A low initial serum sodium level is associated with an increased risk of overcorrection in patients with chronic profound hyponatremia: a retrospective cohort analysis

Abstract Background Even with abundant evidence for osmotic demyelination in patients with hyponatremia, the risk factors for overcorrection have not been fully investigated. Therefore the purpose of this study is to clarify the risks for overcorrection during the treatment of chronic profound hyponatremia. Methods This is a single-center retrospective observational study. We enrolled 56 adult patients with a serum sodium (SNa) concentration of ≤125 mEq/L who were treated in an intensive care unit by nephrologists using a locally developed, fixed treatment algorithm between February 2012 and April 2014. The impact of patient parameters on the incidence of overcorrection was estimated using univariable and multivariable logistic regression models. Overcorrection was defined as an increase of SNa by >10 mEq/L and >18 mEq/L during the first 24 and 48 h, respectively. Results The median age was 78 years, 48.2% were male, and 94.6% of the patients presented with symptoms associated with hyponatremia. The initial median SNa was 115 mEq/L (quartile, 111–119 mEq/L). A total of 11 (19.6%) patients met the criteria for overcorrection with 9 (16.0%) occurring at 24 h, 6 (10.7%) at 48 h, and 4 (7.1%) at both 24 and 48 h. However, none of these patients developed osmotic demyelination. Primary polydipsia, initial SNa, and early urine output were the significant risk factors for overcorrection on univariable analysis. Multivariable analysis revealed that the initial SNa had a statistically significant impact on the incidence of overcorrection with an adjusted odds ratio of 0.84 (95% confidence interval, 0.70–0.98; p = 0.037) for every 1 mEq/L increase. Additionaly, the increase in SNa during the first 4 h and early urine output were significantly higher in patients with overcorrection than in those without (p = 0.001 and 0.005, respectively). Conclusions An initial low level of SNa was associated with an increased risk of overcorrection in patients with profound hyponatremia. In this regard, the rapid increase in SNa during the first 4 h may play an important role

Unintentional Fusion in Preserved Facet Joints without Bone Grafting after Percutaneous Endoscopic Transforaminal Lumbar Interbody Fusion

Introduction: A percutaneous endoscopic transforaminal lumbar interbody fusion (PETLIF) procedure has been previously developed. During postoperative follow-up, in some patients, bone fusion occurred between opened facet joints, despite not having bone grafting in the facet joints. Here, we investigated facet fusion's frequency and tendencies following PETLIF. Methods: A retrospective analysis was conducted on a prospectively collected, nonrandomized series of patients. Forty-two patients (6 males and 36 females, average age: 69.9 years) who underwent single-level PETLIF at our hospital from February 2016 to March 2019 were included in this study. Patients were assessed with lumbar X-ray images and computed tomography (CT) prior to, immediately after, and 1 year after surgery. Results: Pseudarthrosis was not observed in any patients, and facet fusion was observed in 26 of 42 post-PETLIF patients (61.9%) by CT 1 year postoperatively. The average interfacet distance increased from 1.3 mm preoperatively to 4.5 mm postoperatively, and facet fusion was observed under the opened conditions of 3.8 mm at 1 year. Segmental lordotic angle of the fusion segment in the lumbar X-ray images was significantly larger in the facet fusion subgroup prior to surgery, immediately following surgery, and 1 year after surgery compared to the facet non-fusion group (p=0.02, p<0.01, p=0.01, respectively). There were no significant differences in patient background, correction loss of segmental lordosis, interfacet distance, or clinical score between the facet fusion and facet non-fusion subgroups. Conclusions: Facet fusion was achieved over time within the facet joints that were opened through indirect decompression after PETLIF. We hypothesized that the preserved facet joints potentially became the base bed for spontaneous bone fusion due to the preserved facet joint capsule and surrounding soft tissue, which maintained cranio-caudal facet traffic and blood circulation in the facet joints. The complete preservation of the facet joints was a key advantage of minimally invasive lumbar interbody fusion procedures

Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex

CNTNAP2 or AHI1 are autism-associated genes. Here the authors show using knockdown of the genes that this results in reduced excitatory synaptic transmission in layer 2/3 pyramidal neurons in the prefrontal cortex and is associated with impaired social interaction in mice

Acute hyperkalemia in the emergency department: a summary from a Kidney Disease: Improving Global Outcomes conference

International audienceHyperkalemia is a common electrolyte disorder observed in the emergency department. It is often associated with underlying predisposing conditions, such as moderate or severe kidney disease, heart failure, diabetes mellitus, or significant tissue trauma. Additionally, medications, such as inhibitors of the renin-angiotensin-aldosterone system, potassium-sparing diuretics, nonsteroidal anti-inflammatory drugs, succinylcholine, and digitalis, are associated with hyperkalemia. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened a conference in 2018 to identify evidence and address controversies on potassium management in kidney disease. This review summarizes the deliberations and clinical guidance for the evaluation and management of acute hyperkalemia in this setting. The toxic effects of hyperkalemia on the cardiac conduction system are potentially lethal. The ECG is a mainstay in managing hyperkalemia. Membrane stabilization by calcium salts and potassium-shifting agents, such as insulin and salbutamol, is the cornerstone in the acute management of hyperkalemia. However, only dialysis, potassiumbinding agents, and loop diuretics remove potassium from the body. Frequent reevaluation of potassium concentrations is recommended to assess treatment success and to monitor for recurrence of hyperkalemia

Changes in Metabolomic Profiles Induced by Switching from an Erythropoiesis-Stimulating Agent to a Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor in Hemodialysis Patients: A Pilot Study

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of medications for managing renal anemia in patients with chronic kidney disease (CKD). In addition to their erythropoietic activity, HIF-PHIs exhibit multifaceted effects on iron and glucose metabolism, mitochondrial metabolism, and angiogenesis through the regulation of a wide range of HIF-responsive gene expressions. However, the systemic biological effects of HIF-PHIs in CKD patients have not been fully explored. In this prospective, single-center study, we comprehensively investigated changes in plasma metabolomic profiles following the switch from an erythropoiesis-stimulating agent (ESA) to an HIF-PHI, daprodustat, in 10 maintenance hemodialysis patients. Plasma metabolites were measured before and three months after the switch from an ESA to an HIF-PHI. Among 106 individual markers detected in plasma, significant changes were found in four compounds (erythrulose, n-butyrylglycine, threonine, and leucine), and notable but non-significant changes were found in another five compounds (inositol, phosphoric acid, lyxose, arabinose, and hydroxylamine). Pathway analysis indicated decreased levels of plasma metabolites, particularly those involved in phosphatidylinositol signaling, ascorbate and aldarate metabolism, and inositol phosphate metabolism. Our results provide detailed insights into the systemic biological effects of HIF-PHIs in hemodialysis patients and are expected to contribute to an evaluation of the potential side effects that may result from long-term use of this class of drugs

Involvement of tachykinin receptors in Clostridium perfringens beta-toxin-induced plasma extravasation

1. Clostridium perfringens beta-toxin causes dermonecrosis and oedema in the dorsal skin of animals. In the present study, we investigated the mechanisms of oedema induced by the toxin. 2. The toxin induced plasma extravasation in the dorsal skin of Balb/c mice. 3. The extravasation was significantly inhibited by diphenhydramine, a histamine 1 receptor antagonist. However, the toxin did not cause the release of histamine from mouse mastocytoma cells. 4. Tachykinin NK(1) receptor antagonists, [D-Pro(2), D-Trp(7,9)]-SP, [D-Pro(4), D-Trp(7,9)]-SP and spantide, inhibited the toxin-induced leakage in a dose-dependent manner. Furthermore, the non-peptide tachykinin NK(1) receptor antagonist, SR140333, markedly inhibited the toxin-induced leakage. 5. The leakage induced by the toxin was markedly reduced in capsaicin-pretreated mouse skin but the leakage was not affected by systemic pretreatment with a calcitonin gene-related peptide receptor antagonist (CGRP(8-37)). 6. The toxin-induced leakage was significantly inhibited by the N-type Ca(2+) channel blocker, ω-conotoxin MVIIA, and the bradykinin B(2) receptor antagonist, HOE140 (D-Arg-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]-bradykinin), but was not affected by the selective L-type Ca(2+) channel blocker, verapamil, the P-type Ca(2+) channel blocker, ω-agatoxin IVA, tetrodotoxin (TTX), the TTX-resistant Na(+) channel blocker, carbamazepine, or the sensory nerve conduction blocker, lignocaine. 7. These results suggest that plasma extravasation induced by beta-toxin in mouse skin is mediated via a mechanism involving tachykinin NK(1) receptors