Is increased Mean platelet volume associated with neurologic outcome after non-traumatic subarachnoid hemorrhage?

Objective@#This study evaluated the clinical usefulness of mean platelet volume (MPV) for predicting functional outcomes in subarachnoid hemorrhage (SAH) patients. @*Methods@#This is a retrospective analysis of patients who were diagnosed with SAH in the emergency room. Based on their modified Rankin Scale (mRS) score, patients were divided into two groups: 0-2 (good outcome) and 3-6 (poor outcome). Univariable and multivariable analyses were performed to investigate whether MPV, along with other multiple factors, was associated with poor prognosis. Receiver operating characteristic (ROC) curve analysis was performed to determine the value of MPV as a predicting factor of neurological prognosis. Compared to other factors, Hunt Hess grade (HHG) and modified Fisher grade (mFG) considerably influenced the outcomes in both groups (Model 1; model including all factors). Hence, a new model (Model 2) was constructed, comprising multiple factors excluding these two factors. @*Results@#A total of 143 patients were included in this study. Although MPV was different between the two groups, it was not a significant factor in Model 1 in the multivariable analysis. In Model 2, MPV (odds ration [OR], 1.71; 95% confidence interval [CI], 1.05-2.8), age (OR, 1.06; 95% CI, 1.03-1.1), and surgical treatment (OR, 0.37; 95% CI, 0.15-0.87) were significant factors related to poor outcomes. Area under the curve (AUC) of Model 1 was 0.93, 0.85 in HHG; 0.78 in Model 2, 0.65 in mFG, and 0.62 in MPV. @*Conclusion@#Although MPV differed significantly between the good and poor outcome groups, it is insufficient to predict poor outcomes in SAH patients as an independent biomarker.

The cut-off value of transient elastography to the value of hepatic venous pressure gradient in alcoholic cirrhosis

Background/Aims@#The hepatic venous pressure gradient (HVPG) reflects portal hypertension, but its measurement is invasive. Transient elastography (TE) is a noninvasive method for evaluating liver stiffness (LS). We investigated the correlation between the value of LS, LS to platelet ratio (LPR), LS-spleen diameter-to-platelet ratio score (LSPS) and HVPG according to the etiology of cirrhosis, especially focused on alcoholic cirrhosis. @*Methods@#Between January 2008 and March 2017, 556 patients who underwent HVPG and TE were consecutively enrolled. We evaluated LS, LPR, and LSPS according to the etiology of cirrhosis and analyzed their correlations with HVPG. @*Results@#The LS value was higher in patients with alcoholic cirrhosis than viral cirrhosis based on the HVPG (43.5 vs. 32.0 kPa, P<0.001). There were no significant differences in the LPR or LSPS between alcoholic and viral cirrhosis groups, and the areas under the curves for the LPR and LSPS in subgroups according to HVPG levels were not superior to that for LS. In alcoholic cirrhosis, the LS cutoff value for predicting an HVPG ≥10 mmHg was 32.2 kPa with positive predictive value (PPV) of 94.5% and 36.6 kPa for HVPG ≥12 mmHg with PPV of 91.0%. @*Conclusions@#The LS cutoff value should be determined separately for patients with alcoholic and viral cirrhosis. In alcoholic cirrhosis, the LS cutoff values were 32.2 and 36.6 kPa for predicting an HVPG ≥10 and ≥12 mmHg, respectively. However, there were no significant differences in the LPR or LSPS between alcoholic and viral cirrhosis groups.

Outcome Differences of RemnantPreserving versus Non-Preserving Methods in Arthroscopic Anterior Cruciate Ligament Reconstruction: A Meta-analysis with Subgroup analysis

Purpose@#To analyze differences in clinical outcomes of arthroscopic anterior cruciate ligament reconstruction between remnant-preserving and non-preserving methods. @*Methods@#International electronical databases PubMed, Embase, and the Cochrane central database from January 1966 to December 2017 were searched for randomized controlled trials (RCTs) and observational studies that compared differences of clinical outcomes of ACL reconstruction with and without remnant preservation. A metaanalysis of these studies was performed to compare clinical outcomes. Subgroup analyses were conducted to evaluate the role of methodological quality in primary meta-analysis estimates. @*Results@#Five RCTsand six observational studies were included in this meta-analysis and subgroup analysis. The remnant-preserving method in arthroscopic ACL reconstruction showed a statistically significant difference compared to the non-preserving method regarding arthrometric evaluation (side-to-side difference). Lachman test, Lysholm scores, and IKDC subjective scores showed statistically minor difference in meta-analysis, but showed no significant difference in subgroup analysis. Remained parameters including pivot shift test, IKDC grades, incidence of cyclops lesion showed no statistically differences in meta-analysis or subgroup analysis. @*Conclusions@#This meta-analysis with subgroup analysis showed that arthroscopic remnant-preserving ACL reconstruction provided statistically significant but limited clinical relevance in terms of arthrometric evaluation. @*Results@#of Lachman test, Lysholm scores, and IKDC subjective scores demonstrated statistically minor differences.

The Influence of Comorbidities on Reoperations Following Primary Surgery of Lumbar Degenerative Diseases : A Nationwide Population-Based Retrospective Cohort Study from 2009–2016

Objective@#: Spinal degeneration is a progressive disease, worsening over time. Lumbar degenerative disease (LDD) is a major spinal disease in elderly patients. Surgical treatment is considered for medically intractable patients with LDD and reoperation after primary surgery is not uncommon. The surgical outcome is occasionally unpredictable because of comorbidities. In the present study, the relationship between comorbidities and the incidence of reoperation for LDD over time was determined. @*Methods@#: The claims data of the health insurance national database were used to identify a cohort of patients who underwent spinal surgery for LDD in 2009. The patients were followed up until 2016. Medical comorbidity was assessed according to the Charlson comorbidity index (CCI). Cox proportional hazard regression modeling was used to identify significant differences in sex, surgery, age, causative disease, and comorbidity. @*Results@#: The study cohort included 78241 patients; 10328 patients (13.2%) underwent reoperation during the observation period. The reoperation rate was statistically higher (p<0.01) in males, patients 55–74 years and 65–74 years of age, and patients with decompression or discectomy. Significant association was found between increasing reoperation rate and CCI score (p<0.01). Based on multivariate analysis of comorbidities, the significantly higher reoperation rates were observed in patients with peripheral vascular disease, pulmonary lung disease, peptic ulcer, diabetes, and diabetes complications (p<0.01). @*Conclusion@#: The study results indicate the reoperation rate for LDD is associated with patient comorbidities. The comorbidities identified in this study could be helpful in future LDD studies.

Correlation of the grade of hepatic steatosis between controlled attenuation parameter and ultrasound in patients with fatty liver: a multi-center retrospective cohort study

Background/Aims@#The controlled attenuation parameter (CAP), based on transient elastography, is widely used for noninvasive assessment of the degree of hepatic steatosis (HS). We investigated the correlation of the degree HS between CAP and ultrasound (US) in patients with HS. @*Methods@#In total, 986 patients with US-based HS who underwent transient elastography within 1 month were evaluated. The US-based grade of HS was categorized as mild (grade 1), moderate (grade 2), or severe (grade 3). @*Results@#The CAP was significantly correlated with the US-based grade of HS (r = 0.458, p < 0.001). The median CAP value of each US-based HS grade showed a positive correlation with grade (271.1, 303.7, and 326.7 dB/m for grades 1, 2, and 3). In a multivariate analysis, the US-based HS grade, body mass index, serum albumin, alanine aminotransferase, and total cholesterol, and liver stiffness were all significantly correlated with the CAP value (all p < 0.05). The areas under the receiver operating characteristic curves for grade 2 to 3 and grade 3 HS were 0.749 (95% confidence interval [CI], 0.714 to 0.784) and 0.738 (95% CI, 0.704 to 0.772). The optimal cut-off CAP values to maximize the sum of the sensitivity and specificity for grade 2 to 3 and grade 3 HS were 284.5 dB/m (sensitivity 78.6%, specificity 61.7%) and 298.5 dB/m (sensitivity 84.6%, specificity 55.6%). @*Conclusions@#The correlation of the degree of HS between CAP and US was significantly high in patients with HS, and the optimal cut-off CAP values for grade 2 to 3 and grade 3 HS were 284.5 and 298.5 dB/m.

Bone Mineral Density in Diabetes Mellitus Foot Patients for Prediction of Diabetic Neuropathic Osteoarthropathic Fracture

Background@#Diabetic neuropathic osteoarthropathy (DNOAP) is known as debilitating diabetes complications. The aim of study is to compare bone mineral density (BMD) among diabetic foot and DNOAP, and investigate the impact of BMD proceeded from diabetic foot to DNOAP. @*Methods@#A DNOAP group (subgroup A and subgroup B) and control group were examined for this study. Subgroup A (n=21) were patients diagnosed with DNOAP with the development of new foot and ankle fractures, whereas subgroup B (n=4) were patients being managed with the diabetic foot before a diagnosis of DNOAP. BMD was also evaluated before the diagnosis. Control group (n=30) was diabetic foot patients without DNOAP. The demographic data, clinical and radiologic data, comorbidities, and BMD were compared for each group. And optimal BMD score was reviewed to predict fractures in neuropathic arthropathy. @*Results@#BMD was significantly lower in DNOAP group (group A and B) compared with control group. Also neuropathic arthropathy group showed poor radiological results. After comparisons of 2 group lumbar and femur BMD was significantly different, but logistic regression analysis revealed that low femur T-score could be risk predictors of the condition. Base on the data of group B and control group, the cut-off point for predicting foot and ankle fracture-related with DNOAP was -1.65 of femur BMD. @*Conclusions@#Low BMD shows greater incidence in foot and ankle fracture patients associated with neuropathic arthropathy. A femur T score can be a risk predictor of diabetic neuropathic arthropathy for diabetic foot patients.

Clinical Usefulness of ¹⁸F-FC119S Positron-Emission Tomography as an Auxiliary Diagnostic Method for Dementia: An Open-Label, Single-Dose, Evaluator-Blind Clinical Trial

Clinical outcomes of patients with a single hepatocellular carcinoma less than 5 cm treated with transarterial chemoembolization

BACKGROUND/AIMS@#Transarterial chemoembolization (TACE) is performed for single hepatocellular carcinoma (HCC) that are not eligible for surgery or ablation therapy. We investigated the clinical outcomes of patients with a single HCC ≤ 5 cm treated with TACE.@*METHODS@#This study analyzed 175 consecutive patients who underwent TACE as an initial treatment for single HCC ≤ 5 cm. Predictive factors for complete response (CR), recurrence after CR, and overall survival (OS) were evaluated.@*RESULTS@#Total 119 patients (68%) achieved CR after TACE. Tumor size 65 years and absence of liver cirrhosis were predictive factors for non-recurrence after CR (p < 0.05). The OS for all patients was 80.7 ± 5.6 months, and the 1-, 3-, and 5-year OS rates were 88.1%, 64.8%, and 49.9%, respectively. In multivariate analysis for OS, CR (hazard ratio [HR], 0.467; 95% confidence interval [CI], 0.292 to 0.747) and Child class A (HR, 0.390; 95% CI, 0.243 to 0.626) were significant factors. The OS for the CR and Child class A group were 92 and 93.6 months, respectively, and that of the non-CR and Child B, C group were 53.3 and 50.7 months, respectively (p < 0.001).@*CONCLUSIONS@#TACE can be a valid treatment in patients with a single HCC ≤ 5 cm not suitable for curative treatment, especially in patients with Child class A and CR after TACE.

Predictors of intentional intoxication using decision tree modeling analysis: a retrospective study

OBJECTIVE: The suicide rate in South Korea is very high and is expected to increase in coming years. Intoxication is the most common suicide attempt method as well as one of the common reason for presenting to an emergency medical center. We used decision tree modeling analysis to identify predictors of risk for suicide by intentional intoxication. METHODS: A single-center, retrospective study was conducted at our hospital using a 4-year registry of the institute from January 1, 2013 to December 31, 2016. Demographic factors, such as sex, age, intentionality, therapeutic adherence, alcohol consumption, smoking status, physical disease, cancer, psychiatric disease, and toxicological factors, such as type of intoxicant and poisoning severity score were collected. Candidate risk factors based on the decision tree were used to select variables for multiple logistic regression analysis. RESULTS: In total, 4,023 patients with intoxication were enrolled as study participants, with 2,247 (55.9%) identified as cases of intentional intoxication. Reported annual percentages of intentional intoxication among patients were 628/937 (67.0%), 608/1,082 (56.2%), 536/1,017 (52.7), 475/987 (48.1%) from 2013 to 2016. Significant predictors identified based on decision tree analysis were alcohol consumption, old age, psychiatric disease, smoking, and male sex; those identified based on multiple regression analysis were alcohol consumption, smoking, male sex, psychiatric disease, old age, poor therapeutic adherence, and physical disease. CONCLUSION: We identified important predictors of suicide risk by intentional intoxication. A specific and realistic approach to analysis using the decision tree modeling technique is an effective method to determine those groups at risk of suicide by intentional intoxication.

Is higher dose always the right answer in stereotactic body radiation therapy for small hepatocellular carcinoma?

PURPOSE: This study was conducted to compare clinical outcomes and treatment-related toxicities after stereotactic body radiation therapy (SBRT) with two different dose regimens for small hepatocellular carcinomas (HCC) ≤3 cm in size. MATERIALS AND METHODS: We retrospectively reviewed 44 patients with liver-confined HCC treated between 2009 and 2014 with SBRT. Total doses of 45 Gy (n = 10) or 60 Gy (n = 34) in 3 fractions were prescribed to the 95% isodose line covering 95% of the planning target volume. Rates of local control (LC), intrahepatic failure-free survival (IHFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Median follow-up was 29 months (range, 8 to 64 months). Rates at 1 and 3 years were 97.7% and 95.0% for LC, 97.7% and 80.7% for OS, 76% and 40.5% for IHFFS, and 87.3% and 79.5% for DMFS. Five patients (11.4%) experienced degradation of albumin-bilirubin grade, 2 (4.5%) degradation of Child-Pugh score, and 4 (9.1%) grade 3 or greater laboratory abnormalities within 3 months after SBRT. No significant difference was seen in any oncological outcomes or treatment-related toxicities between the two dose regimens. CONCLUSIONS: SBRT was highly effective for local control without severe toxicities in patients with HCC smaller than 3 cm. The regimen of a total dose of 45 Gy in 3 fractions was comparable to 60 Gy in efficacy and safety of SBRT for small HCC.

Effect of intraperitoneal CO₂ concentration on postoperative pain after laparoscopic cholecystectomy

PURPOSE: This study set out to identify the association between the intraperitoneal CO₂ concentrations and postoperative pain by dividing the participants into a control group and 2 experimental groups receiving irrigation (1 L and 2 L), and directly measuring their intraperitoneal CO₂ concentrations with a CO₂ gas detector. METHODS: A total of 101 patients, American Society of Anesthesiologists physical status classification I and II patients aged 18–65 years were enrolled in the study. Group 1 did not receive irrigation with normal saline, while groups 2 and 3 were administered irrigation with 1 L and 2 L of normal saline, respectively, after laparoscopic cholecystectomy. Intraperitoneal CO₂ concentrations were measured with a CO₂ gas detector through the port, and postoperative pain was assessed on a visual analogue scale at 6, 12, and 24 hours after surgery. RESULTS: The intraperitoneal CO₂ concentrations were 1,016.0 ± 960.3 ppm in group 1, 524.5 ± 383.2 ppm in group 2, and 362.2 ± 293.6 ppm in group 3, showing significantly lower concentrations in groups 2 and 3. Postoperative pain was significantly lower in group 3 at 6 hours after surgery, and in groups 2 and 3 at 12 hours after the surgery. However, there was no significant difference between the 3 groups in postoperative pain 24 hours after the surgery. CONCLUSION: This study found a causal relationship between the amount of normal saline used for irrigation and the intraperitoneal CO₂ concentrations in that irrigation with normal saline reduces pain on the day of the surgery.

Urine Methyl Hippuric Acid Levels in Acute Pesticide Poisoning: Estimation of Ingested Xylene Volume and Association with Clinical Outcome Parameters

To determine the relationship between the oral ingestion volume of xylene and methyl hippuric acid (MHA) in urine, we measured MHA in 11 patients whose ingested xylene volume was identified. The best-fit equation between urine MHA and ingested amount of xylene was as follows: y (ingested amount of xylene, mL/kg) = −0.052x² + 0.756x (x = MHA in urine in g/g creatinine). From this equation, we estimated the ingested xylene volume in 194 patients who had ingested pesticide of which the formulation was not available. Our results demonstrated that oxadiazole, dinitroaniline, chloroacetamide, organophosphate, and pyrethroid were xylene-containing pesticide classes, while the paraquat, glyphosate, glufosinate, synthetic auxin, fungicide, neonicotinoid, and carbamate classes were xylene-free pesticides. Sub-group univariate analysis showed a significant association between MHA levels in urine and ventilator necessity in the pyrethroid group. However, this association was not observed in the organophosphate group. Our results suggest that MHA in urine is a surrogate marker for xylene ingestion, and high urine MHA levels may be a risk factor for poor clinical outcome with some pesticide poisoning.

Predictive Factors for Complete Response and Recurrence after Transarterial Chemoembolization in Hepatocellular Carcinoma

BACKGROUND/AIMS: To investigate the predictive factors for complete response (CR) and recurrence after CR in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). METHODS: Among 691 newly diagnosed HCC patients, 287 were treated with TACE as a first therapy. We analyzed the predictive factors for CR, recurrence after CR, and overall survival (OS). RESULTS: Eighty-one patients (28.2%) achieved CR after TACE, and recurrence after CR was detected in 35 patients (43.2%). In multivariate analyses, tumor size (≤5 cm) and single nodularity were predictive factors for CR, with hazard ratios (HRs) of 0.35 (p=0.002) and 0.41 (p20 ng/mL) level and multinodularity exhibited significant relationships with recurrence after CR, with HRs of 2.220 (p=0.026) and 3.887 (p5 cm), multinodularity, elevated serum AFP (>20 ng/mL) level, Child-Turcotte-Pugh score (B and C), and portal vein thrombosis were significant factors for OS. CONCLUSIONS: In patients treated with TACE as a first therapy, tumor size (≤5 cm) and single nodularity were predictive factors for CR, and multinodularity and elevated serum AFP (>20 ng/mL) levels were predictive factors for recurrence after CR. These factors were also significant for OS.

Incidence and Prevalence of Myasthenia Gravis in Korea: A Population-Based Study Using the National Health Insurance Claims Database

BACKGROUND AND PURPOSE: There have been a few national population-based epidemiological studies of myasthenia gravis (MG) with wide variation of incidence and prevalence rates worldwide. Herein we report the first nationwide population-based epidemiological study of MG in Korea. METHODS: We attempted to estimate the incidence and prevalence rates of MG using the Korean National Health Insurance claims database for 2010 to 2013. Cases with MG were defined as those having claim records with a principal diagnosis of MG and the prescription of acetylcholinesterase inhibitors or immunosuppressive agents including corticosteroids and azathioprine within 2 years after the diagnosis. The year 2010 was set as a washout period, such that patients were defined as incident cases if their first records of MG were observed in 2011. RESULTS: In 2011 there were 1,236 incident cases, and the standardized incidence rate was 2.44 per 100,000 person-years. The standardized prevalence rates were 9.67 and 10.66 per 100,000 persons in 2010 and 2011, respectively. The incidence and prevalence rates peaked in the elderly population aged 60 to 69 years for both sexes. CONCLUSIONS: This is one of the largest national population-based epidemiological studies of MG, and it has confirmed the high incidence and prevalence rates of MG in the elderly population of South Korea.

Reference Range of Respiratory Muscle Strength and Its Clinical Application in Amyotrophic Lateral Sclerosis: A Single-Center Study

BACKGROUND AND PURPOSE: Evaluating respiratory function is important in neuromuscular diseases. This study explored the reference ranges of the maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and sniff nasal inspiratory pressure (SNIP) in healthy adults, and applied them to amyotrophic lateral sclerosis (ALS) patients. METHODS: MIP, MEP, and SNIP were measured in 67 healthy volunteers aged from 21 to 82 years. Reference ranges were evaluated by multivariate regression analysis using the generalized additive modeling of location, scale, and shape method. Thirty-six ALS patients were reviewed retrospectively, and abnormal values of MIP, MEP, and SNIP were determined according to the reference ranges. RESULTS: MIP, MEP, and SNIP were abnormal in 57.1%, 51.4%, and 25.7% of the ALS patients, respectively. MIP and SNIP were significantly correlated with the degree of restrictive pattern and respiratory symptoms. The ALS Functional Rating Scale-Revised score was correlated with SNIP. CONCLUSIONS: This study has provided the reference range of respiratory muscle strength in healthy adults. This range is suitable for evaluating respiratory function in ALS patients.

Rapidly resolved IgG4-related retroperitoneal fibrosis after steroid pulse therapy / 영남의대학술지

Retroperitoneal fibrosis (RF) is a disorder characterized by the presence of a retroperitoneal mass and concurrent systemic inflammation. Some cases of RF are recognized as belonging to the spectrum of immunoglobulin G4-related disease (IgG4-RD). Glucocorticoids are highly effective for treatment of retroperitoneal fibrosis, although the optimal dose and duration of therapy have not been established. An initial dose of prednisone (40-60 mg) daily is usually administered with a tapering scheme. We report on a 55-year-old man diagnosed with IgG4-related RF and successfully treated with a 3-day course of daily 250 mg (4 mg/kg) intravenous methylprednisolone, which resulted in the prompt resolution of urinary obstruction and systemic symptoms.

Tumor Volume Reduction Rate during Adaptive Radiation Therapy as a Prognosticator for Nasopharyngeal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to evaluate the prognostic significance of the tumor volume reduction rate (TVRR) measured during adaptive definitive radiation therapy (RT) for nasopharyngeal cancer (NPC). MATERIALS AND METHODS: We reviewed the RT records of 159 NPC patients treated with definitive RT with or without concurrent chemotherapy between January 2006 and February 2013. Adaptive re-planning was performed in all patients at the third week of RT. The pre- and mid-RT gross tumor volumes (GTVs) of the primary tumor and the metastatic lymph nodes were measured and analyzed for prognostic implications. RESULTS: After a median follow-up period of 41.5 months (range, 11.2 to 91.8 months) for survivors, there were 43 treatment failures. The overall survival and progression-free survival (PFS) rates at 5 years were 89.6% and 69.7%, respectively. The mean pre-RT GTV, mid-RT GTV, and TVRR were 45.9 cm3 (range, 1.5 to 185.3 cm3), 26.7 cm3 (1.0 to 113.8 cm3), and -41.9% (range, -87% to 78%), respectively. Patients without recurrence had higher TVRR than those with recurrence (44.3% in the no recurrence group vs. 34.0% in the recurrence group, p=0.004), and those with TVRR > 35% achieved a significantly higher rate of PFS at 5 years (79.2% in TVRR > 35% vs. 53.2% in TVRR ≤ 35%; p < 0.001). In multivariate analysis, TVRR was a significant factor affecting PFS (hazard ratio, 2.877; 95% confidence interval, 1.555 to 5.326; p=0.001). CONCLUSION: TVRR proved to be a significant prognostic factor in NPC patients treated with definitive RT, and could be used as a potential indicator for early therapeutic modification during the RT course.

The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication

Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na+, K+, Cl- HCO3 -, Ca++), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication.

The effects of nonyl phenoxypolyethoxyl ethanol on cell damage pathway gene expression in SK-NSH cells

BACKGROUND/AIMS: Most pesticide formulations contain both chief and additive ingredients. But, the additives may not have been tested as thoroughly as the chief ingredients. The surfactant, nonyl phenoxypolyethoxylethanol (NP40), is an additive frequently present in pesticide formulations. We investigated the effects of NP40 and other constituents of a validamycin pesticide formulation on cell viability and on the expression of genes involved in cell damage pathways. METHODS: The effects of validamycin pesticide ingredients on cell viability and of NP40 on the mRNA expression of 80 genes involved in nine key cellular pathways were examined in the human neuroblastoma SK-N-SH cell line. RESULTS: The chemicals present in the validamycin pesticide formulation were cytotoxic to SK-N-SH cells and NP40 showed the greatest cytotoxicity. A range of gene expression changes were identified, with both up- and down-regulation of genes within the same pathway. However, all genes tested in the necrosis signaling pathway were down-regulated and all genes tested in the cell cycle checkpoint/arrest pathway were up-regulated. The median fold-change in gene expression was significantly higher in the cell cycle checkpoint/arrest pathway than in the hypoxia pathway category (p = 0.0064). The 70 kDa heat shock protein 4 gene, within the heat shock protein/unfolded protein response category, showed the highest individual increase in expression (26.1-fold). CONCLUSIONS: NP40 appeared to be particularly harmful, inducing gene expression changes that indicated genotoxicity, activation of the cell death (necrosis signaling) pathway, and induction of the 70 kDa heat shock protein 4 gene.