Traditional Chinese Medicine Xuebijing Treatment Is Associated with Decreased Mortality Risk of Patients with Moderate Paraquat Poisoning

Paraquat poisoning causes multiple organ injury and high mortality due to severe toxicity and lack of effective treatment. Xuebijing (XBJ) injection, a traditional Chinese medicine preparation of five Chinese herbs (Radix Salviae Miltiorrhiae, Rhizoma Chuanxiong, Flos Carthami, Angelica Sinensis and Radix Paeoniae Rubra), has an anti-inflammatory effect and is widely used in the treatment of sepsis. This retrospective study was designed to evaluate the effects of XBJ combined with conventional therapy on mortality risk of patients with acute paraquat poisoning. Out of 68 patients, 27 were treated with conventional therapy (control group) and 41 were treated with intravenous administration of XBJ (100 ml, twice a day, up to 7 days) plus conventional therapy (XBJ group). Vital organ function, survival time within 28 days and adverse events during the treatment were reviewed. Results indicated that XBJ treatment significantly increased median survival time among patients ingesting 10-30 ml of paraquat (P=0.02) compared with the control group. After adjustment for covariates, XBJ treatment was associated significantly with a lower mortality risk (adjusted HR 0.242, 95% CI 0.113 to 0.516, P=0.001) compared with the control group. Additionally, compared with Day 1, on Day 3 the value of PaO₂/FiO₂ was significantly decreased, and the values of serum alanine aminotransferase, creatinine and troponin T were significantly increased in the control group (all P<0.05), but these values were significant improved in the XBJ group (all P<0.05). Only one patient had skin rash with itch within 30 minutes after injection and no severe adverse events were found in the XBJ group. In conclusion, XBJ treatment is associated with decreased mortality risk of patients with moderate paraquat poisoning, which may be attributed to improved function of vital organs with no severe adverse events.     

Effective Treatment for Paraquat Poisoning in Rats and its Relevance to Treatment of Paraquat Poisoning in Man

After oral administration of a lethal dose of paraquat to rats the plasma concentration remained relatively constant over four to 30 hours and was related to the paraquat content of the small intestine over the first 16 hours. During the first 30 hours the concentration of paraquat in the lung rose progressively above that of the plasma to levels which are known to cause pulmonary damage. A treatment has been devised which prevents the absorption of paraquat into the plasma and prevents accumulation of paraquat in the lung. This treatment consists of a stomach was followed by four administrations of bentonite plus purgatives at two- to three-hour intervals. Even when treatment was delayed until 10 hours after administration of paraquat 80% survival was obtained. The relevance of this treatment to paraquat poisoning in man is discussed in the light of the finding that slices of human lung accumulate paraquat in the same way as those of rat lung.     

Irritable Bowel Syndrome Is Associated with an Increased Risk of Dementia: A Nationwide Population-Based Study

Purpose

Abnormal interaction in the brain–gut axis has emerged as one of the relevant pathophysiological mechanisms for the development of irritable bowel syndrome (IBS). Moreover, the brain–gut axis has recently been demonstrated to be crucial for the maintenance of cognitive performance. Therefore, we assessed the risk of dementia following diagnosis of IBS.

Methods

Using the Taiwan National Health Insurance Research Database (NHIRD) to obtain medical claims data from 2000 to 2011, we employed a random sampling method to enroll32 298 adult patients with IBS and frequency-matched them according to sex, age, and baseline year with 129 192 patients without IBS.

Results

The patients with IBS exhibited an increased risk of dementia [adjusted hazard ratio (aHR) = 1.26, 95% confidence interval (CI) = 1.17–1.35]after adjustment for age, sex, diabetes, hypertension, stroke, coronary artery disease (CAD), head injury, depression, and epilepsy, and the overall incidence of dementia for the cohorts with and without IBS was 4.86 and 3.41 per 1000 person-years, respectively. IBS was associated with an increased risk of dementia in patients older than 50 years in both male and female, and in those with comorbidity or without comorbidity. After adjustment for age, sex, and comorbidity, patients with IBS were also more likely to develop either non- Alzheimer’s disease (AD) dementia (aHR = 1.24, 95% CI = 1.15–1.33) or AD (aHR = 1.76, 95% CI = 1.28–2.43).

Conclusions

IBS is associated with an increased risk of dementia, and this effect is obvious only in patients who are ≥50 years old.     

Statin Therapy Is Associated with Improved Survival in Patients with Non-Serous-Papillary Epithelial Ovarian Cancer: A Retrospective Cohort Analysis

Aim

To determine whether statin use is associated with improved epithelial ovarian cancer (OvCa) survival.

Methods

This is a single-institution retrospective cohort review of patients treated for OvCa between 1992 and 2013. Inclusion criteria were International Federation of Gynecology and Obstetrics (FIGO) stage I–IV OvCa. The primary exposures analyzed were hyperlipidemia and statin use. The primary outcomes were progression-free survival (PFS) and disease-specific survival (DSS).

Results

442 patients met inclusion criteria. The cohort was divided into three groups: patients with hyperlipidemia who used statins (n = 68), patients with hyperlipidemia who did not use statins (n = 28), and patients without hyperlipidemia (n = 346). OvCa outcomes were evaluated. When we analyzed the entire cohort, we found no significant differences in PFS or DSS among the groups. The median PFS for hyperlipidemics using statins, hyperlipidemics not using statins, and non-hyperlipidemics was 21.7, 13.6, and 14.7 months, respectively (p = 0.69). Median DSS for hyperlipidemics using statins, hyperlipidemics not using statins, and non-hyperlipidemics was 44.2, 75.7, and 41.5 months, respectively (p = 0.43). These findings did not change after controlling for confounders. However, a secondary analysis revealed that, among patients with non-serous-papillary subtypes of OvCa, statin use was associated with a decrease in hazards of both disease recurrence (adjusted HR = 0.23, p = 0.02) and disease-specific death (adjusted HR = 0.23, p = 0.04). To augment the findings in the retrospective cohort, the histology-specific effects of statins were also evaluated in vitro using proliferation assays. Here, statin treatment of cell lines resulted in a variable level of cytotoxicity.

Conclusion

Statin use among patients with non-serous-papillary OvCa was associated with improvement in both PFS and DSS.     

Long-Term Prognosis of Patients with Carbon Monoxide Poisoning: A Nationwide Cohort Study

Background

Carbon monoxide poisoning (COP) often produces severe complications and can be fatal. Because this topic has not been well delineated, we investigated long-term prognoses of patients with COP (COP^[+]).

Methods

In this retrospective nationwide cohort study, 441 COP^[+] patients and 8820 COP^[−] controls (120) from 1999 to 2010 were selected from Taiwan’s National Health Insurance Research Database.

Results

Thirty-seven (8.39%) COP^[+] patients and 142 (1.61%) controls died (P<0.0001) during follow-up. Incidence rate ratios (IRR) of death were 5.24 times higher in COP^[+] patients than in controls (P<0.0001). The risk of death was particularly high in the first month after COP (IRR: 308.78; 95% confidence interval [CI]: 40.79–2337.56), 1 to 6 months after (IRR: 18.92; 95% CI: 7.69–46.56), and 6–12 months after (IRR: 4.73; 95% CI: 1.02–21.90). After adjusting for age, gender, and selected comorbidities, the hazard ratio of death for COP^[+] patients was still 4.097 times higher than for controls. Moreover, older age (≥30 years old), male gender, diabetes mellitus, hypertension, and low income were also independent mortality predictors.

Conclusions

COP significantly increases the risk for long-term mortality. Early follow-up and secondary prevention of death are needed for patients with COP.     

Treatment with Oral Active Vitamin D Is Associated with Decreased Risk of Peritonitis and Improved Survival in Patients on Peritoneal Dialysis

Peritonitis is a major complication of peritoneal dialysis (PD) being associated with hospitalization, catheter loss, technique failure, and increased mortality. Data on incidence rates and risk factors for peritonitis episodes vary between centers. In seven Austrian PD units clinical and laboratory data on each peritonitis episode were collected from all patients (n = 726) who performed PD between January 2000 and December 2009. The peritonitis incidence rate was 0.32 episodes/patient-year. In a multivariate analysis the risk of peritonitis was decreased by 57% in patients treated with oral active vitamin D (HR 0.43; 95% CI 0.28–0.64). Renal disease classified as “other or unknown” (HR 1.65; 95% CI 1.08–2.53) and serum albumin <3500 mg/dl (HR 1.49; 95% CI 1.04–2.15) were also associated with an increased risk of peritonitis. Albumin levels <3500 mg/dl (HR 1.89; 95% CI 1.13–3.17), age (HR 1.06 per year; 95% CI 1.03–1.09), and cardiomyopathy (HR 3.01; 95% CI 1.62–5.59) were associated with increased mortality, whereas treatment with oral active vitamin D was associated with a significantly lower risk of death (HR 0.46; 95% CI 0.27–0.81). In this retrospective multi-center study we identified several factors being related to increased risk of peritonitis in PD patients. Treatment with oral active vitamin D was identified as being independently associated with decreased risk of peritonitis, and decreased all-cause mortality in PD patients.     

Nuclear Expression of the Deubiquitinase CYLD Is Associated with Improved Survival in Human Hepatocellular Carcinoma

Background & Aims

The deubiquitinase CYLD removes (K-63)-linked polyubiquitin chains from proteins involved in NF-κB, Wnt/ß-catenin and Bcl-3 signaling. Reduced CYLD expression has been reported in different tumor entities, including hepatocellular carcinoma (HCC). Furthermore, loss of CYLD has been shown to contribute to HCC development in knockout animal models. This study aimed to assess subcellular CYLD expression in tumor tissues and its prognostic significance in HCC patients undergoing liver resection or liver transplantation.

Methods

Subcellular localization of CYLD was assessed by immunohistochemistry in tumor tissues of 95 HCC patients undergoing liver resection or transplantation. Positive nuclear CYLD staining was defined as an immunhistochemical (IHC) score ≥3. Positive cytoplasmic CYLD staining was defined as an IHC score ≥6. The relationship with clinicopathological parameters was investigated. Cell culture experiments were performed to analyze subcellular CYLD expression in vitro.

Results

Cytoplasmic CYLD expression was observed in 57 out of 95 (60%) HCC specimens (^cyt°CYLD⁺). Nuclear CYLD staining was positive in 52 out of 95 specimens (55%, ^nucCYLD⁺). 13 out of 52 ^nucCYLD⁺ patients (25%) showed a lack of cytoplasmic CYLD expression. ^nucCYLD⁺ was associated with prolonged overall survival in patients after resection or liver transplantation (P = 0.007). 5-year overall survival rates were 63% in ^nucCYLD⁺ vs. 26% in ^nucCYLD^- patients. Nuclear CYLD staining strongly correlated with tumor grading (P<0.001) and Ki67 positivity (P = 0.005). ^nucCYLD⁺ did not prove to be an independent prognostic parameter. In vitro, Huh7, Hep3B and HepG2 showed reduced CYLD levels compared to the non-malignant liver cell line THLE-2. Induction of CYLD expression by doxorubicin treatment led to increased cytoplasmic and nuclear expression of CYLD.

Conclusions

Expression of nuclear CYLD is a novel prognostic factor for improved survival in patients with HCC undergoing liver resection or transplantation.     

The CD14 rs2569190 TT Genotype Is Associated with an Improved 30-Day Survival in Patients with Sepsis: A Prospective Observational Cohort Study

According to previous investigations, CD14 is suggested to play a pivotal role in initiating and perpetuating the pro-inflammatory response during sepsis. A functional polymorphism within the CD14 gene, rs2569190, has been shown to impact the pro-inflammatory response upon stimulation with lipopolysaccharide, a central mediator of inflammation in sepsis. In this study, we hypothesized that the strong pro-inflammatory response induced by the TT genotype of CD14 rs2569190 may have a beneficial effect on survival (30-day) in patients with sepsis. A total of 417 adult patients with sepsis (and of western European descent) were enrolled into this observational study. Blood samples were collected for rs2569190 genotyping. Patients were followed over the course of their stay in the ICU, and the 30-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure as a secondary variable. Moreover, organ support-free days were evaluated as a secondary outcome parameter. TT-homozygous patients were compared to C-allele carriers. Kaplan-Meier survival analysis revealed a higher 30-day mortality risk among C-allele carriers compared with T homozygotes (p = 0.0261). To exclude the effect of potential confounders (age, gender, BMI and type of infection) and covariates that varied at baseline with a p-value < 0.2 (e.g., comorbidities), we performed multivariate Cox regression analysis to examine the survival time. The CD14 rs2569190 C allele remained a significant covariate for the 30-day mortality risk in the multivariate analysis (hazard ratio, 2.11; 95% CI, 1.08-4.12; p = 0.0282). The 30-day mortality rate among C allele carriers was 23%, whereas the T homozygotes had a mortality rate of 13%. Additionally, an analysis of organ-specific SOFA scores revealed a significantly higher SOFA-Central nervous system score among patients carrying the C allele compared with T-homozygous patients (1.9±1.1 and 1.6±1.0, respectively; p = 0.0311). In conclusion, CD14 rs2569190 may act as a prognostic variable for the short-term outcome (30-day survival) in patients with sepsis.     

Chronic Hepatitis C Virus Infection Is Associated with the Development of Rheumatoid Arthritis: A Nationwide Population-Based Study in Taiwan

ObjectiveThe association between chronic hepatitis virus infection and rheumatoid arthritis (RA) remains debatable. This nationwide population-based cohort study assessed the risk of RA among patients with a chronic infection of hepatitis B and/or C virus.ResultsAfter adjusting for covariates, chronic HCV infection alone was significantly associated with an increased risk for RA (hazard ratio (HR)  = 2.03, 95% confidence interval (CI)  = 1.27–3.22). The increased risk for RA among participants with chronic HCV infection remained significant after restricting the analysis to those who were prescribed disease-modifying anti-rheumatic drugs. The corresponding HR for the overall sample was 1.89 (95% CI  = 1.15–3.11). However, HBV carriers did not appear to be at a significantly higher risk for RA.ConclusionOur data imply that chronic HCV infection is associated with RA development.     

Hyperlipidemia Is Associated with Chronic Urticaria: A Population-Based Study

The etiology of chronic urticaria (CU) is diverse, with chronic infections and inflammation being reported as considerable contributing factors. Although the prevalence of metabolic syndrome was found to be significantly elevated in patients with CU, no one has specifically estimated the effects on CU following hyperlipidemia. This study aimed to examine the association between hyperlipidemia and CU using a population-based dataset in Taiwan. This study included 9798 adults with CU as cases and 9798 sex- and age-matched controls. These patients were examined for whether they had received a prior diagnosis of hyperlipidemia. We used conditional logistic regression analyses to calculate the odds ratio (OR) and its corresponding 95% confidence interval (CI) for having been previously diagnosed with hyperlipidemia between cases and controls. In total, 7066 (36.1%) patients had received a prior diagnosis of hyperlipidemia, including 4287 (43.8%) among CU cases and 2779 (28.4%) among controls. The conditional logistic regression revealed that the OR of prior hyperlipidemia for cases was 1.97 (95% CI: 1.85~2.09) compared to the controls. Furthermore, compared to patients without CU, patients with CU independently experienced a 1.65-fold (95% CI = 1.55~1.76; p<0.001) increased risk of having a prior hyperlipidemia diagnosis, after adjustments were made. We concluded that CU was associated with having received a prior diagnosis of hyperlipidemia.     

Rheumatoid Arthritis Risk Associated with Periodontitis Exposure: A Nationwide,Population-Based Cohort Study

Background

The risk of periodontitis (PD) is increased in the patient group of rheumatoid arthritis (RA). RA and PD also shared some pathological mechanism. The aim of this study is to investigate the risk of RA associated with PD exposure.

Methods and Findings

This study identified 3 mutually exclusive cohorts using the 1999–2010 Taiwanese National Health Insurance Research Database (NHIRD) to investigate the association between PD and the risk of incident RA. All patients with PD in 2000 were identified from the database of all enrollees as the PD cohort. From the representative database of 1,000,000 enrollees randomly selected in 2010 (LHID2010), individuals without any periodontal disease (PO) during 1999–2010 were selected as the non-PO cohort. Individuals who were not included in the non-PO cohort and received dental scaling (DS) no more than two times per year during 1999–2010 were selected as the DS cohort from LHID2010. Using cox proportional regression analysis, hazard ratios (HRs) with 95% confidence intervals (Cis) were calculated to quantify the association between PD exposure and RA development. In the three-group comparison using the non-PO cohort as reference, we found that the risk of RA was higher in the PD and DS cohorts (HRs, 1.89 and 1.43; 95% CIs, 1.56–2.29 and 1.09–1.87, respectively). For comparisons between two cohorts, the PD cohort had a higher risk of RA than the non-PO and DS cohorts (HRs, 1.91 and 1.35; 95% CIs, 1.57–2.30 and 1.09–1.67, respectively).

Conclusion

PD was associated with an increased risk of RA development.     

The Patient-Provider Relationship Is Associated with Hepatitis C Treatment Eligibility: A Prospective Mixed-Methods Cohort Study

Hepatitis C virus (HCV) treatment has the potential to cure the leading cause of cirrhosis and hepatocellular carcinoma. However, only those deemed eligible for treatment have the possibility of this cure. Therefore, understanding the determinants of HCV treatment eligibility is critical. Given that effective communication with and trust in healthcare providers significantly influences treatment eligibility decisions in other diseases, we aimed to understand patient-provider interactions in the HCV treatment eligibility process. This prospective cohort study was conducted in the VA Pittsburgh Healthcare System. Patients were recruited after referral for gastroenterology consultation for HCV treatment with interferon and ribavirin. Consented patients completed semi-structured interviews and validated measures of depression, substance and alcohol use, and HCV knowledge. Two coders analyzed the semi-structured interviews. Factors associated with patient eligibility for interferon-based therapy were assessed using multivariate logistic regression. Of 339 subjects included in this analysis, only 56 (16.5%) were deemed eligible for HCV therapy by gastroenterology (GI) providers. In the multivariate logistic regression, patients who were older (OR = 0.96, 95%CI = 0.92–0.99, p = .049), reported concerns about the GI provider (OR = 0.40, 95%CI = 0.10–0.87, p = 0.02) and had depression symptoms (OR = 0.32, 95%CI = 0.17–0.63, p = 0.001) were less likely to be eligible. Patients described barriers that included feeling stigmatized and poor provider interpersonal or communication skills. In conclusion, we found that patients’ perceptions of the relationship with their GI providers were associated with treatment eligibility. Establishing trust and effective communication channels between patients and providers may lower barriers to potential HCV cure.     

A Single Nucleotide Polymorphism in Catalase Is Strongly Associated with Ovarian Cancer Survival

Ovarian cancer is the deadliest of all gynecologic cancers. Recent evidence demonstrates an association between enzymatic activity altering single nucleotide polymorphisms (SNP) with human cancer susceptibility. We sought to evaluate the association of SNPs in key oxidant and antioxidant enzymes with increased risk and survival in epithelial ovarian cancer. Individuals (n = 143) recruited were divided into controls, (n = 94): healthy volunteers, (n = 18), high-risk BRCA1/2 negative (n = 53), high-risk BRCA1/2 positive (n = 23) and ovarian cancer cases (n = 49). DNA was subjected to TaqMan SNP genotype analysis for selected oxidant and antioxidant enzymes. Of the seven selected SNP studied, no association with ovarian cancer risk (Pearson Chi-square) was found. However, a catalase SNP was identified as a predictor of ovarian cancer survival by the Cox regression model. The presence of this SNP was associated with a higher likelihood of death (hazard ratio (HR) of 3.68 (95% confidence interval (CI): 1.149–11.836)) for ovarian cancer patients. Kaplan-Meier survival analysis demonstrated a significant median overall survival difference (108 versus 60 months, p<0.05) for those without the catalase SNP as compared to those with the SNP. Additionally, age at diagnosis greater than the median was found to be a significant predictor of death (HR of 2.78 (95% CI: 1.022–7.578)). This study indicates a strong association with the catalase SNP and survival of ovarian cancer patients, and thus may serve as a prognosticator.     

Insurance Status Is Associated with Treatment Allocation and Outcomes after Subarachnoid Hemorrhage

Objective

Subarachnoid hemorrhage (SAH) is a particularly devastating type of stroke which is responsible for one third of all stroke-related years of potential life lost before age 65. Surgical treatment has been shown to decrease both morbidity and mortality after subarachnoid hemorrhage. We hypothesized that payer status other than private insurance is associated with lower allocation to surgical treatment for patients with SAH and worse outcomes.

Design

We examined the association between insurance type and surgical treatment allocation and outcomes for patients with SAH while adjusting for a wide range of patient and hospital factors. We analyzed the Nationwide Inpatient Sample hospital discharge database using survey procedures to produce weighted estimates representative of the United States population.

Patients

We studied 21047 discharges, representing a weighted estimate of 102595 patients age 18 and above with a discharge diagnosis of SAH between 2003 and 2008.

Measurements

Multivariable logistic and generalized linear regression analyses were used to assess for any associations between insurance status and surgery allocation and outcomes.

Main Results

Despite the benefits of surgery 66% of SAH patients did not undergo surgical treatment to prevent rebleeding. Mortality was more than twice as likely for patients with no surgical treatment compared to those who received surgery. Medicare patients were significantly less likely to receive surgical treatment.

Conclusions

Nearly two thirds of patients with SAH don''t receive operative care, and Medicare patients were significantly less likely to receive surgical treatment than other patients. Bias against the elderly and those with chronic illness and disability may play a part in these findings. A system of regionalized care for patients presenting with SAH may reduce disparities and improve appropriate allocation to surgical care and deserves prospective study.     

Exposure to Bovine Leukemia Virus Is Associated with Breast Cancer: A Case-Control Study

Background

Age, reproductive history, hormones, genetics, and lifestyle are known risk factors for breast cancer, but the agents that initiate cellular changes from normal to malignant are not understood. We previously detected bovine leukemia virus (BLV), a common oncogenic virus of cattle, in the breast epithelium of humans. The objective of this study was to determine whether the presence of BLV DNA in human mammary epithelium is associated with breast cancer.

Methods

This was a case-control study of archival formalin fixed paraffin embedded breast tissues from 239 donors, received 2002–2008 from the Cooperative Human Tissue Network. Case definition as breast cancer versus normal (women with no history of breast cancer) was established through medical records and examination of tissues by an anatomical pathologist. Breast exposure to BLV was determined by in situ-PCR detection of a biomarker, BLV DNA, localized within mammary epithelium.

Results

The frequency of BLV DNA in mammary epithelium from women with breast cancer (59%) was significantly higher than in normal controls (29%) (multiply- adjusted odds ratio = 3.07, confidence interval = 1.66–5.69, p = .0004, attributable risk = 37%). In women with premalignant breast changes the frequency of BLV DNA was intermediate (38%) between that of women with breast cancer and normal controls (p for trend < .001).

Conclusions

Among the specimens in this study, the presence of amplified BLV DNA was significantly associated with breast cancer. The odds ratio magnitude was comparable to those of well-established breast cancer risk factors related to reproductive history, hormones, and lifestyle and was exceeded only by risk factors related to genetics (familial breast cancer), high dose ionizing radiation, and age. These findings have the potential for primary and secondary prevention of breast cancer.     

Poor Survival in Rheumatoid Arthritis Associated with Bronchiectasis: A Family-Based Cohort Study

Background

Diffuse bronchiectasis (DB) may occur in rheumatoid arthritis (RA). CFTR (cystic fibrosis transmembrane conductance regulator) mutations predispose RA patients to DB, but the prognosis of RA-associated DB (RA-DB) is unclear.

Methods

We report long-term mortality data from a nationwide family-based association study of patients with RA only, DB only or RA-DB. We assessed mortality as a function of clinical characteristics and CF/CFTR-RD (CFTR-related disorders) mutations in 137 subjects from 24 kindreds. Potential risk factors were investigated by Cox proportional-hazard analysis with shared Gaussian random effects to account for within-family correlations.

Results

During a median follow-up of 11 years after inclusion, 18 patients died, mostly from cardiorespiratory causes. Survival was significantly lower for RA-DB patients than for unaffected relatives and for patients with RA or DB only. RA patients with DB had also a poorer prognosis in terms of survival after RA diagnosis (HR, 8.6; 95% CI, 1.5–48.2; P = 0.014) and from birth (HR, 9.6; 95% CI, 1.1–81.7; P = 0.039). Early onset of DB (HR, 15.4; 95% CI, 2.1–113.2; P = 0.007) and CF/CFTR-RD mutation (HR, 7.2; 95% CI, 1.4–37.1; P = 0.018) were associated with poorer survival in patients with RA-DB. Thus, CF/CFTR-RD mutations in RA patients with early-onset DB defined a subgroup of high-risk patients with higher mortality rates (log-rank test P = 1.28×10⁻⁵).

Conclusion

DB is associated with poorer survival in patients with RA. Early-onset DB and CFTR mutations are two markers that identify RA patients at a high risk of death, for whom future therapeutic interventions should be designed and evaluated.     

Reduction in Non-Protein Respiratory Quotient Is Related to Overall Survival after Hepatocellular Carcinoma Treatment

Background

Transcatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC) that can occasionally lead to the shortening of life expectancy. We aimed to make a new and more accurate prognostic model taking into account the course of disease after TACE.

Methodology/Principal Findings

We performed a prospective cohort study involving 100 HCC patients who underwent TACE at Kobe University Hospital. Indirect calorimetry and blood biochemical examinations were performed before and 7 days after TACE. Time-dependent and time-fixed factors associated with 1-year mortality after TACE were assessed by multivariate analyses. A predictive model of 1-year mortality was established by the combination of odds ratios of these factors. Multivariate analyses showed that the ratio of non-protein respiratory quotient (npRQ) (7 days after/before TACE) and Cancer of Liver Italian Program (CLIP) score were independent factors of 1-year mortality after TACE (p = 0.014 and 0.013, respectively). Patient-specific 1-year mortality risk scores can be calculated by summarizing the individual risk scores and looking up the patient-specific risk on the graph.

Conclusions

The short-term reduction of npRQ was a time-dependent prognostic factor associated with overall survival in HCC patients undergoing TACE. CLIP score was a time-fixed prognostic factor associated with overall survival. Using the prediction model, which consists of the combination of time-dependent (npRQ ratio) and time-fixed (CLIP score) prognostic factors, 1-year mortality risk after TACE would be better estimated by taking into account changes during the course of disease.     

Pre-Transplant Depression Is Associated with Length of Hospitalization,Discharge Disposition,and Survival after Liver Transplantation

Depression after liver transplantation has been associated with decreased survival, but the effects of pre-transplant depression on early and late post-transplant outcomes remain incompletely evaluated. We assessed all patients who had undergone single-organ liver transplantation at a single center over the prior 10 years. A diagnosis of pre-transplant depression, covariates, and the outcomes of interest were extracted from the electronic medical record. Potential covariates included demographics, etiology and severity of liver disease, comorbidities, donor age, graft type, immunosuppression, and ischemic times. In multivariable models adjusting for these factors, we evaluated the effect of pre-transplant depression on transplant length of stay (LOS), discharge disposition (home vs. facility) and long-term survival. Among 1115 transplant recipients with a median follow-up time of 5 years, the average age was 56±11 and MELD was 12±9. Nineteen percent of the study population had a history of pre-transplant depression. Pre-transplant depression was associated with longer LOS (median = 19 vs. 14 days, IRR = 1.25, CI = 1.13,1.39), discharge to a facility (36% vs. 25%, OR 1.70,CI = 1.18,2.45), and decreased survival (HR = 1.54,CI = 1.14,2.08) in this cohort, accounting for other potential confounders. In conclusion, pre-transplant depression was significantly associated with longer transplant length of stay, discharge to a facility, and mortality in this cohort.