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Purpose: Disturbances of electrolytes and renal function have been linked to the prognosis of critically ill patients and recently also of cancer patients. This study aimed to assess electrolyte and renal disorders in glioblastoma patients and evaluate their prognostic effect. Methods: Medical records of patients with newly diagnosed glioblastoma between 2005 and 2018 were retrospectively reviewed for electrolyte and renal function parameters and for demographic, clinical and outcome parameters. Results: Electrolyte and renal function disorders were associated with poorer survival in univariate and Kaplan–Meier analysis. Multivariate analysis revealed hypochloremia as an independent prognostic factor for overall and 1-year survival. Conclusion: Only hypochloremia showed an association with glioblastoma prognosis, independent of other known prognostic factors, as age or molecular status.

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Background: We aimed to describe the incidence of hospital-acquired dyschloremia and its association with in-hospital mortality in general hospitalized patients. Methods: All hospitalized patients from 2009 to 2013 who had normal admission serum chloride and at least two serum chloride measurements in the hospital were studied. The normal range of serum chloride was defined as 100–108 mmol/L. Hospital serum chloride levels were grouped based on the occurrence of hospital-acquired hypochloremia and hyperchloremia. The association of hospital-acquired hypochloremia and hyperchloremia with in-hospital mortality was analyzed using logistic regression. Results: Among the total of 39,298 hospitalized patients, 59% had persistently normal hospital serum chloride levels, 21% had hospital-acquired hypochloremia only, 15% had hospital-acquired hyperchloremia only, and 5% had both hypochloremia and hyperchloremia. Compared with patients with persistently normal hospital serum chloride levels, hospital-acquired hyperchloremia only (odds ratio or OR 2.84; p < 0.001) and both hospital-acquired hypochloremia and hyperchloremia (OR 1.72; p = 0.004) were associated with increased in-hospital mortality, whereas hospital-acquired hypochloremia only was not (OR 0.91; p = 0.54). Conclusions: Approximately 40% of hospitalized patients developed serum chloride derangements. Hospital-acquired hyperchloremia, but not hypochloremia, was associated with increased in-hospital mortality.
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Objective Serum chloride disorders have been gaining increased attention. We aimed to assess the impact of serum chloride on all-cause mortality in critically ill patients in coronary care units (CCUs). Methods We extracted clinical data from the Multiparameter Intelligent Monitoring in Intensive Care III database. We used data for the first CCU admission of each patient; baseline data were extracted within 24 hours after CCU admission. Statistical methods included the Lowess smoothing technique, Cox proportional hazards model, and subgroup analyses. Results A total 5616 patients who met the inclusion criteria were included. We observed a U-shaped relationship between admission chloride levels and 30-day all-cause mortality. In multivariate analysis adjusted for age, ethnicity, and sex, both hyper- and hypochloremia were significant predictors of risk of 30-day, 90-day, and 365-day all-cause mortality. After adjusting additional clinical characteristics, hypochloremia remained a significant predictor of risk of 30-day all-cause mortality (hazard ratio, 1.47; 95% confidence interval, 1.19–1.83). For 90-day and 365-day all-cause mortality, similar significant robust associations were found. Conclusions We observed a U-shaped relationship between admission chloride levels and 30-day all-cause mortality among patients in the CCU. Hypochloremia was associated with increased risk of all-cause mortality in these patients.
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Background: This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the impact of EAD on patients’ in-hospital clinical outcomes. Methods: Patients with the diagnosis of malignancies hospitalized during 1 October 2014 and 30 September 2015 were recruited in Zhongshan Hospital, Fudan University in Shanghai of China. Demographic characteristics, comorbidities, and clinical data, including survival, length of stay and hospital cost, were extracted from the electronic medical record system. Electrolyte and acid-base data were acquired from the hospital laboratory database. Results: Of 25,881 cancer patients with electrolyte data, 15,000 (58.0%) cases had at least one electrolyte and acid-base abnormity. Hypocalcemia (27.8%) was the most common electrolyte disorder, followed by hypophosphatemia (26.7%), hypochloremia (24.5%) and hyponatremia (22.5%). The incidence of simple metabolic acidosis (MAC) and metabolic alkalosis (MAL) was 12.8% and 22.1% respectively. Patients with mixed metabolic acid-base disorders (MAC + MAL) accounted for 30.2%. Lower BMI score, preexisting hypertension and diabetes, renal dysfunction, receiving surgery/chemotherapy, anemia and hypoalbuminemia were screened out as the major risk factors of EAD. In-hospital mortality in patients with EAD was 2.1% as compared to those with normal electrolytes (0.3%). The risk of death significantly increased among patients with severe EAD. Similarly, the length of stay and hospital cost also tripled as the number and grade of EAD increased. Conclusion: EAD is commonly encountered in cancer patients and associated with an ominous prognosis. Patients with comorbidities, renal/liver dysfunction, and anti-tumor therapy have a higher risk of EAD. Regular monitoring of electrolytes, optimum regimen for intravenous infusion, timely correction of modifiable factors and appropriate management of EAD should not be neglected during anti-tumor treatment.
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Background Pulmonary arterial hypertension ( PAH ) is a lethal disease. In resource‐limited countries PAH outcomes are worse because therapy costs are prohibitive. To improve global outcomes, noninvasive and widely available biomarkers that identify high‐risk patients should be defined. Serum chloride is widely available and predicts mortality in left heart failure, but its prognostic utility in PAH requires further investigation. Methods and Results In this study 475 consecutive PAH patients evaluated at the University of Minnesota and Vanderbilt University PAH clinics were examined. Clinical characteristics were compared by tertiles of serum chloride. Both the Kaplan‐Meier method and Cox regression analysis were used to assess survival and predictors of mortality, respectively. Categorical net reclassification improvement and relative integrated discrimination improvement compared prediction models. PAH patients in the lowest serum chloride tertile (≤101 mmol/L: hypochloremia) had the lowest 6‐minute walk distance and highest right atrial pressure despite exhibiting no differences in pulmonary vascular disease severity. The 1‐, 3‐, and 5‐year survival was reduced in hypochloremic patients when compared with the middle‐ and highest‐tertile patients (86%/64%/44%, 95%/78%/59%, and, 91%/79%/66%). After adjustment for age, sex, diuretic use, serum sodium, bicarbonate, and creatinine, the hypochloremic patients had increased mortality when compared with the middle‐tertile and highest‐tertile patients. The Minnesota noninvasive model (functional class, 6‐minute walk distance, and hypochloremia) was as effective as the French noninvasive model (functional class, 6‐minute walk distance, and elevated brain natriuretic peptide or N‐terminal pro–brain natriuretic peptide) for predicting mortality. Conclusions Hypochloremia (≤101 mmol/L) identifies high‐risk PAH patients independent of serum sodium, renal function, and diuretic use.
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Background: This study investigated the associations of fluctuations in serum chloride (Cl-) levels with 30-day mortality after intensive care unit (ICU) admission among critically ill patients. Methods: We retrospectively analyzed the medical records of adult patients (≥18 years old) admitted to the ICU between January 2012 and December 2017. Positive and negative fluctuations in Cl- were defined as the differences between the Cl- upon ICU admission (baseline Cl-) and the maximum and minimum Cl- levels, respectively, measured within 72 h after ICU admission. Results: The final analysis included 18,825 adult patients. In multivariable Cox regression analyses, the risk of 30-day mortality increased by 8% per 1-mmol L- 1 positive fluctuation in Cl- within 72 h (hazard ratio = 1.08, 95% confidence interval: 1.04-1.11, P < 0.001). In subgroup analyses, a positive fluctuation in Cl- was associated with increased 30-day mortality among patients with a severe positive cumulative fluid balance (FB, > 10%), normochloremia (97-110 mmol L- 1) or hyperchloremia (> 110 mmol L- 1) upon ICU admission. Furthermore, a negative fluctuation in the Cl- level during the first 72 h of an ICU stay was associated with a negative cumulative FB (< 0%) or hypochloremia (< 97 mmol L- 1) upon ICU admission. Conclusions: A fluctuation in the Cl- level during the first 72 h of an ICU stay was found to associate independently with increased 30-day mortality among critically ill adult patients. However, the nature of this association differed according to the cumulative FB status or dyschloremia status upon ICU admission.
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Glioblastoma is a devastating malignancy with a dismal survival rate. Currently, there are limited prognostic markers of glioblastoma including IDH1, ATRX, MGMT, PTEN, EGFRvIII, and others. Although these biomarkers for tumor prognosis are available, a surgical biopsy must be performed for these analyses, which has morbidity involved. A non-invasive and readily available biomarker is sought after which provides clinicians prognostic information. Sodium is an electrolyte that is easily and quickly obtained through analysis of a patient’s serum. Hyponatremia has been shown to have a predictive and negative prognostic indication in multiple cancer types, but the role of glioblastoma patients’ serum sodium at the time of diagnosis in predicting glioblastoma patient survival has not been determined. We assessed whether hyponatremia at the time of glioblastoma diagnosis correlates to patient survival and show that in our cohort of 200 glioblastoma patients, sodium, at any level, did not significantly correlate to glioblastoma survival, unlike what is seen in multiple other cancer types. We further demonstrate that inducing hyponatremia in an orthotopic murine model of glioblastoma has no effects on tumor progression and survival.
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Only a few observational studies investigated the association between hypochloremia and mortality in critically ill patients, and these studies included small number of septic patients. Also, no study has evaluated the effect of an increase in chloride (Cl⁻) concentration in hypochloremia on the mortality. A total of 843 Korean septic patients were divided into three groups based on their baseline Cl⁻ level, and Cox analyses were performed to evaluate the 28-day mortality. Moreover, the change in Cl⁻ level (ΔCl) from baseline to 24, 48, or 72 hour was determined, and Cox analyses were also conducted to evaluate the relationship of ΔCl with mortality. 301 (35.7%) patients were hypochloremic (Cl⁻ < 97 mEq/L), and 38 (4.5%) patients were hyperchloremic (Cl⁻ > 110 mEq/L). During the follow-up period, 119 (14.1%) patients died. Hypochloremia was significantly associated with an increased mortality after adjusting for several variables, but an 1 mEq/L increase of ΔCl within 24 hour in patients with hypochloremia was significantly related to a decreased mortality. Caution might be required in severe septic patients with hypochloremia considering their increased mortality rate. However, an increased Cl⁻ concentration might decrease the mortality rate of such patients.
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Over the past few years, chloride has joined the league of essential electrolytes for critically ill patients. Dyschloremia can occur secondary to various etiologic factors before and during patient admission in the intensive care unit. Some cases are disease-related; others, treatment-related. Chloride abnormalities were shown in animal models to have adverse effects on arterial blood pressure, renal blood flow, and inflammatory markers, which have led to several clinical investigations. Hyperchloremia was studied in several settings and correlated to different outcomes, including death and acute kidney injury. Baseline hypochloremia, to a much lesser extent, has been studied and associated with similar outcomes. The chloride content of resuscitation fluids was also a subject of clinical research. In this review, we describe the effect of dyschloremia on outcomes in critically ill patients. We review the major studies assessing the chloride content of resuscitation fluids in the critically ill patient.
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Background Abnormal chloride levels are commonly observed in critically ill patients, but their clinical relevance remains a matter of debate. We examined the association between abnormal chloremia and ICU and hospital mortality. To further refine findings and integrate them into the ongoing discussion on the detrimental effects of chloride-rich solutions, the impact of strong ion difference (SID) on the same end points was assessed. Methods Retrospective cohort study in an academic tertiary intensive care unit on 8830 adult patients who stayed at least 24 h in the ICU was carried out. Patients admitted after elective cardiac surgery were treated as a separate subgroup (n = 2350). Analyses were performed using multivariable logistic regression. All statistical models were extensively adjusted for confounders, including comorbidity, admission diagnosis, other electrolytes and acid–base parameters. ResultsSevere hyperchloremia (>110 mmol/L), but not low (SID) was significantly associated with increased mortality in the ICU (odds ratio vs. normochloremia 1.81; 95 % CI 1.32–2.50; p < 0.001) and the hospital (odds ratio 1.49; 95 % CI 1.14–1.96; p = 0.003). Hyperchloremia and low (SID) were encountered in the majority of patients admitted after cardiac surgery (in 86.9 and 47.2 %, respectively), but were not negatively associated with mortality. Conclusions In the ICU, hyperchloremia at admission was associated with negative outcome. On the other hand, decreased strong ion difference did not have an impact on mortality, precluding a simple extrapolation of these findings to the ongoing discussion on the detrimental effects of chloride-rich solutions. This notion is fueled by the finding that hyperchloremia after cardiac surgery, frequently encountered and probably fluid-induced, did not seem to be deleterious.
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Introduction: Dyschloremia is common in critically ill patients, although its impact has not been well studied. We investigated the epidemiology of dyschloremia and its associations with the incidence of acute kidney injury and other intensive care unit outcomes. Material and methods: This is a single-center, retrospective cohort study at Mayo Clinic Hospital-Rochester. All adult patients admitted to intensive care units from January 1st, 2006, through December 30th, 2012 were included. Patients with known acute kidney injury and chronic kidney disease stage 5 before intensive care unit admission were excluded. We evaluated the association of dyschloremia with ICU outcomes, after adjustments for the effect of age, gender, Charlson comorbidity index and severity of illness score. Results: A total of 6,025 patients were enrolled in the final analysis following the implementation of eligibility criteria. From the cohort, 1,970 patients (33%) developed acute kidney injury. Of the total patients enrolled, 4,174 had a baseline serum chloride. In this group, 1,530 (37%) had hypochloremia, and 257 (6%) were hyperchloremic. The incidence of acute kidney injury was higher in hypochloremic and hyperchloremic patients compared to those with a normal serum chloride level (43% vs.30% and 34% vs. 30%, respectively; P < .001). Baseline serum chloride was lower in the acute kidney injury group vs. the non-acute kidney injury group [100 mmol/L (96-104) vs. 102 mmol/L (98-105), P < .0001]. In a multivariable logistic regression model, baseline serum chloride of ≤94 mmol/L found to be independently associated with the risk of acute kidney injury (OR 1.7, 95% CI 1.1-2.6; P = .01). Discussion: Dyschloremia is common in critically ill patients, and severe hypochloremia is independently associated with an increased risk of development of acute kidney injury.
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Background: Hyponatremia is prognostic of higher mortality in some cancers but has not been well studied in others. We used a longitudinal design to determine the incidence and prognostic importance of euvolemic and hypervolemic hyponatremia in patients following diagnosis with lymphoma, breast (BC), colorectal (CRC), small cell lung (SCLC), or non-small cell lung cancer (NSCLC). Methods: Medical record and tumor registry data from two large integrated delivery networks were combined for patients diagnosed with lymphoma, BC, CRC, or lung cancers (2002-2010) who had ≥1 administration of radiation/chemotherapy within 6 months of diagnosis and no evidence of hypovolemic hyponatremia. Hyponatremia incidence was measured per 1000 person-years (PY). Cox proportional hazard models assessed the prognostic value of hyponatremia as a time-varying covariate on overall survival (OS) and progression-free survival (PFS). Results: Hyponatremia incidence (%, rate) was 76 % each, 1193 and 2311 per 1000 PY, among NSCLC and SCLC patients, respectively; 37 %, 169 in BC; 64 %, 637 in CRC, and 60 %, 395 in lymphoma. Hyponatremia was negatively associated with OS in BC (HR 3.7; P = <.01), CRC (HR 2.4; P < .01), lung cancer (HR 2.4; P < .01), and lymphoma (HR 4.5; P < .01). Hyponatremia was marginally associated with shorter PFS (HR 1.3, P = .07) across cancer types. Conclusions: The incidence of hyponatremia is higher than previously reported in lung cancer, is high in lymphoma, BC, and CRC and is a negative prognostic indicator for survival. Hyponatremia incidence in malignancy may be underestimated. The effects of hyponatremia correction on survival in cancer patients require further study.
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To examine the prevalence of serum magnesium (Mg) alterations and outcomes in hospitalized patients. All admissions to Mayo Clinic in Rochester, Minnesota, from January 1, 2009, through December 31, 2013 (288,120 patients), were screened. Admission Mg from each unique patient and relevant clinical data were extracted from the institutional electronic database. After excluding patients aged less than 18 years, those without Mg measurement, and readmission episodes, a total of 65,974 patients were studied. Magnesium levels of 2.1 mg/dL or higher were found in 20,777 patients (31.5%), and levels less than 1.7 mg/dL were noted in 13,320 (20.2%). Hypomagnesemia was common in patients with hematologic/oncological disorders, and hypermagnesemia was common in those with cardiovascular disease. The lowest hospital mortality, assessed by restricted cubic spline and percentage death, occurred in patients with Mg levels between 1.7 and 1.89 mg/dL. An Mg level of less than 1.7 mg/dL was independently associated with an increased risk of hospital mortality after adjusting for all variables except the admission diagnosis; risk for longer hospital stay and being discharged to a care facility were increased in the fully adjusted model. An elevated Mg level of 2.3 mg/dL or higher was a predictor for all adverse outcomes. The magnitude of Mg elevations in patients with levels of 2.3 mg/dL or higher (N=7908) was associated with worse hospital mortality in a dose-response manner. In patients with cardiovascular diseases, Mg levels of 1.5 to 1.69 mg/dL and 2.3 mg/dL or higher both independently predicted poor outcomes including hospital mortality. Dysmagnesemia in hospitalized patients is common, with hypermagnesemia being most prevalent. Compared with hypomagnesemia, hypermagnesemia is a stronger predictor for poor outcomes. Magnesium supplementation for patients without Mg deficiency should be avoided in the absence of randomized controlled trials documenting a benefit. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
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Although chloride is one of the major electrolytes measured routinely in dairy practice, the amount of attention chloride receives in critically ill patients is limited. There are still a few studies reporting the incidence of derangements of chloride and its association with patients' outcomes. Accordingly, we conducted a retrospective study to assess the prevalence of abnormality of serum chloride level in postoperative patients in the intensive care unit on the early phase of surgery and its association with outcome. We conducted a single-center retrospective observational study. All adult patients who underwent elective thoracic or abdominal surgery and required postoperative intensive care for more than 48 h between 2007 and 2011 were included. Chloride levels were measured on each morning of postoperative day 1 and day 2 in the intensive care unit. We defined all-cause hospital death as the primary outcome and compared serum chloride levels on postoperative day 1 and day 2 between hospital survivors and non-survivors. Comparisons among groups were conducted using the chi-square test for equal proportion, Mann-Whitney U tests, or Kruskal-Wallis test. Among 98 patients included in this study, hypochloremia (less than 98 mmol/L) during the first 48 h occurred in 14 patients (14.3%). The mortality in hypochloremia patients was 28.6%, which is significantly higher than 6.0% in patients with normal chloride concentration (p = 0.007). Even after being adjusted for severity of illness, the incidence of hypochloremia was independently associated with the risk of hospital death (adjusted odds ratio 5.8 (1.1, 30.2), p = 0.04). Hyperchloremia (more than 112 mmol/L) occurred in one patient (1.0%), who was discharged from the hospital at day 9. There was no significant difference in the total volume of infused fluid (p = 0.30), sum of chloride administration (p = 0.33), and use of furosemide (p = 0.75) from intensive care unit admission to the morning of postoperative day 2 between survivors and non-survivors. Hypochloremia observed within 48 h after surgery was not rare and was independently associated with the increased risk of hospital death. Hypochloremia might be a useful indicator of prognosis for patients in the postoperative intensive care unit.
Article
Background Despite recent improvements in treatment of glioblastoma (GBM), some patients still show a short survival. Objective In this study, we sought to develop a new risk score for preoperative assessment of short-term survival (STS, < 6 months) in GBM patients. Methods All adult patients that underwent surgical resection of GBM between 2004 and 2014 were included (n=379). Various demographic and clinical parameters, which are available at admission, were assessed. Variables were evaluated in univariate and multivariate analyses. The score was validated in a separate GBM cohort that underwent surgical resection between 2015 and 2018. Results The following independent predictors of STS were integrated into a new score: body height (Small, <169 cm, 1point), arterial Hypertension (1point), patients’ age (Older: ≤54 years – 0points, 55-74 years – 1point, ≥75 years – 2points), and poor clinical status (Reduced Karnofsky performance status scale: ≤60% – 2points, 70-80% – 1point, ≥90% – 0points). Therefore, the new risk score (SHORT [Term]) ranged from 0 to 6 points and showed a good accuracy of risk estimation for STS in GBM (AUC: 0.715). STS rates were 9.7%, 23.1% and 70% in GBM patients scoring <2 points, 2-4 points and >4 points respectively (P<0.0001). The score was successfully validated (AUC: 0.770). Conclusion This study suggests a risk score for preoperative assessment of STS risk in GBM patients. Still, this risk score needs external validation in larger patients’ cohorts from other institutions. Our score might be a tool to facilitate treatment decisions in GBM patients prior to surgery.
Article
Background: Glioblastoma (GBM) is the most common malignant brain tumor in adults and still carries a dismal prognosis. As several studies detected a connection between inflammation and GBM prognosis, we sought to explore possible associations between routinely investigated inflammatory parameters and GBM outcome. Patients and methods: Patients treated for GBM at our Institution between 2004 and 2014 were included. White blood cell count (WBC), C-reactive protein (CRP) and the ratio of platelets and WBC (Plt/WBC) were evaluated preoperatively. Medical records were reviewed for clinical parameters (age, sex, preoperative clinical condition, genetic alterations). Study endpoints were overall (OS) and 1- and 2-year survival. Results: In the final cohort consisting of 565 individuals with GBM, univariate analysis showed significant associations for WBC, CRP and Plt/WBC ratio with OS. Kaplan-Meier survival plot confirmed significantly poorer OS in patients with WBC>12/nl and with CRP≥2.9 mg/dl. In multivariate analysis, a WBC of >12/nl was an independent prognostic factor for all three outcome parameters and CRP≥2.9 mg/dl for OS and 1-year survival. Conclusion: Preoperative WBC and CRP values were confirmed as independent predictors of GBM outcome. This emphasizes the need for further evaluation of the role of inflammation in the prognosis of GBM.
Article
Electrolytic disorders are common in lung cancer patients. But the association between serum electrolytes levels and survival in patients undergoing lung cancer resections for non–small-cell lung cancer (NSCLC) has been poorly investigated. A retrospective study was conducted on consecutive postoperative NSCLC patients. Pearson's test was used to determine the association between serum sodium and chlorine levels and clinical characteristics, and cox regression and Kaplan-Meier model were applied to analyze risk factors on overall survival. We found that hyponatremia was an independent prognostic factor associated with poor prognosis in NSCLC patients undergoing complete resection (log-rank test, P = 0.004). In addition, we found that hyperchloremia predicted a poor clinical outcome in patients with non-anion-gap (log-rank test, P = 0.011), whereas it predicted a favorable clinical outcome in patients with high-anion-gap (log-rank test, P = 0.002). The serum electrolytes levels may reflect the prognosis of NSCLC patients who receive complete resection. Early detection, monitoring, and management of hyperchloremia and hyponatremia might improve patients’ prognosis.
Article
Background: Postoperative hyperchloremia is known to be related to increases in mortality and morbidity after surgery. However, the relationship between preoperative hyperchloremia and hypochloremia and postoperative mortality and morbidity is not well established. Our aim was to evaluate the relationship between preoperative hyperchloremia or hypochloremia, as assessed using preoperative serum chloride tests, and 90-day mortality and morbidity after noncardiac surgery. Methods: In this retrospective cohort study, we reviewed the medical records of patients >20 years of age who underwent noncardiac surgery between January 2010 and December 2016. Patients were categorized into one of the following groups on the basis of the results of serum chloride testing performed within 1 month before surgery: normochloremia, 97-110 mmol·L; hyperchloremia, >110 mmol·L; and hypochloremia, <97 mmol·L. The primary end point of this study was the difference in postoperative 90-day mortality among the preoperative serum chloride groups. The secondary end point was the difference in postoperative acute kidney injury incidence among the preoperative serum chloride groups. Results: A total of 106,505 patients were included in the final analysis (2147 were allocated to the preoperative hypochloremia group and 617 to the hyperchloremia group). Multivariable Cox regression analysis revealed significantly increased 90-day mortality in the hypochloremia (hazard ratio, 1.46; 95% CI, 1.16-1.84; P = .001) and hyperchloremia (hazard ratio, 1.76; 95% CI, 1.13-2.73; P = .013) groups when compared with the normochloremia group. In addition, multivariable logistic regression analysis revealed a 1.83-fold increased odds of acute kidney injury in the preoperative hypochloremia group when compared with the normochloremia group (odds ratio, 1.83; 95% CI, 1.53-2.19; P < .001). Conclusions: Preoperative hypochloremia and hyperchloremia were related to increased 90-day mortality after noncardiac surgery. In addition, preoperative hypochloremia was related to an increased risk for postoperative acute kidney injury.
Article
Background: Recent studies have suggested that electrolyte disorders might be a negative prognostic factor for some diseases. Objective: The purpose of this study was to systematically evaluate the prognostic role of electrolyte disorders in patients with stage I to III colorectal cancer who received radical surgical resection. Design: This study was retrospectively performed. Settings: The study was conducted at a single tertiary care center. Patients: Patients with colorectal cancer who underwent radical resection in between April 2007 and April 2014 were included. Main outcome measures: The Kaplan-Meier method was adopted to estimate the overall and disease-free survival with and without propensity score matching. Results: In total, our study recruited 5089 eligible patients. In prematching analysis, patients with hypochloremia showed both shorter overall survival (HR = 0.943 (95% CI, 0.908-0.980); p = 0.003) and disease-free survival (HR = 0.957 (95% CI, 0.933-0.981); p < 0.001) than those with normal serum chloride levels. In postmatching analysis, 770 patients from each group were compared, and the results further confirmed that hypochloremia was significantly associated with worse overall survival (HR = 0.646 (95% CI, 0.489-0.855); p = 0.002) and disease-free survival (HR = 0.782 (95% CI, 0.647-0.944); p = 0.01), with the hypochloremia group as a reference. Limitations: The study was limited by its retrospective nature. Conclusions: Hypochloremia diagnosed before treatment can independently prognosticate the overall and disease-free survival for patients with stage I to Ш colorectal cancer after radical resection. Intensive surveillance and management might improve the survival outcome for patients with hypochloremia. See Video Abstract at http://links.lww.com/DCR/A727.
Article
Importance Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor. Objective To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. Design, Setting, and Participants In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis. Interventions Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m²) for 5 days per 28-day cycle (6-12 cycles). Main Outcomes and Measures Progression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group. Results Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone. Conclusions and Relevance In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis. Trial Registration clinicaltrials.gov Identifier: NCT00916409
Article
Background: Chloride plays a role in renal salt sensing, neurohormonal activation, and regulation of diuretic targets, and hypochloremia predicts mortality in acute heart failure (AHF). AHF therapies, such as diuretics, alter chloride homeostasis. We studied the association between (changes in) chloride levels and diuretic responsiveness, decongestion, and mortality in patients with AHF. Methods and results: Patients hospitalized for AHF in the PROTECT trial (n=2033) with serum chloride levels within 24 hours of admission and 14 days later were studied (n=1960). Hypochloremia was defined as serum chloride <96 mEq/L. Mean baseline chloride was 100.8±5.0 mEq/L. Low baseline chloride was associated with high bicarbonate, poor diuretic response, less hemoconcentration, and worsening heart failure (all P<0.01). Newly developed hypochloremia at day 14 was common and associated with a decline in renal function and an increase in blood urea nitrogen (P<0.01). In multivariable analyses, chloride measured at day 14, but not baseline chloride, was strongly and independently associated with mortality through 180 days (hazard ratio per unit decrease: 1.07 [1.03-1.10]; P<0.001). In comparison, sodium was not significantly associated with mortality after multivariable adjustment at any time point. Hypochloremia at baseline that resolved was not associated with mortality (P=0.55), but new or persistent hypochloremia at day 14 was associated with increased mortality (hazard ratio: 3.11 [2.17-4.46]; P<0.001). Conclusions: Low serum chloride at AHF hospital admission was strongly associated with impaired decongestion. New or persistent hypochloremia 14 days later was independently associated with reduced survival, whereas hypochloremia that resolved by day 14 was not. Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00354458.
Article
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