Development and validation of an interpretable model for predicting sepsis mortality across care settings.

There are numerous prognostic predictive models for evaluating mortality risk, but current scoring models might not fully cater to sepsis patients' needs. This study developed and validated a new model for sepsis patients that is suitable for any care setting and accurately forecasts 28-day mortality. The derivation dataset, gathered from 20 hospitals between September 2019 and December 2021, contrasted with the validation dataset, collected from 15 hospitals from January 2022 to December 2022. In this study, 7436 patients were classified as members of the derivation dataset, and 2284 patients were classified as members of the validation dataset. The point system model emerged as the optimal model among the tested predictive models for foreseeing sepsis mortality. For community-acquired sepsis, the model's performance was satisfactory (derivation dataset AUC: 0.779, 95% CI 0.765-0.792; validation dataset AUC: 0.787, 95% CI 0.765-0.810). Similarly, for hospital-acquired sepsis, it performed well (derivation dataset AUC: 0.768, 95% CI 0.748-0.788; validation dataset AUC: 0.729, 95% CI 0.687-0.770). The calculator, accessible at https://avonlea76.shinyapps.io/shiny_app_up/ , is user-friendly and compatible. The new predictive model of sepsis mortality is user-friendly and satisfactorily forecasts 28-day mortality. Its versatility lies in its applicability to all patients, encompassing both community-acquired and hospital-acquired sepsis.

Relationship between body mass index and risk of delirium in an intensive care unit.

OBJECTIVE: Delirium in the intensive care unit (ICU) is a common and critical condition that leads to poor prognosis in older patients, but the association between body mass index (BMI) and the incidence of delirium remains unclear. METHODS: We retrospectively analyzed 5,622 patients admitted to the ICU of a tertiary referral hospital between 2013 and 2022. We collected sociodemographic data, vital signs, laboratory results, and delirium scale scores. We subdivided the patients into four categories: underweight (<18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (>25 kg/m2). The primary outcome was the incidence of delirium according to the BMI categories. We performed multivariable logistic regression analysis, adjusted for sex, age, past smoking and alcohol history, benzodiazepine use, and laboratory abnormalities. RESULTS: Among the 5,622 patients in the ICU (mean age, 72.9 years; male, 60.1%; mean BMI, 24.2 kg/m2), the incidence of delirium was 19.0% (1,069 patients). The mean modified incidence of delirium was higher among underweight patients (odds ratio [OR]=1.51, confidence interval [CI]=1.07-2.12, p = 0.02) than among normal-weight patients. Overweight and obese status were not independently associated with delirium (OR=0.90, CI=0.70-1.17, p = 0.43; OR= 0.97; CI=0.77-1.21, p = 0.78, respectively). The area under the receiver-operating characteristic curve of the multivariable logistic regression model was 0.71 (95% CI=0.69-0.73). CONCLUSIONS: Underweight status is an independent risk factor for delirium in the ICU. Additional caution is required when evaluating underweight patients for delirium. Obese or overweight status are not associated with delirium, providing evidence for the obesity paradox.

The Relationship between Delirium and Statin Use According to Disease Severity in Patients in the Intensive Care Unit.

Objective: The aim of this study was to investigate the association between the use of statins and the occurrence of delirium in a large cohort of patients in the intensive care unit (ICU), considering disease severity and statin properties. Methods: We obtained clinical and demographical information from 3,604 patients admitted to the ICU from January 2013 to April 2020. This included information on daily statin use and delirium state, as assessed by the Confusion Assessment Method for ICU. We used inverse probability of treatment weighting and categorized the patients into four groups based on the Acute Physiology and Chronic Health Evaluation II score (group 1: 0-10 - mild; group 2: 11-20 - mild to moderate; group 3: 21-30 - moderate to severe; group 4: > 30 - severe). We analyzed the association between the use of statin and the occurrence of delirium in each group, while taking into account the properties of statins. Results: Comparisons between statin and non-statin patient groups revealed that only in group 2, patients who were administered statin showed significantly higher occurrence of delirium (p = 0.004, odds ratio [OR] = 1.58) compared to the patients who did not receive statin. Regardless of whether statins were lipophilic (p = 0.036, OR = 1.47) or hydrophilic (p = 0.032, OR = 1.84), the occurrence of delirium was higher only in patients from group 2. Conclusion: The use of statins may be associated with the increases in the risk of delirium occurrence in patients with mild to moderate disease severity, irrespective of statin properties.

Potential Usefulness of Blood Urea Nitrogen to Creatinine Ratio in the Prediction and Early Detection of Delirium Motor Subtype in the Intensive Care Unit.

Prediction and early detection of delirium can improve patient outcomes. A high blood urea nitrogen to creatinine ratio (BCR), which reflects dehydration, has been reported as a risk factor for delirium. Additionally, BCR represents skeletal muscle loss in intensive care unit (ICU) patients, which can have critical implications for clinical outcomes. We investigated whether BCR could be used to predict the occurrence and motor subtype of delirium in ICU patients through a retrospective cohort study that included 7167 patients (50 years or older) admitted to the ICU. Patients were assessed daily using the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for ICU and categorized according to the delirium subtype. Participants were split into 10 groups according to BCR at ICU admission and the prevalence of each delirium subtype was compared. Multivariable logistic regression was then used for analysis. A higher BCR at ICU admission was associated with the development of hypoactive delirium. Moreover, BCR > 24.9 was associated with higher rates of hypoactive delirium. Our findings showed that a high BCR at ICU admission was associated with the development of hypoactive delirium, which suggested that BCR could be a potential biomarker for hypoactive delirium in ICU patients.

Delirium and Anxiety Outcomes Related to Visiting Policy Changes in the Intensive Care Unit During the COVID-19 Pandemic.

Objective: To evaluate the effect of intensive care unit (ICU) visit on the incidence of delirium, delirium subtype, and anxiety level in ICU patients. Methods: Trained psychiatrists and nurses evaluated ICU patients for delirium, delirium subtypes, and anxiety. Propensity score matching (PSM) was used to retrospectively analyze the data. Then, we compared the differences in the incidence of delirium, delirium subtypes, and anxiety level before and after the ICU visit ban. Logistic regression was conducted to identify the risk factors for delirium subtypes and high anxiety levels. Results: After PSM, there was no statistically significant difference in the incidence of delirium between the non-visiting and restrictive visiting groups (non-visiting 27.4% versus restrictive visiting 30.9%, p = 0.162). The proportion of hyperactive and mixed subtypes was higher in the non-visiting than in the restrictive visiting group (non-visiting 35.3 and 30.1% versus restrictive visiting 27.7 and 20.1%, p = 0.002). The anxiety level was higher in the non-visiting than in the restrictive visiting group (state-trait anxiety inventory score: non-visiting 53.46 ± 4.58 versus restrictive visiting 52.22 ± 6.50, p = 0.009). Patients who stayed in the ICU during the visit ban were more likely to have hyperactive (p = 0.005) and mixed subtype (p = 0.001) than those who did not. Moreover, patients who stayed in the ICU during the visit ban were more likely to experience high anxiety levels than those who did not (p < 0.001). Conclusion: Prohibition of ICU visits during COVID-19 pandemic did not affect the incidence of delirium during COVID-19 but could change the delirium subtype and raise anxiety level. Moreover, visiting prohibition was a risk factor for non-hypoactive delirium subtype and high anxiety levels. Therefore, ICU visits are important in dealing with delirium subtypes and anxiety in ICU patients.

Neutrophil-Lymphocyte Ratio as a Potential Biomarker for Delirium in the Intensive Care Unit.

Background: Recognition and early detection of delirium in the intensive care unit (ICU) is essential to improve ICU outcomes. To date, neutrophil-lymphocyte ratio (NLR), one of inflammatory markers, has been proposed as a potential biomarker for brain disorders related to neuroinflammation. This study aimed to investigate whether NLR could be utilized in early detection of delirium in the ICU. Methods: Of 10,144 patients who admitted to the ICU, 1,112 delirium patients (DE) were included in the current study. To compare among inflammatory markers, NLR, C-reactive protein (CRP), and white blood cell (WBC) counts were obtained: the mean NLR, CRP levels, and WBC counts between the initial day of ICU admission and the day of initial delirium onset within DE were examined. The inflammatory marker of 1,272 non-delirium patients (ND) were also comparatively measured as a supplement. Further comparisons included a subgroup analysis based on delirium subtypes (non-hypoactive vs. hypoactive) or admission types (elective vs. emergent). Results: The NLR and CRP levels in DE increased on the day of delirium onset compared to the initial admission day. ND also showed increased CRP levels on the sixth day (the closest day to average delirium onset day among DE) of ICU admission compared to baseline, while NLR in ND did not show significant difference over time. In further analyses, the CRP level of the non-hypoactive group was more increased than that of the hypoactive group during the delirium onset. NLR, however, was more significantly increased in patients with elective admission than in those with emergent admission. Conclusion: Elevation of NLR was more closely linked to the onset of delirium compared to other inflammatory markers, indicating that NLR may play a role in early detection of delirium.

Multiple hypercoagulability disorders at presentation of non-small-cell lung cancer.

Hypercoagulability disorders are commonly encountered in clinical situations in patients with a variety of cancers. However, several hypercoagulability disorders presenting as first symptoms or signs in cancer patients have rarely been reported. We herein described a case of a woman with adenocarcinoma of the lung presenting with deep vein thrombosis, nonbacterial thrombotic endocarditis, recurrent cerebral embolic infarction, and heart failure.

Prognostic impact of minimal pleural effusion in non-small-cell lung cancer.

PURPOSE: Minimal (< 10 mm thick) pleural effusion (PE) may represent an early phase of malignant PE, but its clinical relevance has rarely been studied. Therefore, we examined the proportion of minimal PE in patients with non-small-cell lung cancer (NSCLC) and its impact on survival. We also considered possible accumulation mechanisms in our data set. PATIENTS AND METHODS: On the basis of PE status from chest computed tomography scans at diagnosis, 2,061 patients were classified into three groups: no PE, minimal PE, and malignant PE. Twenty-one variables associated with four factors-patient, stage migration, tumor, and treatment-were investigated for correlation with survival. RESULTS: Minimal PE presented in 272 patients (13.2%). Of 2,061 patients, the proportion of each stage was the following: 5.2% stage I, 10.9% stage II, 13.2% stage IIIA, 23.8% stage IIIB, and 13.9% stage IV. Minimal PE correlated significantly with shorter survival time than did no PE (median survival time, 7.7 v 17.7 months; log-rank P < .001), even after full adjustment with all variables (adjusted hazard ratio, 1.40; 95% CI, 1.21 to 1.62). Prognostic impact of minimal PE was higher in early versus advanced stages (Pinteraction = .001). In 237 patients (87.8%) with minimal PE, pleural invasion or attachment as a direct mechanism was observed, and it was an independent factor predicting worse survival (P = .03). CONCLUSION: Minimal PE is a commonly encountered clinical concern in staging NSCLCs. Its presence is an important prognostic factor of worse survival, especially in early-stage disease.

Erlotinib induced trichomegaly of the eyelashes.

Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used for non-small-cell lung cancer patients. Its untoward cutaneous effects are largely well known and developed in many patients treated with EGFR TKIs. However trichomegaly of eyelash is rarely reported. Although trichomegaly is not a drug-limiting side effect, it could be troublesome of continuing the treatment because of cosmetic issue or eyeball irritation by long eyelashes. Therefore clinicians are needed to pay attention to this uncommon effect. We herein describe erlotinib induced trichomegaly of eyelashes in a woman with adenocarcinoma of the lung.

Lack of association of genetic variations of deoxycytidine kinase with toxicity or survival of non-small-cell lung cancer patients treated with gemcitabine plus cisplatin.

The aim of this study was to determine whether tagging polymorphisms (tSNPs) of deoxycytidine kinase (DCK) have an effect on toxicity or prognosis in patients with non-small-cell lung cancer (NSCLC) treated with gemcitabine plus cisplatin. Three tSNPs (-201 C>T, rs2306744; IVS2+9846 G>A, rs12648166; IVS6+1392 T>C, rs4694362) were chosen using the international HapMap Project and Japanese Single-Nucleotide Polymorphisms. We evaluated the associations of the tSNPs with hematologic toxicity or overall survival of 139 NSCLC patients at stages IIIA/IIIB (59) and IV (80). Hematologic toxicity such as neutropenia, thrombocytopenia, and anemia were not different by the three tSNPs or haplotypes (CGT, CAT, and CAC) of DCK. The genetic variations did not affect survival of the patients (log-rank p: 0.248 for -201 C>T, 0.571 for IVS2+9846 G>A, 0.686 for IVS6+1392 T>C, 0.556 for CGT, 0.453 for CAT, and 0.845 for CAC). In a Cox model, these tSNPs and haplotypes did not reveal prognostic relevance (aHR and 95% CI: 0.954 and 0.611 to 1.489 for -201 C>T; 1.193 and 0.719 to 1.979 for IVS2+9846 G>A; 1.072 and 0.674 to 1.706 for IVS6+1392 T>C, 0,668 and 0.205 to 2.175 for CGT, 1.043 and 0.713 to 1.525 for CAT, and 1.043 and 0.701 to 1.550 for CAC). This is the first study to focus on the association of tSNPs and their haplotypes of DCK with toxicity and survival in NSCLC patients. This suggests that genetic variations of DCK have no effect on the outcomes in the patients treated with gemcitabine-based chemotherapy.

Prognostic effect of age on survival of patients with stage I adenocarcinoma of the lung.

AIMS AND BACKGROUND: It is still unclear whether age is an independent prognostic factor in patients with stage I NSCLC. METHODS: Five hundred and sixty-nine patients with stage I adenocarinoma who underwent surgical resection as first treatment were included. The effect on overall survival of age, gender, smoking habits, Charlson comorbidity index score (CCIS), type of surgery, tumor size and lymphatic or blood vessel invasion was analyzed. RESULTS: When the patients were divided into four groups according to quartiles of age, distributions of gender, smoking habit, CCIS, histology, blood vessel invasion and adjuvant chemotherapy were significantly different among the four groups. Age, gender, smoking habit, CCIS, tumor size and lymphatic and blood vessel invasion were significantly associated with overall survival of the patients in Kaplan-Meier analysis (logrank, P <0.001, P <0.001, P = 0.029, P <0.001, P = 0.001, P = 0.001 and P = 0.007, respectively). Moreover, the highest quartile of age (over 68 years old) was a prominent determinant for a worse prognosis after adjustment for the confounding variables using a Cox proportional hazard model (adjusted hazard ratio = 2.735, 95% confidence interval = 1.623-4.608, P <0.001). CONCLUSIONS: The findings suggest that age is an important determinant of overall survival in patients with stage I adenocarcinoma. Therefore, age should be considered in classifying the patients into groups of higher or lower risk for death as well as in designing clinical trials.

Gender differences in susceptibility to smoking among patients with lung cancer.

BACKGROUND/AIMS: To determine whether female smokers are more or less susceptible to the detrimental pulmonary-function effects of smoking when compared to male smokers among patients with lung cancer. METHODS: Pack-years and pulmonary function indices were compared between 1,594 men and women with lung cancer who were smokers or had a history of smoking. Differences in individual susceptibility to smoking were estimated using a susceptibility index formula. RESULTS: Of the patients, 959 (92.8%) men and 74 (7.2%) women were current smokers. Common histological types of lung cancer were squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, among others. Women had a lower number of pack-years, forced expiratory volume in 1 second (FEV(1), liters), forced vital capacity (FVC, liters), and total lung capacity (TLC, liters) compared to those of men (25.0 ± 19.2 vs. 42.9 ± 21.7 for pack-years; 1.4 ± 0.5 vs. 2.0 ± 0.6 for FEV(1); 3.0 ± 0.7 vs. 2.0 ± 0.6 for FVC; 4.5 ± 0.8 vs. 5.7 ± 1.0 for TLC; all p < 0.001). The susceptibility index for women was significantly higher compared to that of men (1.1 ± 4.1 vs. 0.7 ± 1.1; p = 0.001). A significant inverse association was shown between the susceptibility index and TLC and FVC (r = -0.200 for TLC, -0.273 for FVC; all p < 0.001). CONCLUSIONS: The results suggest that the detrimental effects of smoking on pulmonary function are greater in women, as compared to those in men, among patients with lung cancer.

Differential effect of polymorphisms of CMPK1 and RRM1 on survival in advanced non-small cell lung cancer patients treated with gemcitabine or taxane/cisplatinum.

INTRODUCTION: To determine whether genetic variations in CMPK1 or RRM1, which impact the pharmacodynamics of gemcitabine, differentially affect the outcomes of non-small cell lung cancer (NSCLC) patients treated with gemcitabine or taxane/cisplatinum. METHODS: We conducted retrospective study evaluating the associations between overall survival in 298 NSCLC patients at stages IIIA/IIIB (140) and IV (158), treated with gemcitabine (139) or taxane (159)/cisplatinum and 14 tagging single-nucleotide polymorphisms (tSNPs): 4 in CMPK1 and 10 in RRM1. RESULTS: The wild-type genotypes of CMPK1 IVS1+1057 and IVS1-928 were associated with shorter overall survival in patients treated with the gemcitabine/cisplatinum (adjusted hazards ratio = 1.97 and 1.89; Cox pBonferroni = 0.008 and 0.020), whereas this effect was not observed in patients treated with taxane/cisplatinum. No associations were observed for the other 2 CMPK1 or 10 RRM1 tSNPs. Analysis of the interaction between the CMPK1 and RRM1 genes showed that the survival of patients with CMPK1 IVS1+1057 CC and RRM1 IVS1-2374 TT, IVS7+25 AA, IVS7-425 AA, or IVS8+287 TT was significantly shorter when they were treated with the gemcitabine/cisplatinum (adjusted hazards ratio = 3.00, 2.89, 3.14, and 3.00; Cox pBonferroni = 0.007, 0.012, 0.006, and 0.007). However, these effects were not observed in patients treated with taxane/cisplatinum. CONCLUSIONS: These findings suggest that polymorphisms of CMPK1 and their combination with those of RRM1 are helpful in identifying patients who will benefit less from a gemcitabine/cisplatinum as the first-line regimen.

Fluorescence "turn-on" patterning with polymers having pendant triphenylmethane groups as fluorophore precursors.

A new methodology for creating patterned fluorescence images was developed based on acrylate polymers that have pendant triphenylmethane derivatives as precursor fluorophores. Photoinduced oxidation of the substituted nonfluorescent triphenylmethane substituents on the polymers results in the generation of fluorescent cationic species. Patterned fluorescence images were obtained when the polymer film was subjected to photomasked UV-irradiation. The rate of formation and quality of the patterned images were found to be dependent on the nature of substituents on the methane carbon of the triphenylmethane group. Inefficient image formation takes place with the polymer derived from the H-substituted derivative owing to the inefficient oxidation of the triphenylmethane group. In contrast, photomasked UV-irradiation of a thin polymer film derived from the CN-substituted triphenylmethane derivative leads to fast (1 s irradiation, 12 mW · cm(-2)) and finely resolved patterned fluorescence images.

Effect of BRCA1 haplotype on survival of non-small-cell lung cancer patients treated with platinum-based chemotherapy.

PURPOSE: To determine whether germ-line variations in BRCA1 affect outcome in non-small-cell lung cancer (NSCLC) patients treated with platinum combination chemotherapy. PATIENTS AND METHODS: We evaluated the associations of four tagging BRCA1 polymorphisms and their haplotypes with treatment outcome in 300 NSCLC patients at stages IIIA (16%), IIIB (31%), and IV (53%). RESULTS: The median age was 63 years (range, 28 to 89 years). Histologically, 139 (46.3%) of the patients had squamous cell carcinomas and 137 (45.7%) had adenocarcinomas. Patient median survival time (MST) was 13.0 months. We observed no significant association between any of the tagging polymorphisms [S1613G, IVS13-1893 (A>C), IVS12-1207 (C>T), and IVS12+112 (C>A)] and overall survival. Of the five haplotypes evaluated (AACC, AACA, GCTC, GATC, and AATC), the survival of patients with two copies of the AACC (wild-type) haplotype was significantly shorter than that of patients with zero to one copies (MST, 8.47 v 14.57 months; log-rank P = .0066), even after adjustment for body weight loss, performance status, stage, second-line treatment, and radiation therapy (hazard ratio = 2.097; 95% CI, 1.339 to 3.284). The survival of patients with squamous cell carcinoma and two copies was significantly shorter than that of other patients with squamous cell carcinoma (MST, 6.8 v 15.3 months; log-rank P = 3.6 x 10(-5)), whereas differences in survival between the two adenocarcinoma groups was not significant (log-rank P = .677). CONCLUSION: These findings suggest that the AACC haplotype of the BRCA1 gene is an important prognostic marker in NSCLC patients treated with platinum combination chemotherapy.

Effect of ERCC1 polymorphisms and the modification by smoking on the survival of non-small cell lung cancer patients.

A few reports for ERCC1 SNPs were conducted in patients treated with cisplatin chemotherapy. The aim of this study is to determine whether the SNPs are a prognostic factor related to the treatment or not and if smoking level of the patients have any relationship to the SNPs' effect on the survival. Peripheral blood lymphocytes of 423 consecutive non-small cell lung cancer patients were examined: 245 of the patients received cisplatin combination chemotherapy and 178 received only conservative care. We examined ERCC1 SNPs (codon 118 C/T and 8092 C/A). Whereas ERCC1 118 SNP had no effect on the survival in patients' given no treatment, an effect of the SNP was observed in the treatment group, especially in stage III. When smoking was considered, the risk effect of the T allele was shown to be significantly associated with the group that had more than 50 pack yr (p=0.03). As for the ERCC1 8092 C/A, no significant effects were observed in the treated group and the non-treatment group. These findings may suggest that the ERCC1 118 SNP is an useful prognostic factor related to cisplatin therapy and the effect of this polymorphism appears to be modified by smoking.

A case of pulmonary cryptococcosis with non-small cell lung cancer in idiopathic CD4+ T-lymphocytopenia.

Cryptococcus neoformans commonly causes opportunistic infections in immunocompromised patients, especially in patients with AIDS. CD4+ T-lymphocytopenia in AIDS indicates an increased risk of opportunistic infection and a decline in immunological function. Idiopathic CD4 T-lymphocytopenia (ICL) is characterized by depletions in the CD4+ T-cell subsets, without evidence of HIV infection. Immunodeficiency can exist in the absence of laboratory evidence of HIV infection, and T-cell subsets should be evaluated in patients who present with unusual opportunistic infections. We report a case of pulmonary cryptococcosis and lung cancer in a patient with persistently low CD4+ cell counts, without evidence of HIV infection.

Occupational asthma due to azodicarbonamide.

Azodicarbonamide is a low molecular weight foaming agent for plastics and rubbers. Azodicarbonamide can elicit acute and chronic health related problems due to its potential for pulmonary and cutaneous sensitization. Some cases of occupational asthma associated with exposure to azodicarbonamide have been reported, of which only a few cases were confirmed by specific inhalation challenges. Here, the first case of occupational asthma due to azodicarbonamide in Korea, in which the diagnosis was confirmed by specific inhalation challenge, is reported.