scholarly journals Weighing the prognostic role of hyponatremia in hospitalized patients with metastatic solid tumors: the HYPNOSIS study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Giovanni Fucà ◽  
Luigi Mariani ◽  
Salvatore Lo Vullo ◽  
Giulia Galli ◽  
Rossana Berardi ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Serum Sodium ◽  
Tumor Development ◽  
Sodium Concentration ◽  
Prognostic Impact ◽  
Multivariable Model ◽  
Low Sodium ◽  
Extracellular Sodium

Abstract Previous works linked low sodium concentration with mortality risk in cancer. We aimed at weighing the prognostic impact of hyponatremia in all consecutive patients with metastatic solid tumors admitted in a two-years period at our medical oncology department. Patients were included in two cohorts based on serum sodium concentration on admission. A total of 1025 patients were included, of whom 279 (27.2%) were found to be hyponatremic. The highest prevalence of hyponatremia was observed in biliary tract (51%), prostate (45%) and small-cell lung cancer (38.9%). With a median follow-up of 26.9 months, median OS was 2 months and 13.2 months for the hyponatremia versus control cohort, respectively (HR, 2.65; P < 0.001). In the multivariable model, hyponatremia was independently associated with poorer OS (HR, 1.66; P < 0.001). According to the multivariable model, a nomogram system was developed and validated in an external set of patients. We weighed over time the influence of hyponatremia on survival of patients with metastatic solid tumors and pointed out the possibility to exploit serum sodium assessment to design integrated prognostic tools. Our study also highlights the need for a deeper characterization of the biological role of extracellular sodium levels in tumor development and progression.

The role of transmembrane sodium gradient in rabbit ileal smooth muscle: Utilization of harmaline

1985 ◽  
Vol 5 (8) ◽  
pp. 667-671 ◽  
Author(s):  
M. S. Suleiman
Keyword(s):  
Smooth Muscle ◽  
Contractile Response ◽  
Sodium Concentration ◽  
Exchange Mechanism ◽  
Dependent Manner ◽  
Sodium Gradient ◽  
Extracellular Sodium ◽  
Dose Dependent

Decreasing extracellular sodium concentration was found to produce a contractile response of rabbit ileal smooth muscle. As the concentration decreases, the amplitude of contraction increases, thus producing a dose-dependent curve. Harmaline, a competitor for sodium, was found to inhibit the sodium gradient-dependent contractions in a dose-dependent manner. The results are interpreted as harmaline inhibiting a Na–Ca exchange mechanism present in ileal smooth muscle.

scholarly journals Functional Characterization of Colon-Cancer-Associated Variants in ADAM17 Affecting the Catalytic Domain

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 463
Author(s):  
Jan Philipp Dobert ◽  
Anne-Sophie Cabron ◽  
Philipp Arnold ◽  
Egor Pavlenko ◽  
Stefan Rose-John ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Functional Characterization ◽  
Tumor Development ◽  
Point Mutations ◽  
Modern World ◽  
Protective Effects ◽  
Tissue Samples ◽  
Membrane Bound

Although extensively investigated, cancer is still one of the most devastating and lethal diseases in the modern world. Among different types, colorectal cancer (CRC) is most prevalent and mortal, making it an important subject of research. The metalloprotease ADAM17 has been implicated in the development of CRC due to its involvement in signaling pathways related to inflammation and cell proliferation. ADAM17 is capable of releasing membrane-bound proteins from the cell surface in a process called shedding. A deficiency of ADAM17 activity has been previously shown to have protective effects against CRC in mice, while an upregulation of ADAM17 activity is suspected to facilitate tumor development. In this study, we characterize ADAM17 variants found in tissue samples of cancer patients in overexpression studies. We here focus on point mutations identified within the catalytic domain of ADAM17 and could show a functional dysregulation of the CRC-associated variants. Since the catalytic domain of ADAM17 is the only region structurally determined by crystallography, we study the effect of each point mutation not only to learn more about the role of ADAM17 in cancer, but also to investigate the structure–function relationships of the metalloprotease.

Sodium Loading of Inner Ear Fluids

1976 ◽  
Vol 85 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Herbert Silverstein ◽  
Tiero Takeda
Keyword(s):  
Sodium Chloride ◽  
Serum Sodium ◽  
Total Concentration ◽  
Sodium Concentration ◽  
Ionic Balance ◽  
Low Sodium ◽  
Minute Period ◽  
Concentration Of Ions ◽  
Before And After ◽  
Inner Ear Fluids

A slow intracarotid infusion of hypertonic sodium chloride solution, 350 mEq/L, and potassium chloride, 5 mEq/L, was used to increase serum sodium chloride over a 90-minute period in 85 cats. A slow, steady rise in serum sodium occurred, which reached almost 208 mEq/L at the end of 90 minutes. A concomitant rise in sodium occurred in the cerebrospinal fluid and perilymph. In contrast, the sodium showed only a transient slight increase in the cochlear and vestibular endolymph. Endolymph potassium appeared to rise in order to balance out the increase in sodium concentration of the surrounding and extracellular fluids. The ratio of sodium to potassium ions in both the endolymph and perilymph compartment remained relatively constant before and after the infusion with hypertonic NaCl. After infusion, the total concentration of ions in endolymph was similar to that of perilymph. These experiments indicate that the endolymph compartment has a built-in mechanism for maintaining a low-sodium concentration while keeping ionic balance with the surrounding perilymph and serum.

Bone Marrow Small Adipocytes in Acute Myeloid Leukemia Correlate with Prognosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2874-2874
Author(s):  
Wei Lu ◽  
Jun Shi
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Solid Tumors ◽  
Myeloid Leukemia ◽  
Prognostic Impact ◽  
Biopsy Specimens ◽  
Brown Adipose ◽  
Significant Difference ◽  
Acute Myeloid

Abstract Introduction: Adipocytes have a substantial effect on the outcome and progression of certain solid tumors. However, little attention has been paid to the role of bone marrow (BM) adipocytes in acute myeloid leukemia (AML) because it is difficult to observe adipocytes through clinical BM aspiration. Although it was reported that adipocytes affected the behavior of leukemia cells in vitro, there is still no direct in vivo evidence. In the present study, we investigated the influence of adipocytes by focusing on their changing size in BM from primary AML patients. Methods: We retrospectively analyzed the biopsy specimens of BM from 70 patients with newly diagnosed AML and 70 controls with lymphoma or solid tumors without infiltration of BM. The size and type of adipocytes were analyzed for average diameter (Ad.Dm) and area (Ad.Ar) by tracing each individual adipocyte with Image-Pro Plus 5.1. Then, AML patients were further divided into 32 patients with continuous complete remission and 38 patients who were refractory based on the treatment effects. Adipocyte number (Ad.N; per square millimeter) and the percentage of adipocyte volume per tissue volume (Ad.V/TV) were compared between these two groups. Furthermore, the prognostic impact of adipocytes on the overall survival (OS) and relapse-free survival (RFS) in AML patients was analyzed by Cox regression analysis and Kaplan-Meier curves. Finally, the phenotype of adipocytes was determined by immunohistochemistry of UCP-1 and Perilipin1 to further explore the possible mechanism of the effect of adipocytes on the prognosis. Results: The Ad.Dm and Ad.Ar in BM from AML patients were 38.3±14.7 µm and 559.4±271.9 µm2, respectively, and both values were significantly smaller than those for the controls (P<0.001). The Ad.Dm exhibited no relation to the number of blasts in BM, indicating that the decreased size of adipocytes in AML cannot be attributed to extensive marrow blasts. Adipocytes were classified as small, medium and large adipocytes according to the frequency distribution of Ad.Dm in BM from controls. A significant difference was detected only in the proportion of small adipocytes (Ad.Dm<42.6 µm) between AML patients and controls (43.9% vs 25%, P=0.005). Furthermore, the Ad.V/TV and Ad.N of the adipocytes in the refractory group were 6.70±3.18% and 31.56±11.72/mm2, respectively, which were significantly higher than those of the remission subjects (P<0.001). This outcome prompted us to further analyze the role of small adipocytes in AML. Patients with Ad.V/TV of small adipocytes≤ 2.3% exhibited a longer OS than patients with Ad.V/TV of small adipocytes >2.3% (P<.001). Similarly, the subjects with Ad.N of small adipocytes <10.6/mm2 (P<.001) had a longer OS. Meanwhile, for the remission AML patients, those with Ad.V/TV of small adipocytes ≤2.5% had a shorter RFS than patients with Ad.V/TV of small adipocytes >2.5% (P<.001), and similar significant differences were also found between patients with Ad.N of small adipocytes ≥9.2/mm2 and Ad.N of small adipocytes <9.2/mm2(P<.001). In the biopsy specimens of BM, the subgroup of small adipocytes exhibited expression of Perilipin1 but not mitochondrial membrane protein UCP-1. Combination with the unilocular lipid droplets in adipocytes indicated that small adipocytes did not play a role in the conversion to brown adipose tissue. Conclusions: We first defined a subpopulation of small adipocytes in BM and demonstrated that only these cells but not all adipocytes were related to a poor prognosis in AML patients. The morphological changes of marrow adipocytes could be helpful to judge the prognosis of leukemia and could lead to other therapeutic perspectives. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic role of pretreatment blood lymphocyte count in patients with solid tumors: a systematic review and meta-analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiawen Zhao ◽  
Weijia Huang ◽  
Yongxian Wu ◽  
Yihuan Luo ◽  
Bo Wu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Solid Tumors ◽  
Clinical Outcomes ◽  
Lymphocyte Count ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Cancer Type ◽  
Hazard Ratios

Abstract Background To evaluate the prognostic value of pretreatment lymphocyte counts with respect to clinical outcomes in patients with solid tumors. Methods Systematic literature search of electronic databases (Pubmed, Embase and Web of Science) up to May 1, 2018 was carried out by two independent reviewers. We included Eligible studies assessed the prognostic impact of pretreatment lymphocytes and had reported hazard ratios (HR) with 95% confidence intervals (CIs) for endpoints including overall survival (OS) and progression-free survival (PFS). Only English publications were included. Results A total of 42 studies comprising 13,272 patients were included in this systematic review and meta-analysis. Low pretreatment lymphocyte count was associated with poor OS (HR = 1.27, 95% CI 1.16–1.39, P < 0.001, I2 = 58.5%) and PFS (HR = 1.27, 95% CI 1.15–1.40, P < 0.001, I2 = 25.7%). Subgroup analysis disaggregated by cancer type indicated that low pretreatment lymphocytes were most closely associated with poor OS in colorectal cancer followed by breast cancer and renal cancer. Conclusions Low pretreatment lymphocyte count may represent an unfavorable prognostic factor for clinical outcomes in patients with solid tumors.

scholarly journals How to Adjust the Sodium Concentration in Dialysate Individually and Practically?

2021 ◽  
Vol 1 (2) ◽  
pp. 161-163
Author(s):  
Jingjing Zhang
Keyword(s):  
Serum Sodium ◽  
Observational Studies ◽  
Serum Sodium Level ◽  
Volume Overload ◽  
Sodium Concentration ◽  
Study Data ◽  
Chronic Hemodialysis ◽  
Low Sodium ◽  
Large Cohort Study ◽  
Dialysate Sodium

The optimal dialysate sodium concentration for chronic hemodialysis patients remains controversial. Conflicting data from small observational studies and large cohort study data have not convinced nephrologists to choose either a high or low sodium dialysate. Despite a lack of evidence, I would prescribe individualized dialysate sodium concentrations for patients with a risk of hypertension or volume overload, aligning the dialysate sodium concentration with patients’ predialysis serum sodium level. The concentration of dialysate sodium would usually be 0–2 mEq/L below the patient’s serum sodium concentration. I believe that this strategy would help improve hypertension, intradialytic weight gain, cardiac outcomes, and deliver precision medicine.

scholarly journals Central pontine myelinolysis: not just a low sodium issue

2020 ◽  
Vol 23 (1) ◽  
Author(s):  
Gideon Titus ◽  
Luthando Vazi ◽  
Tholakele Sabela ◽  
Mogamat-Yazied Chothia
Keyword(s):  
Rare Complication ◽  
Central Pontine Myelinolysis ◽  
Sodium Concentration ◽  
Low Sodium ◽  
Severe Hyponatraemia ◽  
Level Of Consciousness ◽  
Pontine Myelinolysis ◽  
The Brain ◽  
Central Pontine

Osmotic demyelination syndrome is a rare complication following treatment of chronic hyponatraemia. We describe a case of a middle-aged man known with hypertension and hypothyroidism who presented with a reduced level of consciousness and a generalised convulsion. Laboratory results revealed severe hyponatraemia and hypokalaemia. Following rapid overcorrection of the serum sodium concentration, his level of consciousness remained unchanged, and he developed quadriplegia. Magnetic resonance imaging of the brain revealed central pontine myelinolysis (CPM). The patient died 3 weeks after hospitalisation. Other than rapid overcorrection of chronic hyponatraemia, this case also highlights the important role of potassium in the pathogenesis of CPM. Therefore, when severe chronic hyponatraemia is accompanied by hypokalaemia, the latter should be corrected first to further reduce the risk of CPM.

scholarly journals Dysnatremia is a predictor for morbidity and mortality in hospitalized patients with COVID-19

2021 ◽  
Author(s):  
Ploutarchos Tzoulis ◽  
Julian A Waung ◽  
Emmanouil Bagkeris ◽  
Ziad Hussein ◽  
Aiyappa Biddanda ◽  
...  
Keyword(s):  
Serum Sodium ◽  
Ventilatory Support ◽  
Kidney Injury ◽  
Length Of Hospital Stay ◽  
Fold Increase ◽  
Sodium Concentration ◽  
Prognostic Impact ◽  
Inpatient Mortality ◽  
Risk Of Death ◽  
Increased Risk

Abstract Background Dysnatremia is an independent predictor of mortality in patients with bacterial pneumonia. There is paucity of data about the incidence and prognostic impact of abnormal sodium concentration in patients with coronavirus disease 19 (COVID-19). Methods This retrospective longitudinal cohort study, including all adult patients who presented with COVID-19 to two hospitals in London over an 8-week period, evaluated the association of dysnatremia (serum sodium &lt; 135 or &gt; 145 mmol/L, hyponatremia and hypernatremia, respectively) at several timepoints with inpatient mortality, need for advanced ventilatory support and acute kidney injury (AKI). Results The study included 488 patients (median age 68 years). At presentation, 24.6% of patients were hyponatremic, mainly due to hypovolemia, and 5.3% hypernatremic. Hypernatremia two days after admission and exposure to hypernatremia at any timepoint during hospitalization were associated with a 2.34-fold (95% CI 1.08 – 5.05, p=0.0014) and 3.05-fold (95% CI 1.69 – 5.49, p&lt;0.0001), respectively, increased risk of death compared to normonatremia. Hyponatremia at admission was linked with a 2.18-fold increase in the likelihood of needing ventilatory support (95% CI 1.34-3.45, p= 0.0011). Hyponatremia was not a risk factor for in-hospital mortality, except for the subgroup of hypovolemic hyponatremia. Sodium values were not associated with the risk for AKI and length of hospital stay. Conclusion Abnormal sodium levels during hospitalization are risk factors for poor prognosis, with hypernatremia and hyponatremia being associated with a greater risk of death and respiratory failure, respectively. Serum sodium values could be used for risk stratification in patients with COVID-19.

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