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Objective: We present the fifth case of candida dubliniensis meningitis in a young immunocompetent host and suggest extracorporeal membrane oxygenation (ECMO) as a potential risk factor for colonization., Methods: A 22-year-old immunocompetent female presented with a diagnosis of bacterial meningitis. Two years prior, she received ECMO for Covid-19 pneumonia complicated by viral myocarditis & Takutsobo cardiomyopathy. Following discharge, she reported headaches of increasing intensity, all refractory to treatments. Brain magnetic resonance imaging (MRI) was inconclusive. Two weeks prior to her presentation, she was admitted for worsening headaches with cranial nerve VI palsy. Lumbar puncture (LP) revealed white blood cell count (WBC) of 166 cells/μL with neutrophilic predominance and her symptoms progressed, despite 5 days of treatment with broad spectrum antibiotics. All cultures returned negative., Results: At her current presentation, repeat LP revealed 835 WBC/mm3, 225 mg/dL protein, and 4 mg/100 mL glucose. Brain MRI revealed nodular enhancement in the brainstem and communicating hydrocephalus. MRI of the lumbar spine revealed meningeal enhancement. Cerebrospinal fluid (CSF) cultures came back positive for C.dubliniensis. Treatment began with Amphotericin B and Flucytosine., Discussion: When clinical suspicion for fungal meningitis is high, repeate LP and CSF analysis is indicated to establish a definitive diagnosis and begin treatment. Additional studies are needed to confirm risk factors, like ECMO, for the colonization of C.dubliniensis, which likely predisposes individuals to invasive candidiasis., Competing Interests: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (© 2024 The Author(s).)

(1) Background: Niemann-Pick type C1 (NP-C1) is a lysosomal storage disorder that results in the defective trafficking of cholesterol and other cellular lipids in the endosomal-lysosomal pathway. This rare autosomal recessive disorder presents in three forms based on the age of onset. The adult form presents in patients greater than 15 years of age but is rarely seen after the age of 30. Common symptoms of the late adult-onset category of NP-C1 include progressive cognitive impairment and ataxia, with psychiatric and movement disorders presenting less frequently than in other forms of NP-C1. Dystonic movement disorders present most frequently, along with chorea, myoclonus, and parkinsonism. Herein, we present a rare case of NP-C1, diagnosed at age 35 with an initial symptom of supranuclear palsy. The goal of the presented case is to highlight the importance of the neurological examination and an inclusive differential diagnosis in patients with new-onset supranuclear palsy. (2) Methods: A single case report. (3) Results: A 46-year-old male with a past medical history of NP-C1 was admitted to the hospital for respiratory distress. He was noted to have a supranuclear gaze palsy with partially preserved voluntary saccades to the right. His mother revealed that he first had difficulty moving his eyes at the age of 34. After multiple consultations and genetic testing one year later, he was diagnosed with NP-C1. (4) Conclusions: Because NP-C1 affects many regions of the brain responsible for eye movements, neurological eye assessments can be a useful tool in diagnoses. Furthermore, eye movement abnormalities may be the initial presenting symptom of NP-C1, predisposing patients to misdiagnosis with progressive supranuclear palsy and other conditions that may mimic early-stage NP-C1. Definitive diagnosis is achieved through genetic testing. Filipin staining test was the gold standard in the past. The NP-C Suspicion Index was developed to assist in diagnoses, but its efficacy is unclear with late adult-onset NP-C1. Although no cure exists, early identification can facilitate an improved symptom management course for patients. Miglustat, a glucosylceramide synthase (GCS) inhibitor, is the approved therapy in Europe specific to NP-C1 for slowing and preventing the neurological manifestations of NP-C1. Delays between symptom onset and treatment initiation are likely to result in poorer outcomes and a progression of neurological symptoms. High doses may present tolerance concerns, especially in cases of delayed treatment and advanced neurological deficit.

One well-documented risk of spinal surgery is cerebrospinal fluid (CSF) leak in the immediate postoperative period. While the majority of CSF leaks occur due to an obvious intraoperative dural tear, several reports have documented delayed CSF leakage from occult intraoperative dural tears. There is a paucity of published literature regarding the true incidence of dural tears in minimally invasive spinal surgery. Furthermore, the types of dural tears that require closure are poorly understood. According to the limited existing literature available, the recommended treatment of dural tears includes primary repair, subarachnoid drainage catheters, and blood patches. However, there are no distinct treatment guidelines between the different etiologies of CSF leakage. The most important aspect in the management of CSF leakage is prevention, including preoperative risk assessment and meticulous intraoperative manipulation. One emerging treatment strategy is to alter the pressure gradient in a manner that stops CSF leakage. This method is based on one of two mechanisms: direct suture or augmented closure with dural substitute material and either reducing the subarachnoid fluid pressure or increasing the epidural space pressure. Bed rest is a key element in the treatment of persistent CSF leaks, as it can reduce the lumbar CSF pressure, thereby preventing CSF leakage. We describe the challenging case of a persistent CSF leak despite multiple attempts at direct repair, as well as our management strategies. Understanding the proper positioning techniques to reduce leakage is crucial for proper management, and orthopedic surgeons, neurosurgeons, and neurointensivists may consider being more aggressive in treating persistent CSF leaks., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Johansen et al.)

Hemiballismus is defined as irregular, involuntary, large-amplitude flinging movements by the limbs, confined to one side of the body. Hemichorea refers to a state of excessive and irregularly timed, non-repetitive and randomly distributed, spontaneous, involuntary, and abrupt movements. It is widely believed that hemiballismus and chorea are suggestive of a lesion to the basal ganglia and subthalamic nucleus (STN). However, there are other etiologies that may influence the clinical presentation. Patients may present with certain common clinical features corresponding to the affected area of the brain. For example, infarctions of the motor cortex present with hemiplegia or paralysis of one side of the body. Similarly, infarctions involving the language areas of the brain present with aphasia and are detrimental to speech production or comprehension and the ability to read and write. Typically, acute-onset hemichorea is suggestive of a lesion in the STN. Herein, we present a rare case of acute hemiballismus and hemichorea following infarction of the left caudate nucleus, as determined by magnetic resonance imaging (MRI) and computerized tomography (CT) imaging modalities., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Babici et al.)

A proatlantal intersegmental artery (PIA) is an exceedingly rare primitive anastomosis between the carotid and vertebrobasilar circulations. PIAs may be accompanied by ipsilateral or bilateral vertebral artery (VA) agenesis and can originate from the cervical internal carotid artery (ICA, type I) or external carotid artery (ECA, type II) before eventually joining the vertebrobasilar system. Several authors have described this anomaly in different clinical scenarios, but to our knowledge, there are no studies documenting VA angioplasty through a type II PIA in the setting of vertebrobasilar stroke. We present the case of vertebrobasilar stroke in which the right VA did not originate from the right subclavian artery but instead from the ECA. The patient was subsequently determined to have a type II PIA. We performed right VA angioplasty via the PIA, followed by partial restoration of vertebrobasilar blood flow. This is the first documented case of intracranial vertebral angioplasty through a type II PIA and serves as a reminder for neuroendovascular surgeons about persistent fetal circulation. In such instances, an angiogram of both the ICA and ECA should be performed to exclude right VA stenosis and visualize persistent fetal circulation. This case underscores the complexity of arterial thrombotic events, the beneficial role of endovascular intervention, and the necessity of future studies to identify the optimal treatment methods for vertebrobasilar stroke., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Babici et al.)

Background The WATCHMAN™ device is a Food and Drug Administration (FDA)-approved device that reduces the risk of stroke from atrial fibrillation (AF) in those who have a contraindication to taking oral anticoagulation. A key aspect of this device implantation is the choice of medical therapy in the months after device implantation with Vitamin K antagonist oral anticoagulants (OAC) being the mainstay of therapy but dual antiplatelet therapy (DAPT) poses as a potential alternative to patients who have a contraindication to OAC use. Methods Our single-center study retroactively followed 150 patients post-WATCHMAN™ implantation and evaluated outcomes at 12 months post-implantation in two cohorts, those treated with OAC or DAPT. Our results were obtained via chart review of a single-center electronic medical records system. Results In our study, 67.33% of study patients were males and 49.33% were on OAC compared to 36.00% that were on DAPT. Ten patients were not able to undergo device implantation. With this analysis, we found similarly low rates of complications such as stroke and device-associated thrombosis (DAT) in both groups. Our DAPT cohort did have a higher number of gastrointestinal (GI) bleeding but this was not significant in our analysis. Discussion Our study compares to larger trials that show similar outcomes between OAC and DAPT post-implantation of the WATCHMAN™ device. The increased number of GI bleeding in our DAPT cohort could be the result of the underlying advanced age and comorbidity of that patient cohort. Conclusion Our results suggest that DAPT is a safe alternative to OAC for patients undergoing WATCHMAN™ implantation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Demiraj et al.)

Acute hypoglycemia may mimic acute ischemic stroke, but to our knowledge this has never been reported as transient hemineglect syndrome. We present a 60-year-old male with known diabetes mellitus who was brought to the hospital as a stroke alert. The patient had undetectable glucose levels upon arrival of emergency medical services (EMS), therefore hypertonic glucose was given. On our assessment in the emergency department (ED)he turned his head to the right side, looking to the right to answer questions when addressed on his left side. The extinction and neglect assessment revealed left-sided extinction on double tactile and visual stimulation. CT perfusion of the brain showed a decreased perfusion in the right cortical area. Given the unclear last known normal, urgent brain magnetic resonance imaging (MRI) was performed; stroke was excluded. The patient was admitted to the Intensive Care Unit where glucose was closely monitored. Electroencephalogram showed absence of seizure or postictal activity. The following morning, the patient returned to baseline and was able to recall the event. The episode was attributed to the severe hypoglycemia because of a recent medication change., Competing Interests: Authors confirm no conflict of interests., (© 2023 Published by Elsevier B.V.)

Chloroma, is an rare malignant tumor characterized by the extramedullary blast proliferation of myeloid lineages that subsequently change the normal architecture of surrounding tissues. Because this is very rare disease, primary central nervous system myeloid sarcoma has not been widely reported. Myeloid sarcoma, as a group of heterogenetic diseases, presents with differential clinical and histological pictures depending upon the primary affected site. We are presenting a 77-year-old gentleman, with past medical history of chronic lymphoblastic leukemia that was not on any treatment and who presented with complaints of lethargy, disorientation, and weakness. CT scan of the head showed left-sided subdural hematoma with significant mass effect with left-to-right shift. Craniotomy and hematoma evacuation was performed and hematoma and subdural lesion was sent for pathological evaluation. Histologic examination of the hematoma revealed solid sheets of small-medium sized atypical hematopoietic cells that was imbedded in an acute and chronic hematoma. To confirm the final diagnosis, flow cytometry was performed and showed two neoplastic clones, consistent with acute myeloid leukemia with monocytic differentiation and a separate mature B-cell lymphoma. To our knowledge we are presenting the first case in the literature of the Intracranial acute myeloid leukemia/myeloid sarcoma and B-cell lymphoma that was found in the same brain lesion., Competing Interests: Authors confirm no conflict of interests., (© 2022 Published by Elsevier B.V.)

Ruptured intracranial aneurysms are often associated with serious neurologic sequelae, often as a result of subarachnoid or intraparenchymal hemorrhage. Less commonly, ruptured intracranial aneurysms can lead to subdural hemorrhage. However, the characteristic clinical presentation and optimal treatment of associated subdural hemorrhage are unclear due to the paucity of such cases that exist in the current literature. Affected patients may complain of nonspecific symptoms such as headaches, nausea, and confusion. Because of the severity of the disease, rapid diagnosis and intervention is required to lower the high morbidity and mortality rates. Commonly used treatment options include endovascular coiling and microsurgical clipping. Neuroendovascular surgery is often preferred, especially in aneurysms not amenable to surgical clipping, in poor surgical candidates, and cases with endovascularly favorable anatomy. The authors present the case of a patient who came to the hospital with ischemic stroke-like symptoms and was found to have a ruptured posterior communicating artery (PCoA) aneurysm and associated acute subdural hematoma (SDH) without obvious subarachnoid hemorrhage (SAH). Endovascular coiling of the aneurysm was performed successfully the following craniotomy for SDH evacuation, and the patient was discharged to a rehabilitation facility., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Babici et al.)

A tricenarian female with a past medical history of status epilepticus secondary to posterior reversible encephalopathy syndrome (PRES) of unknown etiology presented with a 2-week history of double vision, dizziness, elevated blood pressure, and altered mental status. On hospital day 2, she experienced status epilepticus, during which her blood pressure rose to 240/160 from her baseline of around 140/90. The patient was subsequently intubated for airway protection and transferred to the intensive care unit, where she was started on a nicardipine drip. Due to her history of thrombotic microangiopathy, empiric treatment with plasma exchange and prednisone was started but discontinued when ADAMTS13 came back negative. Urine metanephrines also were found to be negative. Computed tomography angiography of the abdomen showed left renal artery stenosis and stent was placed. Remarkably, over the coming days, her blood pressure normalized, and her neurologic symptoms significantly improved. As a result, antihypertensive medications were titrated down, and the patient was finally provided with a cause of her repetitive, life-threatening episodes of PRES., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Brain Circulation.)

Guillain-Barré syndrome after Pfizer and Astra-Zeneca vaccinations against COVID-19 has been previously reported in the literature. The objective of this study was to report the first case of Guillain-Barré following the COVID-19 vaccination with the Johnson & Johnson COVID-19 vaccine. We report the case of a 53-year-old female who presented to the Emergency Department complaining of bilateral lower extremity weakness, paresthesias, and gait difficulties 14 days after having received the Johnson & Johnson COVID-19 vaccination. MRI of the lumbar spine with and without contrast revealed enhancement of the cauda equina nerve roots suggestive of acute inflammatory demyelinating polyradiculoneuropathy. Cerebrospinal fluid (CSF) analysis reported mildly elevated protein low white blood cells (WBCs). Ganglioside (GM1 and GQ1b) antibodies were reported as negative. After intravenous immunoglobulin (IVIg), the patient had significant improvement in her weakness and paresthesia and was discharged home. The case was reported to the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System. Guillain-Barré syndrome after COVID-19 immunization remains a rare complication. A clear mechanism of disease has not been clarified; however, it is believed that there could be some type of molecular mimicry between the spike glycoprotein produced with the help of the vaccines and proteins in the myelin sheath., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Carranza et al.)

Metastases to the brain from primary colorectal carcinoma are rare. Existing literature describing cranial nerve palsy from metastatic colorectal cancer is scattered. To our knowledge, we are the first to describe the combination of CN deficits V, VII, and XII as the initial presentation of colorectal malignancy. The authors present the case of a patient with no past medical history who presented with multiple cranial nerve deficits of the right trigeminal, facial, and hypoglossal nerves. MRI of the brain revealed a mass in Meckel's cave, which explained the involvement of the trigeminal nerve (CN V) but not the facial (CN VII) and hypoglossal (CN XII) nerves. Further workup revealed multiple cardioembolic strokes caused by nonbacterial thrombotic endocarditis (NBTE). Extensive workup for the cause of his NBTE and subsequent cerebrovascular events revealed colorectal adenocarcinoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Babici et al.)

The expansion of indications for neurointerventional procedures, combined with the need to treat a diverse patient population, has driven a need for broader access options. Concurrent arterial and venous access is often necessary for the diagnosis and treatment of various neurovascular diseases. Although complication rates are low, life-threatening severe complications have been reported with these access methods. Moreover, venous access through traditional routes can be challenging in patients with large body habitus. There is a growing trend of utilizing radial artery access for neuroendovascular procedures due to the increased ease of access and similar efficacy. Nevertheless, the use of upper limb veins in neurointerventional procedures is still rare. Upper extremity transvenous access (UETV) has recently emerged as an alternative strategy for neurointerventionalists, but data are limited. This study reports two cases of successful combined upper extremity transvenous access (TVA) and transradial access (TRA) in the treatment of carotid artery-cavernous fistulae. Combined TRA and UETV is a feasible, promising access strategy for patients and may also confer the same safety and patient satisfaction outcomes that have been seen with TRA. Further studies are needed to elucidate the exact impact this strategy has on patient outcomes and satisfaction., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Babici et al.)

Current guidelines do not include radiologic assessment of the carotid arteries before catheter ablation procedures. There are multiple studies describing the risks of periprocedural cardioembolic strokes during cardiac ablation procedure but none describing the risks of periprocedural watershed strokes due to hypoperfusion during cardiac ablation. It is critically important for neurologists, cardiologists, and all other associated health-care workers to recognize the risks of neurologic complications, such as watershed strokes, before cardiac procedures are performed. We are presenting an 84-year-old male who presented to the emergency room with complaints of vision changes after a cardiac ablation procedure for atrial fibrillation. He described spotty vision with decreased visual acuity in both eyes. Magnetic resonance imaging of the brain showed multiple strokes bilaterally. Based on the radiologic features, all the strokes happened at approximately the same time. Of note, subsequent computed tomography angiography of the head and neck showed 65%-70% bilateral stenosis of the internal carotid arteries., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Brain Circulation.)

The surgical plan and the anesthetic approach are vital in determining the proper treatment of lumbar disc herniation in pregnancy. The diagnostic tools available, as well as the anesthetic agents and methods of delivery, vary in pregnant patients due to factors such as radiation exposure and hemodynamics in the patient and fetus. The gestational age also plays an important role in determining treatment options. When possible, surgery should be avoided during the first trimester, especially during the period of organogenesis, as general anesthesia can interfere with this process. However, when focal neurological deficits are present, urgent surgical decompression may be necessary. In such cases, the selection of anesthesia must be guided by maternal indications and the nature of the surgery. Maternal safety and avoidance of fetal hypoxia and subsequent preterm labor are crucial when pregnant patients receive anesthesia. As a result, local anesthesia is often preferred when possible due to the decreased risk of systemic toxicity. Decompression surgery in pregnant females with lumbar disc herniation, using a multidisciplinary approach among the surgeon, obstetrician, and anesthesiologist, is an effective and safe procedure for both the mother and the fetus. We present the case of a pregnant female at four weeks of gestation who presented with lower back pain radiating down her right leg. MRI of the lumbar spine showed large L4-5 disc herniation. She underwent a successful right L4-5 microdiscectomy under local anesthesia and spinal block using bupivacaine and was completely awake throughout the procedure. Postoperatively, she experienced immediate improvement of symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Babici et al.)

Anterior cervical discectomy and fusion (ACDF) is a common treatment modality that has shown good clinical results in patients with cervical degenerative disc disease. ACDF remains the procedure of choice for most patients given its satisfactory clinical outcomes and proven radiological fusion ranging from 90-100%. Five-level ACDF is a very rare type of surgery, even in large spine centers. This type of procedure is unique because, beyond three or four levels, the surgeon needs to switch from a transverse incision to a longitudinal incision along the medial sternocleidomastoid (SCM) muscle border, which is less preferred for cosmetic reasons. Another reason why this procedure is seldom performed is that extreme multilevel ACDF is associated with higher complication and failure rates. Literature covers one, two, and three-level anterior surgeries, but there are few studies reporting the outcomes of five-level ACDF. In the few studies that do report five-level ACDF, the data is controversial. Some studies show the risk of adjacent-segment disease increasing with a higher number of fused levels and increasing incidences of reoperation. Other studies show no changes in the risk of adjacent segment disease in multilevel ACDF in comparison with single-level ACDF. One study even showed a decreased level of adjacent-segment disease and reoperation rates in multilevel ACDF when compared to single-level ACDF. To contribute to current knowledge, we share our experience with five-level ACDF. We report the case of a 63-year-old female who presented with complaints of progressively worsening weakness in the upper extremities. MRI of her cervical spine demonstrated multilevel degenerative disc disease throughout C3-T1 with reversal of normal lordosis and a kyphotic deformity. We performed a successful ACDF at C3-T1 as well as partial corpectomy of the C5 and C6 vertebrae. We did it through a standard transverse incision from the midline to the medial border of the SCM within a preexisting neck crease, demonstrating that in select patients, extreme multilevel ACDF can be performed with proper anatomical dissection and without the need for multiple or longitudinal incisions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Babici et al.)

The spine is the third most common site for metastatic disease following the lung and the liver. Approximately 60-70% of patients with metastatic cancer will have metastasis to the spine, but only 10% of these will be symptomatic. Metastases to the spine may involve the bone, epidural space, or the spinal cord. While chemotherapy and radiation therapy are the primary treatments for metastatic disease, spinal cord compression is an indication for surgical intervention. For vertebral body lesions, anterior vertebral reconstruction and stabilization also have the advantage of providing immediate stability to the vertebral column, but this anterior surgical approach to the upper thoracic spine is fraught with complications. The approach typically involves some combination of thoracotomy, sternotomy, or clavicle resection with anterior dissection into the superior mediastinum. To avoid unnecessary sternotomy and its associated complications, surgical access without sternotomy can be performed in certain cases. A sagittal MRI scan of the spine can be used to evaluate the level of the sternal notch in relation to the upper thoracic spine. If a tangential line can be drawn superior to the sternal notch and inferior to the level of the involved vertebra, surgical access without sternotomy can be performed. We present a case of a 52-year-old female with metastases to the upper thoracic vertebrae who underwent successful T2 corpectomy and T1-3 anterior fusion via a low anterior cervical approach, without sternotomy or clavicle resection., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Babici et al.)

Dural arteriovenous fistulas (dAVF) are rare, acquired intracranial arteriovenous malformations consisting of a pathological shunt located within the intracranial dura matter. The etiology of dAVFs remains unclear, but current thought suggests that these lesions are associated with thrombosis of the dural sinuses and other intracranial veins. dAVF's with severe symptomatology or high-risk angioarchitecture should be treated without delay, and endovascular repair is generally accepted as the first-line treatment. Both transarterial and transvenous approaches can be used to cure dAVFs. Surgery and stereotactic radiosurgery may also be used when endovascular approaches are unsuccessful or not feasible. Some studies, however, have shown that surgery for dAVFs in the anterior cranial fossa is preferred over the endovascular approach. Due to the proximity of some dAVFs to the orbit, endovascular embolization of the dAVF carries a higher risk of complications, primarily due to the formation of dangerous extracranial or intracranial anastomoses. We present the case of a 64-year-old male with an incidentally discovered Borden type III dAVF arising from the anterior branches of the middle meningeal artery and draining into the middle cerebral vein. Due to the location of his dAVF, craniotomy was selected for ligation of the fistula. The procedure went without complication. A catheter angiogram of the brain one month after surgery showed an absence of flow through the arteriovenous fistula and a middle meningeal artery that had returned to its normal caliber., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Babici et al.)

Protection against increased vascular stiffness in young women is lost after menopause. However, little is known about vascular stiffness in older, premenopausal females, because most of the prior work has been conducted in rodents, which live for only 1-3 yr and do not go through menopause. The goal of the current investigation was to quantitate differences in stiffness down the aortic tree and the mechanisms mediating those differences in older, premenopausal (24 ± 0.7 yr) versus young adult (7 ± 0.7 yr) female nonhuman primates. Aortic stiffness (β), calculated from direct and continuous measurements of aortic diameter and pressure in chronically instrumented, conscious macaque monkeys, increased 2.5-fold in the thoracic aorta and fivefold in the abdominal aorta in old premenopausal monkeys. The aortic histological mechanisms mediating increased vascular stiffness, i.e., collagen/elastin ratio, elastin, and collagen disarray, and the number of breaks in elastin and collagen fibers were greater in the old premenopausal versus young monkeys and greater in the abdominal versus the thoracic aorta and greatest in the iliac artery. In addition, more immature and less cross-linked fibers of collagen were found in the aortas of young females. Aortic stiffness increased in old premenopausal female monkeys, more so in the abdominal aorta than in the thoracic aorta. Histological mechanisms mediating the increased aortic stiffness were augmented in the old premenopausal females, greater in the abdominal versus the thoracic aorta, and greatest in the iliac artery. NEW & NOTEWORTHY This is the first study to examine vascular stiffness down the aortic tree in aging premenopausal females (24 ± 0.7 yr old), whereas prior work studied mainly rodents, which are short-lived and do not undergo menopause. Histological mechanisms mediating vascular stiffness in older premenopausal females increased progressively down the aortic tree, with greater increases in the abdominal aorta compared with the thoracic aorta and with the greatest increases and differences observed in the iliac artery.

The goal of this investigation was to compare the effects of chronic (4 wk) transverse aortic constriction (TAC) in Sprague-Dawley rats and C57BL/6J mice. TAC, after 1 day, induced similar left ventricular (LV) pressure gradients in both rats ( n = 7) and mice ( n = 7) (113 ± 5.4 vs. 103 ± 11.5 mmHg), and after 4 wk, the percent increase in LV hypertrophy, as reflected by LV/tibial length (51% vs 49%), was similar in rats ( n = 12) and mice ( n = 12). After 4 wk of TAC, LV systolic and diastolic function were preserved in TAC rats. In contrast, in TAC mice, LV ejection fraction decreased by 31% compared with sham, along with increases in LV end-diastolic pressure (153%) and LV systolic wall stress (86%). Angiogenesis, as reflected by Ki67 staining of capillaries, increased more in rats ( n = 6) than in mice ( n = 6; 10 ± 2 vs. 6 ± 1 Ki67-positive cells/field). Myocardial blood flow fell by 55% and coronary reserve by 28% in mice with TAC ( n = 4), but they were preserved in rats ( n = 4). Myogenesis, as reflected by c-kit-positive myocytes staining positively for troponin I, is another mechanism that can confer protection after TAC. However, the c-kit-positive cells in rats with TAC were all negative for troponin I, indicating the absence of myogenesis. Thus, rats showed relative tolerance to severe pressure overload compared with mice, with mechanisms involving angiogenesis but not myogenesis.

Sex differences are an important component of National Institutes of Health rigor. The goal of this investigation was to test the hypothesis that female mice have greater exercise capacity than male mice, and that it is due to estrogen, nitric oxide, and myosin heavy chain expression. Female C57BL6/J wild-type mice exhibited greater ( P < 0.05) maximal exercise capacity for running distance (489 ± 15 m) than age-matched male counterparts (318 ± 15 m), as well as 20% greater work to exhaustion. When matched for weight or muscle mass, females still maintained greater exercise capacity than males. Increased type I and decreased type II myosin heavy chain fibers in the soleus muscle from females are consistent with fatigue resistance and better endurance in females compared with males. After ovariectomy, female mice no longer demonstrated enhanced exercise, and treatment of male mice with estrogen resulted in exercise capacity similar to that of intact females (485 ± 37 m). Nitric oxide synthase, a downstream target of estrogen, exhibited higher activity in female mice compared with male mice, P < 0.05, whereas ovariectomized females exhibited nitric oxide synthase levels similar to males. Nitric oxide synthase activity also increased in males treated with chronic estrogen to levels of intact females. Nitric oxide synthase blockade with N ω -nitro-l-arginine methyl ester eliminated the sex differences in exercise capacity. Thus estrogen, nitric oxide, and myosin heavy chain expression are important mechanisms mediating the enhanced exercise performance in females.

Background: Elderly patients with advanced chronic kidney disease require accurate outcome descriptions to make treatment decisions., Methods: The PSPA [Parcours de soins des personnes âgées (Treatment pathways for elderly patients)] prospective multicentre cohort study included 573 such patients with a median age of 82 [interquartile range (IQR) 79-86] years and a median estimated glomerular filtration rate of 14 (IQR 11-17) mL/min/1.73 m2 and studied their 5-year outcomes according to the dialysis component of their treatment plans., Results: Mean follow-up for the overall cohort was 34.5 ± 21 months and the 5-year survival rate was 27%. During follow-up, 288 (50%) patients started dialysis and 237 (42%) died before dialysis. At baseline, the four possible dialysis plans were dialysis when needed (38%), stable without mention of a dialysis plan (40%) and dialysis specifically excluded by the patient's (9%) or nephrologist's decision (12%). These baseline plans were associated with death and dialysis start. Follow-up plans were those decided during the study period: dialysis when needed for 47%, stable without mention of a dialysis plan for 20% and dialysis excluded at any time for 32%. For the subgroup of patients who started dialysis, those whose follow-up plan was dialysis started under better conditions than those who had stable or no dialysis follow-up plans before starting. However, survival afterwards did not differ significantly., Conclusions: These findings indicate that nephrology care should accommodate changes over time in older patients' treatment preferences and plans concerning dialysis. These changes are associated with whether, when and how these patients initiate dialysis but are not necessarily associated with post-dialysis survival.

Background: Renal myofibroblast infiltration has been shown to be strongly associated with renal function decline in several chronic renal diseases. The purpose of the present study was to investigate whether early detection of myofibroblast infiltration using alpha-smooth-muscle actin (alpha-SMA) expression in time-zero biopsies predicts renal allograft dysfunction., Methods: We studied renal tissue from 38 renal transplant patients from whom biopsies had been taken after vascular anastomosis during transplantation to ascertain whether myofibroblasts infiltration predicts renal graft survival. Immunohistochemistry was performed on time-zero biopsies to determine alpha-SMA expression, and this was compared to annual glomerular filtration rate (GFR) variation and other parameters including cold ischaemic time (CIT), donor and recipient age, number of acute rejections, and delayed graft function (DGF). GFR was measured by inulin clearance during of 3 years of follow-up after the transplantation. Progressors were defined as patients with an annual GFR decline >5 ml/min/year., Results: We found a significant correlation between interstitial alpha-SMA expression in time-zero biopsies and GFR evolution during the post-transplantation course (r=0.60, P<0.001). Although progressors had greater interstitial alpha-SMA expression than non progressors (7.9+/-0.7 vs 4.3+/-0.4%), they showed only a tendency towards higher glomerular alpha-SMA expression. In addition, progressors had more interstitial fibrosis in time-zero biopsies than non-progressors. There was no relationship between alpha-SMA expression and CIT, donor and recipient ages, number of acute rejections, and occurrence of DGF., Conclusion: This study suggests that alpha-SMA evaluation in time-zero biopsies, especially the combination of alpha-SMA expression and interstitial fibrosis, can strongly predict chronic renal allograft dysfunctions.