Talya Finn

Thrombosis associated with acute cytomegalovirus infection: A meta-analysis

BACKGROUND Thrombosis associated with acute cytomegalovirus (CMV) infection has been reported in the medical literature almost 100 times thus far. Still, the clinical characteristics of patients with both conditions have never been systematically reviewed and described. METHODS A literature search was conducted for all (n=97) reports concerning thrombosis associated with acute CMV infection. The current knowledge concerning this unique association and previous clinical experience are presented here. RESULTS The incidence of thrombosis among acute CMV infection hospitalized patients was 6.4%, and the incidence of acute CMV infection among thrombosis hospitalized patients was 1.9-9.1%. Most (n=64; 65.9%) reported patients were immunocompetent. Mean age of reported patients was 39.7 ± 14.9 years. Female-male ratio was 1:1. DVT/PE, splanchnic vein thrombosis and splenic infarction were the most prevalent thromboses associated with acute CMV infection. While DVT/PE was more prevalent among immunocompromised patients, splanchnic vein thrombosis was more prevalent among immunocompetent patients. Inherited predispositions for thrombosis were significantly more prevalent among immunocompetent patients. Immunocompromised patients were treated with antiviral agents significantly more often. Duration of anticoagulation therapy varied significantly between reported patients. In-hospital mortality rates were 4.9-22.2%. CONCLUSIONS We believe physicians should be alert for symptoms and signs of thrombosis in patients with acute CMV infection, and for symptoms and signs of acute CMV infection in patients with thrombosis.

Multidrug-Resistant Candida haemulonii and C. auris, Tel Aviv, Israel

Clinical features and experimentally deduced virulence indicate that C. auris has the greater lethal potential.

Incidence of cytomegalovirus-associated thrombosis and its risk factors: a case-control study.

INTRODUCTION Cytomegalovirus (CMV)-associated thrombosis has been reported sporadically in the medical literature until now. However, thrombosis incidence and its risk factors have never been studied in a cohort of patients with acute CMV infection. MATERIALS AND METHODS A retrospective case-control study. Medical charts and imaging study reports of all consecutive patients diagnosed with acute CMV infection during the years 2005-2006 in a tertiary medical center were reviewed for the presence of arterial and/or venous thromboses, and their acquired as well as inherited predispositions. The control group included age-matched and sex-matched consecutive patients, in whom acute CMV infection was excluded. Laboratory tests used for acute CMV infection diagnosis/exclusion were also matched, including serology, antigenemia, and PCR. RESULTS Included were 140 patients with acute CMV infection (study group) and 140 consecutive matched patients in whom acute CMV infection was excluded (control group). Among the control group, none of the patients had thrombosis, while among the study group, nine (6.4%; p=0.003) patients had thrombosis: five (3.6%; p=0.025) patients had arterial thrombosis and four (2.9%; p=0.045) patients had venous thrombosis. Binary logistic regression analysis showed that acute CMV infection was independently associated with thrombosis among the whole cohort (p=0.004), while use of oral contraceptives/hormones or pregnancy were independently associated with thrombosis among patients with acute CMV infection (p=0.043). CONCLUSIONS Thrombosis in patients with acute CMV infection is not rare. Acute CMV infection is associated with thrombosis independent of other risk factors for thrombosis. We hope to raise physicians awareness to the association between acute CMV infection and thrombosis.

Vitamin D deficiency prevalence and cardiovascular risk in Israel

Eur J Clin Invest 2011; 41 (3): 263–268

Waist circumference as the predominant contributor to the micro-inflammatory response in the metabolic syndrome: a cross sectional study

BackgroundThe metabolic syndrome (MetS) is associated with the presence of low grade inflammation. Our aim was to analyze the inter-relations between each of the components of the metabolic syndrome (MetS) and four inflammatory markers, namely high sensitivity C-reactive protein (hs-CRP), the erythrocyte sedimentation rate, the concentration of fibrinogen and the white blood cell count.MethodsWe have analyzed data collected between September 2002 and June 2009 in the Tel-Aviv medical center inflammation survey (TAMCIS). We recruited both apparently healthy individuals and individuals presenting with atherothrombotic risk factors. All participants were enrolled during their routine annual health check-up and gave their written informed consent. This is a cross sectional study in which we have fitted linear regression models using inflammatory markers as the dependant variables and adjust them according to the different components of the MetS and multiple other confounders.ResultsIncluded were 12,072 individuals of whom there were 7,760 men at a mean (S.D.) age of 44 (11) years, and 4,312 women aged 44 (11) years. A significant correlation was noted between most components of the MetS and all inflammatory markers, the most significant one being with hs-CRP. In the multi-adjusted regression analysis, waist was the factor that best explained the variability of hs-CRP, in both women and men. It also remained a significant variable for the other inflammatory markers.ConclusionsFrom amongst the various components of the MetS, waist circumference appears to exert the most influence upon the presence and intensity of the micro-inflammatory response.

Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence

ABSTRACT Candida glabrata causes persistent infections in patients treated with fluconazole and often acquires resistance following exposure to the drug. Here we found that clinical strains of C. glabrata exhibit cell-to-cell variation in drug response (heteroresistance). We used population analysis profiling (PAP) to assess fluconazole heteroresistance (FLCHR) and to ask if it is a binary trait or a continuous phenotype. Thirty (57.6%) of 52 fluconazole-sensitive clinical C. glabrata isolates met accepted dichotomous criteria for FLCHR. However, quantitative grading of FLCHR by using the area under the PAP curve (AUC) revealed a continuous distribution across a wide range of values, suggesting that all isolates exhibit some degree of heteroresistance. The AUC correlated with rhodamine 6G efflux and was associated with upregulation of the CDR1 and PDH1 genes, encoding ATP-binding cassette (ABC) transmembrane transporters, implying that HetR populations exhibit higher levels of drug efflux. Highly FLCHR C. glabrata was recovered more frequently than nonheteroresistant C. glabrata from hematogenously infected immunocompetent mice following treatment with high-dose fluconazole (45.8% versus 15%, P = 0.029). Phylogenetic analysis revealed some phenotypic clustering but also variations in FLCHR within clonal groups, suggesting both genetic and epigenetic determinants of heteroresistance. Collectively, these results establish heteroresistance to fluconazole as a graded phenotype associated with ABC transporter upregulation and fluconazole efflux. Heteroresistance may explain the propensity of C. glabrata for persistent infection and the emergence of breakthrough resistance to fluconazole. IMPORTANCE Heteroresistance refers to variability in the response to a drug within a clonal cell population. This phenomenon may have crucial importance for the way we look at antimicrobial resistance, as heteroresistant strains are not detected by standard laboratory susceptibility testing and may be associated with failure of antimicrobial therapy. We describe for the first time heteroresistance to fluconazole in C. glabrata, a finding that may explain the propensity of this pathogen to acquire resistance following exposure to fluconazole and to persist despite treatment. We found that, rather than being a binary all-or-none trait, heteroresistance was a continuously distributed phenotype associated with increased expression of genes that encode energy-dependent drug efflux transporters. Moreover, we show that heteroresistance is associated with failure of fluconazole to clear infection with C. glabrata. Together, these findings provide an empirical framework for determining and quantifying heteroresistance in C. glabrata. Heteroresistance refers to variability in the response to a drug within a clonal cell population. This phenomenon may have crucial importance for the way we look at antimicrobial resistance, as heteroresistant strains are not detected by standard laboratory susceptibility testing and may be associated with failure of antimicrobial therapy. We describe for the first time heteroresistance to fluconazole in C. glabrata, a finding that may explain the propensity of this pathogen to acquire resistance following exposure to fluconazole and to persist despite treatment. We found that, rather than being a binary all-or-none trait, heteroresistance was a continuously distributed phenotype associated with increased expression of genes that encode energy-dependent drug efflux transporters. Moreover, we show that heteroresistance is associated with failure of fluconazole to clear infection with C. glabrata. Together, these findings provide an empirical framework for determining and quantifying heteroresistance in C. glabrata.

Significantly elevated C-reactive protein serum levels are associated with very high 30-day mortality rates in hospitalized medical patients

BACKGROUND There is insufficient data regarding the differential diagnosis and the prognostic value of significantly elevated serum levels of C-reactive protein (CRP) in hospitalized medical patients. DESIGN AND METHODS A retrospective review of medical charts of patients admitted to a tertiary hospitals Internal Medicine ward during a period of 1 year who had at least one CRP serum level measurement of 200mg/L or more. RESULTS Overall, 341 patients with a mean age of 69.8+/-1.0 years were included in the study. Acute infection was the most prevalent diagnosis (n=293; 85.9%) with community-acquired pneumonia being the most common acute infection (n=115; 33.7%). Non-infectious conditions accounted for 9.1% (n=31) of the diagnoses and included mainly malignant metastatic diseases (n=19; 5.6%). Overall, 70 (20.5%) patients died within 30 days of admission. Age and active malignancy, with metastasis or without metastasis, were independently associated with 30-day mortality. CONCLUSION Significantly elevated CRP serum levels are associated with bacterial infections, malignant diseases, and very high rates of 30-day mortality in hospitalized medical patients.

The herd effects of infant PCV7/PCV13 sequential implementation on adult invasive pneumococcal disease, six years post implementation; a nationwide study in Israel

BACKGROUND Introduction of pneumococcal conjugate vaccine (PCV) has nearly eliminated vaccine-type (VT) invasive pneumococcal disease (IPD) in children, yet the reported resulting reduction of adult IPD is variable. We present the indirect impact of sequential PCV7/PCV13 implementation in Israel on adult IPD. METHODS An ongoing nationwide active surveillance was initiated on July 2009 when PCV7 was implemented (with Catch-up). PCV7 was gradually replaced by PCV13 since November 2010. Comorbidity and outcome data were collected from medical files. Incidence rates were calculated for overall and vaccine-type IPD. RESULTS A total of 2579 IPD cases were diagnosed among a population of 5.0-5.5 million adults >18y (2009-2015). Incidence rates were 9.15/100,000 and 10.16/100,000 in the first and second study years, respectively. However, after PCV13 implementation, the rates decreased to 7.19 within four years, and remained stable in the two following years. Within 6years, PCV7-VT-IPD incidence decreased from 2.52 to 0.52 (79%) and PCV13-VT-IPD from 6.15 to 1.81 (71%). Concurrently, non-VT13 incidence increased from 2.99 to 5.25. Approximately 50% of all patients were adults ≥65y, in whom the decrease in PCV13-VT-IPD incidence was smaller and slower (65% vs. >80% decrease in adults <50y). CONCLUSIONS Despite continued reduction in PCV13-VT-IPD, overall IPD was stable during the last two years due to serotype replacement. Yet, the significant decrease in adult IPD, six years post-PCV7/13 implementation emphasizes the importance of indirect protection in achieving overall population impact and should be considered when discussing the potential additional benefits of direct adult PCV vaccination.

Comparison of different anthropometric measurements and inflammatory biomarkers.

Introduction. Different anthropometric variables have been shown to be related to cardiovascular morbidity and mortality. Our aim was to compare the association between different anthropometric measurements and inflammatory status. Methods and results. A cross-sectional study design in which we analyzed the data collected during a five-year period in the Tel Aviv Medical Center Inflammation Survey (TAMCIS). Included in the study were 13,033 apparently healthy individuals at a mean (SD) age of 43. Of these, 8,292 were male and 4,741 female. A significant age-adjusted and multiple-adjusted partial correlation was noted between all anthropometric measurements and all inflammatory biomarkers. There was no significant difference in the correlation coefficients between different biomarkers and anthropometric variables. Conclusion. Most of the common used anthropometric variables are similarly correlated with inflammatory variables. The clinician can choose the variable that he/she finds easiest to use.

Prognostic implications of fluid balance in ST elevation myocardial infarction complicated by cardiogenic shock

Background: Positive fluid balance has been associated with adverse outcomes in patients admitted to general intensive care units. We analysed the relationship between a positive fluid balance and its persistence over time in terms of in-hospital outcomes among ST elevation myocardial infarction (STEMI) patients complicated by cardiogenic shock. Methods: We retrospectively studied fluid intake and output for 96 hours following hospital admission in 48 consecutive adult patients with STEMI complicated by cardiogenic shock, all undergoing primary angioplasty. Daily and accumulated fluid balance was registered at up to 96 hours following admission. The cohort was stratified into two groups based on the presence or absence of positive fluid balance on day 4. Patients’ records were assessed for in-hospital adverse outcomes, as well as 30-day all-cause mortality. Results: A positive fluid balance was present in 19/48 patients (40%). Patients with positive fluid balance were older and more likely to be treated by intra-aortic balloon counter-pulsation and antibiotics. These patients were more likely to develop acute kidney injury and to need new intubation and were less likely to have renal function recovery as well as successful weaning from mechanical ventilation (p < 0.05 for all). Patients with positive fluid balance had higher 30-day mortality (68% vs. 10%; p < 0.001). In a multivariate Cox regression model, for every 1-L increase in positive fluid balance, the adjusted risk for 30-day mortality increased by 24% (hazard ratio: 1.24, 95% confidence interval: 1.07–1.42; p = 0.003). Conclusions: A positive fluid balance was strongly associated with higher 30-day mortality in STEMI complicated by cardiogenic shock.