Endovascular Treatment of Cerebrovascular Lesions Using Nickel- or Nitinol-Containing Devices in Patients with Nickel Allergies.

Nickel is used in many cerebral endovascular treatment devices. However, nickel hypersensitivity is the most common metal allergy, and the relative risk of treatment in these patients is unknown. This retrospective analysis identified patients with nickel or metal allergies who underwent cerebral endovascular treatment with nickel-containing devices. Seven patients with nickel and/or other metal allergies underwent treatment with 9 nickel-containing devices. None experienced periprocedural complications. No patient received treatment with corticosteroids or antihistamines. At a mean clinical follow-up for all patients of 22.8 months (range, 10.5-38.0 months), no patients had symptoms attributable to nickel allergic reactions. The mean radiographic follow-up for all patients at 18.4 months (range, 2.5-37.5 months) showed successful treatment of the targeted vascular pathologies, with no evidence of in-stent stenosis or other allergic or hypersensitivity sequelae. The treatment of cerebrovascular lesions with a nickel-containing device resulted in no adverse outcomes among these patients and was safe and effective.

Emergency Department Visits for Chronic Subdural Hematomas within 30 Days after Surgical Evacuation with and without Middle Meningeal Artery Embolization.

BACKGROUND AND PURPOSE: Middle meningeal artery embolization after surgical evacuation of a chronic subdural hematomas is associated with fewer treatment failures than surgical evacuation. We compared emergency department visits within 30 days for patients with chronic subdural hematomas with and without adjunctive middle meningeal artery embolization. MATERIALS AND METHODS: All cases of chronic subdural hematoma treated from January 1, 2018, through December 31, 2020, were retrospectively reviewed. Treatment was classified as surgery only or surgery combined with middle meningeal artery embolization. The primary outcome was 30-day emergency department presentation and readmission. RESULTS: Of 137 patients who met the study criteria, 28 (20%) underwent surgery combined with middle meningeal artery embolization. Of these 28 patients, 15 (54%) underwent planned middle meningeal artery embolization and 13 (46%) underwent embolization after surgical failure. The mean chronic subdural hematoma size at presentation in the group with surgery only (n = 109, 20.5 [SD, 6.9] mm) was comparable with that in the combined group (n = 28, 18.7 [SD, 4.5] mm; P = .16). A significantly higher percentage of the surgery-only group presented to the emergency department within 30 days compared with the combined group (32 of 109 [29%] versus 2 of 28 [7%] patients; P = .02). No significant difference was found with respect to readmission (16 [15%] versus 1 [4%] patient; P = .11). Nine patients (8%) in the surgery-only group were readmitted for significant reaccumulation or residual subdural hematoma compared with only 1 patient (4%) in the combined group (P = .40). CONCLUSIONS: Surgical evacuation combined with middle meningeal artery embolization in patients with chronic subdural hematoma is associated with fewer 30-day emergency department visits compared with surgery alone.

Outcome of children requiring intensive care following haematopoietic SCT for primary immunodeficiency and other non-malignant disorders.

Haematopoietic SCT (HSCT) is curative for many children with primary immunodeficiencies or other non-malignant conditions. Outcome for those admitted to intensive care following HSCT for oncology diagnoses has historically been very poor. There is no literature available specifically regarding the outcome for children with primary immunodeficiency requiring intensive care following HSCT. We reviewed our post-HSCT admission to intensive care over a 5-year period. A total of 111 children underwent HSCT. Median age at transplant was 1 year 4 months. The most common diagnosis was SCID. In all, 35% had at least one intensive care admission and 44% survived to be discharged from intensive care. Also, 73% of admission episodes requiring invasive ventilation but no inotropes or renal replacement therapy resulted in survival to discharge. Children undergoing HSCT for immunological diagnoses had a high rate of admission to intensive care. No factors were identified that could predict the need for admission. Invasive ventilation alone has a much better outcome than that in historical series. However, the need for multi-organ system support was still associated with a poor outcome. This information is useful when counselling families of children that have deteriorated and been admitted to intensive care during the HSCT procedure.

Differential regulation of Cl- transport proteins by PKC in Calu-3 cells.

Cl- transport proteins expressed in a Calu-3 airway epithelial cell line were differentiated by function and regulation by protein kinase C (PKC) isotypes. mRNA expression of Cl- transporters was semiquantitated by RT-PCR after transfection with a sense or antisense oligonucleotide to the PKC isotypes that modulate the activity of the cystic fibrosis transmembrane conductance regulator [CFTR (PKC-epsilon)] or of the Na/K/2Cl (NKCC1) cotransporter (PKC-delta). Expression of NKCC1 and CFTR mRNAs and proteins was independent of antisense oligonucleotide treatment. Transport function was measured in cell monolayers grown on a plastic surface or on filter inserts. With both culture methods, the antisense oligonucleotide to PKC-epsilon decreased the amount of PKC-epsilon and reduced cAMP-dependent activation of CFTR but not alpha(1)-adrenergic activation of NKCC1. The antisense oligonucleotide to PKC-delta did not affect CFTR function but did block alpha(1)-adrenergic activation of NKCC1 and reduce PKC-delta mass. These results provide the first evidence for mRNA and protein expression of NKCC1 in Calu-3 cells and establish the differential regulation of CFTR and NKCC1 function by specific PKC isotypes at a site distal to mRNA expression and translation in airway epithelial cells.

PKC signaling in CF/T43 cell line: regulation of NKCC1 by PKC-delta isotype.

Cystic fibrosis (CF) airway epithelial cells have a reduced mass of ether-linked diacylglycerols which might alter protein kinase C (PKC)-regulated Cl secretion. PKC regulation of basolateral Na-K-2Cl cotransport (NKCC1) was investigated in CF nasal polyp epithelial cells and a CF/T43 cell line to ascertain whether PKC signaling was altered in CF. NKCC1 was detected as bumetanide-sensitive (86)Rb influx. Methoxamine, a alpha(1)-adrenergic agonist, increased PKC activity in cytosol and a particulate fraction for a prolonged time period, as predicted from previous studies on the generation of diglycerides induced with methoxamine. Short-term stimulation of CF/T43 cells for 40 s promoted a shift in PKC-delta and -zeta to a particulate fraction, increased activity of immune complexes of cytosolic PKC-delta and of particulate PKC-zeta and increased activity of NKCC1. Pretreatment with antisense oligonucleotide to PKC-delta blocked methoxamine-stimulated PKC-delta activity, reduced PKC-delta mass by 61.4%, and prevented methoxamine-stimulated activity of NKCC1. Sense and missense oligonucleotide to PKC-delta and antisense oligonucleotide to PKC-zeta did not alter expression of PKC-delta or the effects of methoxamine. These results demonstrate that PKC-delta-dependent activation of NKCC1 is preserved in CF cells and suggest that regulation of NKCC1 is independent of low ether-linked diglyceride mass.

Antisense oligonucleotide to PKC-epsilon alters cAMP-dependent stimulation of CFTR in Calu-3 cells.

Protein kinase C (PKC) regulates cystic fibrosis transmembrane conductance regulator (CFTR) channel activity but the PKC signaling mechanism is not yet known. The goal of these studies was to identify PKC isotype(s) required for control of CFTR function. CFTR activity was measured as 36Cl efflux in a Chinese hamster ovary cell line stably expressing wild-type CFTR (CHO-wtCFTR) and in a Calu-3 cell line. Chelerythrine, a PKC inhibitor, delayed increased CFTR activity induced with phorbol 12-myristate 13-acetate or with the cAMP-generating agents (-)-epinephrine or forskolin plus 8-(4-chlorophenylthio)adenosine 3',5'- cyclic monophosphate. Immunoblot analysis of Calu-3 cells revealed that PKC-alpha, -betaII, -delta, -epsilon, and -zeta were expressed in confluent cell cultures. Pretreatment of cell monolayers with Lipofectin plus antisense oligonucleotide to PKC-epsilon for 48 h prevented stimulation of CFTR with (-)-epinephrine, reduced PKC-epsilon activity in unstimulated cells by 52.1%, and decreased PKC-epsilon mass by 76.1% but did not affect hormone-activated protein kinase A activity. Sense oligonucleotide to PKC-epsilon and antisense oligonucleotide to PKC-delta and -zeta did not alter (-)-epinephrine-stimulated CFTR activity. These results demonstrate the selective regulation of CFTR function by constitutively active PKC-epsilon.