High serum sodium predicts immunotherapy response in metastatic renal cell and urothelial carcinoma.

OBJECTIVES: The development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) remains an unresolved challenge. Conventional ICI biomarkers typically focus on tumor-related factors such as PD-L1 expression. However, a comprehensive evaluation of the predictive value of serum electrolyte levels, a so far widely unexplored area, is still pending. METHODS: We conducted a post-hoc analysis of baseline sodium, potassium, chloride, magnesium and calcium levels in two independent phase 3 clinical trials: IMvigor211 for mUC comparing atezolizumab to chemotherapy, and IMmotion151 for mRCC comparing atezolizumab+bevacizumab to sunitinib. This analysis aimed to evaluate the prognostic and predictive value of these electrolyte levels in these clinical settings. A total of 1787 patients (IMvigor211 n = 901; IMmotion151 n = 886) were analyzed. RESULTS: We found a linear correlation of baseline serum sodium and chloride with prognosis across both trials, which was not found for potassium, magnesium and calcium. In multivariate analysis, the prognostic capacity of sodium was limited to patients receiving ICI as compared to the control group. Interestingly, in both studies, the chance of achieving an objective response was highest in the patient subgroup with high baseline serum sodium levels of > 140 mmol/L (IMmotion151: Complete response in 17.9% versus 2.0% in patients with mRCC with baseline sodium < 135 mmol/L). Serum sodium outperformed tumor PD-L1 expression as a predictor for immunotherapy efficacy. CONCLUSIONS: Patients exhibiting elevated serum sodium levels derive the greatest benefit from immunotherapy, suggesting that baseline serum concentration could serve as a valuable and cost-effective predictive biomarker for immunotherapy across entities.

Impact of serum sodium concentrations, and effect modifiers on mortality in the Irish Health System.

BACKGROUND: Abnormalities of serum sodium are associated with increased mortality risk in hospitalised patients, but it is unclear whether, and to what extent other factors influence this relationship. We investigated the impact of dysnatraemia on total and cause-specific mortality in the Irish health system while exploring the concurrent impact of age, kidney function and designated clinical work-based settings. METHODS: A retrospective cohort study of 32,666 participants was conducted using data from the National Kidney Disease Surveillance System. Hyponatraemia was defined as < 135 mmol/L and hypernatraemia as > 145 mmol/L with normal range 135-145 mmol/L. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR's) and 95% Confidence Intervals (CIs) while penalised spline models further examined patterns of risk. RESULTS: There were 5,114 deaths (15.7%) over a median follow up of 5.5 years. Dysnatraemia was present in 8.5% of patients overall. In multivariable analysis, both baseline and time-dependent serum sodium concentrations exhibited a U-shaped association with mortality. Hyponatremia was significantly associated with increased risk for cardiovascular [HR 1.38 (1.18-1.61)], malignant [HR: 2.49 (2.23-2.78)] and non-cardiovascular/non-malignant causes of death [1.36 (1.17-1.58)], while hypernatremia was significantly associated with cardiovascular [HR: 2.16 (1.58-2.96)] and non-cardiovascular/ non-malignant deaths respectively [HR: 3.60 (2.87-4.52)]. The sodium-mortality relationship was significantly influenced by age, level of kidney function and the clinical setting at baseline (P < 0.001). For hyponatraemia, relative mortality risks were significantly higher for younger patients (interaction term P < 0.001), for patients with better kidney function, and for patients attending general practice [HR 2.70 (2.15-3.36)] than other clinical settings. For hypernatraemia, age and kidney function remained significant effect modifiers, with patients attending outpatient departments experiencing the greatest risk [HR 9.84 (4.88-18.62)] than patients who attended other clinical locations. Optimal serum sodium thresholds for mortality varied by level of kidney function with a flattening of mortality curve observed for patients with poorer kidney function. CONCLUSION: Serum sodium concentrations outside the standard normal range adversly impact mortality and are associated with specific causes of death. The thresholds at which these risks appear to vary by age, level of kidney function, and are modified in specific clinical settings within the health system.

Retrospective analysis of patients diagnosed with severe hyponatraemia in the emergency department.

Background . We investigated the demographic, aetiological and clinical characteristics of patients who presented to the emergency department and had severe hyponatraemia. Methods . We retrospectively evaluated 1171 patients who presented to the emergency department and were diagnosed with severe hyponatraemia. Results . Over half the patients studied were women (53.5%). The mean age of women was higher (p<0.0001). The most common complaint was dyspnoea (16.8%) and 42.5% of the patients had an oral intake disorder. In addition, 22.3% of the patients were on loop diuretics. About 76.3% of patients were conscious, and the mean sodium level of these patients was higher than the mean sodium level of those who responded to verbal and painful stimuli (p<0.001). Severe isolated hyponatraemia was observed in 61.8% of the patients. The mortality rate was 12.8%. There was no difference between the mean sodium levels of the deceased and discharged patients (p=1.0). The mortality rate was higher in patients who had a history of cirrhosis and cancer, but was lower in patients with a history of coronary artery disease (p=0.0002, p<0.0001 and p=0.04, respectively). Conclusion . Severe hyponatraemia was more prevalent in women, serum sodium levels were higher in conscious patients, and the mortality rate was higher in patients who had a history of cirrhosis and cancer. We found that the mean serum sodium levels did not help in distinguishing between the deceased and discharged patients.

Whole-brain metabolic pattern analysis in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis.

BACKGROUND AND PURPOSE: Faciobrachial dystonic seizures (FBDS) and hyponatremia are the distinct clinical features of autoimmune encephalitis (AE) caused by antibodies against leucine-rich glioma-inactivated 1 (LGI1). The present study aims to explore the pathophysiological patterns and neural mechanisms underlying these symptoms. METHODS: We included 30 patients with anti-LGI1 AE and 30 controls from a retrospective observational cohort. Whole-brain metabolic pattern analysis was performed to assess the pathological network of anti-LGI1 AE, as well as the symptom networks associated with FBDS. Logistic regression was applied to explore independent predictors of FBDS. Finally, we used a multiple regression model to investigate the hyponatremia-associated brain network and its effect on serum sodium levels. RESULTS: The pathological network of anti-LGI1 AE involved hypermetabolism in the cerebellum, subcortical structures and Rolandic area, as well as hypometabolism in the medial prefrontal cortex. The symptom network of FBDS included hypometabolism in the cerebellum and Rolandic area (pFDR <0.05). Hypometabolism in the cerebellum was an independent predictor of FBDS (p < 0.001). Hyponatremia-associated network highlighted a negative effect on the caudate nucleus, frontal and temporal white matter. The metabolism of the hypothalamus was negatively associated with (Pearson's R = -0.180, p = 0.342), while not the independent predictor for serum sodium level (path c' = -7.238, 95% confidence interval = -30.947 to 16.472). CONCLUSIONS: Our results provide insights into the whole-brain metabolic patterns of patients with anti-LGI1 AE, including the symptom network associated with FBDS and the hyponatremia-associated brain network. The findings help us to understand the neural mechanisms underlying anti-LGI1 AE and to evaluate the progress of this disease.

The relationship between B-cell lymphoma 2, interleukin-1ß, interleukin-17, and interleukin-33 and the development of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is among the main complications of diabetes mellitus and has been a major factor of renal failure. This study was designed to address the association between beta-cell lymphoma-2 (Bcl-2), interleukin (IL)-1ß, IL-17, and IL-33 and the development of DN. METHODS: In this study, 20 healthy volunteers and 100 patients were enrolled. According to their biochemical markers, the patients were categorized into five groups: diabetic, chronic renal disease, diabetic chronic renal disease, end-stage renal disease, and diabetic end-stage renal disease. RESULTS: Our results showed a noticeable elevation in IL-1ß and IL-17 levels and a reduction in IL-33 and Bcl-2 levels in all investigated groups compared with those in the healthy group. Positive correlations were found between IL-1ß and fasting blood sugar and between creatinine levels and IL-17, HbA1c%, and sodium levels. However, negative correlations were found between IL-33 and urea and sodium concentrations and between Bcl-2 and HbA1c% and creatinine levels. CONCLUSIONS: The present data revealed a marked relationship between Bcl-2, IL-1ß, IL-17, and IL-33 levels and the onset and progression of DN. Understanding the molecular pathways of these processes could be translated into the development of therapeutic strategies.

Decreased Iron Ion Concentrations in the Peripheral Blood Correlate with Coronary Atherosclerosis.

(1) Background: Obesity and diabetes continue to reach epidemic levels in the population with major health impacts that include a significantly increased risk of coronary atherosclerosis. The imbalance of trace elements in the body caused by nutritional factors can lead to the progression of coronary atherosclerosis. (2) Methods: We measured the concentrations of sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), Zinc (Zn), and iron (Fe) in peripheral blood samples from 4243 patients and performed baseline analysis and propensity matching of the patient datasets. The patients were grouped into acute myocardial infarction (AMI, 702 patients) and stable coronary heart disease (SCAD1, 253 patients) groups. Both of these groups were included in the AS that had a total of 1955 patients. The control group consisted of 2288 patients. The plasma concentrations of calcium, magnesium, and iron were measured using a colorimetric method. For comparison, 15 external quality assessment (EQA) samples were selected from the Clinical Laboratory Center of the Ministry of Health of China. SPSS software was used for statistical analysis. The average values and deviations of all of the indicators in each group were calculated, and a p-value threshold of <0.05 was used to indicate statistical significance. (3) Results: The iron ion concentrations of the acute myocardial infarction (AMI) group were significantly lower than the control group (p < 0.05, AUC = 0.724, AUC = 0.702), irrespective of tendency matching. Compared to the data from the stable coronary artery disease (SCAD) group, the concentration of iron ions in the acute myocardial infarction group was significantly lower (p < 0.05, AUC = 0.710, AUC = 0.682). Furthermore, the iron ion concentrations in the (AMI + SCAD) group were significantly lower (p < 0.05) than in the control group. (4) Conclusions: The data presented in this study strongly indicate that the concentration of iron ions in the peripheral blood is related to coronary atherosclerosis. Decreases in the levels of iron ions in the peripheral blood can be used as a predictive biomarker of coronary atherosclerosis.

Excess serum Na level in rats administered with high doses of (-)-epigallocatechin gallate-casein nanoparticles prepared with sodium caseinate.

(-)-Epigallocatechin gallate (EGCG)-incorporated casein nanoparticles benefit from excellent antioxidant, anti-inflammatory and anti-cancer activities due to their synergistic efficiency, but few studies have evaluated their safety. In this study, the EGCG-casein nanoparticles (EGCG-NPs) formulated using caseinate by ultrasonic treatment were evaluated for their subacute toxicity. The subacute toxicity test of EGCG-NPs through 28-day oral administration in rats did not exhibit adverse effect, with a no-observed-adverse-effect level (NOAEL) of at least 5.0 g per kg body weight (BW) per day, which was equivalent to 500 mg per kg BW EGCG per day. However, the serum Na level in females and males treated with 10.0 g per kg BW EGCG-NPs increased significantly as compared to the control rats (P < 0.05). Similar indications appeared in rats treated with 10.0 g per kg BW pure casein nanoparticles without EGCG, which indicated that high doses of caseinate nanoparticles result in an excess serum Na level. Therefore, we should consider the safety of the nanoparticle formulation of caseinate when it is used as a loading nutrient and a functional substance in foods.

Relationships between sodium levels, haemodynamics and metalloproteinases in heart failure patients.

To estimate the associations between dysnatraemia and inflammatory marker [including interleukin-6 (IL-6)], and tissue remodelling marker [matrix metalloproteinase (MMP)-9 and tissue inhibitor of MMP (TIMP)-1], the pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure (PAP), and left ventricular end-diastolic pressure (EDP), and the prognostic relevance in patients with heart failure. The serum sodium level and circulating levels of IL-6, MMP-9, and TIMP-1 were measured in 173 heart failure patients. Dual heart catheterisation was performed to measure PCWP, mean PAP, and EDP. All-cause mortality was assessed during the follow-up period (mean 88 ± 49 months). Restricted cubic spline (RCS) regression showed a U-shaped association of serum sodium level with TIMP-1, with the lowest values in the 138-140 mmol/L range (P for effect = 0.042, P for non-linearity = 0.017). IL-6 and MMP-9 levels showed non-significant associations with serum sodium level. U-shaped associations of serum sodium level with PCWP (P for effect = 0.004, P for non-linearity = 0.001) and mean PAP (P for effect = 0.042, P for non-linearity = 0.017) were found with the RCS regression model. The random forest model revealed that TIMP-1, MMP-9, and IL-6 were important predictors for serum sodium levels. Restricted cubic spline Cox regressions demonstrated that TIMP-1 levels indicated a U-shaped, concaved, non-linear association with all-cause mortality (P for effect = 0.011, P for non-linearity = 0.022). Dysnatraemia is an index of TIMP-1 aggravation and elevated PCWP, mean PAP; hence, it is associated with worsening all-cause mortality.Clinical Trial Registration: UMIN000023840.

Eosinophil counts can be a predictive marker of immune checkpoint inhibitor-induced secondary adrenal insufficiency: a retrospective cohort study.

Immune checkpoint inhibitors (ICIs) treatment can result in endocrine immune-related adverse events (irAEs), including pituitary dysfunction. Quick diagnosis of secondary adrenal insufficiency (AI) is challenging because no universal definition of ICI-induced secondary AI has been agreed. The aim of this study was to clarify the clinical features of ICI-induced secondary AI that can be used for screening in standard clinical practice. This retrospective study was performed using the medical records of patients who received ICIs at Hirosaki University Hospital between 1 September 2014 and 31 January 2021. Longitudinal clinical data of patients who developed AI were analyzed and compared with the data of thyroid irAEs. Regression analysis showed a significant correlation between ICI-induced secondary AI and absolute or relative eosinophil counts at pre-onset of AI, as well as differences or rate of increase in eosinophil counts at baseline and at pre-onset. Absolute eosinophil counts > 198.36/µL or relative eosinophil counts > 5.6% at pre-onset, and a difference of 65.25/µL or a rate of eosinophil count increase of 1.97 between the baseline and at pre-onset showed the best sensitivity and specificity. This is the first report to demonstrate that eosinophil counts can be a predictor of ICI-induced secondary AI.

Incidence and risk factors associated with preoperative deep venous thrombosis in the young and middle-aged patients after hip fracture.

OBJECTIVE: This study aims to investigate the incidence, occurrence timing and locations of preoperative DVT and identify the associated factors in this group. METHODS: A retrospective analysis of collected data in young and middle-aged (18-59 years) patients who presented with hip fracture between October 2015 and December 2018 was conducted. Before operation, patients were routinely examined for DVT by Duplex ultrasonography (DUS). Electronic medical records were retrieved to collect the data, involving demographics, comorbidities, injury and laboratory biomarkers after admission. Multivariate logistic regression analysis was performed to identify factors that were independently associated with DVT. RESULTS: Eight hundred and fifty-seven patients were included, and 51 (6.0%) were diagnosed with preoperative DVT, with 2.5% for proximal DVT. The average age of patients with DVT is 48.7 ± 9.4 year, while that of patients without DVT is 45.0 ± 10.9 year. The mean time from injury to diagnosis of DVT was 6.8 ± 5.5 days, 43.1% cases occurring at day 2-4 after injury. Among 51 patients with DVT, 97 thrombi were found. Most patients had thrombi at injured extremity (72.5%), 19.6% at uninjured and 7.8% at bilateral extremities. There are significantly difference between patients with DVT and patients without DVT in term of prevalence of total protein (41.2% vs 24.4%, P = 0.008), albumin (54.9% vs 25.6%, P = 0.001), low lactate dehydrogenase (51.0% vs 30.3%, P = 0.002), lower serum sodium concentration (60.8% vs 29.9%, P = 0.001), lower RBC count (68.6% vs 37.0%, P = 0.001), lower HGB (51.0% vs 35.1%, P = 0.022), higher HCT (86.3% vs 35.1%, P = 0.022) and higher platelet count (37.3% vs 11.3%, P = 0.001). The multivariate analyses showed increasing age in year (OR 1.04, 95% CI; P = 0.020), delay to DUS (OR, 1.26; P = 0.001), abnormal LDH (OR, 1.45; P = 0.026), lower serum sodium concentration (OR, 2.56; P = 0.007), and higher HCT level (OR, 4.11; P = 0.003) were independently associated with DVT. CONCLUSION: These findings could be beneficial in informed preventive of DVT and optimized management of hip fracture in specific group of young and mid-aged patients.

Evaluating a standardized protocol for the management of diabetes insipidus in pediatric neurosurgical patients.

OBJECTIVES: Central diabetes insipidus (DI) is a known complication following surgical resection of a suprasellar mass. There are limited data analyzing the outcomes of a standardized protocol for the management of postoperative DI in the pediatric population. We sought to fill this gap and hypothesized that utilizing a standardized protocol for fluid management (3-bag system) would reduce serum sodium fluctuations in the postoperative period after suprasellar surgery. METHODS: A retrospective chart review was performed. Patients were identified with the following criteria: age ≤ 18 years, undergoing a surgical procedure for suprasellar mass that also had postoperative DI. The primary outcome was the variability in serum sodium during the first 48 h and between 48 and 120 h postoperatively. RESULTS: There were 21 encounters pre-protocol and 22 encounters post-protocol for neurosurgical procedures. Use of the standardized protocol was associated with a lower range of sodium within 48 h postoperatively (p=0.065) and 83% lower odds of hypernatremia (Na>150 mmol/L) within 48 h postoperatively (CI 0.039-0.714) after controlling for age, gender, and prior DI diagnosis. History of DI conferred a lower risk of hypernatremia as well as less sodium fluctuation within 48 h postoperatively. Younger patients, those <9.7 years of age were associated with increased risk of hyponatremia and greater sodium fluctuations during the postoperative period. CONCLUSIONS: In patients with postoperative DI after suprasellar surgery, using a standardized protocol for fluid management (3-bag system) appears to reduce serum sodium variability in the first 48 h after surgery.

Perineural invasion, lactate dehydrogenase, globulin, and serum sodium predicting occult metastasis in oral cancer.

OBJECTIVE: This study aimed to develop a nomogram to predict the neck occult metastasis in early (T1-T2 cN0) oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The nomogram was developed in a training cohort of 336 early OSCC patients and was validated in a validation cohort including 88 patients. Independent predictors were calculated by univariate and multivariate logistic regression analyses. RESULTS: In univariate logistical regression analysis, gender, perineural invasion (PNI), blood vessel invasion, mean corpuscular hemoglobin, aspartate aminotransferase, prealbumin, globulin (GLO), lactate dehydrogenase (LDH), serum sodium (NA), and serum chloride were significant associated with neck occult metastasis. Multivariate logistical regression analysis identified PNI (p < .001), LDH (p = .003), GLO (p = .019), and NA (p = .020) as independent predictors of neck occult metastasis. Cut-off values for LDH, GLO, and NA obtained from AUC were 142.5, 26.35, and 139.5, respectively. The nomogram based on PNI and categorical GLO, LDH, and NA exhibited a strong discrimination, with a C-indexes of 0.748 (95%CI = 0.688 to 0.810) in the training cohort and 0.751 (95%CI = 0.639 to 0.863) in the validation cohort. CONCLUSIONS: A nomogram based on PNI, LDH, GLO, and NA for predicting the risk of neck lymph nodes occult metastasis in OSCC could help surgeons with therapy decision-making.

Clinical factors within a week of birth influencing sodium level difference between an arterial blood gas analyzer and an autoanalyzer in VLBWIs: A retrospective study.

ABSTRACT: Neonatologists often experience sodium ion level difference between an arterial blood gas analyzer (direct method) and an autoanalyzer (indirect method) in critically ill neonates. We hypothesize that clinical factors besides albumin and protein in the blood that cause laboratory errors might be associated with sodium ion level difference between the 2 methods in very-low-birth-weight infants during early life after birth. Among very-low-birth-weight infants who were admitted to Jeonbuk National Hospital Neonatal Intensive Care Units from October 2013 to December 2016, 106 neonates were included in this study. Arterial blood sample was collected within an hour after birth. Blood gas analyzer and biochemistry autoanalyzer were performed simultaneously. Seventy-six (71.7%) were found to have sodium ion difference exceeding 4 mmol/L between 2 methods. The mean difference of sodium ion level was 5.9 ±â€Š6.1 mmol/L, exceeding 4 mmol/L. Based on sodium ion level difference, patients were divided into >4 and ≤4 mmol/L groups. The sodium level difference >4 mmol/L group showed significantly (P < .05) higher sodium level by biochemistry autoanalyzer, lower albumin, lower protein, and higher maximum percent of physiological weight than the sodium level difference ≤4 mmol/L group. After adjusting for factors showing significant difference between the 2 groups, protein at birth (odds ratio: 0.835, 95% confidence interval: 0.760-0.918, P < .001) and percent of maximum weight loss (odds ratio: 1.137, 95% confidence interval: 1.021-1.265, P = .019) were factor showing significant associations with sodium level difference >4 mmol/L between 2 methods. Thus, difference in sodium level between blood gas analyzer and biochemistry autoanalyzer in early stages of life could reflect maximum physiology weight loss. Based on this study, if the study to predict the body's composition of extracellular and intracellular fluid is proceeded, it will help neonatologist make clinical decisions at early life of preterm infants.

Effect of hyponatremia normalization on osteoblast function in patients with SIAD.

OBJECTIVE: Hyponatremia is associated with an increased risk of bone fragility and fractures. Many studies suggest that hyponatremia stimulates osteoclast activation, whereas other studies rather reveal a possible role of acute hyponatremia in impairing osteoblast function. We aimed to assess whether and how correction of hyponatremia in hospitalized patients with the syndrome of inappropriate antidiuresis (SIAD) has an impact on bone metabolism. DESIGN AND METHODS: This was a predefined secondary analysis of 88 hospitalized patients with SIAD undergoing a randomized treatment with SGLT-2 inhibitors or placebo for 4 days. Biochemical markers of bone resorption (CTX) and bone formation (PINP) were collected in serum at baseline and after the intervention (day 5). Bone formation index (defined as PINP/CTX) and its difference between day 5 and baseline were calculated. Patients with steroid therapy (n = 6), fractures (n = 10), or whose data were missing (n = 4) were excluded from the analysis. RESULTS: Out of 68 patients, 27 (39.7%) were normonatremic at day 5. These patients showed an increase in serum PINP (P = 0.04), whereas persistent hyponatremic patients did not (P = 0.38), with a relevant difference between these two subgroups (P = 0.005). Serum CTX increased similarly in the two groups (P = 0.43). This produced a 47.9 points higher PINP/CTX difference between discharge and admission in normonatremic patients (95% CI: 17.0-78.7, P = 0.003) compared to patients with persistent hyponatremia, independent of age, sex, BMI, smoking habits, randomization arm, and baseline cortisol levels. CONCLUSIONS: Our predefined post hoc analysis shows that correction of hyponatremia in hospitalized patients with SIAD might have a positive impact on osteoblast function.

Relationships between reproductive hormones and maternal pregnancy physiology in women conceiving with or without in vitro fertilization.

We evaluated maternal pregnancy adaptations and their relationships with circulating hormones in women who conceived with or without in vitro fertilization (IVF). Pregnancies were grouped by corpus luteum (CL) number: 1 CL with physiological plasma relaxin concentration (PRLN; spontaneous pregnancies); 0 CL without circulating RLN (programmed cycles); >1 CL with elevated PRLN (ovarian stimulation). Major findings were that declines in plasma osmolality (Posm) and plasma sodium concentration ([Formula: see text]) were comparable in the 1 CL and 0 CL cohorts, correlated with plasma estradiol and progesterone concentrations but not PRLN; gestational declines in plasma uric acid (UA) concentration (PUA) were attenuated after IVF, especially programmed cycles, partly because of subdued increases of renal UA clearance; and PRLN and cardiac output (CO) were inversely correlated when plasma estradiol concentration was below ∼2.5 ng/mL but positively correlated above ∼2.5 ng/mL. Unexpectedly, PRLN and plasma sFLT1 (PsFLT1) were directly correlated. Although PsFLT1 and CO were not significantly associated, CO was positively correlated with plasma placental growth factor (PLGF) concentration after the first trimester, particularly in women who conceived with 0 CL. Major conclusions are that 1) circulating RLN was unnecessary for gestational falls in Posm and [Formula: see text]; 2) PRLN and CO were inversely correlated during early gestation, suggesting that PRLN in the lower range may have contributed to systemic vasodilation, whereas at higher PRLN RLN influence became self-limiting; 3) evidence for cooperativity between RLN and estradiol on gestational changes in CO was observed; and 4) after the first trimester in women who conceived without a CL, plasma PLGF concentration was associated with recovery of CO, which was impaired during the first trimester in this cohort.

The Content of Minerals in the PCOS Group and the Correlation with the Parameters of Metabolism.

Polycystic ovary syndrome (PCOS) is a common disease in women of childbearing age. It is characterized by excessive androgen production, ovulation disorders, and developing metabolic syndrome. The aim of the study was to check whether selected minerals were related to the pathophysiological mechanisms of PCOS. The concentrations of minerals were determined using an inductively coupled atomic plasma-emission spectrometer (ICP-AES Jobin Yvon JY-24). Blood samples from PCOS and control women were collected, processed, and digested with a microwave system in women with PCOS with and without insulin resistance and in the control group. It was found: zinc (Zn)-10.14 ± 2.11, 9.89 ± 1.44 and 10.30 ± 1.67; nickel (Ni) 0.001 ± 0.0009, 0.001 ± 0.0006 and 0.002 ± 0.00001; iron (Fe) 868.0 ± 155.8, 835.3 ± 156.4 and 833.0 ± 94.6; manganese (Mn) 0.017 ± 0.006, 0.017 ± 0.008 and 0.020 ± 0.009; copper (Cu) 0.714 ± 0.129, 0.713 ± 0.114 and 0.761 ± 0.146; magnesium (Mg) 48.4 ± 8.3, 50.0 ± 8.4 and 45.3 ± 10.7; sodium (Na) 374.3 ± 84.3, 396.3 ± 66.6 and 367.9 ± 88.9; potassium (K) 2541.8 ± 330.9, 2409.6 ± 347.1 and 2336.9 ± 211.4 (µg/g). Some micronutrient deficiencies may have a negative effect on the lipid profile in PCOS patients (Ni, Na). Further studies are needed to better understand dependencies.

Levels of C-Reactive Protein and Sodium May Differentiate a Perforated Appendix from a Nonperforated Appendix in Children.

BACKGROUND: Acute appendicitis (AA) might be amenable to conservative antibiotic treatment, whereas a perforated appendix (PA) necessitates surgery. We investigated the value of clinical-laboratory markers in distinguishing AA from a PA. METHODS: Retrospectively obtained preoperative parameters for 306 consecutive patients (<18 years) with histologically confirmed appendicitis (AA (n = 237) vs. PA (n = 69)), treated at our institution between January 2014 and December 2017. RESULTS: A PA was associated with male preponderance, younger age, decreased sodium level and increased white blood cell count, Tzanakis score, C-reactive protein (CRP) level, and CRP-to-lymphocyte ratio (CLR). Upon discrimination analysis, CLR and CRP displayed the highest accuracy in differentiating a PA from AA. Regression analysis identified levels of CRP, sodium, and the Tzanakis score as independent predictors for a PA. CONCLUSION: Levels of CLR, CRP, sodium, and Tzanakis score might support decision-making regarding treatment options for pediatric appendicitis.

Relevance of maternal sodium level for preeclampsia-associated adverse pregnancy outcomes.

OBJECTIVE: To evaluate maternal sodium levels in women with preeclampsia (PE) or at high risk for preeclampsia and their relevance for severe PE-associated adverse pregnancy outcome and remaining pregnancy duration. STUDY DESIGN: In a retrospective cohort of 198 patients presenting with signs and symptoms of preeclampsia (PE), we investigated maternal sodium level and the sFlt-1/PlGF-ratio within 14 days prior to delivery. MAIN OUTCOME MEASURES: In total, 88 patients (44.4%) developed a maternal and/or fetal and neonatal preeclampsia-associated adverse outcome (AO). The median sodium level was lower in the cohort with vs. without AO (136 vs. 137 mmol/l) and correlated negatively with the sFlt-1/PlGF-ratio (r = -0.19, 95% CI: -0.31 to -0.05) in both groups. Logistic regression revealed a significant association of the maternal sodium level with the development of an AO (+1 mmol/l reduced the odds by 21%, [Odds ratio (OR) of 0.79 (95% CI 0.67-0.93), p < 0.01], whereas the sFlt-1/PlGF showed a contrary effect (+10 units OR of 1.05 (95% CI: 1.02-1.08, p < 0.01)). Linear mixed effects models showed consistent results, with sodium level positively associated with the remaining pregnancy duration. CONCLUSIONS: Our results confirm the relevance of decreased maternal sodium level as a severity marker for PE-associated adverse outcomes.

Diaphragma sellae sinking can predict the onset of hyponatremia after transsphenoidal surgery for pituitary adenomas.

PURPOSE: Sinking of the diaphragma sellae (DS) may stretch the pituitary stalk, which in turn impairs neurohypophyseal function; thus, it may play a role in the development of postoperative hyponatremia. We aimed to assess the factors influencing the development of hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of DS sinking on hyponatremia. METHODS: After applying the inclusion and exclusion criteria, we retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. The pituitary gland was scanned using a 3.0-T magnetic resonance imaging, and sagittal and coronal images were acquired. We evaluated the following: preoperative and postoperative hypothalamus‒pituitary‒thyroid axis function, hypothalamus‒pituitary‒adrenal axis function, intra-operative cerebrospinal fluid leaks, diabetes insipidus, hyponatremia, time from the day of surgery to the day of discharge, and time of hyponatremia onset. RESULTS: Of the 460 patients who had microscopic TSS for pituitary adenoma, 83 experienced postoperative hyponatremia. Hyponatremia occurred approximately 5.25 days postoperatively and persisted for 5.54 days. The lowest average blood sodium level was 123.9 mEq/L, which occurred at 7.49 days after surgery. Logistic regression analysis showed that the risk of hyponatremia was greater for patients with a significant DS sinking depth, a large pituitary stalk deviation angle difference, and a longer postoperative "measurable pituitary stalk". The difference in blood sodium levels between pre-TSS and 2 days post-TSS was also an independent predictor of postoperative hyponatremia onset. CONCLUSION: DS sinking plays an important role in predicting hyponatremia onset after TSS for pituitary adenomas.

Routine Postoperative Chemistry Panels Are Not Necessary for Most Total Joint Arthroplasty Patients.

BACKGROUND: The routine use of traditional chemistry-7 (chem-7) laboratory tests following total joint arthroplasty (TJA) has been called into question with the advent of short-stay procedures. Our objective was to determine the incidence, risk factors, and clinical interventions associated with inpatient abnormal routine postoperative chem-7 panels. METHODS: From 2015 to 2017, 3,162 patients underwent a total of 3,721 TJA procedures, including primary total hip arthroplasty (THA) (n = 1,939; 52.1%) or primary total knee arthroplasty (TKA) (n = 1,782; 47.9%). Patients underwent routine preoperative and postoperative chem-7 testing. Clinical interventions were identified. With use of mixed-effects multivariate logistic regression, potential risk factors for abnormal chemistry panel values (including preoperative chem-7 results, type of surgery, age, sex, race, comorbidities, American Society of Anesthesiologists [ASA] score, and medications) were analyzed. RESULTS: The rates of abnormal preoperative laboratory results were 3.4% for sodium (Na+), 7.4% for potassium (K+), 15.8% for blood urea nitrogen (BUN), and 26.4% for creatinine (Cr). The incidence of abnormal postoperative results was low for K+ (9.7%) and higher for Na+ (25.6%), BUN (55.6%), and Cr (27.9%). Preoperative abnormal laboratory results were a significant predictor of a postoperative abnormality for Na+ (odds ratio [OR] = 2.15; 95% confidence interval [CI] = 1.82 to 2.54), K+ (OR = 4.22; 95% CI = 3.03 to 5.88), and Cr (OR = 3.00; 95% CI = 2.45 to 3.68). Bilateral TJA was associated with increased odds of abnormal postoperative Na+ (OR = 1.56; 95% CI = 1.44 to 1.68). Renal disease was associated with increased odds of abnormal postoperative Cr (OR = 15.21; 95% CI = 5.67 to 40.77). Patients taking loop diuretics had increased odds of abnormal postoperative K+ (OR = 2.10; 95% CI = 1.42 to 3.11) and Cr (OR = 2.28; 95% CI = 1.56 to 3.33). Regarding intervention, 6.7% of hypokalemic patients received potassium chloride (KCl) fluid/tablets. Forty percent of hyponatremic patients received sodium chloride (NaCl) fluid/tablets. The electrolyte-related medicine consultation rate was 0.3% (13 of 3,721). CONCLUSIONS: On the basis of our findings, we recommend postoperative chem-7 testing for patients with an abnormal preoperative laboratory result (Na+, K+, BUN, Cr), preexisting renal disease, bilateral TJA, and prescribed angiotensin-converting enzyme inhibitors (ACE), angiotensin II receptor blockers (ARB), and diuretics. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.