Safety and tolerability of sputum induction in adolescents and adults with suspected pulmonary tuberculosis

Sputum induction by the inhalation of hypertonic saline may increase the yield of microbiological diagnosis of pulmonary tuberculosis (TB). This is particularly relevant in paucibacillary TB, such as in children or human immunodeficiency virus (HIV)-infected patients. Sputum induction must be shown to be safe and tolerable in community settings where invasive diagnostic methods are unavailable. The objective of this study was to describe the changes in physiological parameters and adverse events occurring during sputum induction in ambulatory adult and adolescent TB suspects recruited in community clinics. Sputum induction was performed in HIV-infected (n = 35) and HIV-uninfected (n = 67) TB suspects (n = 102). Oxygen saturation (%), blood pressure (mm Hg), heart rate (/minute), respiratory rate (/minute), and adverse events were monitored at baseline, continuously during the salbutamol pre-treatment and saline nebulization phases, and for 30 min afterwards. During nebulization, there was a statistically significant increase in oxygen saturation (1%, p < 0.0001), systolic BP (7 mm Hg, p < 0.0001), and diastolic BP (2 mm Hg, p = 0.008). Post-nebulization decrease in the systolic BP occurred (4 mm Hg, p = 0.016). These changes were not considered to be clinically significant. Eight minor, transitory, self-resolving adverse events occurred (labored breathing, n = 2; chest pain, n = 2; paroxysmal coughing, n = 1; elevated heart rate, n = 1; vomiting, n = 1; hypotension, n = 1), leading to procedure termination in four participants. No serious adverse events occurred. Induced sputum is safe, tolerable, and feasible in adult and adolescent TB suspects in a community healthcare setting.     

Necrotizing fasciitis caused by <Emphasis Type="Italic">Vibrio vulnificus</Emphasis>: epidemiology,clinical findings,treatment and prevention

Necrotizing fasciitis is a soft-tissue infection with a high risk of fatality. Infection with Vibrio vulnificus can lead to development of necrotizing fasciitis and primary septicemia, and occurs mostly in immunocompromised host-associated diseases such as hepatic disease, diabetes mellitus, chronic renal insufficiency, and adrenal insufficiency. Early recognition and treatment of the infection, which are unclear, are vital to patient welfare. We studied the disease epidemiology and reviewed the prognosis and clinical features of patients treated using our developed protocol. Clinical manifestations and outcomes were retrospectively analyzed for 67 patients with V. vulnificus-mediated necrotizing fasciitis and sepsis. All patients who had contacted seawater or raw seafood with positive culture for vibrio were included. Patients were divided into two groups based on the timing of first fasciotomy and injury; within 24 h (group A) and beyond 24 h (group B). Twenty-three of the 67 patients (40%) had hepatic disease, 17 (25.4%) had chronic renal insufficiency, and 12 (17.9%) exhibited adrenal insufficiency. The most common site of infection was the upper extremity (74.7%). Group B presented with more clinical symptoms including fever (p = 0.02), hemorrhagic bullae (p < 0.0001), and shock (p = 0.007). Group A patients exhibited enhanced survival compared to group B (in hospital mortality: 4.9% vs. 23%; p = 0.005). We conclude that early and appropriate diagnosis for V. vulnificus infection should be made, especially in patients presenting with atypical clinical findings. Early fasciotomy within 24 h remains the highest priority and decreases the mortality rate.     

Impact of administration of vancomycin or linezolid to critically ill patients with impaired renal function

The aim of this study was to assess the impact of vancomycin (VAN) versus linezolid (LZD) on renal function in patients with renal failure (RF) admitted to intensive care units. This was a multicenter, retrospective, comparative cohort study. Renal failure patients were treated with VAN or LZD for proven or suspected infections by multiresistant Gram-positive cocci. Changes in plasma creatinine levels and creatinine clearance at the start and end of treatment were used as endpoints. A total of 147 patients were treated with VAN (group A, n = 68) or LZD (group B, n = 79). Group B included more patients with diabetes mellitus [9 (13.2%) vs. 25 (31.6%); p = 0.007], septic shock [39 (57.4%) vs. 60 (75.9%); p = 0.013] and greater RF (mean ClCr 42.24 ml/min vs. 37.57 ml/min; p = 0.04). Renal function improved in patients from both groups who did not require renal replacement therapy. A greater improvement was seen in group B [percent decrease in Cr (27.94 vs. 9.48; p = 0.02) and percent increase in ClCr (95.96 vs. 55.06; p = 0.05)]. In group A, nine patients (13.2%) experienced an antibiotic-related increase in RF, and antibiotic was discontinued in five patients due to adverse effects. It is reasonable to avoid use of VAN in critically ill patients with acute renal failure.     

Increased Extracellular Survivin in the Synovial Fluid of Rheumatoid Arthritis Patients: Fibroblast-like Synoviocytes as a Potential Source of Extracellular Survivin

Survivin belongs to the family of inhibitor of apoptosis proteins and plays an important role in the hyperplastic growth of tissues and tumors. In this study, we assessed the expression of survivin in rheumatoid synovial fluids (SF) and synovial tissues (ST) of rheumatoid arthritis (RA) patients in order to investigate the role of extracellular survivin in the pathogenesis of RA. The survivin level from SF was significantly higher in RA patients (n = 38) than in osteoarthritis patients (n = 18; 10.68 ± 2.76 vs. 1.0 ± 0.56 pg/ml, p = 0.02). In addition, SF survivin level was higher in erosive RA patients (n = 23) than in non-erosive RA patients (n = 15; 15.26 ± 4.26 vs. 4.47 ± 1.12 pg/ml, p = 0.05). SF survivin level in RA was positively correlated with disease activity score 28, but did not reach statistical significance (r = 0.309, p = 0.07). RA SF survivin level was also positively correlated with peripheral blood leukocyte counts (r = 0.443, p = 0.005). The immunohistochemical staining and Western blot analysis revealed survivin expression in the ST and fibroblast-like synoviocytes of RA patients, respectively. These findings suggest that extracellular survivin may be produced from rheumatoid FLS and may play an important role in the destructive RA process.     

Epidemiology of Streptococcus pneumoniae and Staphylococcus aureus colonization in healthy Venezuelan children

Streptococcus pneumoniae and Staphylococcus aureus cause significant morbidity and mortality worldwide. We investigated both the colonization and co-colonization characteristics for these pathogens among 250 healthy children from 2 to 5 years of age in Merida, Venezuela, in 2007. The prevalence of S. pneumoniae colonization, S. aureus colonization, and S. pneumoniae–S. aureus co-colonization was 28%, 56%, and 16%, respectively. Pneumococcal serotypes 6B (14%), 19F (12%), 23F (12%), 15 (9%), 6A (8%), 11 (8%), 23A (6%), and 34 (6%) were the most prevalent. Non-respiratory atopy was a risk factor for S. aureus colonization (p = 0.017). Vaccine serotypes were negatively associated with preceding respiratory infection (p = 0.02) and with S. aureus colonization (p = 0.03). We observed a high prevalence of pneumococcal resistance against trimethoprim–sulfamethoxazole (40%), erythromycin (38%), and penicillin (14%). Semi-quantitative measurement of pneumococcal colonization density showed that children with young siblings and low socioeconomic status were more densely colonized (p = 0.02 and p = 0.02, respectively). In contrast, trimethoprim–sulfamethoxazole- and multidrug-resistant-pneumococci colonized children sparsely (p = 0.03 and p = 0.01, respectively). Our data form an important basis to monitor the future impact of pneumococcal vaccination on bacterial colonization, as well as to recommend a rationalized and restrictive antimicrobial use in our community.     

Thyroid hormones and their correlations with serum glucose, beta hydroxybutyrate, nonesterified fatty acids, cholesterol, and lipoproteins of high-yielding dairy cows at different stages of lactation cycle

The relationships between circulating thyroid hormones and serum glucose, beta hydroxybutyrate (BHB), nonesterified fatty acid (NEFA), cholesterol and lipoproteins of high-yielding dairy cows were studied in 125 adult Holsteins at various stages of lactation cycle: early (far-off) dry period (n = 24), late (close-up) dry period (n = 10), fresh cows (n = 22), early lactation (n = 13), mid-lactation (n = 27) and late lactation (n = 29). Decreased levels of thyroxin (T₄) and triiodothyronine (T₃) were noted in peripartum cows which were extended to mid- and late-lactation cows, respectively. In fresh cows, glucose showed correlations with T₄ (r = 0.619, P < 0.01) and T₃ (r = 0.627, P < 0.01). In the same cows there were correlations between T₄ and BHB (r = 0.590, P < 0.01) and NEFA (r = 0.470, P < 0.01). In late dry cows, free thyroxin (fT₄) showed correlations with triglyceride (TG) and very-low-density lipoprotein (VLDL; r = −0.638, P < 0.05). Pooled data of the various stages of lactation cycle revealed correlations between glucose and T₄ (r = 0.20, P < 0.05), glucose and T₃ (r = 0.395, P < 0.01), cholesterol and T₃ (r = −0.201, P < 0.05), and free triiodothyronine (fT₃) and high-density lipoprotein (HDL; r = 0.178, P < 0.05). It appears that the time and the pattern of changes and/or correlations of serum thyroid hormones and lipid fractions may vary among dairy cows and other animals.     

Differentiation of <Emphasis Type="Italic">Mycobacterium kansasii</Emphasis> infection from <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> infection: comparison of clinical features,radiological appearance,and outcome

This retrospective study sought to systematically identify clinical and radiological features differentiating Mycobacterium kansasii from Mycobacterium tuberculosis infection. The sample included matched patients with a culture-positive diagnosis of M. tuberculosis infection (n = 121) or M. kansasii infection (n = 62) derived from the databases of two tuberculosis centers. Data on patient background and clinical features were collected, and chest radiographs were analyzed. Sixty percent of the M. kansasii group were native Israelis compared to 15% of the M. tuberculosis group (p = 0.0001). M. tuberculosis infection was associated with a higher rate of human immunodeficiency virus (HIV) infection (p = 0.03) and M. kansasii infection with a higher rate of lung disease (p = 0.0001). M. tuberculosis infection was characterized by a higher likelihood of bilateral disease (p = 0.005), pleural effusions, and lymphadenopathy (p = 0.006 and p = 0.001, respectively). There were ten deaths, all in the M. tuberculosis group. On multivariate logistic regression, the presence of chronic obstructive pulmonary disease and associated lung disease were significant predictors of M. kansasii infection. The findings show that there are group differences between the clinical features of the two infections. In the setting of pulmonary mycobacterial infection, the presence of coinfection with HIV, bilateral disease, pleural effusion, and lymphadenopathy make M. kansasii infection very unlikely.     

Prevalence of toxin genes in consecutive clinical isolates of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> and clinical impact

Even if Panton–Valentine leukocidin (PVL), toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxins (SEB and SEC), and exfoliative toxins (ETA and ETB) may be associated with severe infections, the clinical significance of their presence in clinical isolates of Staphylococcus aureus remains poorly documented. In this study, we evaluated the prevalence of toxin genes and the relationship between their presence and the severity of infection. We screened for the presence of these six toxin genes among 186 consecutive S. aureus clinical isolates (resistant or not to methicillin) during a two-month period. We compared the toxin gene profile between strains recovered from patients presenting uncomplicated infections (n = 151) and from patients suffering from severe infections (n = 35). At least one toxin gene was detected in 55 (29.6%) isolates as follows: pvl (n = 1), tst + sec (n = 5), seb (n = 19), seb + sec (n = 1), sec (n = 28), and eta (n = 1). The proportion of toxin-producing strains among patients with uncomplicated infections (27.8%) and patients with severe infections (37.1%) was not statistically different (p = 0.3044), even if the severity of infection tended to be associated with the presence of sec (p = 0.0655). Although the prevalence of toxin genes was relatively high herein, no statistically significant association between the severity of infection and the presence of toxin genes was observed.     

Obesity-dependent association of TNF-LTA locus with type 2 diabetes in North Indians

Six common genetic variants (rs2229094, rs1041981, rs1800630, rs1800629, rs361525, and rs1800610) in the TNF-LTA locus encoding the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and lymphotoxin-α have been shown to be associated with various metabolic traits including susceptibility to type 2 diabetes, metabolic syndrome, insulin resistance, and increased body mass index (BMI) in Caucasians from different geographic locations and have yielded mixed results. We tested for the association of these variants with type 2 diabetes in North Indians by studying 2,115 participants comprising of 1,073 type 2 diabetes patients and 1,042 controls. We report the association of a promoter region variant of TNF: rs1800630 and non-synonymous LTA variant: rs2229094 with type 2 diabetes [OR = 0.83 (95% CI 0.72–0.95), P = 0.005 and OR = 0.86 (95% CI 0.75–0.98), P = 0.02, respectively]. Although these associations were BMI-dependent, no interactive effect of BMI and variants on type 2 diabetes was detectable. Further, the haplotype carrying all the six major alleles conferred susceptibility to type 2 diabetes [OR = 1.23 (95% CI 1.06–1.42), P = 0.005; P _permuted = 0.02], with the effect much enhanced in non-obese subjects [OR = 1.45 (95% CI 1.19–1.78), P = 2 × 10⁻⁴: P _permuted = 3 × 10⁻⁴]. The minor allele of rs2229094 was associated with lower hsCRP, BMI, and waist circumference (WC), while the minor allele of rs1800630 showed association with lower BMI and WC (all P < 0.01). This is the first report demonstrating association of rs1800630 and rs2229094 with type 2 diabetes in any population, suggesting an important role of the TNF-LTA locus in type 2 diabetes in North Indians.     

Preliminary Evidence for the Cross-Cultural Utility of the Type D Personality Construct in the Ukraine

Background  Type D personality is a risk indicator in cardiac patients. The validity and reliability of the Type D Scale (DS14) have been confirmed in Western Europe but not outside this context. Purpose  We examined the structural, convergent, and divergent validity and the reliability of the DS14 in the Ukrainian setting. Method  Healthy Ukrainian respondents (n = 250) completed the DS14, the Eysenck Personality Questionnaire, the State Trait Anxiety Inventory, and the Beck Depression Inventory. A subsample (n = 57) completed the DS14 again after 4 weeks. Results  The prevalence of Type D personality was 22.4%. The two-factor structure and the validity of the DS14 were confirmed. The DS14 subscales were internally consistent (Cronbach’s α = 0.86/0.71; mean inter-item correlation = 0.48/0.27) and stable over a 4-week period (r = 0.85/0.63). Type D individuals had significantly higher mean scores on anxiety (p < 0.001), depressive symptoms (p < 0.001), and negative affect (p < 0.001), and lower scores on positive affect (p < 0.001) compared to non-Type D individuals. Conclusion  Preliminary evidence suggests that the Ukrainian DS14 is a valid and reliable measure. Future studies are warranted to test the utility of the scale in cardiac patients in the Ukraine, including whether Type D also predicts adverse health outcomes beyond the boundaries of Western Europe.     

Multiplexed analysis of angiogenesis and lymphangiogenesis factors predicts outcome for non-small cell lung cancer patients

Angiogenesis and lymphangiogenesis are key components of non-small cell lung cancer (NSCLC) tumor growth and metastatic spread; however, the prognostic and predictive role of angiogenic and lymphangiogenic biomarkers remains controversial for NSCLC patients. We assessed VEGF, VEGFC, VEGFD, VEGFR3 protein expression, tumor microvessel, and lymphatic vessel (LmVD) density by immunohistochemistry in 103 NSCLC; biomarkers were analyzed individually as well as multiplexed with each other. No correlations were identified between VEGF, VEGFC, VEGFD, or LmVD and clinical characteristics. VEGFR3 was correlated with VEGFC (p = 0.03), VEGFD (p < 0.0001), and intratumor LmVD (p = 0.03). Tumors that did not express VEGFR3 had a worse prognosis (log rank p = 0.03). VEGF was significantly correlated with survival in adenocarcinomas (log rank p = 0.014) but not in squamous cell carcinomas (log rank p = 0.5). Multivariate Cox regression analysis confirmed the independent prognostic potential of VEGFR3 (hazard ratio (HR) = 0.05; 95% confidence intervals (CI) = 0.008–0.32, p = 0.002) for all patients and VEGF (HR = 8.69, 95% CI = 1.4–53.69, p = 0.02) for adenocarcinomas. When biomarkers were multiplexed, only stage and VEGFC expression were independent predictors of survival for all patients. Weighted expression of VEGFC, VEGFR3, and stage was used to build a prognostic classifier for stage I–IIIA patients; patients in the low risk group had prolonged survival compared with high risk patients (log rank p = 0.02). There was no association between biomarkers and early recurrence or response to treatment. Angiogenic and lymphangiogenic biomarkers studied define subgroups of patients at high risk and may be useful for prognostic stratification of NSCLC patients especially those with early stage disease.     

Risk factors for multidrug-resistant tuberculosis in a tuberculosis unit in Madrid,Spain

The setting for this retrospective cohort study was a specialised tuberculosis unit in Madrid, Spain. The objective was to describe the risk factors for multidrug-resistant tuberculosis (MDR-TB). The medical records of all patients admitted to the unit were reviewed retrospectively to identify factors associated with multidrug resistance. Patients with positive culture for M. tuberculosis and with available drug-susceptibility tests were included. The variables assessed were age, gender, country of origin, homelessness, alcohol consumption, intravenous drug use, methadone substitution therapy, contact with a tuberculosis patient, sputum smear, site of disease, previous tuberculosis treatment, HIV infection, history of imprisonment, diabetes mellitus and chronic obstructive pulmonary disease. Thirty patients with MDR-TB and 666 patients with non-MDR-TB were included from the years 1997 to 2006. The only factors associated with MDR-TB in multivariate analysis were previous tuberculosis treatment (OR: 3.44; 95% CI: 1.58–7.50; p = 0.003), age group 45–64 years (OR: 3.24; 95% CI: 1.34–7.81; p = 0.009) and alcohol abuse (OR: 0.12; 95% CI: 0.03 to 0.55; p = 0.003). In our study, patients who had had previous treatment for tuberculosis, who were 45–64 years of age or who had no history of alcohol abuse were more likely to have MDR-TB.     

Anxiety, depression and saliva cortisol in women with a medical disorder during pregnancy

Anxiety and depression during pregnancy increase the risk for an adverse pregnancy outcome and neurodevelopmental problems in the child. The aim of this study was to investigate anxiety and depression in women with a medical disorder of pregnancy compared with control antenatal women, and any association with saliva cortisol. One hundred and twenty pregnant women (60 with a known medical disorder and 60 without, mean gestation 32 weeks) completed five self-rating questionnaires (Spielberger State and Trait Anxiety, Edinburgh Postnatal Depression Scale (EPDS), the Adult Wellbeing Scale and a Life Events Questionnaire). Diurnal saliva samples were obtained from 39 women with a medical disorder and 50 controls for cortisol analysis. The medical disorders group were significantly more anxious and depressed than the controls (mean (SD)) state anxiety 40.0 (11.5) vs. 31.6 (8.8), p = 0.00; trait anxiety 39.4 (9.5) vs. 35.2 (9.2), p = 0.02; adult wellbeing 15.9 (7.5) vs. 12.3 (7.5) p = 0.01; and EPDS 9.6 (5.4) vs. 5.9 (4.8), p = 0.00). There was no difference in the life events scores between the groups. The subgroup of women suffering from hyperemesis gravidarum had particularly high EPDS scores, (16.2 (3), n = 5, p = 0.00) compared with controls. There were no significant differences in the cortisol levels between the groups. Some women with a medical disorder during pregnancy showed considerably elevated levels of anxiety and depression. Health professionals need to be aware that these women need extra psychological support.     

PI3-Kinase-dependent electrogenic intestinal transport of glucose and amino acids

Intestinal glucose and amino acid transport is stimulated by the serum- and glucocorticoid-inducible kinase isoforms SGK1, SGK2, and SGK3 and protein kinase B which are, in turn, stimulated following activation of the phosphoinositol-3 kinase (PI3 kinase). The present study has been performed to explore whether pharmacological inhibition of the PI3 kinase affects electrogenic jejunal transport of glucose and amino acids. In Ussing chamber experiments, glucose (20 mM), phenylalanine (20 mM), glutamine (20 mM), cysteine (20 mM), and proline (20 mM) generated lumen negative currents (I _glc, I _phe, I _gln, I _cys, and I _pro), respectively, which gradually declined following application of the PI3 kinase inhibitor Wortmannin (1 μM). Within 40 min, Wortmannin treatment significantly decreased I _glc by 39 ± 10% (n = 5), I _phe by 70 ± 7% (n = 4), I _gln by 69 ± 8% (n = 4), I _cys by 67 ± 8% (n = 6), and I _prol by 79 ± 12% (n = 3). A similar decline of I _glc was observed following application of the PI3 kinase inhibitor LY294002 (50 μM). Exposure to the inhibitors did not significantly alter transepithelial potential difference and resistance in the absence of substrates for electrogenic transport. The observations suggest that the electrogenic transport of glucose and several amino acids requires the continued activity of PI3 kinase. R. Rexhepaj and F. Artunc shared first authorship.     

Pathology of testis and epididymis in native goats in southern Iran

A slaughterhouse-based survey was conducted to determine the type and the prevalence of lesions in the testis and epididymis of native bucks reared in southern Iran. Testis, epididymis, and tunica, which belonged to 425 bucks of various age groups, were inspected. The specimens were collected randomly during a 6-month period. Various abnormalities in testis and the epididymis were observed. Grossly, testicular mineralization was the most prevalent abnormality (n = 183, 45%) followed by degeneration or hypoplasia (n = 26, 6.4%), adhesion (n = 20, 4.9%), cryptorchidism (n = 12, 2.9%), congenital testicular cyst (n = 9, 2.2%), abscess (n = 4, 0.9%), and orchitis (n = 1, 0.2%). As the age of the bucks increased, the percentages of mineralization increased significantly (p < 0.05). Based on the results of the gross examination, congenital epididymal cysts were the most prevalent abnormality (n = 57, 14.4%) then followed by epididymal abscess (n = 12, 2.9%), melanosis (n = 10, 2.5%), and epididymitis (n = 3, 0.7%). Congenital epididymal cysts, 1 to 2 mm in diameter, were mostly located on the head of the epididymis. On histopathological examination, mineralization showed the highest prevalence rate in testis followed by hypoplasia and degeneration, besnoitiosis, orchitis, and edema. Besnoitiosis was also the predominant lesion in the head and tail of the epididymis followed by epididymitis, hypoplasia or degeneration, melanosis, and sperm granuloma. Besnoitia cysts were found in 11.3% of the testes, 14.1% of the epididymal heads, and 7.5% of the epididymal tails.     

Bloodstream infections among human immunodeficiency virus-infected adult patients: epidemiology and risk factors for mortality

This study was undertaken to describe the epidemiology and sensitivity pattern of pathogens causing community-acquired (CA) and nosocomial (N) bloodstream infection (BSI) in adult HIV-infected patients and to establish risk factors for mortality. The type of study was a retrospective analysis of BSI episodes prospectively collected through a blood culture surveillance program from January 1991 to December 2006. We used non-conditional logistic regression methods with death as a dependent variable. One thousand and seventy-seven episodes of BSI (6%) occurred in HIV-infected patients out of 16,946 episodes during the period of study. CA and N BSI were 634 (59%) and 443 (41%) respectively. S. pneumoniae and S. aureus were the most frequent pathogens (n = 279, 44%) in CA BSI. Coagulase-negative staphylococci and S. aureus were the most frequent micro-organisms isolated in N cases (n = 169, 38%). Cotrimoxazole resistance was common in CA and N BSI and was caused by gram-negative bacilli (50% and 61% respectively). However, resistance rates to ceftriaxone were low (3%). Crude mortality accounted for 140 cases (13%). The independent risk factors associated with mortality were: liver cirrhosis (OR: 2.90, p = 0.001), corticosteroids treatment (OR: 3.51, p < 0.001), neutropenia (OR: 2.21, p = 0.02), inappropriate empirical therapy (OR: 2.44, p = 0.006), and isolate of C. albicans (OR: 7.58, p = 0.010). BSI in adult HIV-infected patients was often caused by gram-positive pathogens in both CA and N settings. Inappropriate empirical therapy and the presence of other immunosuppressive factors were independent risk factors for mortality. Ceftriaxone could be used as the initial empiric therapy for HIV-infected patients with suspected CA BSI. This study was partially presented at the 18th European Congress of Clinical Microbiology and Infectious Diseases (Barcelona, April 2008).     

LYVE-1 upregulation and lymphatic invasion correlate with adverse prognostic factors and lymph node metastasis in neuroblastoma

Neuroblastoma (NB) accounts for 15% of all childhood cancer deaths. The majority of patients have widespread lymphatic and/or haematogenous metastases at diagnosis, but lymphangiogenesis has not been well documented. Sixty-seven NBs were immunostained for the lymphatic endothelial marker, LYVE-1, and the lymphatic density (LD) and lymphatic invasion (LI), were counted in LYVE-1-expressing lymphatics. LYVE-1-stained lymphatic vessels and LI were present in 26/67 (39%) and 14/67 (21%) of the NBs, respectively. Central LD (CLD) and LI were higher in NBs from stage 4 (p = 0.012, p = 0.004, respectively), high-risk group (p = 0.030, p = 0.002), NBs with high mitosis karyorrhexis index (MKI) (p = 0.011, p = 0.005), unfavourable histology group (p = 0.040, p = 0.017) and distant lymph node metastasis (LNM) (p < 0.001 for each). Marginal LD (MLD) was higher in patients with LNM (p < 0.001). CLD and MLD correlated with LI (p < 0.001 each). Total LYVE-1 protein levels, quantified by a sensitive enzyme-linked immunosorbent assay (n = 55), were also higher in NBs from patients with stage 4 disease (p = 0.046), high-risk group (p = 0.028), MYCN-amplified NBs (p = 0.034) and LNM (p = 0.038). Kaplan–Meier analysis showed that the presence of CLD was associated with both worse OS at 5 years (77% [95% CI: 62–87%] versus 60% [95% CI: 32–80%], p = 0.062) and EFS (74% [95% CI: 58–85%] versus 43% [95% CI: 15–69%], p = 0.070) and LI with OS (71% [95% CI: 57–81%] versus 56% [95% CI: 26–78%], p = 0.055). Significant upregulation of LYVE-1 and the presence of LI in patients with stage 4 and high-risk disease, MYCN-amplification and LNM suggests that LYVE-1 may have value as predictors of outcome.     

Proliferating activity in columnar cell lesions of the breast

With the introduction of mammographic screening, columnar cell lesions (CCLs) are observed more and more frequently because they are often associated with microcalcifications. Until now, the proliferative activity of these lesions has not been previously evaluated. Ki67 index was performed by immunohistochemistry in CCLs without atypia [columnar cell change (CCC) n = 20 and columnar cell hyperplasia without atypia (CCH without atypia) n = 20], flat epithelial atypia (FEA DIN1A n = 20), low-grade intraductal carcinoma (DIN1C n = 20), high-grade intraductal carcinoma (DIN 2–3 n = 20). Adjacent terminal duct-lobular unit (TDLU) of normal breast tissue served as control. Ki-67 index is extremely low and close in CCLs without atypia (CCC mean 0.1% and CCH mean 0.76%) and paradoxically is lower than in normal TDLU (mean 2.4%) (p < 0.001). In the FEA, in comparison with normal TDLU and CCLs without atypia, the Ki67 is higher (mean 8.2%) (p < 0.001) but extremely close to those of DIN1C (mean 8.9%) (p = 0.6 NS). Lastly, the Ki67 index is higher in DIN 2–3 (mean 25.4%) than in CCLs without atypia and FEA (p < 0.001). CCLs are disparate lesions having in common cells with columnar configuration but different proliferative characteristics. These data represent findings of biological interest which could help us to better understand these controversial lesions.     

Prognostic value of procalcitonin in <Emphasis Type="Italic">Legionella</Emphasis> pneumonia

The diagnostic reliability and prognostic implications of procalcitonin (PCT) (ng/ml) on admission in patients with community-acquired pneumonia (CAP) due to Legionella pneumophila are unknown. We retrospectively analysed PCT values in 29 patients with microbiologically proven Legionella-CAP admitted to the University Hospital Basel, Switzerland, between 2002 and 2007 and compared them to other markers of infection, namely, C-reactive protein (CRP) (mg/l) and leukocyte count (10⁹/l), and two prognostic severity assessment scores (PSI and CURB65). Laboratory analysis demonstrated that PCT values on admission were >0.1 in over 93%, >0.25 in over 86%, and >0.5 in over 82% of patients with Legionella-CAP. Patients with adverse medical outcomes (59%, n = 17) including need for ICU admission (55%, n = 16) and/or inhospital mortality (14%, n = 4) had significantly higher median PCT values on admission (4.27 [IQR 2.46–9.48] vs 0.97 [IQR 0.29–2.44], p = 0.01), while the PSI (124 [IQR 81–147] vs 94 [IQR 75–116], p = 0.19), the CURB65 (2 [IQR 1–2] vs 1 [1–3], p = 0.47), CRP values (282 [IQR 218–343], p = 0.28 vs 201 [IQR 147–279], p = 0.28), and leukocyte counts (12 [IQR 10–21] vs 12 [IQR 9–15], p = 0.58) were similar. In receiver operating curves, PCT concentrations on admission had a higher prognostic accuracy to predict adverse outcomes (AUC 0.78 [95%CI 0.61–96]) as compared to the PSI (0.64 [95%CI 0.43–0.86], p = 0.23), the CURB65 (0.58 [95%CI 0.36–0.79], p = 0.21), CRP (0.61 [95%CI 0.39–0.84], p = 0.19), and leukocyte count (0.57 [95%CI 0.35–0.78], p = 0.12). Kaplan-Meier curves demonstrated that patients with initial PCT values above the optimal cut-off of 1.5 had a significantly higher risk of death and/or ICU admission (log rank p = 0.003) during the hospital stay. In patients with CAP due to Legionella, PCT levels on admission might be an interesting predictor for adverse medical outcomes. Jeannine Haeuptle, Roya Zaborsky, and Rico Fiumefreddo contributed equally to this article.