Tubulointerstitial nephritis is a main renal manifestation caused by pathogenic leptospira that accumulate mostly in the proximal tubules, thereby inducing tubular injury and tubulointerstitial nephritis. To elucidate the role of leptospira outer membrane proteins in tubulointerstitial nephritis, outer membrane proteins from pathogenic Leptospira shermani and nonpathogenic Leptospira patoc extracted by Triton X-114 were administered to cultured mouse proximal tubule cells. A dose-dependent increase of monocyte chemoattractant protein–1 (MCP-1), RANTES, nitrite, and tumor necrosis factor–α (TNF-α) in the culture supernatant was observed 48 h after incubating Leptospira shermani outer membrane proteins with mouse proximal tubule cells. RT competitive-PCR experiments showed that Leptospira shermani outer membrane proteins (0.2 μg/ml) increased the expression of MCP-1, nitric oxide synthase (iNOS), RANTES, and TNF-α mRNA by 3.0-, 9.4-, 2.5-, and 2.5-fold, respectively, when compared with untreated cells. Outer membrane proteins extract from avirulent Leptospira patoc did not induce significant effects. The pathogenic outer membrane proteins extract contain a major component of a 32-kD lipoprotein (LipL32), which is absent in the nonpathogenic leptospira outer membrane. An antibody raised against LipL32 prevented the stimulatory effect of Leptospira shermani outer membrane proteins extract on MCP-1 and iNOS mRNA expression in cultured proximal tubule cells, whereas recombinant LipL32 significantly stimulated the expression of MCP-1 and iNOS mRNAs and augmented nuclear binding of nuclear factor–κB (NF-κB) and AP-1 transcription factors in proximal tubule cells. An antibody raised against LipL32 also blunted the effects induced by the recombinant LipL32. This study demonstrates that LipL32 is a major component of pathogenic leptospira outer membrane proteins involved in the pathogenesis of tubulointerstitial nephritis.

Leptospirosis is the most widespread zoonosis. Chronic human infection and asymptomatic colonization have been reported. However, renal involvement in those with leptospira chronic exposure remains undetermined. In 2007, a multistage sampling survey for chronic kidney disease (CKD) was conducted in a southern county of Taiwan, an area with a high prevalence of dialysis. Additionally, an independent cohort of 88 participants from a leptospira-endemic town was followed for two years after a flooding in 2009. Risks of CKD, stages of CKD, associated risk factors as well as kidney injury markers were compared among adults with anti-leptospira antibody as defined by titers of microscopic agglutination test (MAT). Of 3045 survey participants, the individuals with previous leptospira exposure disclosed a lower level of eGFR (98.3±0.4 vs 100.8±0.6 ml/min per 1.73 m², P<0.001) and a higher percentage of CKD, particularly at stage 3a-5 (14.4% vs 8.5%), than those without leptospira exposure. Multivariable linear regression analyses indicated the association of leptospiral infection and lower eGFR (95% CI -4.15 to -1.93, P < 0.001). In a leptospiral endemic town, subjects with a MAT titer ≥400 showed a decreased eGFR and higher urinary kidney injury molecule–1 creatinine ratio (KIM1/Cr) level as compared with those having lower titers of MAT (P<0.05). Furthermore, two participants with persistently high MAT titers had positive urine leptospira DNA and deteriorating renal function. Our data are the first to show that chronic human exposure of leptospirosis is associated significantly with prevalence and severity of CKD and may lead to deterioration of renal function. This study also shed light on the search of underlying factors in areas experiencing CKD of unknown aetiology (CKDu) such as Mesoamerican Nephropathy. Chronic kidney disease (CKD) has a high and increasing worldwide prevalence. Leptospirosis, an important re-emerging infectious disease caused by the pathogenic spirochete Leptospira, is the most widespread zoonosis throughout the world, particularly in tropical and subtropical regions. Chronic human infection and asymptomatic colonization have been reported. However, the evidence of renal involvement in those with leptospira exposure history or human carrier remains undetermined. In this study we found that those individuals with previous leptospira exposure disclosed a lower renal function and a higher percentage of CKD. Additionally, in our cohort study, those with a high serum titer by leptospira agglutination test showed decreased renal function and higher kidney injury marker. We are the first to identify the association between CKD and leptospiral infection. This information may provide a novel approach for CKD of unknown aetiology but also significantly impact global control of leptospirosis and CKD burden.

A low bystander cardiopulmonary resuscitation (CPR) rate is one of the factors associated with low cardiac arrest survival. This study aimed to assess knowledge, attitudes, and willingness towards performing CPR and the barriers for implementation of bystander-initiated CPR. Telephone interviews were conducted using an author-designed and validated structured questionnaire in Taiwan. After obtaining a stratified random sample from the census, the results were weighted to match population data. The factors affecting bystander-initiated CPR were analysed using logistic regression. Of the 1073 respondents, half of them stated that they knew how to perform CPR correctly, although 86.7% indicated a willingness to perform CPR on strangers. The barriers to CPR performance reported by the respondents included fear of legal consequences (44%) and concern about harming patients (36.5%). Most participants expressed a willingness to attend only an hour-long CPR course. Respondents who were less likely to indicate a willingness to perform CPR were female, healthcare providers, those who had no cohabiting family members older than 65 years, those who had a history of a stroke, and those who expressed a negative attitude toward CPR. The expressed willingness to perform bystander CPR was high if the respondents possessed the required skills. Attempts should be made to recruit potential bystanders for CPR courses or education, targeting those respondent subgroups less likely to express willingness to perform CPR. The reason for lower bystander CPR willingness among healthcare providers deserves further investigation.

Current evidence demonstrates considerable variability in cardiac arrest survival in and out of hospital and, therefore, substantial opportunity to save many more lives.1–3 The Formula for Survival4 postulates that optimal survival from cardiac arrest requires high-quality science, education of lay providers and healthcare professionals, and a well-functioning Chain of Survival5 (implementation). The Education, Implementation, and Teams (EIT) Task Force of the International Liaison Committee on Resuscitation (ILCOR) set out to define the key PICO (population, intervention, comparator, outcome) questions related to resuscitation education (including teamwork skills) and systems-level implementation that would be reviewed by 2015. The selection of questions was supported through the use of an online anonymous task force member–only voting process where the results were considered in the ultimate consensus decisions of the task force. Topics from the 2010 evidence review process were scrutinized for relevance, the potential to improve outcomes, and the likelihood of new evidence being published since 2010. Finally, PICO questions for which the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was not as well developed at the time of PICO selection were deferred until at least after the 2015 cycle. We planned to reduce the total number of PICO questions reviewed to provide more in-depth and evidence-based reviews of the included questions. New topics were determined on the basis of the evolving literature and changes in resuscitation practice. Input on the selection of PICO questions was sought from the general public through the ILCOR website and from ILCOR member resuscitation councils through their council chairs and individual task force members. The EIT Task Force performed detailed systematic reviews based on the recommendations of the Institute of Medicine of the National Academies6 and using the methodological approach proposed by the …