Clinical Outcomes and Microbiological Characteristics of Severe Pneumonia in Cancer Patients: A Prospective Cohort Study

Introduction

Pneumonia is the most frequent type of infection in cancer patients and a frequent cause of ICU admission. The primary aims of this study were to describe the clinical and microbiological characteristics and outcomes in critically ill cancer patients with severe pneumonia.

Methods

Prospective cohort study in 325 adult cancer patients admitted to three ICUs with severe pneumonia not acquired in the hospital setting. Demographic, clinical and microbiological data were collected.

Results

There were 229 (71%) patients with solid tumors and 96 (29%) patients with hematological malignancies. 75% of all patients were in septic shock and 81% needed invasive mechanical ventilation. ICU and hospital mortality rates were 45.8% and 64.9%. Microbiological confirmation was present in 169 (52%) with a predominance of Gram negative bacteria [99 (58.6%)]. The most frequent pathogens were methicillin-sensitive S. aureus [42 (24.9%)], P. aeruginosa [41(24.3%)] and S. pneumonia [21 (12.4%)]. A relatively low incidence of MR [23 (13.6%)] was observed. Adequate antibiotics were prescribed for most patients [136 (80.5%)]. In multivariate analysis, septic shock at ICU admission [OR 5.52 (1.92–15.84)], the use of invasive MV [OR 12.74 (3.60–45.07)] and poor Performance Status [OR 3.00 (1.07–8.42)] were associated with increased hospital mortality.

Conclusions

Severe pneumonia is associated with high mortality rates in cancer patients. A relatively low rate of MR pathogens is observed and severity of illness and organ dysfunction seems to be the best predictors of outcome in this population.     

Epidemic and Endemic Malaria Transmission Related to Fish Farming Ponds in the Amazon Frontier

Fish farming in the Amazon has been stimulated as a solution to increase economic development. However, poorly managed fish ponds have been sometimes associated with the presence of Anopheles spp. and consequently, with malaria transmission. In this study, we analyzed the spatial and temporal dynamics of malaria in the state of Acre (and more closely within a single county) to investigate the potential links between aquaculture and malaria transmission in this region. At the state level, we classified the 22 counties into three malaria endemicity patterns, based on the correlation between notification time series. Furthermore, the study period (2003–2013) was divided into two phases (epidemic and post-epidemic). Higher fish pond construction coincided both spatially and temporally with increased rate of malaria notification. Within one malaria endemic county, we investigated the relationship between the geolocation of malaria cases (2011–2012) and their distance to fish ponds. Entomological surveys carried out in these ponds provided measurements of anopheline abundance that were significantly associated with the abundance of malaria cases within 100 m of the ponds (P < 0.005; r = 0.39). These results taken together suggest that fish farming contributes to the maintenance of high transmission levels of malaria in this region.     

Unidirectional Expiratory Valve Method to Assess Maximal Inspiratory Pressure in Individuals without Artificial Airway

Introduction

Maximal Inspiratory Pressure (MIP) is considered an effective method to estimate strength of inspiratory muscles, but still leads to false positive diagnosis. Although MIP assessment with unidirectional expiratory valve method has been used in patients undergoing mechanical ventilation, no previous studies investigated the application of this method in subjects without artificial airway.

Objectives

This study aimed to compare the MIP values assessed by standard method (MIP_sta) and by unidirectional expiratory valve method (MIP_uni) in subjects with spontaneous breathing without artificial airway. MIP_uni reproducibility was also evaluated.

Methods

This was a crossover design study, and 31 subjects performed MIP_sta and MIP_uni in a random order. MIP_sta measured MIP maintaining negative pressure for at least one second after forceful expiration. MIP_uni evaluated MIP using a unidirectional expiratory valve attached to a face mask and was conducted by two evaluators (A and B) at two moments (Tests 1 and 2) to determine interobserver and intraobserver reproducibility of MIP values. Intraclass correlation coefficient (ICC_[2,1]) was used to determine intraobserver and interobserver reproducibility.

Results

The mean values for MIP_uni were 14.3% higher (-117.3 ± 24.8 cmH₂O) than the mean values for MIP_sta (-102.5 ± 23.9 cmH₂O) (p<0.001). Interobserver reproducibility assessment showed very high correlation for Test 1 (ICC_[2,1] = 0.91), and high correlation for Test 2 (ICC_[2,1] = 0.88). The assessment of the intraobserver reproducibility showed high correlation for evaluator A (ICC_[2,1] = 0.86) and evaluator B (ICC_[2,1] = 0.77).

Conclusions

MIP_uni presented higher values when compared with MIP_sta and proved to be reproducible in subjects with spontaneous breathing without artificial airway.     

Kefir Grains Change Fatty Acid Profile of Milk during Fermentation and Storage

Several studies have reported that lactic acid bacteria may increase the production of free fatty acids by lipolysis of milk fat, though no studies have been found in the literature showing the effect of kefir grains on the composition of fatty acids in milk. In this study the influence of kefir grains from different origins [Rio de Janeiro (AR), Viçosa (AV) e Lavras (AD)], different time of storage, and different fat content on the fatty acid content of cow milk after fermentation was investigated. Fatty acid composition was determined by gas chromatography. Values were considered significantly different when p<0.05. The highest palmitic acid content, which is antimutagenic compost, was seen in AV grain (36.6g/100g fatty acids), which may have contributed to increasing the antimutagenic potential in fermented milk. Higher monounsaturated fatty acid (25.8g/100g fatty acids) and lower saturated fatty acid (72.7g/100g fatty acids) contents were observed in AV, when compared to other grains, due to higher Δ9-desaturase activity (0.31) that improves the nutritional quality of lipids. Higher oleic acid (25.0g/100g fatty acids) and monounsaturated fatty acid (28.2g/100g fatty acids) and lower saturated fatty acid (67.2g/100g fatty acids) contents were found in stored kefir relatively to fermented kefir leading to possible increase of antimutagenic and anticarcinogenic potential and improvement of nutritional quality of lipids in storage milk. Only high-lipidic matrix displayed increase polyunsaturated fatty acids after fermentation. These findings open up new areas of study related to optimizing desaturase activity during fermentation in order to obtaining a fermented product with higher nutritional lipid quality.     

In and out of refugia: historical patterns of diversity and demography in the North American Caesar's mushroom species complex

Some of the effects of past climate dynamics on plant and animal diversity make‐up have been relatively well studied, but to less extent in fungi. Pleistocene refugia are thought to harbour high biological diversity (i.e. phylogenetic lineages and genetic diversity), mainly as a product of increased reproductive isolation and allele conservation. In addition, high extinction rates and genetic erosion are expected in previously glaciated regions. Some of the consequences of past climate dynamics might involve changes in range and population size that can result in divergence and incipient or cryptic speciation. Many of these dynamic processes and patterns can be inferred through phylogenetic and coalescent methods. In this study, we first delimit species within a group of closely related edible ectomycorrhizal Amanita from North America (the American Caesar's mushrooms species complex) using multilocus coalescent‐based approaches; and then address questions related to effects of Pleistocene climate change on the diversity and genetics of the group. Our study includes extensive geographical sampling throughout the distribution range, and DNA sequences from three nuclear protein‐coding genes. Results reveal cryptic diversity and high speciation rates in refugia. Population sizes and expansions seem to be larger at midrange latitudes (Mexican highlands and SE USA). Range shifts are proportional to population size expansions, which were overall more common during the Pleistocene. This study documents responses to past climate change in fungi and also highlights the applicability of the multispecies coalescent in comparative phylogeographical analyses and diversity assessments that include ancestral species.     

Nfu facilitates the maturation of iron‐sulfur proteins and participates in virulence in Staphylococcus aureus

The acquisition and metabolism of iron (Fe) by the human pathogen Staphylococcus aureus is critical for disease progression. S. aureus requires Fe to synthesize inorganic cofactors called iron‐sulfur (Fe‐S) clusters, which are required for functional Fe‐S proteins. In this study we investigated the mechanisms utilized by S. aureus to metabolize Fe‐S clusters. We identified that S. aureus utilizes the Suf biosynthetic system to synthesize Fe‐S clusters and we provide genetic evidence suggesting that the sufU and sufB gene products are essential. Additional biochemical and genetic analyses identified Nfu as an Fe‐S cluster carrier, which aids in the maturation of Fe‐S proteins. We find that deletion of the nfu gene negatively impacts staphylococcal physiology and pathogenicity. A nfu mutant accumulates both increased intracellular non‐incorporated Fe and endogenous reactive oxygen species (ROS) resulting in DNA damage. In addition, a strain lacking Nfu is sensitive to exogenously supplied ROS and reactive nitrogen species. Congruous with ex vivo findings, a nfu mutant strain is more susceptible to oxidative killing by human polymorphonuclear leukocytes and displays decreased tissue colonization in a murine model of infection. We conclude that Nfu is necessary for staphylococcal pathogenesis and establish Fe‐S cluster metabolism as an attractive antimicrobial target.