Summary Edwardsiella tarda, a member of the family Enterobacteriaceae, is a rare human pathogen. Gastroenteritis is the most frequently reported manifestation of E. tarda infection. In contrast, extraintestinal infection with E. tarda has rarely been reported. This study made a retrospective case and microbiological data review of patients with extraintestinal E. tarda infections to further understand this disease. This study retrospectively reviewed the charts of all isolates of E. tarda cultures from clinical specimens other than faeces at Chang Gung Memorial Hospital, Taoyuan, Taiwan from October 1998 through December 2001. Edwardsiella tarda was isolated from 22 clinical specimens from 22 hospitalised patients (13 females and nine males). The extraintestinal manifestations of E. tarda infection included biliary tract infection, bacteraemia, skin and soft tissue infection, liver abscess, peritonitis, intra-abdominal abscess, and tubo-ovarian abscess. The major underlying diseases predisposing to E. tarda extraintestinal infection were hepatobiliary diseases, malignancy and diabetes mellitus. The overall mortality rate of E. tarda extraintestinal infection in the present series was 22.7% (5/22), and four (40%) of 10 patients with bacteraemia expired. Although rare, human E. tarda extraintestinal infections can have diverse clinical manifestations and moreover may cause severe and life-threatening infections. Consequently, E. tarda should be considered a potentially important pathogen.

Over the past few decades, mechanisms of programmed cell death have attracted the scientific community because they are involved in diverse human diseases. Initially, apoptosis was considered as a crucial mechanistic pathway for programmed cell death; recently, an alternative regulated mode of cell death was identified, mimicking the features of both apoptosis and necrosis. Several lines of evidence have revealed that dysregulation of necroptosis leads to pathological diseases such as cancer, cardiovascular, lung, renal, hepatic, neurodegenerative, and inflammatory diseases. Regulated forms of necrosis are executed by death receptor ligands through the activation of receptor-interacting protein kinase (RIPK)-1/3 and mixed-lineage kinase domain-like (MLKL), resulting in the formation of a necrosome complex. Many papers based on genetic and pharmacological studies have shown that RIPKs and MLKL are the key regulatory effectors during the progression of multiple pathological diseases. This review focused on illuminating the mechanisms underlying necroptosis, the functions of necroptosis-associated proteins, and their influences on disease progression. We also discuss numerous natural and chemical compounds and novel targeted therapies that elicit beneficial roles of necroptotic cell death in malignant cells to bypass apoptosis and drug resistance and to provide suggestions for further research in this field.

Background: Direct evidence of lung cancer risk in Asian users of angiotensin-converting enzyme inhibitors (ACEIs) is lacking. Methods: The ACEI cohort comprised 22,384 patients aged ≥ 18 years with a first prescription of ACEI. The comparison angiotensin receptor blocker (ARB) cohort consisted of age-, sex- and comorbidity-matched patients at a ratio of 1:1. The primary outcome was the incidence of lung cancer, which was evaluated using a proportional hazard model. Results: The overall incidence rates of lung cancer in the ACEI and ARB cohorts were 16.6 and 12.2 per 10,000 person-years, respectively. The ACEI cohort had a significantly higher risk of lung cancer than the ARB cohort (adjusted hazard ratio [aHR]. = 1.36; 95% confidence interval [CI]. = 1.11–1.67). Duration–response and dose–response analyses revealed that compared with patients who did not receive ACEIs, patients who received ACEIs for more than 45 days per year (aHR = 1.87; 95% CI = 1.48–2.36) and patients who received more than 540 defined daily doses of ACEIs per year (aHR =1.80; 95% CI = 1.43–-2.27) had a significantly higher risk of lung cancer. The cumulative incidence of lung cancer was also significantly higher in the ACEI cohort than in the ARB cohort (log-rank test, p = 0.002). Conclusions: ACEI use is associated with an increased risk of lung cancer compared with ARB use. Patients using ARBs have a significantly lower risk of lung cancer than non-ARB users.

Alcohol use disorder (AUD) is a spectrum of high risk behaviors including alcohol abuse and dependence. Chronic kidney disease (CKD) is progressive loss of renal function for more or equal to 3 months or presence of any irreversible kidney damage. Common risk factors of CKD have been identified, but the impact of alcohol consumption on kidney function is controversial. The study aims to investigate the relationship between alcohol use disorder and CKD on a national scale. This retrospective cohort study was conducted using Taiwan’s National Health Insurance research database. Patients aged 20 years or older, without CKD and with the diagnosis of AUD (ICD-9-CM codes 303.X; 305.0, V113) from years 2000 to 2013 were enrolled. Control cohort was selected to match the demographics of the target population. Patients were followed until the end of 2013 or earlier if they developed CKD, died, or lost follow up. Baseline characteristics and comorbidities were identified for risk stratification. We identified 11639 patients in the AUD cohort and 46556 patients in the control cohort. Compared to patients in the control cohort, those in the AUD group were more likely to have multiple comorbidities (p < 0.001 for all comorbidities). After adjustment of age, gender, baseline comorbidities, and nonsteroidal anti-inflammatory drug use, the diagnosis of AUD was associated with an increased risk of CKD development (aHR = 1.62, 95% CI, 1.46–1.81). During the mean follow up periods of 6.47 (standard deviation (SD) = 3.80) years for the AUD cohort and 7.23 (SD = 3.75) years for the control cohort, the overall incidence density of CKD was significantly higher in patients with AUD than those in the control cohort (3.48 vs 6.51 per 1000 person-years, aHR = 1.68, 95% CI, 1.50–1.87). Kaplan-Meier analysis showed that the AUD cohort had a higher cumulative incidence of CKD than the control cohort (log-rank test, p value < 0.001). Patients with AUD had higher risks of CKD in all the stratified groups, except for the subgroup with age over 65 years old. Our study suggested that AUD was associated with an increased incidence of newly diagnosed CKD by nearly two folds. Young age, in particular, had a higher association between AUD and CKD. Considering the preventable nature of AUD, establishing effective health policies is imperative to reduce high-risk alcohol behaviors and thereby prevent alcohol-related kidney disease. Further prospective studies are warranted to further elucidate the causation of AUD on kidney function.

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder with limited clinical treatments. The occurrence of PD includes both genetic and environmental toxins, such as the pesticides paraquat (PQ), as major contributors to PD pathology in both invertebrate and mammalian models. Calycosin, an isoflavone phytoestrogen, has multiple pharmacological properties, including neuroprotective activity. However, the paucity of information regarding the neuroprotective potential of calycosin on PQ-induced neurodegeneration led us to explore whether calycosin can mitigate PD-like phenotypes and the underlying molecular mechanisms. We used a PQ-induced PD model in Drosophila as a cost-effective in vivo screening platform to investigate the neuroprotective efficacy of natural compounds on PD. We reported that calycosin shows a protective role in preventing dopaminergic (DA) neuronal cell death in PQ-exposed Canton S flies. Calycosin-fed PQ-exposed flies exhibit significant resistance against PQ-induced mortality and locomotor deficits in terms of reduced oxidative stress, loss of DA neurons, the depletion of dopamine content, and phosphorylated JNK-caspase-3 levels. Additionally, mechanistic studies show that calycosin administration improves PQ-induced mitochondrial dysfunction and stimulates mitophagy and general autophagy with reduced pS6K and p4EBP1 levels, suggestive of a maintained energy balance between anabolic and catabolic processes, resulting in the inhibition of neuronal cell death. Collectively, this study substantiates the protective effect of calycosin against PQ-induced neurodegeneration by improving DA neurons’ survival and reducing apoptosis, likely via autophagy induction, and it is implicated as a novel therapeutic application against toxin-induced PD pathogenesis.

Objective To analyze the incidence rates and risk factors for bacteremia in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD). Methods The records of 898 consecutive patients undergoing dialysis from January 2003 to December 2008 were reviewed retrospectively. Episodes of bacteremia were recorded. China Medical University (Taichung, Taiwan). Results The overall incidence rate of bacteremia was 7.63 per 100 patient-years in HD patients and 3.56 per 100 patient-years in PD patients and it was higher in HD patients each year from 2003 to 2008. S. aureus (27.53%) was the most common pathogen in HD patients, whereas Coagulase-negative Staphylococcus (21.3%) was the most common pathogen in PD patients. Vascular access infection was the most common etiology in HD patients, whereas peritonitis was the most common etiology in PD patients. Older age, shorter dialysis vintage, use of HD rather than PD, current smoker, use of a venous dialysis catheter, presence of diabetes mellitus, higher comorbidity score, and lower serum albumin were significant risk factors for bacteremia. Diabetes mellitus and lower serum albumin were significant risk factors for bacteremia-associated mortality. Conclusion Placement of a permanent access (fistula, graft, or PD catheter) prior to initiation of dialysis, smoking cessation, and better nutritional status (i.e. higher serum albumin) were associated with a reduced risk of bacteremia in dialysis patients. Higher serum albumin was also associated with a reduced bacteremia-associated mortality.