODUCTION: Brain pathology in patients with congenital heart disease (CHD) is associated with neuro-developmental delay. Imaging studies support vascular etiology for both white and gray matter lesions. In this retrospective study, we described the pathological changes in the brains of patients with CHD. MATERIAL AND METHODS: Last twenty autopsy cases in pediatric patients with CHD at our institution were retrieved and autopsy reports were reviewed. Available hematoxylin-eosin, special, and immunostains were evaluated, and at least one section from each case was stained with anti-glial fibrillary acidic protein (GFAP), anti-amyloid precursor protein (APP), and anti-HLA-DR antibody. Staining pattern of these immunostains was compared to staining pattern in five control cases. Control cases comprised of 2 cases with no significant pathological changes, and 3 cases with telencephalic leukoencephalopathy. The following histological features were assessed: necrotic cells in cortex, hippocampus, and cerebellum, APP and GFAP staining pattern, and the presence of focal lesions and amphophilic globules. Twenty patients (10 males, 10 females) were identified, with age range between 2 weeks and 19 years. RESULTS: The pathological findings were as follows: 10 cases had changes consistent with acute global hypoperfusion, 8 cases showed features consistent with chronic global hypoperfusion, 4 cases presented focal white matter necrosis (2 with intra-vascular emboli), and 16 cases showed diffuse moderate to severe gliosis, including 7 cases with amphophilic globules. Subarachnoid hemorrhages were present in 5 cases, subdural hemorrhage in 4 cases, intra-ventricular hemorrhage in 2 cases, and germinal matrix hemorrhage in 1 case. CONCLUSIONS: In conclusion, diffuse gliosis is the prominent pathological feature in CHD cases. Most of the pathological changes are known to occur in cerebral hypoperfusion regardless of primary cause. Better techniques to improve cerebral perfusion are warranted in the management of these patients.

Neuropathology Evaluation of in Utero Correction of Myelomeningocele and Complications of Late-Onset GBS Infection.

Background: Myelomeningocele (MMC) causes significant morbidity and mortality. Efforts have been directed to correct this defect in utero. The neuropathology literature on antenatally repaired MMC and associated complications in humans is limited. Case report: A 12-day-old female, who underwent prenatal MMC repair via a two-layer closure (dural replacement patch, primary skin closure), was born at 34 weeks' gestation. Her group B streptococcus positive mother received appropriate antepartum prophylactic antibiotics. She remained stable until day 11 of life when she underwent rapid clinical deterioration. Despite aggressive intervention, she expired on day 12. Review of placental pathology showed maternal and fetal inflammatory response. Autopsy revealed Gram-positive cocci and inflammation within the basilar leptomeninges and lumbosacral region. Neural and dermal elements were present within the MMC repair. Conclusion: This case documents integration of the dermal matrix patch to neural elements, adhering the spinal cord to scar tissue, the clinical implications of which remain unclear.

Diabetic Ketoacidosis in Pregnancy: Clinical Risk Factors, Presentation, and Outcomes.

CONTEXT: Diabetic ketoacidosis (DKA) in pregnancy is an obstetric emergency with risk of maternofetal death. OBJECTIVE: This work aimed to evaluate DKA events in pregnant women admitted to our inpatient obstetric service, and to examine associated clinical risk factors, presentation, and pregnancy outcomes. METHODS: A retrospective cohort study was conducted at the Mayo Clinic, Rochester, Minnesota, USA, and included women aged 17 to 45 years who were treated for DKA during pregnancy between January 1, 2004 and December 31, 2021. Main outcome measures included maternal and fetal death along with a broad spectrum of maternal and fetal pregnancy outcomes. RESULTS: A total of 71 DKA events were identified in 58 pregnancies among 51 women, 48 (82.8%) of whom had type 1 diabetes. There were no maternal deaths, but fetal demise occurred in 10 (17.2%) pregnancies (6 miscarriages and 4 stillbirths). Maternal social stressors were frequently present (n = 30, 51.0%), and glycemic control was suboptimal (median first trimester glycated hemoglobin A1c = 9.0%). Preeclampsia was diagnosed in 17 (29.3%) pregnancies. Infants born to women with DKA were large for gestational age (n = 16, 33.3%), suffered from neonatal hypoglycemia (n = 29, 60.4%) and required intensive care unit admission (n = 25, 52.1%). CONCLUSION: DKA is associated with a high rate of maternofetal morbidity and fetal loss. Prenatal education strategies for women with diabetes mellitus should include a strong focus on DKA prevention, and clinicians and patients should have a high index of suspicion for DKA in all pregnant women who present with symptoms that could be attributed to this condition.

Intraabdominal pressure as a marker for physiologic and pathologic processes in pregnancy.

Increased intraabdominal pressure (IAP) can result in compression of the abdominal-pelvic venous system leading to signs and symptoms of end organ dysfunction. It has been hypothesized as a pathophysiologic process of preeclampsia. We aim to evaluate the role of IAP in normotensive vs preeclamptic, and singleton vs twin pregnancies. We hypothesized that IAP would be higher in preeclamptics and twins.Women undergoing scheduled cesarean delivery were enrolled in four groups: Singletons- Preeclamptic and Normotensive, Twins- Preeclamptic and Normotensive. Elevated IAP was seen in singleton pregnancies with preeclampsia, representing a pathologic process; and in all twin pregnancies, suggesting a physiologic process.

Intraoperative Diagnosis for Pediatric Brain Tumors.

Central nervous system (CNS) tumors are now the most common type of solid tumor in individuals aged 0-19 years, with an incidence rate in the United States around 5 per 100,000, accounting for about 1 out of 4 childhood cancers. Pediatric pathologists encounter brain tumor cases with varying frequency, but many of these encounters begin in the context of intraoperative consultation or "frozen section." This review provides an overview of the technical aspects of intraoperative consultation specific to, or more helpful in, CNS tumors, emphasizing helpful cytologic and histologic features of the more commonly encountered pediatric CNS tumors, and illustrating some common diagnostic pitfalls and how these may be avoided.

Characterization of knee dysfunction and related risk factors during pregnancy.

BACKGROUND: Knee pain can be a common complaint during pregnancy; however, the severity of symptoms and their associated risk factors have not been described. QUESTIONS/PURPOSES: The aim of this study was to characterize knee-related dysfunction and describe risk factors in a general obstetric population. PATIENTS AND METHODS: Patients in obstetric clinics completed the International Knee Documentation Committee (IKDC) questionnaire to assess their knee function, as well as the Pregnancy Physical Activity Questionnaire (PPAQ), a validated tool to assess physical activity. Age, weeks gestation, height, weight, and history of knee problems prior to pregnancy were analyzed to identify independent associations with IKDC score and determine predictors of knee dysfunction. RESULTS: 310 patients were included in this study, of which 68, 111 and 131 were in their first, second and trimesters, respectively. Mean age of the total study group was 30.3 ± 5.5 years. Knee function decreased with each trimester, from a mean IKDC score of 88.9 ± 13.0 in the first trimester, 84.5 ± 16.8 in the second, and 82.0 ± 20.0 in the third, with corresponding decreases in activity levels of 258.5 ± 141.7, 254.0 ± 141.5, and 246.1 ± 156.6 MET-h/wk. Of the total study group, 26.1% had IKDC scores <75, including 13.2%, 25.2%, and 33.6% in the first, second and third trimesters. Risk factors for knee dysfunction included high activity levels of PPAQ ≥ 500 MET-h/wk (OR 2.8), history of knee problems (OR 2.7), age <25 years (OR 2.6), and BMI ≥ 30 kg/m2 (OR 1.9). CONCLUSION: In our cohort, 26.1% of pregnant women reported severe knee dysfunction, and this was associated with high levels of activity, younger age, greater BMI, and history of knee problems. These findings may have implications for women who wish to maintain training and fitness during pregnancy. Future studies are recommended to assess the need for intervention, as well as to identify optimal methods to prevent and address symptoms in this population. LEVEL OF EVIDENCE: IV, Case Series.

Pediatric Metastatic Hepatoblastoma With an ARID1A Mutation and Rhabdoid Cells.

The small cell undifferentiated component of hepatoblastoma is an uncommon histologic component and is distinguished from small cell undifferentiated like pattern (originally called hepatoblastoma and now recognized to be malignant rhabdoid tumor) by the bi-allelic SMARCB1 mutations or copy number alterations in the latter. AT-rich interactive domain-containing protein 1A (ARID1A) is a part of the ATP-dependent switch/sucrose non-fermentable complex assembly, but mutations have not been reported as drivers of malignant rhabdoid tumor. ARID1A mutations in hepatocellular carcinoma are associated with poor prognosis but its significance in hepatoblastoma is unknown. We report a unique case of hepatoblastoma in a 19-month-old female with an unusual/atypical small cell undifferentiated component with ARID1A and beta-catenin mutations. It had an aggressive clinical course despite treatment, with metastases to the left psoas muscle, perihepatic and paratracheal lymph nodes, spinal cord, and leptomeninges. Leptomeningeal metastases resulted in diffuse cerebral edema and death. The initial diagnostic biopsy did not reveal rhabdoid cells while all metastatic foci showed cells with rhabdoid morphology in the autopsy specimens. Although this rhabdoid component resembled malignant rhabdoid tumor morphologically, molecular analyses failed to show mutations or deletions of SMARCB1.

Catastrophic congenital hemangioma with severe coagulopathy leading to fatal cardiac failure: Case report and review.

We present a complex case of a neonate, delivered urgently for hydrops fetalis, with a large vascular mass of the extremity, diagnosed postnatally as a congenital hemangioma. The patient suffered immediate cardiac compromise and severe coagulopathy atypical for the diagnosis and subsequently died from these complications. Treatment was imperative but challenging due to a lack of a standardized treatment approach and few historical reports of equally critically ill patients. In this report, we review potential medical and surgical interventions and discuss treatment considerations in similar, life-threatening cases of congenital hemangiomas.

Management of Complicated Monochorionic Twin Gestations: An Evidence-Based Protocol.

IMPORTANCE: Monochorionic (MC) twins are hemodynamically connected by vascular anastomoses within the single shared placenta. The transfer of fluid or blood from one fetus to the other may result in development of pathologic complications, such as twin-twin transfusion syndrome, twin anemia polycythemia sequence, selective intrauterine growth restriction, and twin reversed arterial perfusion sequence. Monoamniotic gestations, which comprise a small fraction of MC pregnancies, can also present with unique challenges, particularly antepartum umbilical cord entanglement. All these complications carry a high risk of fetal morbidity and mortality if not recognized and managed in a timely fashion. OBJECTIVE: The purpose of this article is to review evidence-based management of complicated MC twin gestations and propose a standardized approach to surveillance. EVIDENCE ACQUISITION: Monochorionic gestations account for the majority of complications that occur in twin pregnancies; however, there is unclear evidence on the appropriate surveillance for and management of specific complications associated with these pregnancies. RESULTS: This article summarizes management for each specific type of MC complication in a structured and clear manner. CONCLUSIONS: Early pregnancy ultrasound, ideally between 10 and 13 weeks' gestation, is critical for the diagnosis and characterization of twin pregnancies. To improve outcomes for MC twins, appropriate fetal surveillance should be initiated at 16 weeks' gestation and continued until delivery.

Neuropathological effects of chronically implanted, intracortical microelectrodes in a tetraplegic patient.

Objective.Intracortical microelectrode arrays (MEA) can be used as part of a brain-machine interface system to provide sensory feedback control of an artificial limb to assist persons with tetraplegia. Variability in functionality of electrodes has been reported but few studies in humans have examined the impact of chronic brain tissue responses revealed postmortem on electrode performancein vivo. Approach.In a tetraplegic man, recording MEAs were implanted into the anterior intraparietal area and Brodmann's area 5 (BA5) of the posterior parietal cortex and a recording and stimulation array was implanted in BA1 of the primary somatosensory cortex (S1). The participant expired from unrelated causes seven months after MEA implantation. The underlying tissue of two of the three devices was processed for histology and electrophysiological recordings were assessed.Main results.Recordings of neuronal activity were obtained from all three MEAs despite meningeal encapsulation. However, the S1 array had a greater encapsulation, yielded lower signal quality than the other arrays and failed to elicit somatosensory percepts with electrical stimulation. Histological examination of tissues underlying S1 and BA5 implant sites revealed localized leptomeningeal proliferation and fibrosis, lymphocytic infiltrates, astrogliosis, and foreign body reaction around the electrodes. The BA5 recording site showed focal cerebral microhemorrhages and leptomeningeal vascular ectasia. The S1 site showed focal tissue damage including vascular recanalization, neuronal loss, and extensive subcortical white matter necrosis. The tissue response at the S1 site included hemorrhagic-induced injury suggesting a likely mechanism for reduced function of the S1 implant.Significance.Our findings are similar to those from animal studies with chronic intracortical implants and suggest that vascular disruption and microhemorrhage during device implantation are important contributors to overall array and individual electrode performance and should be a topic for future device development to mitigate tissue responses. Neurosurgical considerations are also discussed.

Timing of delivery with coronavirus disease 2019 pneumonia requiring intensive care unit admission.

Approximately 4% of pregnant patients with coronavirus disease 2019 require intensive care unit admission. Given the practical implications of advanced ventilatory and circulatory support techniques, urgent or emergent delivery for nonreassuring fetal status frequently presents a logistical impossibility. This article proposes a protocol for obstetrical management of patients in these situations, emphasizing coordinated preparation among obstetrical, anesthesiology, and intensivist teams for planned preterm delivery at gestational ages when neonatal outcomes are likely to be favorable.

Obstetric Anesthetic Management for Parturients with Hereditary Angioedema: A Case Report and Suggested Protocol.

Hereditary angioedema (HAE) is a disease manifested by repeated episodes of localized submucosal or subcutaneous edematous episodes, potentially triggered by emotional stress, mechanical trauma, or intake of estrogens. We present our experience managing two parturients with HAE. Multidisciplinary care is essential for planning and executing the specialized care of these patients, and management included extensive planning among obstetric, anesthesiology, and allergy and immunology teams. Pregnancy has been shown to have a variable effect on triggering HAE episodes. First-line treatment includes C1 esterase inhibitor concentrate, which can also be used for prophylaxis in high-risk patients. Neuraxial analgesia is recommended to avoid general anesthesia and was established early in both individuals. Vaginal delivery was well tolerated without need for emergent treatment for angioedema symptoms.