Search

Background: Universally accepted and validated instruments for predicting the outcome of patients presenting to the emergency department (ED) with severe dyspnoea do not exist so far, nor are they regularly used by the emergency physicians. This study hence aimed to establish whether red blood cell distribution width (RDW) may be a predictive parameter of 1-year mortality in a population of patients admitted to the ED with severe dyspnoea attributable to different underlying disorders. Methods: We retrospectively evaluated all the patients undergoing arterial blood gas analysis for severe dyspnoea (irrespective of the cause) during admission to ED of University Hospital of Verona from September 1, 2014 to November 31, 2014. Results: The final study population consisted of 287 patients for whom complete clinical and laboratory information was available. Overall, 36 patients (12.5%) died after a 1-year follow-up. The RDW value was found to be considerably increased in patients who deceased during the follow-up compared to those who survived (17.2% versus 14.8%; p 15.0% displayed a 72% increased risk of 1-year mortality after multiple adjustments. Conclusions: The measurement of RDW, a very simple and inexpensive laboratory parameter, may represent an important factor for predicting medium-term mortality in patients presenting to the ED with severe dyspnoea.

Background: The effects of fermented food consumption on the small intestine microbiome and its role on host homeostasis are largely uncharacterised as our knowledge on intestinal microbiota relies mainly on faecal samples analysis. We investigated changes in small intestinal microbial composition and functionality, short chain fatty acid (SCFA) profiles, and on gastro-intestinal (GI) permeability in ileostomy subjects upon the consumption of fermented milk products., Results: We report the results from a randomised, cross-over, explorative study where 16 ileostomy subjects underwent 3, 2-week intervention periods. In each period, they consumed either milk fermented by Lacticaseibacillus rhamnosus CNCM I-3690, or milk fermented by Streptococcus thermophilus CNCM I-1630 and Lactobacillus delbrueckii subsp. bulgaricus CNCM I-1519, or a chemically acidified milk (placebo) daily. We performed metataxonomic, metatranscriptomic analysis, and SCFA profiling of ileostomy effluents as well as a sugar permeability test to investigate the microbiome impact of these interventions and their potential effect on mucosal barrier function. Consumption of the intervention products impacted the overall small intestinal microbiome composition and functionality, mainly due to the introduction of the product-derived bacteria that reach in several samples 50% of the total microbial community. The interventions did not affect the SCFA levels in ileostoma effluent, or gastro-intestinal permeability and the effects on the endogenous microbial community were negligible. The impact on microbiome composition was highly personalised, and we identified the poorly characterised bacterial family, Peptostreptococcaceae, to be positively associated with a low abundance of the ingested bacteria. Activity profiling of the microbiota revealed that carbon- versus amino acid-derived energy metabolism of the endogenous microbiome could be responsible for the individual-specific intervention effects on the small intestine microbiome composition and function, reflected also on urine microbial metabolites generated through proteolytic fermentation., Conclusions: The ingested bacteria are the main drivers of the intervention effect on the small intestinal microbiota composition. Their transient abundance level is highly personalised and influenced by the energy metabolism of the ecosystem that is reflected by its microbial composition ( http://www., Clinicaltrials: gov , ID NCT NCT02920294). Video Abstract., (© 2023. The Author(s).)

Fermented foods and beverages are a significant source of dietary bacteria that enter the gastrointestinal (GI) tract. However, little is known about how these microbes survive and adapt to the small intestinal environment. Colony-forming units (CFU) enumeration and viability qPCR of Lacticaseibacillus rhamnosus CNCM I-3690 in the ileal effluent of 10 ileostomy subjects during 12-h post consumption of a dairy product fermented with this strain demonstrated the high level of survival of this strain during human small intestine passage. Metatranscriptome analyses revealed the in situ transcriptome of L. rhamnosus in the small intestine, which was contrasted with transcriptome data obtained from in vitro cultivation. These comparative analyses revealed substantial metabolic adaptations of L. rhamnosus during small intestine transit, including adjustments of carbohydrate metabolism, surface-protein expression, and translation machinery. The prominent presence of L. rhamnosus in the effluent samples did not elicit an appreciable effect on the composition of the endogenous small intestine microbiome, but significantly altered the ecosystem's overall activity profile, particularly of pathways associated with carbohydrate metabolism. Strikingly, two of the previously recognized gut-brain metabolic modules expressed in situ by L. rhamnosus (inositol degradation and glutamate synthesis II) are among the most dominantly enriched activities in the ecosystem's activity profile. This study establishes the survival capacity of L. rhamnosus in the human small intestine and highlights its functional adjustment in situ , which we postulate to play a role in the probiotic effects associated with this strain.

Background: The aim of this study was to investigate the association between serum albumin levels in the ED and the severity of SARS-CoV-2 infection., Methods: This is a retrospective observational study conducted from 15 March 2020 to 5 April 2020 at the EDs of three different hospitals in Italy. Data from 296 patients suffering from COVID-19 consecutively evaluated at EDs at which serum albumin levels were routinely measured on patients' arrival in the ED were analysed. Albumin levels were measured, and whether these levels were associated with the presence of severe SARS-CoV-2 infection or 30-day survival was determined. Generalised estimating equation models were used to assess the relationship between albumin and study outcomes, and restricted cubic spline (RCS) regression was used to plot the adjusted dose-effect relationship for possible clinical confounding factors., Results: The mean albumin level recorded on entry was lower in patients with severe SARS-CoV-2 infection than in those whose infections were not severe (3.5 g/dL (SD 0.3) vs 4 g/dL (SD 0.5)) and in patients who had died at 30 days post-ED arrival compared with those who were alive at this time point (3.3 g/dL (SD 0.3) vs 3.8 g/dL (SD 0.4)). Albumin <3.5 g/dL was an independent risk factor for both severe infection and death at 30 days, with adjusted odd ratios of 2.924 (1.509-5.664) and 2.615 (1.131-6.051), respectively. RCS analysis indicated that there was an adjusted dose-response association between the albumin values recorded on ED and the risk of severe infection and death., Conclusion: Albumin levels measured on presentation to the ED may identify patients with SARS-CoV-2 infection in whom inflammatory processes are occurring and serve as a potentially useful marker of disease severity and prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

This study sought to compare point-of-care ultrasound (POCUS) and conventional X-rays for detecting fractures in children. This was a prospective, non-randomized, convenience-sample study conducted in five medical centers. It evaluated pediatric patients with trauma. POCUS and X-ray examination results were treated as dichotomous variables with fracture either present or absent. Descriptive statistics were calculated in addition to prevalence, sensitivity, specificity, positive predictive value and negative predictive value, including 95% confidence intervals (CIs). The Cohen κ coefficient was determined as a measurement of the level of agreement. A total of 554 examinations were performed with POCUS and X-ray. On physical examination, swelling, localized hematoma and functional limitation were found in 66.73%, 33.78% and 53.74% of participants, respectively. The most-studied areas were limbs and hands/feet (58.19% and 38.27%), whereas the thorax was less represented (3.54%). Sensitivity of POCUS was 91.67% (95% CI, 76.41-97.82%) for high-skill providers and 71.50 % (95% CI, 64.75-77.43%) for standard-skill providers. Specificity was 88.89% (95% CI, 73.00-96.34%) and 82.91% (95% CI, 77.82-87.06%) for high- and standard-skill providers, respectively. Positive predictive value was 89.19% (95% CI, 73.64-96.48%) and 75.90% (95% CI, 69.16-81.59%) for high- and standard-skill providers, respectively. Negative predictive value was 91.43% (95% CI, 75.81-97.76%) and 79.44% (95% CI, 74.21-83.87%) for high- and standard-skill providers, respectively. The Cohen κ coefficient showed very good agreement (0.81) for high-skill providers, but moderate agreement (0.54) for standard-skill providers. We noted good diagnostic accuracy of POCUS in evaluating fracture, with excellent sensitivity, specificity, and positive and negative predictive value for high-skill providers., Competing Interests: Conflict of interest disclosure The authors declare that they have no conflict of interest. There is no funding source for this study., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Fucoidan represents fucose-rich sulfated polysaccharides derived from brown seaweeds, which exerts various biological activities applicable for functional foods and therapeutic agents. The objective of the present study was to investigate in vivo effects of fucoidan extracted from Okinawa mozuku ( Cladosiphon okamuranus ), common edible seaweed in Japan, on immune responses and microbiota composition in zebrafish. We treated larvae and adult zebrafish with Okinawa mozuku (OM) fucoidan by immersion (100 and 500 μg/mL, 3 days) and by feeding (3 weeks), respectively. The effect of OM fucoidan on immune responses in zebrafish larvae was evaluated by live imaging of neutrophils and macrophages as well as quantitative polymerase chain reaction of pro- and anti-inflammatory cytokine genes. Whole microbiota of zebrafish larvae and intestinal microbiota of adult zebrafish treated with OM fucoidan were analyzed by Illumina MiSeq pair-end sequencing of the V3-V4 region of 16S rRNA genes. Fucoidan treatment only slightly affected the composition of the larvae microbiota and the number of neutrophils and macrophages, while pro- and anti-inflammatory cytokine gene expression levels were upregulated in the larvae treated with 500 μg/mL OM fucoidan. In contrast, feeding of OM fucoidan clearly altered the intestinal microbiota composition of adult zebrafish, which was characterized by the emergence and predominance of multiple bacterial operational taxonomic units (OTUs) affiliated with Rhizobiaceae and Comamonadaceae at the expense of E. coli -related Enterobacteriaceae, the dominant OTUs throughout the studied samples. These changes were accompanied by decreased expression levels of pro-inflammatory cytokine il1b in the intestines of the adult zebrafish. Our current study provides the first insights into in vivo modulatory effects of fucoidan on microbiota and immune responses of unchallenged zebrafish, which underscores the potential of fucoidan to play a modulatory role in the diet-microbiota-host interplay., (Copyright © 2020 Ikeda-Ohtsubo, López Nadal, Zaccaria, Iha, Kitazawa, Kleerebezem and Brugman.)

Despite its limitations, conventional radiography is the method of choice for fracture evaluation in the emergency department. Only a few studies, moreover in limited populations, have evaluated the possible benefits of ultrasound (US), and especially of point-of-care ultrasound (POCUS), in the diagnosis of fractures. We sought to compare the accuracy of POCUS with that of conventional radiography in the diagnosis of bone fractures. This prospective study with a non-randomly allocated convenience sample was conducted at two academic medical centers. Four physicians, with focused training in musculoskeletal POCUS, evaluated consecutive patients with suspected orthopedic injury. US and X-ray examination results were treated as dichotomous variables with either fracture present or fracture absent. Descriptive statistics were calculated in addition to prevalence, sensitivity, specificity, positive predictive value and negative predictive value including 95% confidence intervals (CIs). Cohen's κ coefficient was determined as a measurement of the level of agreement. Four hundred sixty-nine patients (404 adult and 65 pediatric) ranging in age from 1-97 y were enrolled at two different hospitals. Seven hundred six examinations, both US and X-ray, were performed in 634 suspected fractures in adults (age ≥18 y) and 72 in children. On physical examination, swelling, localized hematoma and functional limitation were found in 64.61%, 34.97% and 53.52, respectively. The sensitivity of US examination was 93.89% (CI: 89.74%-96.49%) for all patients and 94.30% (CI: 89.77%-96.98%) and 91.67% (CI: 76.41%-97.82%) in adult and pediatric groups, respectively. Specificity was 94.13% (CI: 91.53-95.99), 94.56% (CI: 91.89-96.41) and 88.89% (CI: 73.00-96.38) for the whole group, adults and children, respectively. The positive predictive value was 88.48% (CI: 83.62%-92.08%), 88.35% (CI: 82.97%-92.24%) and 89.19% (CI: 73.64%-96.48%) for the whole group, adults and children, respectively. The negative predictive value was 96.98% (CI: 94.86%-98.27%), 97.43% (CI: 95.31%-98.64%) and 91.43% (CI: 75.81%-97.76%) in the three groups, respectively. Cohen's κ coefficient revealed high agreement of 0.87 for both the whole group and adult patients and 0.81 for pediatric patients. We found that POCUS has significant diagnostic accuracy in evaluating fracture compared with plain radiography, with excellent sensitivity, specificity and positive and negative predictive values., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Streptococcus suis is a Gram-positive bacterium and a zoonotic pathogen residing in the nasopharynx or the gastrointestinal tract of pigs with a potential of causing life-threatening invasive disease. It is endemic in the porcine production industry worldwide, and it is also an emerging human pathogen. After invasion, the pathogen adapts to cause bacteremia and disseminates to different organs including the brain. To gain insights in this process, we infected piglets with a highly virulent strain of S. suis, and bacterial transcriptomes were obtained from blood and different organs (brain, joints, and heart) when animals had severe clinical symptoms of infection. Microarrays were used to determine the genome-wide transcriptional profile at different infection sites and during growth in standard growth medium in vitro. We observed differential expression of around 30% of the Open Reading Frames (ORFs) and infection-site specific patterns of gene expression. Genes with major changes in expression were involved in transcriptional regulation, metabolism, nutrient acquisition, stress defenses, and virulence, amongst others, and results were confirmed for a subset of selected genes using RT-qPCR. Mutants were generated in two selected genes, and the encoded proteins, i.e., NADH oxidase and MetQ, were shown to be important virulence factors in coinfection experiments and in vitro assays. The knowledge derived from this study regarding S. suis gene expression in vivo and identification of virulence factors is important for the development of novel diagnostic and therapeutic strategies to control S. suis disease.

Background: Streptococcus suis is a zoonotic pathogen, causing meningitis and septicemia. We previously demonstrated that the gastrointestinal tract (GIT) is an entry site for zoonotic S. suis infection. Here we studied the contribution of Streptococcal adhesin Protein (SadP) to host-pathogen interaction at GIT level., Methods: SadP expression in presence of Intestinal Epithelial Cells (IEC) was compared with expression of other virulence factors by measuring transcript levels using quantitative Real Time PCR (qRT-PCR). SadP variants were identified by phylogenetic analysis of complete DNA sequences. The interaction of SadP knockout and complementation mutants with IEC was tested in vitro., Results: Expression of sadP was significantly increased in presence of IEC. Sequence analysis of 116 invasive strains revealed five SadP sequence variants, correlating with genotype. SadP1, present in zoonotic isolates of clonal complex 1, contributed to binding to both human and porcine IEC and translocation across human IEC. Antibodies against the globotriaosylceramide Gb3/CD77 receptor significantly inhibited adhesion to human IEC., Conclusion: SadP is involved in the host-pathogen interaction in the GIT. Differences between SadP variants may determine different affinities to the Gb3/CD77 host-receptor, contributing to variation in adhesion capacity to host IEC and thus to S. suis zoonotic potential.

Two-component systems (TCS) regulate diverse processes such as virulence, stress responses, metabolism and antibiotic resistance in bacteria but are absent in humans, making them promising targets for novel antibacterials. By incorporating recently described TCS histidine kinase autophosphorylation inhibitors (HKAIs) into ε-poly-L-lysine capped nanoparticles (NPs) we could overcome the Gram negative (Gr-) permeability barrier for the HKAIs. The observed bactericidal activity against Gr- bacteria was shown to be due to the enhanced delivery and internalization of the HKAIs and not an inhibitory or synergistic effect of the NPs. The NPs had no adverse effects on mammalian cell viability or the immune function of macrophages in vitro and showed no signs of toxicity to zebrafish larvae in vivo. These results show that HKAIs are promising antibacterials for both Gr- and Gr+pathogens and that NPs are a safe drug delivery technology that can enhance the selectivity and efficacy of HKAIs against bacteria., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In S. suis the ComX-inducing peptide (XIP) pheromone regulates ComR-dependent transcriptional activation of comX (or sigX ) the regulator of the late competence regulon. The aims of this study were to identify the ComR-regulated genes and in S. suis using genome-wide transcriptomics and identify their function based on orthology and the construction of specific knockout mutants. The ComX regulon we identified, includes all homologs of the "transformasome" a type 4-like pilus DNA binding and transport apparatus identified in Streptococcus pneumoniae, Streptococcus mutans , and Streptococcus thermophilus . A conserved CIN-box (YTACGAAYW), predicted to be bound by ComX, was found in the promoters of operons encoding genes involved in expression of the transformasome. Mutants lacking the major pilin gene comYC were not transformable demonstrating that the DNA uptake pilus is indeed required for competence development in S. suis . Competence was a transient state with the comX regulon shut down after ~15 min even when transcription of comX had not returned to basal levels, indicating other mechanisms control the exit from competence. The ComX regulon also included genes involved in DNA repair including cinA which we showed to be required for high efficiency transformation. In contrast to S. pneumoniae and S. mutans the ComX regulon of S. suis did not include endA which converts the transforming DNA into ssDNA, or ssbA , which protects the transforming ssDNA from degradation. EndA appeared to be essential in S. suis so we could not generate mutants and confirm its role in DNA transformation. Finally, we identified a putative homolog of fratricin, and a putative bacteriocin gene cluster, that were also part of the CIN-box regulon and thus may play a role in DNA release from non-competent cells, enabling gene transfer between S. suis pherotypes or S. suis and other species. S. suis mutants of oppA , the binding subunit of the general oligopeptide transporter were not transformable, suggesting that it is required for the import of XIP.

Natural genetic transformation is a transient, rapidly progressing energy-consuming process characterized by expression of the transformasome and competence-associated regulatory genes. This transient state is tightly controlled to avoid potentially adverse effects of genetic recombination on genome integrity during cell division. We investigated the global response of Streptococcus suis to exposure to the SigX competence-inducing peptide (XIP), and thus to the activation of the competence machinery, using time series analysis together with PCA analysis, gene clustering followed by heatmap visualisation, and GO enrichment analysis. We explored the possible regulatory link between metabolism and competence, and predicted the physiological adaptation of S. suis during competence induction, progression and exit using transcriptome analysis. We showed that competence development is associated with a suppression of basal metabolism, which may have consequences for the microbe's resilience to fluctuations in the environment, as competence is costly in terms of use of energy and protein translation. Furthermore our data suggest that several basal metabolic pathways are incompatible with activation of competence in S. suis. This study also showed that targeting specific pathways during the development of competence, might render S. suis more vulnerable toward novel antibiotic therapies.

Streptococcus suis is an encapsulated Gram-positive bacterium, and the leading cause of sepsis and meningitis in young pigs resulting in considerable economic losses in the porcine industry. It is also considered an emerging zoonotic agent. In the environment, both avirulent and virulent strains occur in pigs, and virulent strains appear to cause disease in both humans and pigs. There is a need for a convenient, reliable and standardized animal model to assess S. suis virulence. A zebrafish (Danio rerio) larvae infection model has several advantages, including transparency of larvae, low cost, ease of use and exemption from ethical legislation up to 6 days post fertilization, but has not been previously established as a model for S. suis. Microinjection of different porcine strains of S. suis in zebrafish larvae resulted in highly reproducible dose- and strain-dependent larval death, strongly correlating with presence of the S. suis capsule and to the original virulence of the strain in pigs. Additionally we compared the virulence of the two-component system mutant of ciaRH, which is attenuated for virulence in both mice and pigs in vivo. Infection of larvae with the ΔciaRH strain resulted in significantly higher survival rate compared to infection with the S10 wild-type strain. Our data demonstrate that zebrafish larvae are a rapid and reliable model to assess the virulence of clinical porcine S. suis isolates.

Here we show that S. suis, a major bacterial pathogen of pigs and emerging pathogen in humans responds to a peptide pheromone by developing competence for DNA transformation. This species does not fall within any of the phylogenetic clusters of streptococci previously shown to regulate competence via peptide pheromones suggesting that more species of streptococci may be naturally competent. Induction of competence was dependent on ComX, a sigma factor that controls the streptococcal late competence regulon, extracellular addition of a comX-inducing peptide (XIP), and ComR, a regulator of comX. XIP was identified as an N-terminally truncated variant of ComS. Different comS alleles are present among strains of S. suis. These comS alleles are not functionally equivalent and appear to operate in conjuction with a cognate ComR to regulate comX through a conserved comR-box promoter. We demonstrate that these 'pherotypes' can be genetically transferred between strains, suggesting that similar approaches might be used to control competence induction in other lactic acid bacteria that lack ComR/ComS homologues but possess comX and the late competence regulon. The approaches described in this paper to identify and optimize peptide-induced competence may also assist other researchers wishing to identify natural competence in other bacteria. Harnessing natural competence is expected to accelerate genetic research on this and other important streptococcal pathogens and to allow high-throughput mutation approaches to be implemented, opening up new avenues for research.

Background: Little is known about the involvement of human herpesviruses 6 and 7 (HHV-6 and HHV-7) in autoimmune connective tissue diseases (ACTD)., Objective: To determine the prevalence of active infection with HHV-6 and HHV-7 in patients with ACTD., Study Design: The presence and quantity of HHV-6 DNA was determined by quantitative real-time PCR in a cross-sectional study of serum, peripheral blood mononuclear cells, and tissues obtained from 58 ACTD patients and 38 healthy subjects (HS). Specific anti-HHV-6 antibody titer was also measured., Results: HHV-6 serum viremia occurred in a significantly higher proportion of ACTD patients compared to HS [26/58 (44.8%) vs. 1/38 (2.6%), p=0.001] with the highest reactivation frequency [7/10 (70%)] observed in patients with scleroderma. Moreover, HHV-6 in serum was associated with ACTD activity (22/38 vs. 4/20, p<0.05). Higher titers of HHV-6 antibodies were found in ACTD patients than in HS, although HHV-6 seroprevalence among patients with ACTD and HS was similar. HHV-7 viremia was not detected in any patients or HS controls., Conclusion: The frequent reactivation of HHV-6 in scleroderma and other ACTD, especially when active, suggests that HHV-6 may play a role in the pathogenesis of these diseases.

Background: The effect of pityriasis rosea (PR) on the outcome of pregnancy has not been previously reported., Objective: We sought to investigate the possible impact of PR in pregnant women., Methods: In all, 38 women who developed PR during pregnancy were observed. In one of them, who developed PR at 10 weeks' gestation and aborted 2 weeks later, plasma, peripheral blood mononuclear cells, maternal skin, and placental and embryonic tissues were studied by quantitative calibrated real-time polymerase chain reaction for human herpesviruses (HHV)-6 and -7. Controls included plasma from 36 healthy blood donors, plasma and paraffin-embedded tissue sections from 12 patients with other dermatitides, and from placental and embryonic tissues from one woman who presented with a 19-week intrauterine fetal death., Results: Of the 38 women, 9 had a premature delivery and 5 miscarried. In particular, 62% of the women who developed PR within 15 weeks' gestation aborted. Neonatal hypotonia, weak motility, and hyporeactivity were noted in 6 cases. In the patient studied in detail, HHV-6 DNA was detected in plasma, peripheral blood mononuclear cells, skin, and placenta and embryonic tissues, whereas HHV-7 DNA was absent. HHV-6 p41 antigen was detected by immunohistochemistry in skin lesions, placenta, and embryonic tissues. No herpesvirus DNA was detected in plasma and tissues from control subjects., Limitations: This is a case series study with a small number of patients., Conclusion: PR may be associated with an active HHV-6 infection. In pregnancy, PR may foreshadow premature delivery with neonatal hypotonia and even fetal demise especially if it develops within 15 weeks' gestation.

Objective: We evaluated the impact of fluconazole prophylaxis for extremely low birth weight infants on invasive candidiasis incidence, invasive candidiasis-related mortality rates, and fluconazole susceptibility of Candida isolates., Methods: Extremely low birth weight infants <5 days of age, except those with liver dysfunction, were eligible for fluconazole prophylaxis. NICU infants (all birth weights) with invasive candidiasis between April 2002 and March 2006 were compared with those with invasive candidiasis before fluconazole prophylaxis (2000-2001)., Results: Twenty-two infants had invasive candidiasis (all candidemia) during fluconazole prophylaxis; before fluconazole prophylaxis, there were 19 cases (candidemia: 17 cases; meningitis: 2 cases). Invasive candidiasis incidence in NICU infants decreased from 0.6% (19 of 3012 infants) before fluconazole prophylaxis to 0.3% (22 of 6393 infants) in 2002-2006 and that in extremely low birth weight infants decreased 3.6-fold. No Candida-attributable deaths occurred during 2002-2006 fluconazole prophylaxis, compared with 4 (21%) before fluconazole prophylaxis. The onset of invasive candidiasis was later during 2002-2006 (23.5 vs 12 days), but risk factors were similar. The invasive candidiasis species distribution remained stable. Of 409 infants who received fluconazole prophylaxis, 119 (29%) received 42 days. Shorter fluconazole prophylaxis duration was related to intravenous access no longer being necessary in 242 cases (59%), noninvasive candidiasis-related death in 29 (7%), hospital transfer in 8 (2%), invasive candidiasis diagnosis in 8 (2%), and transient increase in serum transaminase levels in 4 (1%). One hundred twenty-seven infants (31%) who received fluconazole prophylaxis developed cholestasis during hospitalization, two thirds of whom had other predisposing conditions. On multivariate logistic regression necrotizing enterocolitis and increasing days of total parenteral nutrition, but not increasing number of doses on days of fluconazole, were significantly associated with the development of cholestasis., Conclusion: During 4 years of fluconazole prophylaxis, the incidence of invasive candidiasis and invasive candidiasis-associated mortality rates in extremely low birth weight infants were reduced significantly, without the emergence of fluconazole-resistant Candida species.

We report the case of a 73-year-old man who had been on hydroxyurea for essential thrombocythemia since 1988. After 12 years of treatment he developed a symmetrical dermatomyositis-like eruption together with a leg ulceration and five squamous cell carcinomas of the face. The possible pathogenetic mechanisms of these known side effects are discussed.

Objectives: We assessed the impact of intravenous fluconazole prophylaxis (FP) in extremely low birth weight (ELBW [<1000 g]) infants on the incidence of and outcome from invasive candidiasis (IC) in all infants admitted to a neonatal intensive care unit (NICU)., Study Design: Beginning April 1, 2002, FP was given to ELBW infants aged < 5 days admitted to the NICU of Woman's Hospital of Texas. Infants in NICU in whom IC developed during the first 2 years of FP (FP period) were compared with those with IC during 2000-2001., Results: During 2000-2001 and the FP period, the incidence of IC in ELBW infants decreased from 7% (15 of 206) to 2% (5 of 240) (P=.01), and the IC-related mortality rate decreased from 12% (4 of 33) to 0 (0 of 40) (P=.04); the incidence of IC increased from 0.1% (4 of 2806) to 0.2% (8 of 3372) in infants of birth weight > or = 1000 g (P=.06), and no IC-related deaths occurred. During the FP period, IC developed in older infants (24 vs 12 days; P=.12) who had similar risk factors for IC., Conclusion: Invasive candidiasis occurred in our NICU in spite of FP and shifted to bigger, more mature infants who had a better outcome.